NCBI Conserved Domain Search

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the synaptotagmin family, mostly plants; The synaptotagmin family includes Arabidopsis thaliana synaptotagmins (AtSYT1-5) and similar proteins. AtSYT1, also called NTMC2T1.1, or synaptotagmin A (SYTA), plays an important role in maintaining plasma membrane integrity during freezing and osmotic stresses. It may function in membrane resealing during calcium-dependent freezing tolerance. It regulates endocytosis and endosome recycling at the plasma membrane and cell-to-cell trafficking of cabbage leaf curl virus (CaLCuV) and tobacco mosaic virus (TMV) movement proteins via plasmodesmata. AtSYT2, also called NTMC2T1.2, or synaptotagmin B (SYTB), may play an important role in regulating an unconventional protein trafficking from the cytosol to the extracellular matrix. AtSYT3 (also called NTMC2T1.3, or synaptotagmin C, or SYTC), AtSYT4 (also called NTMC2T2.2, or synaptotagmin D, or SYTD) and AtSYT5 (also called NTMC2T2.1, or synaptotagmin E, or SYTE) may also be involved in membrane trafficking. This model corresponds to the SMP domain of SYT family proteins, which may be implicated in lipid transport.

Pssm-ID: 439233 Cd Length: 189 Bit Score: 252.08 E-value: 3.77e-81

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  60 PSWVVFSQRQKLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMILSSLKFSRFTLGTVSPQFTGVSIIEDGADCI 139
Cdd:cd21677    1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLEQYKPSFISSIKFKKLTLGTVPPRIEGVKVVESDEDEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 140 TLELELQWDGNPSIILDINTRLGVALPVQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVGGDISAI 219
Cdd:cd21677   81 ILDVDFRWAGDPDIVLAVKLLPGLSLPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLKLLGGDDMAL 160

                        170       180
                 ....*....|....*....|....*....
gi 225446229 220 PGISDAIKDTIDNAIEDSIMWPVRKVVPI 248
Cdd:cd21677  161 PGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 144.52 E-value: 3.44e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229   71 LTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMILSSLKFSRFTLGTVSPQFTGV-SIIEDGADciTLELELQWDG 149
Cdd:COG5038   223 VEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSFIDALALDEFTLGSKPPRIDGIrSYPSTESD--TVVMDVDFSF 300

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  150 NPSIILDIN-------------------TRLGVA-LPVQVKNIGFTGVFRLMFKpLVDEFPCFGAVCFSLRQKKKLDLTL 209
Cdd:COG5038   301 TPHDISDVTatsarasvnpkislvvkkgKSFGSFtLPILVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEFDFIL 379

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  210 KVVGG-----DISAIPGISDAIKDTIDNAIEDSIMWPvrKVVPI-LPGDYSDLELKPVGTLEVKLVQAKELTNKDII--G 281
Cdd:COG5038   380 VPLGGdffgvDIFAIPGLSRFIQEIINSTLGPMLLPP--NSLTIdISQIMAGDSGTAIGVVEVKIKSAEGLKKSDSTinG 457

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  282 KSDPFAVLyvrPLPNRMK-TSKTINNQLNPVWNEHFeFIVEDASTQHLVVKIYDNEGLQASELIGCAQVQLRELEPGKVK 360
Cdd:COG5038   458 TVDPYITV---TFSDRVIgKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQNPVK 533

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  361 dawwklvKDLEVQ--RDTKNRGQVHLELLYVPFGMENG--------------------------FTNPFAPKFSM----- 407
Cdd:COG5038   534 -------KNELYEflRNTKNVGRLTYDLRFFPVIEDKKelkgsvepledsntgilkvtlrevkaLDELSSKKDNKsaely 606

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  408 -----------------------------------------------------TSLEKVLKNGVDGTEVAENGNAVMQKK 434
Cdd:COG5038   607 tnakevystgklkftnhpswnlqynvlvtdrknssikvvtfdvqsgkviategSTLPDLIDRTLDTFLVFPLRNPKGRIF 686

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  435 REVIVR------------------GVLSITVISAEDLPVVDLMGKADPYVVLILKKSEiRNKTRVVNDSLNPVWNQtFDF 496
Cdd:COG5038   687 ITNYWKpiynaggsssktvydtpiGAIRVSVRKANDLRNEIPGGKSDPYATVLVNNLV-KYRTIYGSSTLNPIWNE-ILY 764

                         570       580
                  ....*....|....*....|...
gi 225446229  497 VVEDGLHDMLILEVWDHDTFGKD 519
Cdd:COG5038   765 VPVTSKNQRLTLECMDYEESGDD 787

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended synaptotagmin (E-Syt) family; The extended synaptotagmin (E-Syt) family includes a group of Ca2+-regulated intrinsic membrane proteins, such as E-Syt1, E-Syt2 and E-Syt3. They are composed of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five (E-Syt1) or three C-terminal cytoplasmic C2-domains (E-Syt2 and E-Syt3). The ER-membrane anchor and C2 domains are required for tethering, while the SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell. This model corresponds to the SMP domain, which has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain.

Pssm-ID: 439226 Cd Length: 177 Bit Score: 126.52 E-value: 9.20e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  73 WLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMILSSLKFSRFTLGTVSPQFTGVSIIEDGA--DCITLELELQWDGN 150
Cdd:cd21670    5 WLNKIIKQLWPYINEYVEKLLKEKIEPSIRALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVdrDEIILDLDISYDGD 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 151 PSIILDINTRlgvaLPVQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVgGDISAIPGISDAIKDTI 230
Cdd:cd21670   85 ADIEVSVGTG----IKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGL-ANLLDIPGLSNLLRKII 159

                        170
                 ....*....|....*...
gi 225446229 231 DNAIEDSIMWPVRKVVPI 248
Cdd:cd21670  160 VDQIASFLVLPNRITIPL 177

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 113.18 E-value: 5.89e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  441 GVLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKD- 519
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDd 80

                          90       100
                  ....*....|....*....|....
gi 225446229  520 YMGRCILTLTRVILEGEYKETFQL 543
Cdd:pfam00168  81 FIGEVRIPLSELDSGEGLDGWYPL 104

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the tricalbin (TCB) family; The tricalbin (TCB) family includes Saccharomyces cerevisiae TCB1-3 and similar proteins. They may play a role in membrane trafficking. This model corresponds to the SMP domain of TCB family proteins, which may be implicated in lipid transport.

Pssm-ID: 439234 Cd Length: 203 Bit Score: 111.11 E-value: 5.41e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  70 KLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMILSSLKFSRFTLGTVSPQFTGVSIIE---------------- 133
Cdd:cd21678    2 SVEWLNYFLQKFWLIYEPVLSETIVTNVNPVLAENCPSFLDSLRLTEFTLGTKAPRIEGVRTYPkteddvvvmdwefsft 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 134 --DGADCITLELELQWdgNPSIILDI---NTRLGVALPVQVKNIGFTGVFRLMFKpLVDEFPCFGAVCFSLRQKKKLDLT 208
Cdd:cd21678   82 pnDTSDLTAKQIKNKV--NPKIVLTArvgKGVVGIDLPILVEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPPEIDFV 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 225446229 209 LKVVGG--DISAIPGISDAIKDTIDNAIEDSIMWPVRKVVPI 248
Cdd:cd21678  159 LKPLGGgfDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDL 200

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.

