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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 514 PQVVSQIHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSPEFDVKGLFYRKKPGKPIIVQIWNHNLISDEFL 593
Cdd:cd04046     1 PQVVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSNLLCDEFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2024438464 594 GQVALKGDPGEQQSVRTLHLQDRGNRRSNDLPGTIAVRMLSSNILT 639
Cdd:cd04046    81 GQATLSADPNDSQTLRTLPLRKRGRDAAGEVPGTISVKVTSSDDLT 126

Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). Calcium activated neutral protease (large subunit).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464   13 YAALKKECLRKKQLFEDPLFPANDDSLFYKSRIQG-IQWKRPKEICSDPHLFVDGISSHDLHQGQVGNCWFVAACSSLAS 91
Cdd:smart00230   1 YEALRQYCKESGTLFEDPLFPANNGSLFFSQRQRKfVVWKRPHEIFENPPFIVGGASRTDICQGVLGDCWLLAALASLTL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464   92 REALWQKVIPdwKEQEWNaekpESYAGIFHFQFWRFGQWLDVVIDDRLPTLHNQLIYCHSNSKNEFWCALVEKAYAKLSG 171
Cdd:smart00230  81 REKLLDRVIP--HDQEFS----ENYAGIFHFRFWRFGKWVDVVIDDRLPTYNGELVFMHSNSRNEFWSALLEKAYAKLNG 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464  172 CYEALDGGNTADALVDFTGGVSEPIDLTEGDYTTDEakrnlLFERVLKVHNRGGLISCSIKAMSAADMEARLACGLVKGH 251
Cdd:smart00230 155 CYEALKGGSTTEALEDLTGGVAESIDLKEASKDPDN-----LFEDLFKAFERGSLMGCSIGAGTAVEEEEQKDCGLVKGH 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464  252 AYAVTDVRKVRLGHgllsffksekLDMIRMRNPWGEREWNGPWSDTSEEWQKVSKSEREKMGMTVEDDGEFWMTFEDFCR 331
Cdd:smart00230 230 AYSVTDVREVQGRR----------QELLRLRNPWGQVEWNGPWSDDSPEWRSVSASEKKNLGLTFDDDGEFWMSFEDFLR 299

                          330
                   ....*....|....*....
gi 2024438464  332 YFTDIIKCRLINTSYLSIH 350
Cdd:smart00230 300 HFDKVEICNLNPDSLEERS 318

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 514 PQVVSQIHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSPEFDVKGLFYRKKPGKPIIVQIWNHNLISDEFL 593
Cdd:cd04046     1 PQVVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSNLLCDEFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2024438464 594 GQVALKGDPGEQQSVRTLHLQDRGNRRSNDLPGTIAVRMLSSNILT 639
Cdd:cd04046    81 GQATLSADPNDSQTLRTLPLRKRGRDAAGEVPGTISVKVTSSDDLT 126

Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, participate in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction. Catalytic domain and the two calmodulin-like domains are separated by C2-like domain III. Domain III plays an important role in calcium-induced activation of calpain involving electrostatic interactions with subdomain II. Proposed to mediate calpain's interaction with phospholipids and translocation to cytoplasmic/nuclear membranes. CD includes subdomain III of typical and atypical calpains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 351 KTWEEAVLHGAWTRHddplkNRSGGCINHKDTFLQNPQYVFDVKKAED-----EVLISIQQKPKRTSRKEGKgENLAIGF 425
Cdd:cd00214     1 RKWHTKSFNGEWRRG-----QTAGGCRNNPDTFWTNPQFRIRVPEPDDdegkcTVLIALMQKNRRHLRKKGL-DLLTIGF 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024438464 426 DIHKV-ELNRNYRMHTLQQKV---ASSIYINSRSVFLRTDLKEGRYVIIPTTFDPGHVGEFLLRIFTDVPSDCREL 497
Cdd:cd00214    75 HVYKVpGENRHLRRDFFLHKApraRSSTFINTREVSLRFRLPPGEYVIVPSTFEPGEEGEFLLRVFSEKSIKSSEL 150

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464  520 IHVLTAAGLKNQDSQGGADPYVIIKCEGQ---KVRSAVKKDTVSPEFDVKGLFYRKKP-GKPIIVQIWNHNLIS-DEFLG 594
Cdd:smart00239   4 VKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPeLAELEIEVYDKDRFGrDDFIG 83

