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Conserved domains on  [gi|345478677|ref|NP_001230889|]
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E3 ubiquitin-protein ligase NEDD4-like isoform 7 [Homo sapiens]

Protein Classification

C2_NEDD4_NEDD4L and HECTc domain-containing protein( domain architecture ID 11559386)

protein containing domains C2_NEDD4_NEDD4L, WW, and HECTc

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 578-907 3.32e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


:

Pssm-ID: 214523  Cd Length: 328  Bit Score: 510.24  E-value: 3.32e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   578 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 657
Cdd:smart00119   1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   658 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 734
Cdd:smart00119  80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   735 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 814
Cdd:smart00119 160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   815 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 893
Cdd:smart00119 240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                          330
                   ....*....|....
gi 345478677   894 REKLLMAVENAQGF 907
Cdd:smart00119 315 REKLLLAINEGKGF 328
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-153 2.57e-84

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 266.14  E-value: 2.57e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDENRLT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 153
Cdd:cd04033   81 RDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 436-466 4.77e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


:

Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 61.00  E-value: 4.77e-12
                         10        20        30
                 ....*....|....*....|....*....|.
gi 345478677 436 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 466
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 485-517 2.74e-11

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


:

Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 58.77  E-value: 2.74e-11
                           10        20        30
                   ....*....|....*....|....*....|...
gi 345478677   485 PLPPGWEERIHLDGRTFYIDHNSKITQWEDPRL 517
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 198-224 9.33e-10

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


:

Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.43  E-value: 9.33e-10
                          10        20
                  ....*....|....*....|....*..
gi 345478677  198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30
 
Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 578-907 3.32e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


Pssm-ID: 214523  Cd Length: 328  Bit Score: 510.24  E-value: 3.32e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   578 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 657
Cdd:smart00119   1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   658 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 734
Cdd:smart00119  80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   735 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 814
Cdd:smart00119 160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   815 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 893
Cdd:smart00119 240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                          330
                   ....*....|....
gi 345478677   894 REKLLMAVENAQGF 907
Cdd:smart00119 315 REKLLLAINEGKGF 328
HECTc cd00078
HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It ...
 554-908 1.21e-166

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.


Pssm-ID: 238033 [Multi-domain]  Cd Length: 352  Bit Score: 489.00  E-value: 1.21e-166
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 554 FEMKLHRNNIFEESYRRIMSVKRPDvLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINP 633
Cdd:cd00078    1 LKITVRRDRILEDALRQLSKVSSSD-LKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNP 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 634 NSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPT--ELDLMF 711
Cdd:cd00078   80 SSFA-DEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGDedDLELTF 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 712 CIDEEN-FGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCG 790
Cdd:cd00078  159 TIELDSsFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELLICG 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 791 LGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELygsngPQLFTIEQWGSP- 869
Cdd:cd00078  239 SEDIDLEDLKKNTEYKGGYSSDSPTIQWFWEVLESFTNEERKKFLQFVTGSSRLPVGGFADL-----NPKFTIRRVGSPd 313

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 345478677 870 EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 908
Cdd:cd00078  314 DRLPTAHTCFNLLKLPPYSSKEILREKLLYAINEGAGFG 352
HUL4 COG5021
Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];
435-907 9.51e-163

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227354 [Multi-domain]  Cd Length: 872  Bit Score: 497.75  E-value: 9.51e-163
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP-RLKFPVHMRSKTSLNPN-------DLGPLPPGWEERIHLDGRTFYIDHN 506
Cdd:COG5021  388 KPTGWSSSIEDLGQFLFSDFLTSSSTYEDLrREQLGRESDESFYVASNvqqqrasREGPLLSGWKTRLNNLYRFYFVEHR 467

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 507 SKITQWEDPRLQNPA--ITGPAVPYSREFKQKYDYFRKKLKKPADIPnrFEMKLHRNNIFEESYRRIMSvKRPDVLKARL 584
Cdd:COG5021  468 KKTLTKNDSRLGSFIslNKLDIRRIKEDKRRKLFYSLKQKAKIFDPY--LHIKVRRDRVFEDSYREIMD-ESGDDLKKTL 544

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 585 WIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLcNEDHLSYFTFIGRVAGLAVFHGKLLD 664
Cdd:COG5021  545 EIEFVGEEGIDAGGLTREWLFLLSKEMFNPDYGLFEYITEDLYTLPINPLSSI-NPEHLSYFKFLGRVIGKAIYDSRILD 623

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 665 GFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILEN--DPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKRE 742
Cdd:COG5021  624 VQFSKAFYKKLLGKPVSLVDLESLDPELYRSLVWLLNNdiDETILDLTFTVEDDSFGESRTVELIPNGRNISVTNENKKE 703

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 743 YIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGD-VDVNDWRQHSIYKnGYCPNHPVIQWFWK 821
Cdd:COG5021  704 YVKKVVDYKLNKRVEKQFSAFKSGFSEIIPPDLLQIFDESELELLIGGIPEdIDIDDWKSNTAYH-GYTEDSPIIVWFWE 782

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 822 AVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDLREKLLMA 900
Cdd:COG5021  783 IISEFDFEERAKLLQFVTGTSRIPINGFKDLQGSDGVRKFTIEKGGTDdDRLPSAHTCFNRLKLPEYSSKEKLRSKLLTA 862


                 ....*..
gi 345478677 901 VENAQGF 907
Cdd:COG5021  863 INEGAGF 869
HECT pfam00632
HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl ...
 605-908 1.11e-131

HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl Terminus.


Pssm-ID: 459880  Cd Length: 304  Bit Score: 396.98  E-value: 1.11e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  605 FLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCN-EDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLN 683
Cdd:pfam00632   1 TLLSKELFDPNYGLFEYETEDDRTYWFNPSSSESPdLELLDYFKFLGKLLGKAIYNGILLDLPFPPFFYKKLLGEPLTLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  684 DMESVDSEYYNSLKWIL---ENDPTELDLMFCIDEenFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQM 760
Cdd:pfam00632  81 DLESIDPELYKSLKSLLnmdNDDDEDLGLTFTIPV--FGESKTIELIPNGRNIPVTNENKEEYIRLYVDYRLNKSIEPQL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  761 NAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTG 840
Cdd:pfam00632 159 EAFRKGFYSVIPKEALSLFTPEELELLICGSPEIDVEDLKKNTEYDGGYTKNSPTIQWFWEILEEFSPEQRRLFLKFVTG 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  841 TSRVPMNGFAELygsngpQLFTIEQWGS--PEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 908
Cdd:pfam00632 239 SSRLPVGGFKSL------PKFTIVRKGGddDDRLPTAHTCFNRLKLPDYSSKEILKEKLLIAIEEGEGFG 302
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-153 2.57e-84

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 266.14  E-value: 2.57e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDENRLT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 153
Cdd:cd04033   81 RDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
C2 pfam00168
C2 domain;
21-123 1.63e-29

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 112.80  E-value: 1.63e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRL 99
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQK----KKTKVVKNTLNPVWNETFTFSVPDPENAVLeIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....
gi 345478677  100 TRDDFLGQVDVPLSHLPTEDPTME 123
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 21-121 4.50e-29

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 111.43  E-value: 4.50e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677    21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRL 99
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELeIEVYDKDRF 76

                           90       100
                   ....*....|....*....|..
gi 345478677   100 TRDDFLGQVDVPLSHLPTEDPT 121
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRH 98
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
22-123 3.90e-12

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 70.56  E-value: 3.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   22 LRVKVVSGIDLAKKDIFGASDPYVKLslYVADENrelaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLT 100
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVKL--FLNEKS----VYKTKVVKKTLNPVWNEEFTIEVlNRVKDVLTINVNDWDSGE 1115