Pssm-ID: 439225 Cd Length: 165 Bit Score: 108.18 E-value: 2.07e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  90 SELIRTNVEPILEQ-YRPMILSSLKFSRFTLGTVSPQFTGVSIIEDGADC--ITLELELQWDGNPSIILDIN---TRLGV 163
Cdd:cd21669    2 EQLIRESLQELLEEvKKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDlqLVLDLDLEYAGDFSVVLSAKlggGGLGL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 164 ALPVQVKNIGFTGVFRLMFKpLVDEFPCFGAVCFSLRQKKKLDLTLKVVGG-DISAIPGISDAIKDTIDNAIEDSIMWPV 242
Cdd:cd21669   82 PVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRPLGGvDLMELPGLSSWLEKLLTDALVELLVEPN 160


                 ....*
gi 225446229 243 RKVVP 247
Cdd:cd21669  161 RIVID 165

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 102.92 E-value: 3.09e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKD-YM 521
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDdFL 79

                         90
                 ....*....|....*...
gi 225446229 522 GRCILTLTRVILEGEYKE 539
Cdd:cd00030   80 GEVEIPLSELLDSGKEGE 97

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 102.01 E-value: 6.36e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTsKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQAS 341
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKT-KVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|..
gi 225446229  342 ELIGCAQVQLRELEPGKVKDAW 363
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGW 101

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: 99.48 E-value: 5.13e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229   442 VLSITVISAEDLPVVDLMGKADPYVVL-ILKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKD- 519
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVsLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDd 80

                           90
                   ....*....|....*....
gi 225446229   520 YMGRCILTLTRVILEGEYK 538
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHE 99

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: 96.40 E-value: 4.84e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229   263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASE 342
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 225446229   343 LIGCAQVQLRELEPGKVKDAW 363
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEKL 101

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 93.67 E-value: 5.67e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVrpLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASEL 343
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSL--GGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                         90       100
                 ....*....|....*....|....
gi 225446229 344 IGCAQVQLRELE-PGKVKDAWWKL 366
Cdd:cd00030   79 LGEVEIPLSELLdSGKEGELWLPL 102

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: 94.28 E-value: 5.70e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLM------GKADPYVvlILKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHD 514
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYV--IVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 225446229 515 TFGKDYMGRCILTLTRVILEGEYKETFQLDEAKSGRLNLHLKW 557
Cdd:cd08391   79 PDKDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

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: 84.65 E-value: 1.12e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDII------GKSDPFAVLYVrplPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDn 335
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRV---GAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFD- 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 225446229 336 EGLQASELIGCAQVQLRELEPGKVKDAWWKLvkdlevqRDTKNrGQVHLEL 386
Cdd:cd08391   77 EDPDKDDFLGRLSIDLGSVEKKGFIDEWLPL-------EDVKS-GRLHLKL 119

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 83.89 E-value: 2.38e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRplpNRMKTSKTINNQLNPVWNEHFEFIVEDAsTQHLVVKIYDNEGLQAS 341
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVLELV---NARLQTHTIYKTLNPEWNKIFTFPIKDI-HDVLEVTVYDEDKDKKP 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 225446229 342 ELIGCAQVQLRELEPGKVKdaWWKLvKDLEVQRDTKnrGQVHLELLYV 389
Cdd:cd08377   77 EFLGKVAIPLLSIKNGERK--WYAL-KDKKLRTRAK--GSILLEMDVI 119

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: 79.15 E-value: 1.04e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGK-DYM 521
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNGEKVF-KTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKdDLL 79

                         90       100
                 ....*....|....*....|....*...
gi 225446229 522 GRCILTLTRVILEGEYKETFQLDEAKSG 549
Cdd:cd04040   80 GSAYIDLSDLEPEETTELTLPLDGQGGG 107

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: 78.52 E-value: 3.66e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDLMGkADPYVVLILKKSEIrnKTRVVNDSLNPVWNQTFDFVVEDgLHDMLILEVWDHDTFGKD 519
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKV--KTRVIKKNLNPVWNEELTLSVPN-PMAPLKLEVFDKDTFSKD 76

                         90
                 ....*....|....
gi 225446229 520 -YMGRCILTLTRVI 532
Cdd:cd04038   77 dSMGEAEIDLEPLV 90

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: 75.54 E-value: 2.35e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLM--GKADPYVVLILkkSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTF-G 517
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRSgkGKSDPYAILSV--GAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFaG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 225446229 518 KDYMGRCILTLTRVILEGEYKETFQL----------DEAKSGRLNLHLKW 557
Cdd:cd04024   79 KDYLGEFDIALEEVFADGKTGQSDKWitlkstrpgkTSVVSGEIHLQFSW 128

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: 75.38 E-value: 3.04e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 438 IVRGVLSITVISAEDLPVVDLMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHD-MLILEVWDH 513
Cdd:cd04026   10 VKDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDrRLSIEVWDW 89

                         90
                 ....*....|
gi 225446229 514 DTFGK-DYMG 522
Cdd:cd04026   90 DRTTRnDFMG 99

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 73.87 E-value: 7.42e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnkTRVVNDSLNPVWNQTFDFVVEDgLHDMLILEVWDHDTFGK-D 519
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQ--THTIYKTLNPEWNKIFTFPIKD-IHDVLEVTVYDEDKDKKpE 77

                         90
                 ....*....|..
gi 225446229 520 YMGRCILTLTRV 531
Cdd:cd08377   78 FLGKVAIPLLSI 89

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: 73.23 E-value: 1.75e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDI--IGKSDPFAVLYVRPlpNRMKTSkTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQ 339
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRsgKGKSDPYAILSVGA--QRFKTQ-TIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFA 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 225446229 340 ASELIGCAQVQLREL---EPGKVKDAWWKLvKDLEVQRDTKNRGQVHLEL 386
Cdd:cd04024   78 GKDYLGEFDIALEEVfadGKTGQSDKWITL-KSTRPGKTSVVSGEIHLQF 126

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

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 72.68 E-value: 1.90e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKK-SEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKDY 520
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDH 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 225446229 521 MGRCILTLTRVILEGEYKETFQLDEAKSGRLNL 553
Cdd:cd04036   81 LGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEV 113

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: 72.97 E-value: 1.99e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKA-DPYVVLILKKSEIRNKTRVVNDSLNPVWNQTFdFVVEDGLHDMLILEVWDHDTFGKD 519
Cdd:cd04044    2 GVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELARTKVKKDTSNPVWNETK-YILVNSLTEPLNLTVYDFNDKRKD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 225446229 520 -YMGRCILTL----TRVILEGEYKEtFQLDEAKSGRLNLHLKWMP 559
Cdd:cd04044   81 kLIGTAEFDLssllQNPEQENLTKN-LLRNGKPVGELNYDLRFFP 124

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: 71.45 E-value: 4.36e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVrplpNRMK--TSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQAS 341
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYL----NGEKvfKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKD 76

                         90       100
                 ....*....|....*....|
gi 225446229 342 ELIGCAQVQLRELEPGKVKD 361
Cdd:cd04040   77 DLLGSAYIDLSDLEPEETTE 96

