NCBI Conserved Domain Search

Conserved domains on [gi|767920434|ref|XP_011510417|]

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fer-1-like protein 5 isoform X6 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1708-1840

6.58e-69

C2 domain sixth 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 sixth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176020 Cd Length: 133 Bit Score: 227.93 E-value: 6.58e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1708 ELRCIIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEADFNWRFIFTMDYLAAERTCVQSQKDY 1787
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767920434 1788 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAKQCSI 1840
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2E_Ferlin

cd04037

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1464-1587

5.73e-57

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: 193.15 E-value: 5.73e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1543
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767920434 1544 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1587
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

C2D_Ferlin

cd04017

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1053-1188

1.01e-56

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: 193.14 E-value: 1.01e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1053 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1132
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920434 1133 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1188
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

164-273

3.31e-42

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: 150.42 E-value: 3.31e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920434  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111

C2A_Ferlin

cd08373

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

5-134

2.11e-38

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: 140.08 E-value: 2.11e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

669-742

5.76e-28

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 108.45 E-value: 5.76e-28

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920434   669 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 742
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76

Ferlin_C super family

cl24672

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1858-1969

1.99e-18

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

The actual alignment was detected with superfamily member pfam16165:

Pssm-ID: 435183 Cd Length: 154 Bit Score: 84.05 E-value: 1.99e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1858 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1901
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767920434  1902 PAGRGQSEPNQyptLHPPLRTNTSFTWLRSPVQNFCYIFWKRYRFKLIAFMVISIIALMLFNFIYSAP 1969
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147

C2 super family

cl14603

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

341-445

6.31e-10

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.

The actual alignment was detected with superfamily member cd04018:

Pssm-ID: 472691 [Multi-domain] Cd Length: 151 Bit Score: 59.57 E-value: 6.31e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  341 KHQSVNPQLEVELI-GEKLPCLSSYIKFRVLDCRKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGG 419
Cdd:cd04018    53 KKNSYNPEWNEQIVfPEMFPPLCERIKIQIRDWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGS 126

                          90       100
                  ....*....|....*....|....*.
gi 767920434  420 KKApFRIQEEGACIPDSVRDGLAYRG 445
Cdd:cd04018   127 PRE-YSLLDDHQDLNEGLGEGVAYRG 151

DysFN

smart00693

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

757-815

7.69e-08

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal proteins, dysferlin, myoferlin and hypothetical proteins. Due to an insertion of a dysferlin domain within a second dysferlin domain we have chosen to predict these domains in two parts: the N-terminal region and the C-terminal region.

Pssm-ID: 214777 Cd Length: 62 Bit Score: 50.99 E-value: 7.69e-08

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920434    757 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQ-DSWTVE 815
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEdDNWSLD 62

FerA super family

cl06973

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

597-647

7.28e-07

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

The actual alignment was detected with superfamily member pfam08165:

Pssm-ID: 462389 Cd Length: 65 Bit Score: 47.96 E-value: 7.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   597 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 647
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65

FerI super family

cl06959

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

273-312

8.29e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

The actual alignment was detected with superfamily member pfam08151:

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.07 E-value: 8.29e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920434   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1708-1840

6.58e-69

Pssm-ID: 176020 Cd Length: 133 Bit Score: 227.93 E-value: 6.58e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1708 ELRCIIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEADFNWRFIFTMDYLAAERTCVQSQKDY 1787
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767920434 1788 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAKQCSI 1840
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2E_Ferlin

cd04037

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1464-1587

5.73e-57

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 193.15 E-value: 5.73e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1543
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767920434 1544 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1587
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

C2D_Ferlin

cd04017

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1053-1188

1.01e-56

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 193.14 E-value: 1.01e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1053 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1132
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920434 1133 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1188
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

164-273

3.31e-42

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 150.42 E-value: 3.31e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920434  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111

C2A_Ferlin

cd08373

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

5-134

2.11e-38

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 140.08 E-value: 2.11e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

669-742

5.76e-28

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 108.45 E-value: 5.76e-28

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920434   669 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 742
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76