                          90       100
                  ....*....|....*....|...
gi 345478677  101 RDDFLGQVDVPLSHLPTEDPTME 123
Cdd:COG5038  1116 KNDLLGTAEIDLSKLEPGGTTNS 1138
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 436-466 4.77e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 61.00  E-value: 4.77e-12
                         10        20        30
                 ....*....|....*....|....*....|.
gi 345478677 436 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 466
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 435-466 6.40e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 60.69  E-value: 6.40e-12
                           10        20        30
                   ....*....|....*....|....*....|..
gi 345478677   435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 466
Cdd:smart00456   2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 435-464 6.66e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 60.60  E-value: 6.66e-12
                          10        20        30
                  ....*....|....*....|....*....|
gi 345478677  435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP 464
Cdd:pfam00397   1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 485-517 2.74e-11

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 58.77  E-value: 2.74e-11
                           10        20        30
                   ....*....|....*....|....*....|...
gi 345478677   485 PLPPGWEERIHLDGRTFYIDHNSKITQWEDPRL 517
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 487-517 9.47e-11

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 57.15  E-value: 9.47e-11
                         10        20        30
                 ....*....|....*....|....*....|.
gi 345478677 487 PPGWEERIHLDGRTFYIDHNSKITQWEDPRL 517
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 486-515 1.86e-10

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 56.36  E-value: 1.86e-10
                          10        20        30
                  ....*....|....*....|....*....|
gi 345478677  486 LPPGWEERIHLDGRTFYIDHNSKITQWEDP 515
Cdd:pfam00397   1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 198-224 9.33e-10

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.43  E-value: 9.33e-10
                          10        20
                  ....*....|....*....|....*..
gi 345478677  198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 198-224 2.58e-09

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 52.92  E-value: 2.58e-09
                         10        20
                 ....*....|....*....|....*..
gi 345478677 198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:cd00201    3 GWEERWDPDGRVYYYNHNTKETQWEDP 29
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 198-224 9.77e-09

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 51.45  E-value: 9.77e-09
                           10        20
                   ....*....|....*....|....*..
gi 345478677   198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:smart00456   5 GWEERKDPDGRPYYYNHETKETQWEKP 31
PLN02223 PLN02223
phosphoinositide phospholipase C
 20-115 1.42e-04

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 45.40  E-value: 1.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  20 RILRVKVVSG----IDLaKKDIFGASDP--YVKLSLYVA--DENrelaLVQTKTIKKTLNPKWNEEFYFRVN-PSNHRLL 90
Cdd:PLN02223 409 KILKVKIYMGdgwiVDF-KKRIGRLSKPdlYVRISIAGVphDEK----IMKTTVKNNEWKPTWGEEFTFPLTyPDLALIS 483

                         90       100
                 ....*....|....*....|....*
gi 345478677  91 FEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:PLN02223 484 FEVYDYEVSTADAFCGQTCLPVSEL 508
 
Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 578-907 3.32e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


Pssm-ID: 214523  Cd Length: 328  Bit Score: 510.24  E-value: 3.32e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   578 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 657
Cdd:smart00119   1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   658 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 734
Cdd:smart00119  80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   735 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 814
Cdd:smart00119 160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   815 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 893
Cdd:smart00119 240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                          330
                   ....*....|....
gi 345478677   894 REKLLMAVENAQGF 907
Cdd:smart00119 315 REKLLLAINEGKGF 328
HECTc cd00078
HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It ...
 554-908 1.21e-166

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.


Pssm-ID: 238033 [Multi-domain]  Cd Length: 352  Bit Score: 489.00  E-value: 1.21e-166
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 554 FEMKLHRNNIFEESYRRIMSVKRPDvLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINP 633
Cdd:cd00078    1 LKITVRRDRILEDALRQLSKVSSSD-LKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNP 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 634 NSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPT--ELDLMF 711
Cdd:cd00078   80 SSFA-DEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGDedDLELTF 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 712 CIDEEN-FGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCG 790
Cdd:cd00078  159 TIELDSsFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELLICG 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 791 LGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELygsngPQLFTIEQWGSP- 869
Cdd:cd00078  239 SEDIDLEDLKKNTEYKGGYSSDSPTIQWFWEVLESFTNEERKKFLQFVTGSSRLPVGGFADL-----NPKFTIRRVGSPd 313

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 345478677 870 EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 908
Cdd:cd00078  314 DRLPTAHTCFNLLKLPPYSSKEILREKLLYAINEGAGFG 352
HUL4 COG5021
Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];
435-907 9.51e-163

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227354 [Multi-domain]  Cd Length: 872  Bit Score: 497.75  E-value: 9.51e-163
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP-RLKFPVHMRSKTSLNPN-------DLGPLPPGWEERIHLDGRTFYIDHN 506
Cdd:COG5021  388 KPTGWSSSIEDLGQFLFSDFLTSSSTYEDLrREQLGRESDESFYVASNvqqqrasREGPLLSGWKTRLNNLYRFYFVEHR 467

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 507 SKITQWEDPRLQNPA--ITGPAVPYSREFKQKYDYFRKKLKKPADIPnrFEMKLHRNNIFEESYRRIMSvKRPDVLKARL 584
Cdd:COG5021  468 KKTLTKNDSRLGSFIslNKLDIRRIKEDKRRKLFYSLKQKAKIFDPY--LHIKVRRDRVFEDSYREIMD-ESGDDLKKTL 544

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 585 WIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLcNEDHLSYFTFIGRVAGLAVFHGKLLD 664
Cdd:COG5021  545 EIEFVGEEGIDAGGLTREWLFLLSKEMFNPDYGLFEYITEDLYTLPINPLSSI-NPEHLSYFKFLGRVIGKAIYDSRILD 623

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 665 GFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILEN--DPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKRE 742
Cdd:COG5021  624 VQFSKAFYKKLLGKPVSLVDLESLDPELYRSLVWLLNNdiDETILDLTFTVEDDSFGESRTVELIPNGRNISVTNENKKE 703

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 743 YIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGD-VDVNDWRQHSIYKnGYCPNHPVIQWFWK 821
Cdd:COG5021  704 YVKKVVDYKLNKRVEKQFSAFKSGFSEIIPPDLLQIFDESELELLIGGIPEdIDIDDWKSNTAYH-GYTEDSPIIVWFWE 782

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677 822 AVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDLREKLLMA 900
Cdd:COG5021  783 IISEFDFEERAKLLQFVTGTSRIPINGFKDLQGSDGVRKFTIEKGGTDdDRLPSAHTCFNRLKLPEYSSKEKLRSKLLTA 862


                 ....*..
gi 345478677 901 VENAQGF 907
Cdd:COG5021  863 INEGAGF 869
HECT pfam00632
HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl ...
 605-908 1.11e-131

HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl Terminus.