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

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 71.14 E-value: 8.03e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKKSEIR-NKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGK-D 519
Cdd:cd04043    2 LFTIRIVRAENLKADSSNGLSDPYVTLVDTNGKRRiAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKhD 81

                         90
                 ....*....|
gi 225446229 520 YMGRCILTLT 529
Cdd:cd04043   82 LCGRASLKLD 91

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

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 71.63 E-value: 1.18e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 257 ELKPVGTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNR--------------------------MKTSKTINNQLNP 310
Cdd:cd08676   23 AEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRErnsekskkrkshrkkavlkdtvpaksIKVTEVKPQTLNP 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 225446229 311 VWNEHFEFIVEDASTQHLVVKIYDNEglqaSELIGCAQVQLRELEPGKVkDAWWKL 366
Cdd:cd08676  103 VWNETFRFEVEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSCGL-DSWFKL 153

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-2 (E-Syt2) and similar proteins; Extended synaptotagmin-2 (E-Syt2), also called Chr2Syt, tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. It binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. E-Syt2 plays a role in fibroblast growth factor (FGF) signaling via its role in the rapid internalization of FGFreceptor 1 (FGFR1) that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. E-Syt2 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to SMP domain.

Pssm-ID: 439236 Cd Length: 179 Bit Score: 71.84 E-value: 1.46e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  69 QKLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMiLSSLKFSRFTLGTVSPQFTGVSIIEDGAD--CITLELELQ 146
Cdd:cd21680    3 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAH-LSTFSFTKIDLGDQPLRINGVKVYTENVDkrQIILDLQIS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 147 WDGNPSIILDINTRLGVAlpvQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVGG--DISAIPGISD 224
Cdd:cd21680   82 FVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNllDIPGLNGLSD 158

                        170       180
                 ....*....|....*....|....
gi 225446229 225 AIkdtIDNAIEDSIMWPVRKVVPI 248
Cdd:cd21680  159 TI---ILDIISNYLVLPNRITVPL 179

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

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 69.71 E-value: 5.50e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVL-ILKKSEIRNK--------------------------TRVVNDSLNPVWNQTF 494
Cdd:cd08676   29 VLKVTVIEAKGLLAKDVNGFSDPYCMLgIVPASRERNSekskkrkshrkkavlkdtvpaksikvTEVKPQTLNPVWNETF 108

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 225446229 495 DFVVEDGLHDMLILEVWDHDtfgKDYMGRCILTLTRVILEGE 536
Cdd:cd08676  109 RFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCGL 147

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: 68.05 E-value: 7.40e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKKSeiRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKD-Y 520
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNE--KYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDeF 78

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 225446229 521 MGRCILTLTRVILEGEYKETFQLDEAKsGRLNLHL 555
Cdd:cd08376   79 IGRCEIDLSALPREQTHSLELELEDGE-GSLLLLL 112

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: 66.15 E-value: 3.39e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDgLHDMLILEVWDHDTFGK-DYM 521
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTVY-KSKTIYKNLNPVWDEKFTLPIED-VTQPLYIKVFDYDRGLTdDFM 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 225446229 522 GRCILTLTRVILEGEYKETFQLD----EAKSGRLNLHLKWMP 559
Cdd:cd04042   80 GSAFVDLSTLELNKPTEVKLKLEdpnsDEDLGYISLVVTLTP 121

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 67.35 E-value: 4.19e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDLMGKADPYV---VLILKKSEIRNKTRVVNDSLNPVWNQTF---DFVVEDgLHDMLI-LEVWD 512
Cdd:cd04020   26 TGELHVWVKEAKNLPALKSGGTSDSFVkcyLLPDKSKKSKQKTPVVKKSVNPVWNHTFvydGVSPED-LSQACLeLTVWD 104


                 ....*..
gi 225446229 513 HDTFGKD 519
Cdd:cd04020  105 HDKLSSN 111

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 72.48 E-value: 4.56e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  441 GVLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGK-D 519
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVY-KTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKnD 1118

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 225446229  520 YMGRCILTLTRVILEGEYKETFQLDEAKSG--RLNLHLKW 557
Cdd:COG5038  1119 LLGTAEIDLSKLEPGGTTNSNIPLDGKTFIvlDGTLHPGF 1158

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 64.51 E-value: 8.32e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLIL-KKSEirnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTfgKDY 520
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVgKTTQ---KSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKT--GKS 75

                         90       100
                 ....*....|....*....|....*.
gi 225446229 521 MGRCILTLTRVILEGE--YKETFQLD 544
Cdd:cd04050   76 LGSLTLPLSELLKEPDltLDQPFPLD 101

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

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 64.92 E-value: 9.26e-13

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLILKKSeIRNKTRVVNDSLNPVWNQTFDFVVEDgLHDMLILEVWDHDTFGKD 519
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLVNGI-VKGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEKVGKD 77

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: 65.35 E-value: 9.33e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 438 IVRGVLSITVISAEDLPVVDLMGKADPYV-VLILKKSEIRNK--TRVVNDSLNPVWNQTFDF--VVEDGLHDMLI-LEVW 511
Cdd:cd04031   13 KVTSQLIVTVLQARDLPPRDDGSLRNPYVkVYLLPDRSEKSKrrTKTVKKTLNPEWNQTFEYsnVRRETLKERTLeVTVW 92

                         90       100
                 ....*....|....*....|....*.
gi 225446229 512 DHDTFGK-DYMGRCILTLTRVILEGE 536
Cdd:cd04031   93 DYDRDGEnDFLGEVVIDLADALLDDE 118

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: 65.26 E-value: 9.64e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 438 IVRgvlsITVISAEDLPVVDLMGKADPYVVLILKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFG 517
Cdd:cd04037    1 LVR----VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLG 76


                 ..
gi 225446229 518 KD 519
Cdd:cd04037   77 SD 78

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: 64.20 E-value: 1.38e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDL-MGKADPYVVLILKKS-EIRNKTRVVNDSLNPVWNQT-FDFVVEDGL--HDMLILEVWDHDT 515
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVWEETwFVLVTPDEVkaGERLSCRLWDSDR 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 225446229 516 F-GKDYMGRCILTLTRvILEGEYKETFQLD 544
Cdd:cd04041   81 FtADDRLGRVEIDLKE-LIEDRNWMGRRED 109

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

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 64.21 E-value: 1.92e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDnEGLQASEL 343
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMD-EDYVMDDH 80

                         90
                 ....*....|....*
gi 225446229 344 IGCAQVQLRELEPGK 358
Cdd:cd04036   81 LGTVLFDVSKLKLGE 95

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 64.28 E-value: 1.96e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYvVLILKKSEIRNKTRVVNDSLNPVWNQTFDFVVED-GLHDM--LILEVWDHDTF- 516
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPY-VIIQCRTQERKSKVAKGDGRNPEWNEKFKFTVEYpGWGGDtkLILRIMDKDNFs 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 225446229 517 GKDYMGRCILTLTRVILEGEYKETFQLDEAK 547
Cdd:cd04049   80 DDDFIGEATIHLKGLFEEGVEPGTAELVPAK 110