                   ....
gi 2024438464  595 QVAL 598
Cdd:smart00239  84 QVTI 87

Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). Calcium activated neutral protease (large subunit).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464   13 YAALKKECLRKKQLFEDPLFPANDDSLFYKSRIQG-IQWKRPKEICSDPHLFVDGISSHDLHQGQVGNCWFVAACSSLAS 91
Cdd:smart00230   1 YEALRQYCKESGTLFEDPLFPANNGSLFFSQRQRKfVVWKRPHEIFENPPFIVGGASRTDICQGVLGDCWLLAALASLTL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464   92 REALWQKVIPdwKEQEWNaekpESYAGIFHFQFWRFGQWLDVVIDDRLPTLHNQLIYCHSNSKNEFWCALVEKAYAKLSG 171
Cdd:smart00230  81 REKLLDRVIP--HDQEFS----ENYAGIFHFRFWRFGKWVDVVIDDRLPTYNGELVFMHSNSRNEFWSALLEKAYAKLNG 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464  172 CYEALDGGNTADALVDFTGGVSEPIDLTEGDYTTDEakrnlLFERVLKVHNRGGLISCSIKAMSAADMEARLACGLVKGH 251
Cdd:smart00230 155 CYEALKGGSTTEALEDLTGGVAESIDLKEASKDPDN-----LFEDLFKAFERGSLMGCSIGAGTAVEEEEQKDCGLVKGH 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464  252 AYAVTDVRKVRLGHgllsffksekLDMIRMRNPWGEREWNGPWSDTSEEWQKVSKSEREKMGMTVEDDGEFWMTFEDFCR 331
Cdd:smart00230 230 AYSVTDVREVQGRR----------QELLRLRNPWGQVEWNGPWSDDSPEWRSVSASEKKNLGLTFDDDGEFWMSFEDFLR 299

                          330
                   ....*....|....*....
gi 2024438464  332 YFTDIIKCRLINTSYLSIH 350
Cdd:smart00230 300 HFDKVEICNLNPDSLEERS 318

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 514 PQVVSQIHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSPEFDVKGLFYRKKPGKPIIVQIWNHNLISDEFL 593
Cdd:cd04046     1 PQVVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSNLLCDEFL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2024438464 594 GQVALKGDPGEQQSVRTLHLQDRGNRRSNDLPGTIAVRMLSSNILT 639
Cdd:cd04046    81 GQATLSADPNDSQTLRTLPLRKRGRDAAGEVPGTISVKVTSSDDLT 126

Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, participate in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction. Catalytic domain and the two calmodulin-like domains are separated by C2-like domain III. Domain III plays an important role in calcium-induced activation of calpain involving electrostatic interactions with subdomain II. Proposed to mediate calpain's interaction with phospholipids and translocation to cytoplasmic/nuclear membranes. CD includes subdomain III of typical and atypical calpains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 351 KTWEEAVLHGAWTRHddplkNRSGGCINHKDTFLQNPQYVFDVKKAED-----EVLISIQQKPKRTSRKEGKgENLAIGF 425
Cdd:cd00214     1 RKWHTKSFNGEWRRG-----QTAGGCRNNPDTFWTNPQFRIRVPEPDDdegkcTVLIALMQKNRRHLRKKGL-DLLTIGF 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024438464 426 DIHKV-ELNRNYRMHTLQQKV---ASSIYINSRSVFLRTDLKEGRYVIIPTTFDPGHVGEFLLRIFTDVPSDCREL 497
Cdd:cd00214    75 HVYKVpGENRHLRRDFFLHKApraRSSTFINTREVSLRFRLPPGEYVIVPSTFEPGEEGEFLLRVFSEKSIKSSEL 150

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 519 QIHVLTAAGLKNQDSQGGADPYVIIKCEG-QKVRSAVKKDTVSPEFDVKGLF-YRKKPGKPIIVQIWNHNLIS-DEFLGQ 595
Cdd:cd00030     2 RVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFpVLDPESDTLTVEVWDKDRFSkDDFLGE 81