Pssm-ID: 459880  Cd Length: 304  Bit Score: 396.98  E-value: 1.11e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  605 FLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCN-EDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLN 683
Cdd:pfam00632   1 TLLSKELFDPNYGLFEYETEDDRTYWFNPSSSESPdLELLDYFKFLGKLLGKAIYNGILLDLPFPPFFYKKLLGEPLTLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  684 DMESVDSEYYNSLKWIL---ENDPTELDLMFCIDEenFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQM 760
Cdd:pfam00632  81 DLESIDPELYKSLKSLLnmdNDDDEDLGLTFTIPV--FGESKTIELIPNGRNIPVTNENKEEYIRLYVDYRLNKSIEPQL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  761 NAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTG 840
Cdd:pfam00632 159 EAFRKGFYSVIPKEALSLFTPEELELLICGSPEIDVEDLKKNTEYDGGYTKNSPTIQWFWEILEEFSPEQRRLFLKFVTG 238

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  841 TSRVPMNGFAELygsngpQLFTIEQWGS--PEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 908
Cdd:pfam00632 239 SSRLPVGGFKSL------PKFTIVRKGGddDDRLPTAHTCFNRLKLPDYSSKEILKEKLLIAIEEGEGFG 302
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-153 2.57e-84

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 266.14  E-value: 2.57e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDENRLT 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 153
Cdd:cd04033   81 RDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
C2 pfam00168
C2 domain;
21-123 1.63e-29

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 112.80  E-value: 1.63e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRL 99
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQK----KKTKVVKNTLNPVWNETFTFSVPDPENAVLeIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....
gi 345478677  100 TRDDFLGQVDVPLSHLPTEDPTME 123
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEGLDG 100
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 22-127 2.60e-29

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 112.16  E-value: 2.60e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadenRELALVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLT 100
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSL------GGKQKFKTKVVKNTLNPVWNETFEFPVlDPESDTLTVEVWDKDRFS 74

                         90       100
                 ....*....|....*....|....*..
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPTMERPYT 127
Cdd:cd00030   75 KDDFLGEVEIPLSELLDSGKEGELWLP 101
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 21-121 4.50e-29

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 111.43  E-value: 4.50e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677    21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRL 99
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELeIEVYDKDRF 76

                           90       100
                   ....*....|....*....|..
gi 345478677   100 TRDDFLGQVDVPLSHLPTEDPT 121
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRH 98
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 22-121 4.44e-21

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 89.16  E-value: 4.44e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadENRELAlvQTKTIKKTLNPKWNEEFYFRVNP-SNHRLLFEVFDENRLT 100
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYL----NGEKVF--KTKTIKKTLNPVWNESFEVPVPSrVRAVLKVEVYDWDRGG 74

                         90       100
                 ....*....|....*....|.
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPT 121
Cdd:cd04040   75 KDDLLGSAYIDLSDLEPEETT 95
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 22-115 2.18e-20

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 87.70  E-value: 2.18e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRelALVQTKTIKKTLNPKWNEEFYFRVNPSNH--RLLFEVFDENRL 99
Cdd:cd04026   15 LTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNE--TKQKTKTIKKTLNPVWNETFTFDLKPADKdrRLSIEVWDWDRT 92

                         90
                 ....*....|....*.
gi 345478677 100 TRDDFLGQVDVPLSHL 115
Cdd:cd04026   93 TRNDFMGSLSFGVSEL 108
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 21-112 3.36e-19

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 85.07  E-value: 3.36e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDiFGASDPYVKLSLyvADENrelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd04038    3 LLKVRVVRGTNLAVRD-FTSSDPYVVLTL--GNQK-----VKTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKDTFS 74

                         90
                 ....*....|..
gi 345478677 101 RDDFLGQVDVPL 112
Cdd:cd04038   75 KDDSMGEAEIDL 86
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 21-150 1.21e-18

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 82.35  E-value: 1.21e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyvadENRELalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd08377    2 FLQVKVIRASGLAAADIGGKSDPFCVLEL----VNARL---QTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYDEDKDK 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 345478677 101 RDDFLGQVDVPLSHLpteDPTMERPYTFKDfllrpRSHKSRVKGFLRLKM 150
Cdd:cd08377   75 KPEFLGKVAIPLLSI---KNGERKWYALKD-----KKLRTRAKGSILLEM 116
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 5-122 3.04e-18

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 81.61  E-value: 3.04e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   5 LGEPVYGLSEDEGESrILRVKVVSGIDLAKKDIFGASDPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNP 84
Cdd:cd08386    2 LGRIQFSVSYDFQES-TLTLKILKAVELPAKDFSGTSDPFVKIYL-LPDKKHKL---ETKVKRKNLNPHWNETFLFEGFP 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 345478677  85 SN---HRLLF-EVFDENRLTRDDFLGQVDVPLSHLPTEDPTM 122
Cdd:cd08386   77 YEklqQRVLYlQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQT 118
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 22-121 3.63e-18

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 81.52  E-value: 3.63e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR-----LLFEVFDE 96
Cdd:cd04009   18 LRVEILNARNLLPLDSNGSSDPFVKVELLPRHLFPDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSvegalLLFTVKDY 97

                         90       100
                 ....*....|....*....|....*
gi 345478677  97 NRLTRDDFLGQVDVPLSHLPTEDPT 121
Cdd:cd04009   98 DLLGSNDFEGEAFLPLNDIPGVEDT 122
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 5-113 3.79e-18

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 81.16  E-value: 3.79e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   5 LGEPVYGLSEDEGESRiLRVKVVSGIDLAKKDIFGASDPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNP 84
Cdd:cd08385    2 LGKLQFSLDYDFQSNQ-LTVGIIQAADLPAMDMGGTSDPYVKVYL-LPDKKKKF---ETKVHRKTLNPVFNETFTFKVPY 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 345478677  85 S---NHRLLFEVFDENRLTRDDFLGQVDVPLS 113
Cdd:cd08385   77 SelgNKTLVFSVYDFDRFSKHDLIGEVRVPLL 108
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 21-113 1.47e-17

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 79.26  E-value: 1.47e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIF------GASDPYVKLSlyVADEnrelaLVQTKTIKKTLNPKWNEEFYFRVNP-SNHRLLFEV 93
Cdd:cd08391    2 VLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVR--VGAQ-----TFKSKVIKENLNPKWNEVYEAVVDEvPGQELEIEL 74

                         90       100
                 ....*....|....*....|
gi 345478677  94 FDENRlTRDDFLGQVDVPLS 113
Cdd:cd08391   75 FDEDP-DKDDFLGRLSIDLG 93
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 21-140 1.08e-16

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 77.08  E-value: 1.08e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIF--GASDPYVKLSlyVADENRElalvqTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDEN 97
Cdd:cd04024    2 VLRVHVVEAKDLAAKDRSgkGKSDPYAILS--VGAQRFK-----TQTIPNTLNPKWNYWCEFPIFSAQNQLLkLILWDKD 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 345478677  98 RLTRDDFLGQVDVPLSHL----PTEDPTMerPYTFKDFLLRPRSHKS 140
Cdd:cd04024   75 RFAGKDYLGEFDIALEEVfadgKTGQSDK--WITLKSTRPGKTSVVS 119
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 20-115 1.84e-16

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 76.43  E-value: 1.84e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  20 RILRVKVVSGIDL--AKKDIFGASDPYVKLSLYVADENRElALVQTKTIKK-TLNPKWNEEFYFRV-NPSNHRLLFEVFD 95
Cdd:cd00275    2 LTLTIKIISGQQLpkPKGDKGSIVDPYVEVEIHGLPADDS-AKFKTKVVKNnGFNPVWNETFEFDVtVPELAFLRFVVYD 80

                         90       100
                 ....*....|....*....|
gi 345478677  96 ENRlTRDDFLGQVDVPLSHL 115
Cdd:cd00275   81 EDS-GDDDFLGQACLPLDSL 99
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 21-154 3.61e-16

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 75.67  E-value: 3.61e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGAS-DPYVKLSLyvaDENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRL 99
Cdd:cd04044    3 VLAVTIKSARGLKGSDIIGGTvDPYVTFSI---SNRRELA--RTKVKKDTSNPVWNETKYILVNSLTEPLNLTVYDFNDK 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 345478677 100 TRDDFLGQVDVPLSHLpTEDPTMERPYtfKDFLlrpRSHKSRvkGFLRLKMAYMP 154
Cdd:cd04044   78 RKDKLIGTAEFDLSSL-LQNPEQENLT--KNLL---RNGKPV--GELNYDLRFFP 124
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-121 3.98e-16