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: 64.34 E-value: 2.48e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 435 REVIVRGVLSITVISAEDLPVVDLMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDFVVEdgLHDM----LI 507
Cdd:cd08402    9 RYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESFSFEVP--FEQIqkvhLI 86

                         90       100
                 ....*....|....*....|
gi 225446229 508 LEVWDHDTFGK-DYMGRCIL 526
Cdd:cd08402   87 VTVLDYDRIGKnDPIGKVVL 106

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 63.89 E-value: 2.80e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRplpNRMKTSKTINNQ-LNPVWNEHFEFIVEDAS---TQHLVVKIYDNEG 337
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQCR---TQERKSKVAKGDgRNPEWNEKFKFTVEYPGwggDTKLILRIMDKDN 77

                         90
                 ....*....|....*..
gi 225446229 338 LQASELIGCAQVQLREL 354
Cdd:cd04049   78 FSDDDFIGEATIHLKGL 94

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: 63.76 E-value: 3.46e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYV-VLILKKSEI--RNKTRVVNDSLNPVWNQTFDF-VVEDGLHDM-LILEVWDHDTFG 517
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVkVSLLQGGKKlkKKKTSVKKGTLNPVFNEAFSFdVPAEQLEEVsLVITVVDKDSVG 95

                         90
                 ....*....|
gi 225446229 518 KD-YMGRCIL 526
Cdd:cd00276   96 RNeVIGQVVL 105

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: 63.03 E-value: 7.20e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRN-----KTRVVNDSLNPVWNQTFDFVV--EDGLHD--MLILEVWD 512
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLFPdvptpKTQVKKKTLFPLFDESFEFNVppEQCSVEgaLLLFTVKD 96

                         90       100
                 ....*....|....*....|
gi 225446229 513 HDTFGK-DYMGRCILTLTRV 531
Cdd:cd04009   97 YDLLGSnDFEGEAFLPLNDI 116

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: 62.28 E-value: 8.20e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLIL-----KKSEirnkTRVVNDSLNPVWNQTFDF-VVEDGLHD-MLILEVWDHDT 515
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLlpdkkKKFE----TKVHRKTLNPVFNETFTFkVPYSELGNkTLVFSVYDFDR 93

                         90
                 ....*....|....*....
gi 225446229 516 FGK-DYMGRCILTLTRVIL 533
Cdd:cd08385   94 FSKhDLIGEVRVPLLTVDL 112

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: 62.29 E-value: 9.54e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPfavlYVR-PLPNRM-KTSKTINNQLNPVWNEHFEFIVEDAsTQHLVVKIYD-NEGLQ 339
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDP----YVKfKYGGKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDyDRGLT 75

                         90       100
                 ....*....|....*....|..
gi 225446229 340 AsELIGCAQVQLRELEPGKVKD 361
Cdd:cd04042   76 D-DFMGSAFVDLSTLELNKPTE 96

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 62.17 E-value: 1.12e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVV--DLMGKADPYV-VLIL---KKSEIRNKTRVVND-SLNPVWNQTFDFVVEDGLHDMLILEVWDHDT 515
Cdd:cd00275    4 LTIKIISGQQLPKPkgDKGSIVDPYVeVEIHglpADDSAKFKTKVVKNnGFNPVWNETFEFDVTVPELAFLRFVVYDEDS 83

                         90
                 ....*....|....*
gi 225446229 516 FGKDYMGRCILTLTR 530
Cdd:cd00275   84 GDDDFLGQACLPLDS 98

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: 62.37 E-value: 1.29e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDLMGKADPYVVLILK--KSEI-RNKTRVVNDSLNPVWNQTFDFVVEdgLHD----MLILEVWD 512
Cdd:cd08384   12 RRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKpdAGKKsKHKTQVKKKTLNPEFNEEFFYDIK--HSDlakkTLEITVWD 89

                         90
                 ....*....|....*....
gi 225446229 513 HDtFGK--DYMGRCILTLT 529
Cdd:cd08384   90 KD-IGKsnDYIGGLQLGIN 107

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

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 61.91 E-value: 1.32e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDLMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDFVV--EDGLHDMLILEVWDHD 514
Cdd:cd04030   15 RQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLlpdKSKSTRRKTSVKKDNLNPVFDETFEFPVslEELKRRTLDVAVKNSK 94

                         90       100
                 ....*....|....*....|..
gi 225446229 515 TF---GKDYMGRCILTLTRVIL 533
Cdd:cd04030   95 SFlsrEKKLLGQVLIDLSDLDL 116

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: 61.65 E-value: 1.87e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 259 KPVGTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIV--EDASTQHLVVKIYDNE 336
Cdd:cd08387   13 KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVppQELPKRTLEVLLYDFD 92

                         90       100       110
                 ....*....|....*....|....*....|
gi 225446229 337 GLQASELIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd08387   93 QFSRDECIGVVELPLAEVDLSEKLDLWRKI 122

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: 61.13 E-value: 2.38e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVrpLPNRMKT--SKTINNQLNPVWNEHFEFIV--EDASTQHLVVKIYDNEG 337
Cdd:cd08385   16 NQLTVGIIQAADLPAMDMGGTSDPYVKVYL--LPDKKKKfeTKVHRKTLNPVFNETFTFKVpySELGNKTLVFSVYDFDR 93

                         90       100       110
                 ....*....|....*....|....*....|....
gi 225446229 338 LQASELIGCAQVQLRELEPGKVKDAWwklvKDLE 371
Cdd:cd08385   94 FSKHDLIGEVRVPLLTVDLGHVTEEW----RDLE 123

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: 60.40 E-value: 3.35e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVD-LMGKADPYVVLILKKSEirNKTRVVNDSLNPVWN-QTFDFVVEDGL--HDMLILEVWDHDTFGK 518
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTT--YKTDVVKKSLNPVWNsEWFRFEVDDEElqDEPLQIRVMDHDTYSA 78

                         90
                 ....*....|....*....
gi 225446229 519 -DYMGRCILTLTRVILEGE 536
Cdd:cd08688   79 nDAIGKVYIDLNPLLLKDS 97

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-3 (E-Syt3) and similar proteins; Extended synaptotagmin-3 (E-Syt3), also called Chr3Syt, binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt3 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.

Pssm-ID: 439237 Cd Length: 177 Bit Score: 62.15 E-value: 3.38e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  69 QKLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQyRPMILSSLKFSRFTLGTVSPQFTGVSIIEDGAD--CITLELELQ 146
Cdd:cd21681    1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIRE-KSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDrrQVILDLQIC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 147 WDGNPSIILDINTrlgvaLPVQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVgGDISAIPGISDAI 226
Cdd:cd21681   80 YIGDCEINVEIKK-----CKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGL-TNLLDIPGINDMS 153

                        170       180
                 ....*....|....*....|..
gi 225446229 227 KDTIDNAIEDSIMWPVRKVVPI 248
Cdd:cd21681  154 DSLIEDLIASHLVLPNRFTVPL 175

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

Pssm-ID: 175998 [Multi-domain] Cd Length: 127 Bit Score: 60.74 E-value: 3.64e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLpVVDLMGKADPYVVLILKKSEIRnkTRVVNDSLNPVWNQTFDF-VVEDGLHDMLILEVWDHD-TFG 517
Cdd:cd04032   27 LATLTVTVLRATGL-WGDYFTSTDGYVKVFFGGQEKR--TEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDnGWD 103

                         90       100
                 ....*....|....*....|....*..
gi 225446229 518 KDYMGRCiltlTRVILEGEYKETFQLD 544
Cdd:cd04032  104 DDLLGTC----SVVPEAGVHEDSCQLN 126

Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell.