                  ....
gi 2024438464 596 VALK 599
Cdd:cd00030    82 VEIP 85

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 520 IHVLTAAGLKNQDSQGGADPYVIIKC--EGQKVRSAVKKDTVSPEFDVKGLF-YRKKPGKPIIVQIWNHNLIS-DEFLGQ 595
Cdd:pfam00168   5 VTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFsVPDPENAVLEIEVYDYDRFGrDDFIGE 84

                          90
                  ....*....|....*
gi 2024438464 596 VALKGDPGEQQSVRT 610
Cdd:pfam00168  85 VRIPLSELDSGEGLD 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 517 VSQIHVLTAAGLKNQDSQGGADPYVIIKCEGQKV--RSAVKKDTVSPEF----DVKGLFyrkkPGKPII-VQIWNHNLI- 588
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKIndRDNYIPNTLNPVFgkmfELEATL----PGNSILkISVMDYDLLg 76

                  ....*..
gi 2024438464 589 SDEFLGQ 595
Cdd:cd04037    77 SDDLIGE 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 519 QIHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVS-PEFDVKGLFYRKKPGKP----IIVQIWNHNLIS-DEF 592
Cdd:cd04049     4 EVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGRnPEWNEKFKFTVEYPGWGgdtkLILRIMDKDNFSdDDF 83

                  ....
gi 2024438464 593 LGQV 596
Cdd:cd04049    84 IGEA 87

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2024438464 521 HVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSPEFDvKGLFYRKKPG--KPIIVQIWNHNLIS-DEFLGQV 596
Cdd:cd04025     5 HVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWN-EVFEFELMEGadSPLSVEVWDWDLVSkNDFLGKV 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 519 QIHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSP------EFDVKGLFYRKKPGKPIIVQIWNHNLI-SDE 591
Cdd:cd08682     2 QVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPvwkeecSFELPGLLSGNGNRATLQLTVMHRNLLgLDK 81

                  ....*..
gi 2024438464 592 FLGQVAL 598
Cdd:cd08682    82 FLGQVSI 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 520 IHVLTAAGLKNQDSQGGADPYVIIKCEGQKVRSAVKKDTVSPEFDVKGLFYRKKP----GKPIIVQIWNHN--LISDEFL 593
Cdd:cd04022     4 VEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlsNLVLEVYVYNDRrsGRRRSFL 83

                          90
                  ....*....|....*..
gi 2024438464 594 GQVALKGD--PGEQQSV 608
Cdd:cd04022    84 GRVRISGTsfVPPSEAV 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 520 IHVLTAAGLknQDSQGGADPYVIIKCE--GQKVRSAVKKDTVSPEFDVKGLFYRKKPGKPIIVQIWNHNLISDE-FLGQV 596
Cdd:cd08678     3 VKNIKANGL--SEAAGSSNPYCVLEMDepPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSkFLGLA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2024438464 597 A-----LKGDPGEQQSvrtLHLQDRgNRRSNDLPGTIAVRML 633
Cdd:cd08678    81 IvpfdeLRKNPSGRQI---FPLQGR-PYEGDSVSGSITVEFL 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 520 IHVLTAAGLKNqdSQGGADPYVIIKCEGQKV-----RSAVKKDTVSPE------FDVKGLFYRKKPGK----------PI 578
Cdd:cd04010     4 VRVIECSDLAL--KNGTCDPYASVTLIYSNKkqdtkRTKVKKKTNNPQfdeafyFDVTIDSSPEKKQFempeedaeklEL 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024438464 579 IVQIWNHNLIS-DEFLGQV--ALKGdPGEQQSV---------RTLHLQDRGNRRSND 623
Cdd:cd04010    82 RVDLWHASMGGgDVFLGEVriPLRG-LDLQAGShqawyflqpREEKSTPPGTRSSKD 137

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024438464 513 YPQVVSQIHV--LTAAGLKNQDSQGGADPYViiKC-------EGQKVRSAVKKDTVSPEFDVKGLFY----RKKPGKPII 579
Cdd:cd04035    10 YDPANSALHCtiIRAKGLKAMDANGLSDPYV--KLnllpgasKATKLRTKTVHKTRNPEFNETLTYYgiteEDIQRKTLR 87

                          90       100
                  ....*....|....*....|..
gi 2024438464 580 VQIWNHNLISDEFLGQ--VALK 599
Cdd:cd04035    88 LLVLDEDRFGNDFLGEtrIPLK 109