Ferlin_C

pfam16165

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1858-1969

1.99e-18

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

Pssm-ID: 435183 Cd Length: 154 Bit Score: 84.05 E-value: 1.99e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1858 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1901
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767920434  1902 PAGRGQSEPNQyptLHPPLRTNTSFTWLRSPVQNFCYIFWKRYRFKLIAFMVISIIALMLFNFIYSAP 1969
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147

pfam00168

C2 domain;

1463-1562

1.19e-15

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 74.28 E-value: 1.19e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1463 CLVRVYMVRAINLQPQDYNGLCDPYVILKL------GKTELgnrdmyQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFD 1536
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldgkqkKKTKV------VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                           90       100
                   ....*....|....*....|....*.
gi 767920434  1537 LFSPDDKIGTTVIDLENRLLSGFGAH 1562
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDG 100

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1464-1558

1.64e-14

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: 70.98 E-value: 1.64e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLG-------KTElgnrdmYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFD 1536
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpkekkKTK------VVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD 74

                            90       100
                    ....*....|....*....|..
gi 767920434   1537 LFSPDDKIGTTVIDLENRLLSG 1558
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGG 96

C2C_Ferlin

cd04018

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

341-445

6.31e-10

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: 59.57 E-value: 6.31e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  341 KHQSVNPQLEVELI-GEKLPCLSSYIKFRVLDCRKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGG 419
Cdd:cd04018    53 KKNSYNPEWNEQIVfPEMFPPLCERIKIQIRDWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGS 126

                          90       100
                  ....*....|....*....|....*.
gi 767920434  420 KKApFRIQEEGACIPDSVRDGLAYRG 445
Cdd:cd04018   127 PRE-YSLLDDHQDLNEGLGEGVAYRG 151

DysFN

smart00693

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

757-815

7.69e-08

Pssm-ID: 214777 Cd Length: 62 Bit Score: 50.99 E-value: 7.69e-08

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920434    757 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQ-DSWTVE 815
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEdDNWSLD 62

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1731-1834

1.02e-07

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 51.72 E-value: 1.02e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1731 TSDIYIKGWLYGLEKDMQKTDIHYHSLTgeadFNWRFIFTMDYLAAERtcvqsqkdyiwsldatsmkfpARLIIQVWDND 1810
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTLN----PVWNETFEFEVPPPEL---------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|....
gi 767920434   1811 IFSPDDFLGVLELDLSDMPLPARH 1834
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGGRH 98

FerA

pfam08165

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

597-647

7.28e-07

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

Pssm-ID: 462389 Cd Length: 65 Bit Score: 47.96 E-value: 7.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   597 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 647
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65

pfam00168

C2 domain;

2-92

7.79e-07

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 49.24 E-value: 7.79e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434     2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 767920434    77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

2-93

1.07e-06

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 49.02 E-value: 1.07e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434      2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 767920434     76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

168-264

4.73e-06

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 47.10 E-value: 4.73e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434    168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSAM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767920434    240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

168-270

2.09e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 45.39 E-value: 2.09e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSAMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 767920434   241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104

pfam00168

C2 domain;

1054-1167

3.05e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 44.62 E-value: 3.05e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1054 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1131
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 767920434  1132 RDFWGKESLWGRsvwppmVWLDLQDRIL--PPMRWHPL 1167
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSgeGLDGWYPL 104

COG5038

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

1465-1551

1.13e-04

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 47.45 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1465 VRVYMVRAINLQPQDY--NGLCDPYVILKLGKTELGnRDMYQPNTLDPIFGMMFELTCNiPLEKDLEIQLYDFDLFSPDD 1542
Cdd:COG5038   438 VEVKIKSAEGLKKSDStiNGTVDPYITVTFSDRVIG-KTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDK 515


                  ....*....
gi 767920434 1543 KIGTTVIDL 1551
Cdd:COG5038   516 VVGSTQLDL 524

FerI

pfam08151

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

273-312

8.29e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.07 E-value: 8.29e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920434   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42

pfam00168

C2 domain;

1800-1836

9.55e-04

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 40.38 E-value: 9.55e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 767920434  1800 ARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAK 1836
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1054-1165

3.69e-03

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 38.62 E-value: 3.69e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1054 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1130
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 767920434   1131 QRDFWGKESLWGRsvwppmVWLDLQDRILPPMRWH 1165
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1708-1840