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 75.39  E-value: 3.98e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadENRELalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTR 101
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKY----GGKTV--YKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDYDRGLT 75

                         90       100
                 ....*....|....*....|
gi 345478677 102 DDFLGQVDVPLSHLPTEDPT 121
Cdd:cd04042   76 DDFMGSAFVDLSTLELNKPT 95
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-149 5.95e-16

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 75.07  E-value: 5.95e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvaDENRelalVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLF---EVFDEN 97
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDF---DGQK----KRTRTKPKDLNPVWNEKLVFNVsDPSRLSNLVlevYVYNDR 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 345478677  98 RLTR-DDFLGQVDVPLSHLPTEDPTMERPYTfkdflLRPRSHKSRVKGFLRLK 149
Cdd:cd04022   75 RSGRrRSFLGRVRISGTSFVPPSEAVVQRYP-----LEKRGLFSRVRGEIGLK 122
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 22-116 2.90e-15

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 72.68  E-value: 2.90e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLt 100
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASDEK----KRTKTIKNSINPVWNETFEFRIQSQVKNVLeLTVMDEDYV- 76

                         90
                 ....*....|....*.
gi 345478677 101 RDDFLGQVDVPLSHLP 116
Cdd:cd04036   77 MDDHLGTVLFDVSKLK 92
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 21-115 5.02e-15

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 72.44  E-value: 5.02e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPSN-HRLLFEV--FDEN 97
Cdd:cd08387   17 ILNVKLIQARNLQPRDFSGTADPYCKVRL-LPDRSNTK---QSKIHKKTLNPEFDESFVFEVPPQElPKRTLEVllYDFD 92

                         90
                 ....*....|....*...
gi 345478677  98 RLTRDDFLGQVDVPLSHL 115
Cdd:cd08387   93 QFSRDECIGVVELPLAEV 110
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 22-150 6.24e-15

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 72.22  E-value: 6.24e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVklSLYVADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDEN---- 97
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYV--TVQVGKTKK-----RTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDddik 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  98 -----RLTR--DDFLGQVDVPLSHLPTEdptMERPYTfkdflLRPRSHKSRVKGFLRLKM 150
Cdd:cd04027   76 srlkqKFTResDDFLGQTIIEVRTLSGE---MDVWYN-----LEKRTDKSAVSGAIRLHI 127
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 22-118 1.39e-14

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 71.46  E-value: 1.39e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVnPSNHR----LLFEVFDEN 97
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSLLQ--GGKKLKKKKTSVKKGTLNPVFNEAFSFDV-PAEQLeevsLVITVVDKD 92

                         90       100
                 ....*....|....*....|.
gi 345478677  98 RLTRDDFLGQVDVPLSHLPTE 118
Cdd:cd00276   93 SVGRNEVIGQVVLGPDSGGEE 113
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 21-121 1.68e-14

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 70.70  E-value: 1.68e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyvadENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT 100
Cdd:cd04045    2 VLRLHIRKANDLKNLEGVGKIDPYVRVLV----NGIVKG--RTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMDYEKVG 75

                         90       100
                 ....*....|....*....|.
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPT 121
Cdd:cd04045   76 KDRSLGSVEINVSDLIKKNED 96
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 22-115 4.51e-14

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 69.21  E-value: 4.51e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDI-FGASDPYVKLSLYVADEnrelALVQTKTIKKTLNPKWNEEFYFRVNP----SNHRLLFEVFDE 96
Cdd:cd04041    3 LVVTIHRATDLPKADFgTGSSDPYVTASFAKFGK----PLYSTRIIRKDLNPVWEETWFVLVTPdevkAGERLSCRLWDS 78

                         90
                 ....*....|....*....
gi 345478677  97 NRLTRDDFLGQVDVPLSHL 115
Cdd:cd04041   79 DRFTADDRLGRVEIDLKEL 97
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 13-118 4.73e-14

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 70.48  E-value: 4.73e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  13 SEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQ----------------------TKTIKKTL 70
Cdd:cd08676   21 REAEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRERNSEKSKkrkshrkkavlkdtvpaksikvTEVKPQTL 100

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 345478677  71 NPKWNEEFYFRVN-PSNHRLLFEVFDENrltrDDFLGQVDVPLSHLPTE 118
Cdd:cd08676  101 NPVWNETFRFEVEdVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSC 145
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 22-137 7.76e-14

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 68.87  E-value: 7.76e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSlyVADENRElalvQTKTIKKTLNPKWNEEFYFRVNPSNhRLLFEVFDENRLTR 101
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVIT--VDGGQTH----STDVAKKTLDPKWNEHFDLTVGPSS-IITIQVFDQKKFKK 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 345478677 102 DD--FLGQVDVPL-SHLPTEDPTMERpytfkdFLLRPRS 137
Cdd:cd08382   75 KDqgFLGCVRIRAnAVLPLKDTGYQR------LDLRKLK 107
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 22-115 9.56e-14

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 68.94  E-value: 9.56e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKdIFGASDPYVKLSLYVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPSNHR------------- 88
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFARVTLNYSSKTDTK---RTKVKKKTNNPRFDEAFYFELTIGFSYekksfkveeedle 76

                         90       100       110
                 ....*....|....*....|....*....|
gi 345478677  89 ---LLFEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:cd08675   77 kseLRVELWHASMVSGDDFLGEVRIPLQGL 106
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 22-108 1.30e-13

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 68.31  E-value: 1.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPY--VKlslyVADEnrelALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRL 99
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYciVK----VDNE----VIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTL 73


                 ....*....
gi 345478677 100 TRDDFLGQV 108
Cdd:cd04054   74 SRDDVIGKV 82
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 16-114 1.85e-13

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 68.04  E-value: 1.85e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  16 EGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLY---VADENRelalvQTKTIKKTLNPKWNEEFYFRvNPSNHRLL-- 90
Cdd:cd04031   12 DKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLpdrSEKSKR-----RTKTVKKTLNPEWNQTFEYS-NVRRETLKer 85

                         90       100
                 ....*....|....*....|....*..
gi 345478677  91 ---FEVFDENRLTRDDFLGQVDVPLSH 114
Cdd:cd04031   86 tleVTVWDYDRDGENDFLGEVVIDLAD 112
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 22-115 2.69e-13

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 67.51  E-value: 2.69e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadENRELalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLT 100
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFY----NGQTL---ETSVVKKSCYPRWNEVFEFELMEGADSPLsVEVWDWDLVS 74

                         90
                 ....*....|....*
gi 345478677 101 RDDFLGQVDVPLSHL 115
Cdd:cd04025   75 KNDFLGKVVFSIQTL 89
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 21-108 3.34e-13

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 67.44  E-value: 3.34e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADenRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDEN 97
Cdd:cd08405   16 RITVNIIKARNLKAMDINGTSDPYVKVWLMYKD--KRVEKKKTVIKKRTLNPVFNESFIFNIPLERLRettLIITVMDKD 93

                         90
                 ....*....|.
gi 345478677  98 RLTRDDFLGQV 108
Cdd:cd08405   94 RLSRNDLIGKI 104
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 21-120 4.26e-13

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 66.51  E-value: 4.26e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyvADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRL 99
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRL--GNEKY-----KSKVCSKTLNPQWLEQFDLHLFDDQSQILeIEVWDKDTG 73

                         90       100
                 ....*....|....*....|.
gi 345478677 100 TRDDFLGQVDVPLSHLPTEDP 120
Cdd:cd08376   74 KKDEFIGRCEIDLSALPREQT 94
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 22-132 8.09e-13