Pssm-ID: 465339 Cd Length: 180 Bit Score: 61.98 E-value: 4.06e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229   69 QKLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMiLSSLKFSRFTLGTVSPQFTGVSIIEDGAD--CITLELELQ 146
Cdd:pfam17047   3 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTH-LSTFSFTKVDVGQQPLRINGVKVYTENVDkrQIILDLQIS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  147 WDGNPSIILDINTRLGVAlpvQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVGG--DISAIPGISD 224
Cdd:pfam17047  82 FVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNllDVPGLNGLSD 158

                         170       180
                  ....*....|....*....|....*
gi 225446229  225 AIkdtIDNAIEDSIMWPVRKVVPIL 249
Cdd:pfam17047 159 TI---ILDIISNYLVLPNRITVPLV 180

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: 60.89 E-value: 4.16e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLIL----KKSEIRnKTRVVNDSLNPVWNQTFDFVVE-DGLHDM-LILEVWDHD 514
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLmykdKRVEKK-KTVIKKRTLNPVFNESFIFNIPlERLRETtLIITVMDKD 93

                         90
                 ....*....|...
gi 225446229 515 TFGK-DYMGRCIL 526
Cdd:cd08405   94 RLSRnDLIGKIYL 106

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

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 60.04 E-value: 5.58e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYV-VLILKKSEIRNKTRVVNDSLNPVWNQTFDF--VVEDGLHDM-LILEVWDHDTFG 517
Cdd:cd08386   17 TLTLKILKAVELPAKDFSGTSDPFVkIYLLPDKKHKLETKVKRKNLNPHWNETFLFegFPYEKLQQRvLYLQVLDYDRFS 96

                         90       100
                 ....*....|....*....|
gi 225446229 518 K-DYMGRCILTLTRVILEGE 536
Cdd:cd08386   97 RnDPIGEVSLPLNKVDLTEE 116

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: 60.25 E-value: 6.76e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 450 AEDLPVVDLMGKADPYV-VLILKKSEirnKTRVVNDSLNPVWNQTFDF---VVEDGLHDML------ILEVWDHDTFGKD 519
Cdd:cd04017   10 ARDLLAADKSGLSDPFArVSFLNQSQ---ETEVIKETLSPTWDQTLIFdevELYGSPEEIAqnpplvVVELFDQDSVGKD 86


                 ....*..
gi 225446229 520 -YMGRCI 525
Cdd:cd04017   87 eFLGRSV 93

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: 59.49 E-value: 8.31e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 261 VGTLEVKLVQAKELTNKDIIGKS-DPFAVLYVRPLPNRMKTsKTINNQLNPVWNEHFEFIVeDASTQHLVVKIYDNEGLQ 339
Cdd:cd04044    1 IGVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELART-KVKKDTSNPVWNETKYILV-NSLTEPLNLTVYDFNDKR 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 225446229 340 ASELIGCAQVQLREL-EPGKVKDAwwklvkDLEVQRDTKNRGQVHLELLYVP 390
Cdd:cd04044   79 KDKLIGTAEFDLSSLlQNPEQENL------TKNLLRNGKPVGELNYDLRFFP 124

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

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 58.73 E-value: 1.39e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 269 VQAKELTNKDIIGKSDPFAVLYVRPlPNRMKTSK-----TINNQLNPVWNE--HFEFIVEdaSTQHLVVKIYD----NEG 337
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKT-GGSGQWVEigrteVIKNNLNPDFVTtfTVDYYFE--EVQKLRFEVYDvdskSKD 83

                         90
                 ....*....|....*..
gi 225446229 338 LQASELIGCAQVQLREL 354
Cdd:cd04048   84 LSDHDFLGEAECTLGEI 100

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

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 58.41 E-value: 1.71e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVrplpNRM-KTSKTI--NNQlNPVWNEHFEFIVEDASTQHLVVKIYDnEGL 338
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRI----GGVtKKTKTDfrGGQ-HPEWDEELRFEITEDKKPILKVAVFD-DDK 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 225446229 339 QASELIGCAQVQLRE-LEPGKVKDaWwklvkdLEVQRDTKNRGQVHLELLY 388
Cdd:cd08681   75 RKPDLIGDTEVDLSPaLKEGEFDD-W------YELTLKGRYAGEVYLELTF 118

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-1 (E-Syt1) and similar proteins; Extended synaptotagmin-1 (E-Syt1), also called membrane-bound C2 domain-containing protein (MBC2), binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It also binds calcium via the C2 domains and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. E-Syt1 tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt1 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.

Pssm-ID: 439235 Cd Length: 176 Bit Score: 60.19 E-value: 1.78e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  69 QKLTWLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMiLSSLKFSRFTLGTVSPQFTGVSI-IEDGADCITLELELQW 147
Cdd:cd21679    1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNH-LQTFSFTKVDLGEKPLKVVGVKAhTEFDKRQIILDLHISY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 148 DGNPSIILDINTRLGVAlpvQVKNIGFTGVFRLMFKPLVDEFPCFGAVCFSLRQKKKLDLTLKVVgGDISAIPGISdAIK 227
Cdd:cd21679   80 VGDVEINVEVKKYFCKA---GVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGM-TNLLDIPGLS-SMS 154

                        170       180
                 ....*....|....*....|..
gi 225446229 228 DT-IDNAIEDSIMWPVRKVVPI 248
Cdd:cd21679  155 DTmIMDTIASFLVLPNRLTVPL 176

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: 58.45 E-value: 2.08e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLIL-----KKSEIRNKTrvVNDSLNPVWNQTFDFV---VEDGLHDMLILEVWDHD 514
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKLRTKT--VHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDED 94


                 ....*...
gi 225446229 515 TFGKDYMG 522
Cdd:cd04035   95 RFGNDFLG 102

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: 58.94 E-value: 2.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLILKKSEirNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFG-KD 519
Cdd:cd08375   15 GRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQE--HKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSpDD 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 225446229 520 YMGRCILTLTRVILE-----GEYKETFQLDEAKSG----RLNLH 554
Cdd:cd08375   93 FLGRTEIRVADILKEtkeskGPITKRLLLHEVPTGevvvKLDLQ 136

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 58.50 E-value: 2.40e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLilKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDG---LHDMLILEVWDH--DTFG 517
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVEL--DFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDrrSGRR 79

                         90
                 ....*....|....*....
gi 225446229 518 KDYMGRCILTLTRVILEGE 536
Cdd:cd04022   80 RSFLGRVRISGTSFVPPSE 98

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: 58.35 E-value: 2.50e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSeiRNKTRVVNDSLNPVWNQTFDFVVEDGlHDMLILEVWDHD-------- 514
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKT--KKRTKTIPQNLNPVWNEKFHFECHNS-SDRIKVRVWDEDddiksrlk 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 225446229 515 -TFGK---DYMGRCILTLTrvILEGEYKETFQLDE-----AKSGRLNLHL 555
Cdd:cd04027   80 qKFTResdDFLGQTIIEVR--TLSGEMDVWYNLEKrtdksAVSGAIRLHI 127