6.58e-69

Pssm-ID: 176020 Cd Length: 133 Bit Score: 227.93 E-value: 6.58e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1708 ELRCIIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEADFNWRFIFTMDYLAAERTCVQSQKDY 1787
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767920434 1788 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAKQCSI 1840
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2E_Ferlin

cd04037

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1464-1587

5.73e-57

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 193.15 E-value: 5.73e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1543
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767920434 1544 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1587
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

C2D_Ferlin

cd04017

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

1053-1188

1.01e-56

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 193.14 E-value: 1.01e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1053 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1132
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920434 1133 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1188
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

164-273

3.31e-42

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 150.42 E-value: 3.31e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920434  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111

C2A_Ferlin

cd08373

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

5-134

2.11e-38

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 140.08 E-value: 2.11e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

669-742

5.76e-28

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 108.45 E-value: 5.76e-28

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920434   669 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 742
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76

Ferlin_C

pfam16165

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1858-1969

1.99e-18

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

Pssm-ID: 435183 Cd Length: 154 Bit Score: 84.05 E-value: 1.99e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1858 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1901
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767920434  1902 PAGRGQSEPNQyptLHPPLRTNTSFTWLRSPVQNFCYIFWKRYRFKLIAFMVISIIALMLFNFIYSAP 1969
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

1465-1553

2.85e-16

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 76.34 E-value: 2.85e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1465 VRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGnRDMYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDKI 1544
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79


                  ....*....
gi 767920434 1545 GTTVIDLEN 1553
Cdd:cd00030    80 GEVEIPLSE 88

pfam00168

C2 domain;

1463-1562

1.19e-15

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 74.28 E-value: 1.19e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1463 CLVRVYMVRAINLQPQDYNGLCDPYVILKL------GKTELgnrdmyQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFD 1536
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldgkqkKKTKV------VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                           90       100
                   ....*....|....*....|....*.
gi 767920434  1537 LFSPDDKIGTTVIDLENRLLSGFGAH 1562
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDG 100

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1464-1558

1.64e-14

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 70.98 E-value: 1.64e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLG-------KTElgnrdmYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFD 1536
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpkekkKTK------VVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD 74

                            90       100
                    ....*....|....*....|..
gi 767920434   1537 LFSPDDKIGTTVIDLENRLLSG 1558
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGG 96

C2A_Synaptotagmin-8

cd08387

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...

1464-1558

8.11e-12

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: 64.35 E-value: 8.11e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKL---GKTELGNRDMYQpnTLDPIFG--MMFELTCNIPLEKDLEIQLYDFDLF 1538
Cdd:cd08387    17 ILNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKK--TLNPEFDesFVFEVPPQELPKRTLEVLLYDFDQF 94

                          90       100
                  ....*....|....*....|
gi 767920434 1539 SPDDKIGTTVIDLENRLLSG 1558
Cdd:cd08387    95 SRDECIGVVELPLAEVDLSE 114

C2A_RIM1alpha

cd04031

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...

1467-1558

1.48e-10

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: 60.72 E-value: 1.48e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKL--GKTELGNRDM-YQPNTLDPIFGMMFELTcNIP----LEKDLEIQLYDFDLFS 1539
Cdd:cd04031    20 VTVLQARDLPPRDDGSLRNPYVKVYLlpDRSEKSKRRTkTVKKTLNPEWNQTFEYS-NVRretlKERTLEVTVWDYDRDG 98

                          90
                  ....*....|....*....
gi 767920434 1540 PDDKIGTTVIDLENRLLSG 1558
Cdd:cd04031    99 ENDFLGEVVIDLADALLDD 117

C2A_Synaptotagmin-like

cd04024

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...