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 66.15  E-value: 8.09e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLY-VADENRELalvQTKTIKKTLNPKWNEEF-YFRVNPSNHR---LLFEVFDE 96
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLLpGASKATKL---RTKTVHKTRNPEFNETLtYYGITEEDIQrktLRLLVLDE 93

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 345478677  97 NRLtRDDFLGQVDVPLSHLptedpTMERPYTFKDFL 132
Cdd:cd04035   94 DRF-GNDFLGETRIPLKKL-----KPNQTKQFNICL 123
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 27-115 1.07e-12

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 65.28  E-value: 1.07e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  27 VSGIDLAKKDIFGASDPYVKLSLYVADeNRELALVQTKTIKKTLNPKWNEefyFRV--------NPSNHrLLFEVFDENR 98
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEISRQSED-GTWVLVYRTEVIKNTLNPVWKP---FTIplqklcngDYDRP-IKIEVYDYDS 81

                         90
                 ....*....|....*..
gi 345478677  99 LTRDDFLGQVDVPLSHL 115
Cdd:cd04047   82 SGKHDLIGEFETTLDEL 98
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 19-111 1.33e-12

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 65.38  E-value: 1.33e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  19 SRILRVKVVSGIDLAKKDIFGASDPYVKLSlyvaDENRElalVQTKTIKKTLNPKWNEEFYF-RVNPSNhRLLFEVFDEN 97
Cdd:cd04046    2 QVVTQVHVHSAEGLSKQDSGGGADPYVIIK----CEGES---VRSPVQKDTLSPEFDTQAIFyRKKPRS-PIKIQVWNSN 73

                         90
                 ....*....|....
gi 345478677  98 RLtRDDFLGQVDVP 111
Cdd:cd04046   74 LL-CDEFLGQATLS 86
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 20-108 1.41e-12

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 65.45  E-value: 1.41e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  20 RILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKtiKKTLNPKWNEEFYFRVNPSN---HRLLFEVFDE 96
Cdd:cd08384   13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVK--KKTLNPEFNEEFFYDIKHSDlakKTLEITVWDK 90

                         90
                 ....*....|..
gi 345478677  97 NRLTRDDFLGQV 108
Cdd:cd08384   91 DIGKSNDYIGGL 102
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 27-117 2.91e-12

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 64.13  E-value: 2.91e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  27 VSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNE----EFYFrvnPSNHRLLFEVFD----ENR 98
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTtftvDYYF---EEVQKLRFEVYDvdskSKD 83

                         90
                 ....*....|....*....
gi 345478677  99 LTRDDFLGQVDVPLSHLPT 117
Cdd:cd04048   84 LSDHDFLGEAECTLGEIVS 102
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
22-123 3.90e-12

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 70.56  E-value: 3.90e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   22 LRVKVVSGIDLAKKDIFGASDPYVKLslYVADENrelaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLT 100
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVKL--FLNEKS----VYKTKVVKKTLNPVWNEEFTIEVlNRVKDVLTINVNDWDSGE 1115

                          90       100
                  ....*....|....*....|...
gi 345478677  101 RDDFLGQVDVPLSHLPTEDPTME 123
Cdd:COG5038  1116 KNDLLGTAEIDLSKLEPGGTTNS 1138
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 6-123 4.16e-12

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 63.81  E-value: 4.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   6 GEPVYGLSEDEgESRILRVKVVSGIDLA----KKDIfgaSDPYVKLSLyVADENRELALvQTKTIKKTLNPKWNEEFYFR 81
Cdd:cd08521    1 GEIEFSLSYNY-KTGSLEVHIKECRNLAyadeKKKR---SNPYVKVYL-LPDKSKQSKR-KTSVKKNTTNPVFNETLKYH 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 345478677  82 VNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTME 123
Cdd:cd08521   75 ISKSqleTRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSE 119
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 436-466 4.77e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 61.00  E-value: 4.77e-12
                         10        20        30
                 ....*....|....*....|....*....|.
gi 345478677 436 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 466
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 435-466 6.40e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 60.69  E-value: 6.40e-12
                           10        20        30
                   ....*....|....*....|....*....|..
gi 345478677   435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 466
Cdd:smart00456   2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 435-464 6.66e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 60.60  E-value: 6.66e-12
                          10        20        30
                  ....*....|....*....|....*....|
gi 345478677  435 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP 464
Cdd:pfam00397   1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 22-118 7.90e-12

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 63.57  E-value: 7.90e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVNP---SNHRLLFEVFDENR 98
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLSDPYVKIHLMQ--NGKRLKKKKTTIKKRTLNPYYNESFSFEVPFeqiQKVHLIVTVLDYDR 94

                         90       100
                 ....*....|....*....|
gi 345478677  99 LTRDDFLGQVDVPLSHLPTE 118
Cdd:cd08402   95 IGKNDPIGKVVLGCNATGAE 114
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 22-134 1.78e-11

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 62.40  E-value: 1.78e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVADEnrelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLT 100
Cdd:cd08375   17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEH-------KTKVVSDTLNPKWNSSMQFFVKDLEQDVLcITVFDRDFFS 89

                         90       100       110
                 ....*....|....*....|....*....|....
gi 345478677 101 RDDFLGQVDVPLSHLPTEDPTMERPYTfKDFLLR 134
Cdd:cd08375   90 PDDFLGRTEIRVADILKETKESKGPIT-KRLLLH 122
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 485-517 2.74e-11

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 58.77  E-value: 2.74e-11
                           10        20        30
                   ....*....|....*....|....*....|...
gi 345478677   485 PLPPGWEERIHLDGRTFYIDHNSKITQWEDPRL 517
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 21-107 2.76e-11

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 61.41  E-value: 2.76e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSL-YVADENRElalvqtKTIKKTLNPKWNEEFYFRVN-PSNHRLLFEVFDENR 98
Cdd:cd04037    1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLgKKKINDRD------NYIPNTLNPVFGKMFELEATlPGNSILKISVMDYDL 74


                 ....*....
gi 345478677  99 LTRDDFLGQ 107
Cdd:cd04037   75 LGSDDLIGE 83
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 21-130 2.88e-11

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 61.04  E-value: 2.88e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSlyVADENRElalvqTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRL 99
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELT--VGKTTQK-----SKVKERTNNPVWEEGFTFLVrNPENQELEIEVKDDKTG 73

                         90       100       110
                 ....*....|....*....|....*....|..
gi 345478677 100 TRddfLGQVDVPLSHLPT-EDPTMERPYTFKD 130
Cdd:cd04050   74 KS---LGSLTLPLSELLKePDLTLDQPFPLDN 102
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 22-108 3.10e-11

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 61.83  E-value: 3.10e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVAdenreLALVQTK---TIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFD 95
Cdd:cd08410   16 LNVDIIRAKQLLQTDMSQGSDPFVKIQLVHG-----LKLIKTKktsCMRGTIDPFYNESFSFKVPQEeleNVSLVFTVYG 90

                         90
                 ....*....|...
gi 345478677  96 ENRLTRDDFLGQV 108
Cdd:cd08410   91 HNVKSSNDFIGRI 103
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 39-154 8.30e-11

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 60.46  E-value: 8.30e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  39 GASDPYVklslyVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLshlpte 118
Cdd:cd08678   16 GSSNPYC-----VLEMDEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSKFLGLAIVPF------ 84

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 345478677 119 DPTMERPYTFKDFLLRPR-SHKSRVKGFLRLKMAYMP 154
Cdd:cd08678   85 DELRKNPSGRQIFPLQGRpYEGDSVSGSITVEFLFME 121
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 487-517 9.47e-11

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 57.15  E-value: 9.47e-11
                         10        20        30
                 ....*....|....*....|....*....|.
gi 345478677 487 PPGWEERIHLDGRTFYIDHNSKITQWEDPRL 517
Cdd:cd00201    1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 22-113 1.11e-10