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 63.62 E-value: 2.58e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  258 LKPVGTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRmkTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEG 337
Cdd:COG5038  1036 VENSGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVY--KTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDS 1113

                          90       100
                  ....*....|....*....|.
gi 225446229  338 LQASELIGCAQVQLRELEPGK 358
Cdd:COG5038  1114 GEKNDLLGTAEIDLSKLEPGG 1134

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: 58.03 E-value: 2.69e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 446 TVISAEDLPvvDLMGKADPYVVLILKksEIRNKTRVVNDSLNPVWNQTFDFVVEDGLH--DMLILEVWDHDTFGKD-YMG 522
Cdd:cd08373    1 LVVSLKNLP--GLKGKGDRIAKVTFR--GVKKKTRVLENELNPVWNETFEWPLAGSPDpdESLEIVVKDYEKVGRNrLIG 76

                         90
                 ....*....|....
gi 225446229 523 RCILTLTRVILEGE 536
Cdd:cd08373   77 SATVSLQDLVSEGL 90

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

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 58.03 E-value: 2.86e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLILkkSEIRNKTRVVNDS-LNPVWNQTFDF-VVEDGLHdMLILEVWDHDTFGK 518
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRI--GGVTKKTKTDFRGgQHPEWDEELRFeITEDKKP-ILKVAVFDDDKRKP 77

                         90       100
                 ....*....|....*....|....*.
gi 225446229 519 DYMGRCILTLTRVILEGEYKETFQLD 544
Cdd:cd08681   78 DLIGDTEVDLSPALKEGEFDDWYELT 103

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: 57.88 E-value: 3.01e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIrnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGK-DYM 521
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTL--ETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKnDFL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 225446229 522 GRCILTLTRVILEGEYKETFQL---------DEAKSGRLNLHLK 556
Cdd:cd04025   80 GKVVFSIQTLQQAKQEEGWFRLlpdpraeeeSGGNLGSLRLKVR 123

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

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 57.19 E-value: 4.58e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 448 ISAEDLPVVDLMGKADPYVVlILKKSEIRN-----KTRVVNDSLNPVWNqTFDFVVED---GLHDM-LILEVWDHDTFGK 518
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLE-ISRQSEDGTwvlvyRTEVIKNTLNPVWK-PFTIPLQKlcnGDYDRpIKIEVYDYDSSGK 84

                         90       100
                 ....*....|....*....|....*.
gi 225446229 519 -DYMGRCILTLTRviLEGEYKETFQL 543
Cdd:cd04047   85 hDLIGEFETTLDE--LLKSSPLEFEL 108

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: 57.29 E-value: 5.63e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVrpLP-----NRMKTsKTINNQLNPVWNEHFEFI---VEDASTQHLVVKIYD 334
Cdd:cd04035   16 ALHCTIIRAKGLKAMDANGLSDPYVKLNL--LPgaskaTKLRT-KTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLD 92

                         90       100
                 ....*....|....*....|....*..
gi 225446229 335 nEGLQASELIGCAQVQLRELEPGKVKD 361
Cdd:cd04035   93 -EDRFGNDFLGETRIPLKKLKPNQTKQ 118

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: 56.88 E-value: 5.94e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 266 VKLVQAKELTNKDIIGKSDPfavlYVR-PLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASELI 344
Cdd:cd08376    4 IVLVEGKNLPPMDDNGLSDP----YVKfRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFI 79

                         90
                 ....*....|.
gi 225446229 345 GCAQVQLRELE 355
Cdd:cd08376   80 GRCEIDLSALP 90

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: 56.88 E-value: 8.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 269 VQAKELTNKdiIGKSDPFAVLYVRPLPnrmKTSKTINNQLNPVWNEHFEF----IVEDASTQHLVVKIYdNEGLQASeLI 344
Cdd:cd08373    3 VSLKNLPGL--KGKGDRIAKVTFRGVK---KKTRVLENELNPVWNETFEWplagSPDPDESLEIVVKDY-EKVGRNR-LI 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 225446229 345 GCAQVQLRElepgkvkdawwkLVKDLEVQ-----RDTKNR---GQVHLELLYVP 390
Cdd:cd08373   76 GSATVSLQD------------LVSEGLLEvteplLDSNGRptgATISLEVSYQP 117

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: 57.34 E-value: 8.32e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 261 VGTLEVKLVQAKELTNKDIIGkSDPFAVLYvrpLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQhLVVKIYDNEGLQA 340
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLT---LGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKDTFSK 75

                         90
                 ....*....|....
gi 225446229 341 SELIGCAQVQLREL 354
Cdd:cd04038   76 DDSMGEAEIDLEPL 89

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: 56.86 E-value: 8.59e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLpnrMKTSKTINNQ--LNPVWNEHFEFIVEDASTQH----LVVKIYDNE 336
Cdd:cd04051    1 TLEITIISAEDLKNVNLFGKMKVYAVVWIDPS---HKQSTPVDRDggTNPTWNETLRFPLDERLLQQgrlaLTIEVYCER 77

                         90
                 ....*....|....*...
gi 225446229 337 GLQASELIGCAQVQLREL 354
Cdd:cd04051   78 PSLGDKLIGEVRVPLKDL 95

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: 56.64 E-value: 1.06e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTI--NNQLNPVWNEHFEFIVEDASTQ--HLVVKIYDNEG 337
Cdd:cd08402   15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTikKRTLNPYYNESFSFEVPFEQIQkvHLIVTVLDYDR 94


                 ....*...
gi 225446229 338 LQASELIG 345
Cdd:cd08402   95 IGKNDPIG 102

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: 56.47 E-value: 1.15e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILkKSEIRNKTRVVND-SLNPVWNQTFDFVVEDGL----HDMLILEVWDHDTFG 517
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWI-DPSHKQSTPVDRDgGTNPTWNETLRFPLDERLlqqgRLALTIEVYCERPSL 80


                 ..
gi 225446229 518 KD 519
Cdd:cd04051   81 GD 82

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: 56.44 E-value: 1.20e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKT--INNQLNPVWNEHFEFIVEDASTQH--LVVKIYDNEG 337
Cdd:cd00276   14 ERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTsvKKGTLNPVFNEAFSFDVPAEQLEEvsLVITVVDKDS 93


                 ....*....
gi 225446229 338 LQASELIGC 346
Cdd:cd00276   94 VGRNEVIGQ 102

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

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 56.36 E-value: 1.27e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 258 LKPVGTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTI--NNQLNPVWNEHFEFIVEDASTQH--LVVKIY 333
Cdd:cd08403   10 LPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSvkKNTLNPTYNEALVFDVPPENVDNvsLIIAVV 89

                         90       100       110
                 ....*....|....*....|....*....|
gi 225446229 334 DNEGLQASELIGCAQVQLRelEPGKVKDAW 363
Cdd:cd08403   90 DYDRVGHNELIGVCRVGPN--ADGQGREHW 117