1466-1553

5.39e-10

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: 58.97 E-value: 5.39e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1466 RVYMVRAINLQPQD--YNGLCDPYVILKLGKTELGNRDMyqPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1543
Cdd:cd04024     4 RVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRFKTQTI--PNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                          90
                  ....*....|
gi 767920434 1544 IGTTVIDLEN 1553
Cdd:cd04024    82 LGEFDIALEE 91

C2C_Ferlin

cd04018

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

341-445

6.31e-10

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 59.57 E-value: 6.31e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  341 KHQSVNPQLEVELI-GEKLPCLSSYIKFRVLDCRKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGG 419
Cdd:cd04018    53 KKNSYNPEWNEQIVfPEMFPPLCERIKIQIRDWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGS 126

                          90       100
                  ....*....|....*....|....*.
gi 767920434  420 KKApFRIQEEGACIPDSVRDGLAYRG 445
Cdd:cd04018   127 PRE-YSLLDDHQDLNEGLGEGVAYRG 151

C2_ArfGAP

cd04038

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...

1464-1552

2.23e-09

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: 57.72 E-value: 2.23e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGlCDPYVILKLGKTELGNRDMYqpNTLDPIFGMmfELTCNIP-LEKDLEIQLYDFDLFSPDD 1542
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIK--KNLNPVWNE--ELTLSVPnPMAPLKLEVFDKDTFSKDD 77

                          90
                  ....*....|
gi 767920434 1543 KIGTTVIDLE 1552
Cdd:cd04038    78 SMGEAEIDLE 87

C2D_Tricalbin-like

cd04040

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...

1465-1551

6.59e-08

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: 52.57 E-value: 6.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1465 VRVYMVRAINLQPQDYNGLCDPYVILKLG-----KTELGNRdmyqpnTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFS 1539
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKK------TLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                          90
                  ....*....|..
gi 767920434 1540 PDDKIGTTVIDL 1551
Cdd:cd04040    75 KDDLLGSAYIDL 86

DysFN

smart00693

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

757-815

7.69e-08

Pssm-ID: 214777 Cd Length: 62 Bit Score: 50.99 E-value: 7.69e-08

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920434    757 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQ-DSWTVE 815
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEdDNWSLD 62

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1731-1834

1.02e-07

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 51.72 E-value: 1.02e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1731 TSDIYIKGWLYGLEKDMQKTDIHYHSLTgeadFNWRFIFTMDYLAAERtcvqsqkdyiwsldatsmkfpARLIIQVWDND 1810
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTLN----PVWNETFEFEVPPPEL---------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|....
gi 767920434   1811 IFSPDDFLGVLELDLSDMPLPARH 1834
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGGRH 98

C2B_MCTP_PRT

cd08376

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

1464-1553

1.13e-07

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: 52.26 E-value: 1.13e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMYQpnTLDPIFGMMFELtcNIPLEKD--LEIQLYDFDLFSPD 1541
Cdd:cd08376     1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSK--TLNPQWLEQFDL--HLFDDQSqiLEIEVWDKDTGKKD 76

                          90
                  ....*....|..
gi 767920434 1542 DKIGTTVIDLEN 1553
Cdd:cd08376    77 EFIGRCEIDLSA 88

C2A_fungal

cd04041

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...

1464-1551

3.15e-07

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: 50.72 E-value: 3.15e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYN-GLCDPYVILKLGKTelgNRDMYQPNT----LDPIFgmmfELTC-------NIPLEKDLEIQ 1531
Cdd:cd04041     2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKF---GKPLYSTRIirkdLNPVW----EETWfvlvtpdEVKAGERLSCR 74

                          90       100
                  ....*....|....*....|
gi 767920434 1532 LYDFDLFSPDDKIGTTVIDL 1551
Cdd:cd04041    75 LWDSDRFTADDRLGRVEIDL 94

FerA

pfam08165

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

597-647

7.28e-07

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

Pssm-ID: 462389 Cd Length: 65 Bit Score: 47.96 E-value: 7.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   597 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 647
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65

pfam00168

C2 domain;

2-92

7.79e-07

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 49.24 E-value: 7.79e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434     2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 767920434    77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

C2_Intersectin

cd08375

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...

1465-1549

8.64e-07

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: 50.08 E-value: 8.64e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1465 VRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMyqPNTLDPIFG--MMFeltcnipLEKDLE-----IQLYDFDL 1537
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVV--SDTLNPKWNssMQF-------FVKDLEqdvlcITVFDRDF 87

                          90
                  ....*....|..
gi 767920434 1538 FSPDDKIGTTVI 1549
Cdd:cd08375    88 FSPDDFLGRTEI 99

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

2-93

1.07e-06

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 49.02 E-value: 1.07e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434      2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 767920434     76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96

C2B_Munc13-like

cd04009

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...