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 59.96  E-value: 1.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDI-FGASDPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDEN 97
Cdd:cd08390   16 LTVSLIKARNLPPRTKdVAHCDPFVKVCL-LPDERRSL---QSKVKRKTQNPNFDETFVFQVSFKelqRRTLRLSVYDVD 91

                         90
                 ....*....|....*.
gi 345478677  98 RLTRDDFLGQVDVPLS 113
Cdd:cd08390   92 RFSRHCIIGHVLFPLK 107
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 486-515 1.86e-10

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 56.36  E-value: 1.86e-10
                          10        20        30
                  ....*....|....*....|....*....|
gi 345478677  486 LPPGWEERIHLDGRTFYIDHNSKITQWEDP 515
Cdd:pfam00397   1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 22-150 2.85e-10

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 59.33  E-value: 2.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDifGASDPYVKLSLYVAdeNRELALVQTKTIKKTLNPKWNEEFYFRV--NPSNHRLLFEVFDE--- 96
Cdd:cd04010    2 LSVRVIECSDLALKN--GTCDPYASVTLIYS--NKKQDTKRTKVKKKTNNPQFDEAFYFDVtiDSSPEKKQFEMPEEdae 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 345478677  97 -----------NRLTRDDFLGQVDVPLSHLPTEDPTMERPYtfkdfLLRPRSHKSRVK----------GFLRLKM 150
Cdd:cd04010   78 klelrvdlwhaSMGGGDVFLGEVRIPLRGLDLQAGSHQAWY-----FLQPREEKSTPPgtrsskdnslGSLRLKI 147
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 198-224 9.33e-10

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.43  E-value: 9.33e-10
                          10        20
                  ....*....|....*....|....*..
gi 345478677  198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:pfam00397   4 GWEERWDPDGRVYYYNHETGETQWEKP 30
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 22-110 9.58e-10

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 57.52  E-value: 9.58e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENR 98
Cdd:cd08403   16 LTLTIIKARNLKAMDITGFSDPYVKVSLMC--EGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVDnvsLIIAVVDYDR 93

                         90
                 ....*....|..
gi 345478677  99 LTRDDFLGQVDV 110
Cdd:cd08403   94 VGHNELIGVCRV 105
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 24-106 1.04e-09

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 57.27  E-value: 1.04e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  24 VKVVSGIDLAKKDIFGASDPYVKLSlyvaDENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR-LLFEVFDENRLTRD 102
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYVTLV----DTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLwISATVWDRSFVGKH 80


                 ....
gi 345478677 103 DFLG 106
Cdd:cd04043   81 DLCG 84
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 18-125 2.33e-09

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 56.20  E-value: 2.33e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  18 ESRILRVKVVSGIDLAKKDI-FGASDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEF-YFRVNPS---NHRLLFE 92
Cdd:cd08388   14 EKKALLVNIIECRDLPAMDEqSGTSDPYVKLQLLPEKEHK----VKTRVLRKTRNPVYDETFtFYGIPYNqlqDLSLHFA 89

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 345478677  93 VFDENRLTRDDFLGQVDVPLSHLPTEDP---TMERP 125
Cdd:cd08388   90 VLSFDRYSRDDVIGEVVCPLAGADLLNEgelLVSRE 125
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 198-224 2.58e-09

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 52.92  E-value: 2.58e-09
                         10        20
                 ....*....|....*....|....*..
gi 345478677 198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:cd00201    3 GWEERWDPDGRVYYYNHNTKETQWEDP 29
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 22-113 3.22e-09

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 55.90  E-value: 3.22e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDI-FGASDPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDEN 97
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVKT--YLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREELPtrvLNLSVWHRD 94

                         90
                 ....*....|....*.
gi 345478677  98 RLTRDDFLGQVDVPLS 113
Cdd:cd08393   95 SLGRNSFLGEVEVDLG 110
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 22-152 3.56e-09

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 55.35  E-value: 3.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKdifGASDPYVKLSLyvadENRELAlvQTKTIKKtLNPKWNEEFYFRVNPSN---HRLLFEVFDENR 98
Cdd:cd08383    2 LRLRILEAKNLPSK---GTRDPYCTVSL----DQVEVA--RTKTVEK-LNPFWGEEFVFDDPPPDvtfFTLSFYNKDKRS 71

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 345478677  99 LTRDDFLGQvdVPLSHLPTedptmerpYTFKD--FLLRPRSHKSRVKGFLRLKMAY 152
Cdd:cd08383   72 KDRDIVIGK--VALSKLDL--------GQGKDewFPLTPVDPDSEVQGSVRLRARY 117
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 22-115 3.63e-09

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 55.75  E-value: 3.63e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGAsDPYVKLSlyVADENRElalvQTKTIKKTLNPKWNEEFYFRVNPSNHrLLFEVFDENRLTR 101
Cdd:cd04021    4 LQITVESAKLKSNSKSFKP-DPYVEVT--VDGQPPK----KTEVSKKTSNPKWNEHFTVLVTPQST-LEFKVWSHHTLKA 75

                         90
                 ....*....|....
gi 345478677 102 DDFLGQVDVPLSHL 115
Cdd:cd04021   76 DVLLGEASLDLSDI 89
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 198-224 9.77e-09

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 51.45  E-value: 9.77e-09
                           10        20
                   ....*....|....*....|....*..
gi 345478677   198 GWEEKVDNLGRTYYVNHNNRTTQWHRP 224
Cdd:smart00456   5 GWEERKDPDGRPYYYNHETKETQWEKP 31
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 22-113 1.00e-08

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 54.19  E-value: 1.00e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLaKKDIFGASDPYVKlslyVADENRElalVQTKTIKKTLNPKWNEEFYF-RVN-PSNHRLLFEVFDENRL 99
Cdd:cd04032   30 LTVTVLRATGL-WGDYFTSTDGYVK----VFFGGQE---KRTEVIWNNNNPRWNATFDFgSVElSPGGKLRFEVWDRDNG 101

                         90
                 ....*....|....
gi 345478677 100 TRDDFLGQVDVPLS 113
Cdd:cd04032  102 WDDDLLGTCSVVPE 115
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 62-151 2.01e-08

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 53.21  E-value: 2.01e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  62 QTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVplshlPTEDPTMerpYTFKD--FLLRPRSHK 139
Cdd:cd08401   37 RTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDVLRRDSVIGKVAI-----KKEDLHK---YYGKDtwFPLQPVDAD 108

                         90
                 ....*....|..
gi 345478677 140 SRVKGFLRLKMA 151
Cdd:cd08401  109 SEVQGKVHLELR 120
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 22-107 2.72e-08

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 53.59  E-value: 2.72e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENrelaLVQTKT-IKK-TLNPKWNEEFYFRVnPS----NHRLLFEVFD 95
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKR----ISKKKThVKKcTLNPVFNESFVFDI-PSeeleDISVEFLVLD 91

                         90
                 ....*....|..
gi 345478677  96 ENRLTRDDFLGQ 107
Cdd:cd08404   92 SDRVTKNEVIGR 103
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 22-119 3.20e-08

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 53.05  E-value: 3.20e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDL-----AKKDIFGAS-----DPYVKLSLyvaDENRelaLVQTKTIKKTLNPKWNEEFYFRVNpSNHRLLF 91
Cdd:cd04014    6 LKIKICEAVDLkptdwSTRHAVPKKgsqllDPYVSIDV---DDTH---IGKTSTKPKTNSPVWNEEFTTEVH-NGRNLEL 78