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 56.52 E-value: 1.51e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVvlilkKSEIRN---KTRV-VNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGK 518
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFV-----KAQLGNqvlRTRPsQTRNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNK 76

                         90
                 ....*....|....
gi 225446229 519 D-YMGRCILTLTRV 531
Cdd:cd04019   77 DePLGRAVIPLNDI 90

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

Pssm-ID: 176011 [Multi-domain] Cd Length: 126 Bit Score: 55.36 E-value: 2.37e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnkTRVVNDSLNPVWNQTFDFVVEDgLHDMLILEVWDHDTFGKDYM 521
Cdd:cd04046    4 VTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVR--SPVQKDTLSPEFDTQAIFYRKK-PRSPIKIQVWNSNLLCDEFL 80


                 ....*.
gi 225446229 522 GRCILT 527
Cdd:cd04046   81 GQATLS 86

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 55.42 E-value: 2.89e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYvrpLPNRMKTSKTINNQLNPVWNEHFEFIVEDAS---TQHLVVKIYDNE 336
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELD---FDGQKKRTRTKPKDLNPVWNEKLVFNVSDPSrlsNLVLEVYVYNDR 74

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

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 55.59 E-value: 2.92e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQT--FDFVVEDGLHDMLILEVWDHDT 515
Cdd:cd08403   14 GRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKNTLNPTYNEAlvFDVPPENVDNVSLIIAVVDYDR 93

                         90
                 ....*....|
gi 225446229 516 FG-KDYMGRC 524
Cdd:cd08403   94 VGhNELIGVC 103

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 55.13 E-value: 4.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIR---NKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILE--VWDHDTFG 517
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRiskKKTHVKKCTLNPVFNESFVFDIPSEELEDISVEflVLDSDRVT 96

                         90
                 ....*....|
gi 225446229 518 K-DYMGRCIL 526
Cdd:cd08404   97 KnEVIGRLVL 106

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

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 54.64 E-value: 4.54e-09

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEF 318
Cdd:cd08386   17 TLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLF 72

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 53.76 E-value: 6.01e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 457 DLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKDYMGRCILTLTRVILEGE 536
Cdd:cd04052    8 SKTGLLSPYAELYLNGKLVY-TTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATS 86

                         90       100
                 ....*....|....*....|....
gi 225446229 537 Y-KETFQLDEAKSGRLNLHLKWMP 559
Cdd:cd04052   87 VgQQWFPLSGNGQGRIRISALWKP 110

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

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 53.75 E-value: 8.95e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPfavlYVRPLPNRMKTSKT--INNQLNPVWNEHFEFIVEdASTQHLVVKIYDNEGLQ 339
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDP----YVRVLVNGIVKGRTvtISNTLNPVWDEVLYVPVT-SPNQKITLEVMDYEKVG 75

                         90
                 ....*....|....*
gi 225446229 340 ASELIGCAQVQLREL 354
Cdd:cd04045   76 KDRSLGSVEINVSDL 90

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: 53.90 E-value: 1.05e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVL-YVRPLPNRMKTS---KTINNQLNPVWNEHFEFIVeDASTQHLVVKIYDNEGLQ 339
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKIsLYDPDGNGEIDSvqtKTIKKTLNPKWNEEFFFRV-NPREHRLLFEVFDENRLT 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 225446229 340 ASELIGCAQVQLRELEPGKVKDAWWKLVKDLeVQRDTKNRGQV--HLEL 386
Cdd:cd04033   81 RDDFLGQVEVPLNNLPTETPGNERRYTFKDY-LLRPRSSKSRVkgHLRL 128

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

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 52.65 E-value: 2.07e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKdiiGKSDPFAVLYVrplpNRMKTSKT-INNQLNPVWNEHFEF--IVEDASTQHLVVKIYDNEGLQ 339
Cdd:cd08383    1 SLRLRILEAKNLPSK---GTRDPYCTVSL----DQVEVARTkTVEKLNPFWGEEFVFddPPPDVTFFTLSFYNKDKRSKD 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 225446229 340 ASELIGcaQVQLRELEPGKVKDAWWKL---VKDLEVQrdtknrGQVHLELLY 388
Cdd:cd08383   74 RDIVIG--KVALSKLDLGQGKDEWFPLtpvDPDSEVQ------GSVRLRARY 117

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: 52.63 E-value: 2.47e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVRP----LPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQH----LVVKIYDN 335
Cdd:cd04009   18 LRVEILNARNLLPLDSNGSSDPFVKVELLPrhlfPDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSVegalLLFTVKDY 97

                         90       100
                 ....*....|....*....|..
gi 225446229 336 EGLQASELIGCAQVQLRELePG 357
Cdd:cd04009   98 DLLGSNDFEGEAFLPLNDI-PG 118

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 51.80 E-value: 2.79e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVRplpNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQAsel 343
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVELTVG---KTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS--- 75

                         90       100
                 ....*....|....*....|....*
gi 225446229 344 IGCAQVQLREL--EPGKVKDAWWKL 366
Cdd:cd04050   76 LGSLTLPLSELlkEPDLTLDQPFPL 100

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: 52.49 E-value: 2.89e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVRplpNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASE 342
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYN---GQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKND 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 225446229 343 LIGCAQVQLRELEPGKVKDAWWKLVKDLEVQRDTK-NRGQVHLEL 386
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQEEGWFRLLPDPRAEEESGgNLGSLRLKV 122

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

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 51.80 E-value: 4.08e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 448 ISAEDLPVVDLMGKADPYVVLILKKSEIRN-----KTRVVNDSLNPVWNQTfdFVVEDGLHDM--LILEVWDHDTFGK-- 518
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQwveigRTEVIKNNLNPDFVTT--FTVDYYFEEVqkLRFEVYDVDSKSKdl 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 225446229 519 ---DYMGRCILTLTRVILEGEYKETFQLDEAKS 548
Cdd:cd04048   85 sdhDFLGEAECTLGEIVSSPGQKLTLPLKGGKG 117

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: 52.04 E-value: 4.22e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTI--NNQLNPVWNEHFEFIV--EDASTQHLVVKIYDNEG 337
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVikKRTLNPVFNESFIFNIplERLRETTLIITVMDKDR 94


                 ....*...
gi 225446229 338 LQASELIG 345
Cdd:cd08405   95 LSRNDLIG 102

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 52.20 E-value: 4.35e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 258 LKPVGTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKT--INNQLNPVWNEHFEFIV--EDASTQHLVVKIY 333
Cdd:cd08410   10 LPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTscMRGTIDPFYNESFSFKVpqEELENVSLVFTVY 89

                         90
                 ....*....|..
gi 225446229 334 DNEGLQASELIG 345
Cdd:cd08410   90 GHNVKSSNDFIG 101

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

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 51.50 E-value: 5.94e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVrpLPNRMKTSK----TINNQLNPVWNEHFEFIV--EDASTQHLVVKIYDNEG 337
Cdd:cd04030   18 LIVTVHKCRNLPPCDSSDIPDPYVRLYL--LPDKSKSTRrktsVKKDNLNPVFDETFEFPVslEELKRRTLDVAVKNSKS 95

                         90       100       110
                 ....*....|....*....|....*....|.
gi 225446229 338 LQASE--LIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd04030   96 FLSREkkLLGQVLIDLSDLDLSKGFTQWYDL 126