1466-1553

2.74e-06

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: 48.77 E-value: 2.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1466 RVYMVRAINLQPQDYNGLCDPYVILKLGKTELGN-----RDMYQPNTLDPIFGMMFELtcNIPLEKDLE------IQLYD 1534
Cdd:cd04009    19 RVEILNARNLLPLDSNGSSDPFVKVELLPRHLFPdvptpKTQVKKKTLFPLFDESFEF--NVPPEQCSVegalllFTVKD 96

                          90
                  ....*....|....*....
gi 767920434 1535 FDLFSPDDKIGTTVIDLEN 1553
Cdd:cd04009    97 YDLLGSNDFEGEAFLPLND 115

C2A_Synaptotagmin-1-5-6-9-10

cd08385

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...

1458-1551

3.34e-06

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: 48.03 E-value: 3.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1458 DFPQPCLVrVYMVRAINLQPQDYNGLCDPYVILKLgkteLGNRD-MYQP----NTLDPIFGMMFelTCNIPL----EKDL 1528
Cdd:cd08385    12 DFQSNQLT-VGIIQAADLPAMDMGGTSDPYVKVYL----LPDKKkKFETkvhrKTLNPVFNETF--TFKVPYselgNKTL 84

                          90       100
                  ....*....|....*....|...
gi 767920434 1529 EIQLYDFDLFSPDDKIGTTVIDL 1551
Cdd:cd08385    85 VFSVYDFDRFSKHDLIGEVRVPL 107

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

169-270

3.86e-06

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 47.45 E-value: 3.86e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  169 VRVKVFEARQL----MGNNIKPVVKVSIAG-QQHQTRIKMGN-NPFFNEIFfqNFHEVPAKffDETILIQVVNSSAMRYK 242
Cdd:cd00030     1 LRVTVIEARNLpakdLNGKSDPYVKVSLGGkQKFKTKVVKNTlNPVWNETF--EFPVLDPE--SDTLTVEVWDKDRFSKD 76

                          90       100
                  ....*....|....*....|....*...
gi 767920434  243 AEIGRFQTDIGFIYHSPGHTllRKWLGL 270
Cdd:cd00030    77 DFLGEVEIPLSELLDSGKEG--ELWLPL 102

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

168-264

4.73e-06

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 47.10 E-value: 4.73e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434    168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSAM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767920434    240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

C2B_Synaptotagmin-7

cd08405

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...

1467-1545

1.50e-05

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: 46.64 E-value: 1.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKL---GKTELGNRDMYQPNTLDPIFGMMFELtcNIPLEK----DLEIQLYDFDLFS 1539
Cdd:cd08405    19 VNIIKARNLKAMDINGTSDPYVKVWLmykDKRVEKKKTVIKKRTLNPVFNESFIF--NIPLERlretTLIITVMDKDRLS 96


                  ....*.
gi 767920434 1540 PDDKIG 1545
Cdd:cd08405    97 RNDLIG 102

C2_PKC_alpha_gamma

cd04026

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...

1472-1545

1.63e-05

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: 46.49 E-value: 1.63e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767920434 1472 AINLQPQDYNGLCDPYVILKLG---KTELGNRDMYQPNTLDPIFGMMFELTCNiPLEKD--LEIQLYDFDLFSPDDKIG 1545
Cdd:cd04026    22 AKNLIPMDPNGLSDPYVKLKLIpdpKNETKQKTKTIKKTLNPVWNETFTFDLK-PADKDrrLSIEVWDWDRTTRNDFMG 99

pfam00168

C2 domain;

168-270

2.09e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 45.39 E-value: 2.09e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSAMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 767920434   241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104

C2A_Rabphilin_Doc2

cd04035

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...