                         90       100
                 ....*....|....*....|....*...
gi 345478677  92 EVFDENRLTRDDFLGQVDVPLSHLPTED 119
Cdd:cd04014   79 TVFHDAAIGPDDFVANCTISFEDLIQRG 106
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 22-115 6.56e-08

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 51.89  E-value: 6.56e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLYvADENRElALVQTKTIKKTLNPKWNEEFYFRVNPS--NHRLLfEVFDEN-- 97
Cdd:cd04030   18 LIVTVHKCRNLPPCDSSDIPDPYVRLYLL-PDKSKS-TRRKTSVKKDNLNPVFDETFEFPVSLEelKRRTL-DVAVKNsk 94

                         90       100
                 ....*....|....*....|
gi 345478677  98 -RLTRD-DFLGQVDVPLSHL 115
Cdd:cd04030   95 sFLSREkKLLGQVLIDLSDL 114
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
12-129 7.29e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 56.69  E-value: 7.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   12 LSEDEGES-RILRVKVVSGIDLAKKDIF--GASDPYVKLSLyvadENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHR 88
Cdd:COG5038   427 MAGDSGTAiGVVEVKIKSAEGLKKSDSTinGTVDPYITVTF----SDRVIG--KTRVKKNTLNPVWNETFYILLNSFTDP 500

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 345478677   89 LLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFK 129
Cdd:COG5038   501 LNLSLYDFNSFKSDKVVGSTQLDLALLHQNPVKKNELYEFL 541
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 24-108 1.34e-07

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 51.94  E-value: 1.34e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  24 VKVVSGIDLAKKDifGASDPYVKLSLyVADENRELALvQTKTIKKTLNPKWNEEFYFR-VNPS--NHRLL-FEVFDENRL 99
Cdd:cd04020   33 VKEAKNLPALKSG--GTSDSFVKCYL-LPDKSKKSKQ-KTPVVKKSVNPVWNHTFVYDgVSPEdlSQACLeLTVWDHDKL 108


                 ....*....
gi 345478677 100 TRDDFLGQV 108
Cdd:cd04020  109 SSNDFLGGV 117
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 21-118 1.75e-07

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 50.79  E-value: 1.75e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLyvadenrelalvQTKTIKKTL------NPKWNEEFYFRVNPSN----HRLL 90
Cdd:cd04049    2 TLEVLLISAKGLQDTDFLGKIDPYVIIQC------------RTQERKSKVakgdgrNPEWNEKFKFTVEYPGwggdTKLI 69

                         90       100
                 ....*....|....*....|....*...
gi 345478677  91 FEVFDENRLTRDDFLGQVDVPLSHLPTE 118
Cdd:cd04049   70 LRIMDKDNFSDDDFIGEATIHLKGLFEE 97
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 23-111 2.21e-07

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 49.88  E-value: 2.21e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  23 RVKVVSGIDLAKKDIfgasDPYVKLSlyVADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-----FEVFDEN 97
Cdd:cd04011    7 RVRVIEARQLVGGNI----DPVVKVE--VGGQKK-----YTSVKKGTNCPFYNEYFFFNFHESPDELFdkiikISVYDSR 75

                         90
                 ....*....|....*.
gi 345478677  98 RLTRDDFLG--QVDVP 111
Cdd:cd04011   76 SLRSDTLIGsfKLDVG 91
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 39-115 3.07e-07

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 49.52  E-value: 3.07e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 345478677  39 GASDPYVKLSLyvadeNRELaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDEnRLTRDDFLGQVDVPLSHL 115
Cdd:cd04052   11 GLLSPYAELYL-----NGKL-VYTTRVKKKTNNPSWNASTEFLVtDRRKSRVTVVVKDD-RDRHDPVLGSVSISLNDL 81
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
 34-151 4.07e-07

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 50.10  E-value: 4.07e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  34 KKDIFGASDPYVKLSlyVADENRELALVQ--------TKTIKKTLNPKW-NEEFYFRVNPSNhRLLFEV---FDENRLTR 101
Cdd:cd08691   14 KKGMFFNPDPYVKIS--IQPGKRHIFPALphhgqecrTSIVENTINPVWhREQFVFVGLPTD-VLEIEVkdkFAKSRPII 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 345478677 102 DDFLGQVDVPLSHLPTEDPTMERPYTFKdflLRPRSHKSRVKGFLRLKMA 151
Cdd:cd08691   91 RRFLGKLSIPVQRLLERHAIGDQELSYT---LGRRTPTDHVSGQLTFRFE 137
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 21-148 1.90e-06

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 47.61  E-value: 1.90e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADEnrelalVQTKTIKK--TlNPKWNEEFYFRVNPS----NHRLL-FEV 93
Cdd:cd04051    1 TLEITIISAEDLKNVNLFGKMKVYAVVWIDPSHK------QSTPVDRDggT-NPTWNETLRFPLDERllqqGRLALtIEV 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 345478677  94 FDENRLTRDDFLGQVDVPLSHLPtEDPTMERPYTFKDFLLRPRShkSRVKGFLRL 148
Cdd:cd04051   74 YCERPSLGDKLIGEVRVPLKDLL-DGASPAGELRFLSYQLRRPS--GKPQGVLNF 125
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 16-105 1.96e-06

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 47.45  E-value: 1.96e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  16 EGESRILRVKVVSGIDLAKKDIfGASDPYVKLSLYVADENRELAlvQTKTIKKTLNPKWNEEFYFRVN--PSNHRLLFEV 93
Cdd:cd08685    8 EGQNRKLTLHVLEAKGLRSTNS-GTCNSYVKISLSPDKEVRFRQ--KTSTVPDSANPLFHETFSFDVNerDYQKRLLVTV 84

                         90
                 ....*....|..
gi 345478677  94 FDENRLTRDDFL 105
Cdd:cd08685   85 WNKLSKSRDSGL 96
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 41-124 2.04e-06

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 47.82  E-value: 2.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  41 SDPYVKLSLyVADENRElalVQTKTIKK--TLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:cd04029   37 SNPYVKTYL-LPDKSRQ---SKRKTSIKrnTTNPVYNETLKYSISHSqleTRTLQLSVWHYDRFGRNTFLGEVEIPLDSW 112


                 ....*....
gi 345478677 116 PTEDPTMER 124
Cdd:cd04029  113 NFDSQHEEC 121
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 63-122 2.34e-06

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 46.86  E-value: 2.34e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 345478677  63 TKTIKKTLNPKWNEEFYFRVNP--SNHRLLFEVFDENRLTRDDFLGQVDVPLSHL----PTEDPTM 122
Cdd:cd04039   41 TSWRRHTLNPVFNERLAFEVYPheKNFDIQFKVLDKDKFSFNDYVATGSLSVQELlnaaPQPDPET 106
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 62-115 2.48e-06

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 47.45  E-value: 2.48e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  62 QTKTIKKTLNPKWNEEFYFRV------NPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:cd08682   34 STSVKEKTTSPVWKEECSFELpgllsgNGNRATLQLTVMHRNLLGLDKFLGQVSIPLNDL 93
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 22-123 9.97e-06

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 45.38  E-value: 9.97e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKD-IFGASDPYVKLslyvadenrELALVQTKT--IKKTLNPKWN-EEFYFRVNP---SNHRLLFEVF 94
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEV---------KFGSTTYKTdvVKKSLNPVWNsEWFRFEVDDeelQDEPLQIRVM 71

                         90       100
                 ....*....|....*....|....*....
gi 345478677  95 DENRLTRDDFLGQVDVPLSHLPTEDPTME 123
Cdd:cd08688   72 DHDTYSANDAIGKVYIDLNPLLLKDSVSQ 100
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-120 1.12e-05