1467-1553

2.89e-05

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: 45.35 E-value: 2.89e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKL-----GKTELgnRDMYQPNTLDPIFG--MMFE-LTCNIPLEKDLEIQLYDFDLF 1538
Cdd:cd04035    19 CTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKL--RTKTVHKTRNPEFNetLTYYgITEEDIQRKTLRLLVLDEDRF 96

                          90
                  ....*....|....*
gi 767920434 1539 SpDDKIGTTVIDLEN 1553
Cdd:cd04035    97 G-NDFLGETRIPLKK 110

C2_NEDD4_NEDD4L

cd04033

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...

1464-1569

2.98e-05

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: 45.81 E-value: 2.98e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVILKLGKT-ELGNRDMYQPNT----LDPIFGMMFELTCNiPLEKDLEIQLYDFDLF 1538
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPdGNGEIDSVQTKTikktLNPKWNEEFFFRVN-PREHRLLFEVFDENRL 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 767920434 1539 SPDDKIGTTVIDLENRLLSGFGAHCGLS-KSY 1569
Cdd:cd04033    80 TRDDFLGQVEVPLNNLPTETPGNERRYTfKDY 111

pfam00168

C2 domain;

1054-1167

3.05e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 44.62 E-value: 3.05e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  1054 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1131
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 767920434  1132 RDFWGKESLWGRsvwppmVWLDLQDRIL--PPMRWHPL 1167
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSgeGLDGWYPL 104

C2B_Synaptotagmin

cd00276

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...

1467-1554

3.55e-05

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: 45.27 E-value: 3.55e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYV---ILKLG------KTELgnrdmyQPNTLDPIFG--MMFELTCNIPLEKDLEIQLYDF 1535
Cdd:cd00276    18 VVVLKARNLPPSDGKGLSDPYVkvsLLQGGkklkkkKTSV------KKGTLNPVFNeaFSFDVPAEQLEEVSLVITVVDK 91

                          90
                  ....*....|....*....
gi 767920434 1536 DLFSPDDKIGTTVIDLENR 1554
Cdd:cd00276    92 DSVGRNEVIGQVVLGPDSG 110

C2A_C2C_Synaptotagmin_like

cd08391

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...

1463-1559

4.55e-05

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: 44.98 E-value: 4.55e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1463 CLVRVYMVRAINLQPQDYN------GLCDPYVILKLG----KTELGNrdmyqpNTLDPIFGMMFELTCNIPLEKDLEIQL 1532
Cdd:cd08391     1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGaqtfKSKVIK------ENLNPKWNEVYEAVVDEVPGQELEIEL 74

                          90       100
                  ....*....|....*....|....*..
gi 767920434 1533 YDFDLfSPDDKIGTTVIDLENRLLSGF 1559
Cdd:cd08391    75 FDEDP-DKDDFLGRLSIDLGSVEKKGF 100

C2B_Rabphilin_Doc2

cd08384

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...

1467-1545

4.79e-05

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: 45.03 E-value: 4.79e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKLgKTELGNRDMYQPN----TLDPIFG--MMFELTCNIPLEKDLEIQLYDFDLFSP 1540
Cdd:cd08384    17 VGIIRCVNLAAMDANGYSDPFVKLYL-KPDAGKKSKHKTQvkkkTLNPEFNeeFFYDIKHSDLAKKTLEITVWDKDIGKS 95


                  ....*
gi 767920434 1541 DDKIG 1545
Cdd:cd08384    96 NDYIG 100

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

1055-1167

7.67e-05

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 43.59 E-value: 7.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1055 LFCYIYQARNLVSNQILTFQGPFIRVVFLN-HSQCTQTLRSSAGPTWAQTLIFQHlllyenpqdTKESPPLVVLELWQRD 1133
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPV---------LDPESDTLTVEVWDKD 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 767920434 1134 FWGKESLWGRSVWPPMvwlDLQDRILPPMRWHPL 1167
Cdd:cd00030    72 RFSKDDFLGEVEIPLS---ELLDSGKEGELWLPL 102

C2B_Munc13

cd04027

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...

1463-1558

1.06e-04

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: 44.10 E-value: 1.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1463 CLVRVYMVRAINLQPQDYNGLCDPYVILKLGKTELGNRDMYQpnTLDPIFGMMFELTCNIPLEKdLEIQLY--DFDLFS- 1539
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQ--NLNPVWNEKFHFECHNSSDR-IKVRVWdeDDDIKSr 77

                          90       100
                  ....*....|....*....|....*..
gi 767920434 1540 --------PDDKIGTTVIDLenRLLSG 1558
Cdd:cd04027    78 lkqkftreSDDFLGQTIIEV--RTLSG 102

COG5038

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

1465-1551

1.13e-04

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 47.45 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1465 VRVYMVRAINLQPQDY--NGLCDPYVILKLGKTELGnRDMYQPNTLDPIFGMMFELTCNiPLEKDLEIQLYDFDLFSPDD 1542
Cdd:COG5038   438 VEVKIKSAEGLKKSDStiNGTVDPYITVTFSDRVIG-KTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDK 515


                  ....*....
gi 767920434 1543 KIGTTVIDL 1551
Cdd:COG5038   516 VVGSTQLDL 524

COG5038

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

1467-1555

1.87e-04

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 46.68 E-value: 1.87e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKLGKTELgNRDMYQPNTLDPIFGMMFELTCNIPLEKDLEIQLYDFDLFSPDDKIGT 1546
Cdd:COG5038  1044 IMLRSGENLPSSDENGYSDPFVKLFLNEKSV-YKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGT 1122


                  ....*....
gi 767920434 1547 TVIDLENRL 1555
Cdd:COG5038  1123 AEIDLSKLE 1131

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

1730-1827

1.88e-04

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 42.44 E-value: 1.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1730 KTSDIYIKGWLYGLEKdmQKTDIHYHSLtgeaDFNWRFIFTMDYLAAERTcvqsqkdyiwsldatsmkfpaRLIIQVWDN 1809
Cdd:cd00030    18 GKSDPYVKVSLGGKQK--FKTKVVKNTL----NPVWNETFEFPVLDPESD---------------------TLTVEVWDK 70

                          90
                  ....*....|....*...
gi 767920434 1810 DIFSPDDFLGVLELDLSD 1827
Cdd:cd00030    71 DRFSKDDFLGEVEIPLSE 88

C2B_Synaptotagmin

cd00276

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...

171-248

2.14e-04

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 43.34 E-value: 2.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434  171 VKVFEARQLM----GNNIKPVVKVSIAGQ-----QHQTRIKMGN-NPFFNEIFfqNFhEVPAKFFDE-TILIQVVNSSAM 239
Cdd:cd00276    18 VVVLKARNLPpsdgKGLSDPYVKVSLLQGgkklkKKKTSVKKGTlNPVFNEAF--SF-DVPAEQLEEvSLVITVVDKDSV 94


                  ....*....
gi 767920434  240 RYKAEIGRF 248
Cdd:cd00276    95 GRNEVIGQV 103

C2A_MCTP_PRT

cd04042

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

1464-1553

2.35e-04

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: 42.65 E-value: 2.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1464 LVRVYMVRAINLQPQDYNGLCDPYVilklgKTELGNRDMYQPNT----LDPIFGmmfELTCnIPLE---KDLEIQLYDFD 1536
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYV-----KFKYGGKTVYKSKTiyknLNPVWD---EKFT-LPIEdvtQPLYIKVFDYD 71

                          90
                  ....*....|....*..
gi 767920434 1537 LFSPDDKIGTTVIDLEN 1553
Cdd:cd04042    72 RGLTDDFMGSAFVDLST 88

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

31-102

2.51e-04

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 42.05 E-value: 2.51e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767920434   31 KKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKERFIGLATVLLKPLLKQPSEVLFVKDL 102
Cdd:cd00030    33 KFKTKVVKNTlNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELWLPL 102

C2A_Tricalbin-like

cd04044

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...

1471-1552

3.03e-04

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: 42.54 E-value: 3.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1471 RAINLQPQDY-NGLCDPYVILKLGKTELGNRDMYQPNTLDPIFGMMFELTCNiPLEKDLEIQLYDFDLFSPDDKIGTTVI 1549
Cdd:cd04044    10 SARGLKGSDIiGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRKDKLIGTAEF 88


                  ...
gi 767920434 1550 DLE 1552
Cdd:cd04044    89 DLS 91

C2A_Synaptotagmin-15-17

cd08390

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...