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 45.38  E-value: 1.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKkdifGASDPYVKLSL--YVAdenrelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLfEVFDENRL 99
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVVEVKLgnYKG---------STKAIERTSNPEWNQVFAFSKDRLQGSTL-EVSVWDKD 67

                         90       100
                 ....*....|....*....|..
gi 345478677 100 T-RDDFLGQVDVPLSHLPTEDP 120
Cdd:cd08378   68 KaKDDFLGGVCFDLSEVPTRVP 89
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
22-120 1.77e-05

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 48.60  E-value: 1.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadeNRelaLVQTKTIKK--TLNPKWNEEFYFRVNPSNHRLLFEVFDENRL 99
Cdd:COG5038   713 IRVSVRKANDLRNEIPGGKSDPYATVLV-----NN---LVKYRTIYGssTLNPIWNEILYVPVTSKNQRLTLECMDYEES 784

                          90       100
                  ....*....|....*....|.
gi 345478677  100 TRDDFLGQVDVPLSHLPTEDP 120
Cdd:COG5038   785 GDDRNLGEVNINVSNVSKKDE 805
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 21-152 1.86e-05

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 44.93  E-value: 1.86e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  21 ILRVKVVSGIDLAKKDIFGASDPYVKLSlyVADENRelalvQTKTIKKT-LNPKWNEEFYFRVNPS-NHRLLFEVFDENR 98
Cdd:cd08681    2 TLVVVVLKARNLPNKRKLDKQDPYCVLR--IGGVTK-----KTKTDFRGgQHPEWDEELRFEITEDkKPILKVAVFDDDK 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 345478677  99 lTRDDFLGQVDVPLShlptedPTMERpYTFKDFLlrPRSHKSRVKGFLRLKMAY 152
Cdd:cd08681   75 -RKPDLIGDTEVDLS------PALKE-GEFDDWY--ELTLKGRYAGEVYLELTF 118
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 26-115 4.21e-05

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 44.17  E-value: 4.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  26 VVSGIDLAKKdiFGASDPYVKLSLyvadenRELALvQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENRLTRD 102
Cdd:cd08373    2 VVSLKNLPGL--KGKGDRIAKVTF------RGVKK-KTRVLENELNPVWNETFEWPLAGSPDPdesLEIVVKDYEKVGRN 72

                         90
                 ....*....|...
gi 345478677 103 DFLGQVDVPLSHL 115
Cdd:cd08373   73 RLIGSATVSLQDL 85
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 42-115 6.22e-05

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 43.44  E-value: 6.22e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 345478677  42 DPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNP----SNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:cd08381   34 DPYVKT--YLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPvedlQQRVLQVSVWSHDSLVENEFLGGVCIPLKKL 109
PLN02223 PLN02223
phosphoinositide phospholipase C
 20-115 1.42e-04

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 45.40  E-value: 1.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  20 RILRVKVVSG----IDLaKKDIFGASDP--YVKLSLYVA--DENrelaLVQTKTIKKTLNPKWNEEFYFRVN-PSNHRLL 90
Cdd:PLN02223 409 KILKVKIYMGdgwiVDF-KKRIGRLSKPdlYVRISIAGVphDEK----IMKTTVKNNEWKPTWGEEFTFPLTyPDLALIS 483

                         90       100
                 ....*....|....*....|....*
gi 345478677  91 FEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:PLN02223 484 FEVYDYEVSTADAFCGQTCLPVSEL 508
C2D_MCTP_PRT_plant cd08379
C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 32-117 4.37e-04

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 176025 [Multi-domain]  Cd Length: 126  Bit Score: 41.24  E-value: 4.37e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  32 LAKKDIFGASDPYVklslyVADENRELalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT------RDDFL 105
Cdd:cd08379   15 LRAKDGRGSTDAYC-----VAKYGPKW--VRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFDNSQSHwkeavqPDVLI 87

                         90
                 ....*....|..
gi 345478677 106 GQVDVPLSHLPT 117
Cdd:cd08379   88 GKVRIRLSTLED 99
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 22-108 5.12e-04

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 40.99  E-value: 5.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvADENRElalvqTKTIKKTLNPKWNEEFYFrvnpsNHRLLF---------- 91
Cdd:cd04017    3 LRAYIYQARDLLAADKSGLSDPFARVSF--LNQSQE-----TEVIKETLSPTWDQTLIF-----DEVELYgspeeiaqnp 70

                         90       100
                 ....*....|....*....|..
gi 345478677  92 -----EVFDENRLTRDDFLGQV 108
Cdd:cd04017   71 plvvvELFDQDSVGKDEFLGRS 92
PLN02952 PLN02952
phosphoinositide phospholipase C
 1-115 6.16e-04

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 43.45  E-value: 6.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   1 MATGLGEPVYGLSEDEGESRILRVKVVSG----IDLAKK--DIFGASDPYVKLslYVADENRELALVQTKTIKKTLNPKW 74
Cdd:PLN02952 451 MKKGFHDEVFDPKKKLPVKKTLKVKVYLGdgwrLDFSHThfDSYSPPDFYTKM--YIVGVPADNAKKKTKIIEDNWYPAW 528

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 345478677  75 NEEFYFRVN-PSNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 115
Cdd:PLN02952 529 NEEFSFPLTvPELALLRIEVREYDMSEKDDFGGQTCLPVSEL 570
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-126 7.33e-04

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 40.73  E-value: 7.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  22 LRVKVVSGIDLAKKDIFGASDPYVKLSLyvadenrELALVQTKTIK-KTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRL 99
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQL-------GNQVLRTRPSQtRNGNPSWNEELMFVAaEPFEDHLILSVEDRVGP 74

                         90       100
                 ....*....|....*....|....*..
gi 345478677 100 TRDDFLGQVDVPLShlptedpTMERPY 126
Cdd:cd04019   75 NKDEPLGRAVIPLN-------DIERRV 94
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 5-122 7.59e-04

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 40.83  E-value: 7.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677   5 LGEPVYGLSEDEGesrILRVKVVSGIDL-AKKDIFGASDPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVN 83
Cdd:cd04028   17 MGDIQLGLYDKKG---QLEVEVIRARGLvQKPGSKVLPAPYVKV--YLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVS 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 345478677  84 PSNHRLLFEVF-DENRLTRDDFLGQVDVPLSHLPTEDPTM 122
Cdd:cd04028   92 PTGKTLQVIVWgDYGRMDKKVFMGVAQILLDDLDLSNLVI 131
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 25-106 9.78e-04

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 40.69  E-value: 9.78e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  25 KVVSGIDLAKKDIfgaSDPYVKLSLyvADENrelalVQTKTIKKTLNPKWNEEFYFRVN-PS-NHRLLFEVFDENRLTRD 102
Cdd:cd04018   22 NVKKAFLGEKKEL---VDPYVEVSF--AGQK-----VKTSVKKNSYNPEWNEQIVFPEMfPPlCERIKIQIRDWDRVGND 91


                 ....
gi 345478677 103 DFLG 106
Cdd:cd04018   92 DVIG 95
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 63-116 4.78e-03

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040 [Multi-domain]  Cd Length: 127  Bit Score: 38.20  E-value: 4.78e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 345478677  63 TKTIKKTLnPKWNEEFYFRVNPSNHRLLFEVFDENrLTRDDFLGQVDVPLSHLP 116
Cdd:cd08394   35 TIAVRGSQ-PCWEQDFMFEINRLDLGLVIELWNKG-LIWDTLVGTVWIPLSTIR 86
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 43-124 9.06e-03

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 37.50  E-value: 9.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345478677  43 PYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTED 119
Cdd:cd08392   39 PYVKV--CLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADllsSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFED 116


                 ....*
gi 345478677 120 PTMER 124
Cdd:cd08392  117 TDSQR 121
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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