1467-1558

4.84e-04

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: 41.86 E-value: 4.84e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYN-GLCDPYVILKLGKTELGNRDMY-QPNTLDPIFGMMFELtcNIP----LEKDLEIQLYDFDLFSP 1540
Cdd:cd08390    18 VSLIKARNLPPRTKDvAHCDPFVKVCLLPDERRSLQSKvKRKTQNPNFDETFVF--QVSfkelQRRTLRLSVYDVDRFSR 95

                          90
                  ....*....|....*...
gi 767920434 1541 DDKIGTTVIDLENRLLSG 1558
Cdd:cd08390    96 HCIIGHVLFPLKDLDLVK 113

C2_KIAA0528-like

cd08688

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...

1481-1557

6.45e-04

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: 41.14 E-value: 6.45e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1481 NGLCDPYVILKLGKTElgNRDMYQPNTLDPIFG---MMFELTCNIPLEKDLEIQLYDFDLFSPDDKIGTTVIDLeNRLLS 1557
Cdd:cd08688    18 SDLTDAFVEVKFGSTT--YKTDVVKKSLNPVWNsewFRFEVDDEELQDEPLQIRVMDHDTYSANDAIGKVYIDL-NPLLL 94

C2B_RasA1_RasA4

cd04025

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...

1055-1148

7.44e-04

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: 41.32 E-value: 7.44e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1055 LFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQhllLYENPqdtkesPPLVVLELWQRDF 1134
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFE---LMEGA------DSPLSVEVWDWDL 72

                          90
                  ....*....|....
gi 767920434 1135 WGKESLWGRSVWPP 1148
Cdd:cd04025    73 VSKNDFLGKVVFSI 86

FerI

pfam08151

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

273-312

8.29e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.07 E-value: 8.29e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920434   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42

C2_SRC2_like

cd04051

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...

31-94

9.15e-04

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: 41.06 E-value: 9.15e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920434   31 KKRTRVVE--GNDPVWNETLIWHLWNRPLE-NDSFLQVTLQDMGSQKKERFIGLATVLLKPLLKQPS 94
Cdd:cd04051    34 KQSTPVDRdgGTNPTWNETLRFPLDERLLQqGRLALTIEVYCERPSLGDKLIGEVRVPLKDLLDGAS 100

pfam00168

C2 domain;

1800-1836

9.55e-04

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 40.38 E-value: 9.55e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 767920434  1800 ARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAK 1836
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100

C2_Intersectin

cd08375

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...

1781-1828

2.10e-03

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 40.45 E-value: 2.10e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767920434 1781 VQSQKDYIWSldaTSMKFPAR------LIIQVWDNDIFSPDDFLGVLELDLSDM 1828
Cdd:cd08375    54 VSDTLNPKWN---SSMQFFVKdleqdvLCITVFDRDFFSPDDFLGRTEIRVADI 104

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

1054-1165

3.69e-03

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 38.62 E-value: 3.69e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434   1054 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1130
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 767920434   1131 QRDFWGKESLWGRsvwppmVWLDLQDRILPPMRWH 1165
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100

C2B_Synaptotagmin-1

cd08402

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...

1467-1549

4.10e-03

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: 39.69 E-value: 4.10e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920434 1467 VYMVRAINLQPQDYNGLCDPYVILKL---GKTELGNRDMYQPNTLDPIFGMMFelTCNIPLEK----DLEIQLYDFDLFS 1539
Cdd:cd08402    19 VVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESF--SFEVPFEQiqkvHLIVTVLDYDRIG 96

                          90
                  ....*....|
gi 767920434 1540 PDDKIGTTVI 1549
Cdd:cd08402    97 KNDPIGKVVL 106

C2B_Synaptotagmin

cd00276

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...

31-80

8.73e-03

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 38.33 E-value: 8.73e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920434   31 KKRTRVVEGN-DPVWNETLIWHLWNRPLENDSfLQVTLQDMGSQKKERFIG 80
Cdd:cd00276    52 KKKTSVKKGTlNPVFNEAFSFDVPAEQLEEVS-LVITVVDKDSVGRNEVIG 101

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