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

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 51.15 E-value: 7.89e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVedGLHDMLILEVWDHDTFGK 518
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVDGGQTH-STDVAKKTLDPKWNEHFDLTV--GPSSIITIQVFDQKKFKK 74

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

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 51.11 E-value: 8.20e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 266 VKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASELIG 345
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYVTLVDTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCG 84


                 ....*.
gi 225446229 346 CAQVQL 351
Cdd:cd04043   85 RASLKL 90

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: 51.10 E-value: 8.66e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGK-SDPFAVLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIV--EDASTQHLVVKIYDNEGLQ 339
Cdd:cd08390   15 QLTVSLIKARNLPPRTKDVAhCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVsfKELQRRTLRLSVYDVDRFS 94

                         90       100
                 ....*....|....*....|....*....
gi 225446229 340 ASELIGCAQVQLRELEPGKVKDAWWKLVK 368
Cdd:cd08390   95 RHCIIGHVLFPLKDLDLVKGGVVWRDLEP 123

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

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 51.12 E-value: 8.93e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 225446229 443 LSITVISAEdLPVVDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVEDglHDMLILEVWDHDTFGKDYM 521
Cdd:cd04021    4 LQITVESAK-LKSNSKSFKPDPYVEVTVDGQPPK-KTEVSKKTSNPKWNEHFTVLVTP--QSTLEFKVWSHHTLKADVL 78

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

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 50.72 E-value: 9.46e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVD-LMGKADPYVVLIL--KKSEI-RNKTRVVNDSLNPVWNQTFDFVVEdglHDMLI-----LEVW 511
Cdd:cd08521   14 GSLEVHIKECRNLAYADeKKKRSNPYVKVYLlpDKSKQsKRKTSVKKNTTNPVFNETLKYHIS---KSQLEtrtlqLSVW 90

                         90       100       110
                 ....*....|....*....|....*....|...
gi 225446229 512 DHDTFG-KDYMGRCILTLTRVILEGEYKETFQL 543
Cdd:cd08521   91 HHDRFGrNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 51.11 E-value: 9.61e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPN---RMKTsKTINNQLNPVWNEHFEFIVEDAS-TQHLVVKIYDNEG 337
Cdd:cd04026   13 NKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKnetKQKT-KTIKKTLNPVWNETFTFDLKPADkDRRLSIEVWDWDR 91

                         90       100
                 ....*....|....*....|....*....
gi 225446229 338 LQASELIGCAQVQLRELEPgKVKDAWWKL 366
Cdd:cd04026   92 TTRNDFMGSLSFGVSELIK-MPVDGWYKL 119

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: 51.20 E-value: 9.78e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDLMGKADPYVVLILKKSEIRN-----KTRVVNDSLNPVWNQTFDFVVEDGLHDMLIlEVWDHDTF 516
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGeidsvQTKTIKKTLNPKWNEEFFFRVNPREHRLLF-EVFDENRL 79

                         90
                 ....*....|...
gi 225446229 517 GKD-YMGRCILTL 528
Cdd:cd04033   80 TRDdFLGQVEVPL 92

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

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 50.45 E-value: 1.56e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKdIIGKSDPFA-VLYVRPLPNRMKTSKTINNQLNPVWNEHFEFIV---------------EDASTQH 327
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFArVTLNYSSKTDTKRTKVKKKTNNPRFDEAFYFELtigfsyekksfkveeEDLEKSE 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 225446229 328 LVVKIYDNEGLQASELIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd08675   80 LRVELWHASMVSGDDFLGEVRIPLQGLQQAGSHQAWYFL 118

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

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 49.98 E-value: 1.58e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDlmGKA-DPYVVLILK---KSEIRNKTRVVNDSLNPVWNQTF--DFVVEDGLHD-MLILEVWD 512
Cdd:cd08381   12 NGTLFVMVMHAKNLPLLD--GSDpDPYVKTYLLpdpQKTTKRKTKVVRKTRNPTFNEMLvyDGLPVEDLQQrVLQVSVWS 89

                         90       100       110
                 ....*....|....*....|....*....|..
gi 225446229 513 HDTFG-KDYMGRCILTLTRVILEGEYKETFQL 543
Cdd:cd08381   90 HDSLVeNEFLGGVCIPLKKLDLSQETEKWYPL 121

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

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 49.56 E-value: 1.70e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKA----DPYVVLILKKSEIRnkTRVVNDSLNPVWNQTFDFVVedGLHDM---LILEVWDH 513
Cdd:cd04039    1 GVVFMEIKSITDLPPLKNMTRTgfdmDPFVIISFGRRVFR--TSWRRHTLNPVFNERLAFEV--YPHEKnfdIQFKVLDK 76

                         90       100
                 ....*....|....*....|..
gi 225446229 514 DTF-GKDYMGRCILTLTRVILE 534
Cdd:cd04039   77 DKFsFNDYVATGSLSVQELLNA 98

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 49.74 E-value: 2.46e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDL-MGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDFVVE--DGLHDMLILEVWDHDTF 516
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVKTYLlpdKSNRGKRKTSVKKKTLNPVFNETLRYKVEreELPTRVLNLSVWHRDSL 96


                 ...
gi 225446229 517 GKD 519
Cdd:cd08393   97 GRN 99

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

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 48.72 E-value: 4.09e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 271 AKELTNKDIIGKSDPFAVLYvRPLPNRMKT----SKTINNQLNPVWNehfEFIVE-------DAStQHLVVKIYDNEGLQ 339
Cdd:cd04047    9 GKKLDKKDFFGKSDPFLEIS-RQSEDGTWVlvyrTEVIKNTLNPVWK---PFTIPlqklcngDYD-RPIKIEVYDYDSSG 83

                         90       100
                 ....*....|....*....|..
gi 225446229 340 ASELIGCAQVQLRELEPGKVKD 361
Cdd:cd04047   84 KHDLIGEFETTLDELLKSSPLE 105

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

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 48.50 E-value: 6.14e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEDLPVVDL-MGKADPYVVL-ILKKSEIRNKTRVVNDSLNPVWNQTFDF--VVEDGLHDM-LILEVWDHD 514
Cdd:cd08388   15 KKALLVNIIECRDLPAMDEqSGTSDPYVKLqLLPEKEHKVKTRVLRKTRNPVYDETFTFygIPYNQLQDLsLHFAVLSFD 94

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 225446229 515 TFGKD-YMGRCILTLTRVILEGEyketfqldeaksGRLNLHLKWMP 559
Cdd:cd08388   95 RYSRDdVIGEVVCPLAGADLLNE------------GELLVSREIQP 128

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

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 47.90 E-value: 9.00e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 263 TLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPnrMKTSKTINNQLNPVWNEhfEFIVEDASTQH-LVVKIYDNEGLQAS 341
Cdd:cd04054    1 SLYIRIVEGKNLPAKDITGSSDPYCIVKVDNEV--IIRTATVWKTLNPFWGE--EYTVHLPPGFHtVSFYVLDEDTLSRD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 225446229 342 ELIG--CAQVQLRELEPGKVkDAWWKLVkdlEVQRDTKNRGQVHLEL 386
Cdd:cd04054   77 DVIGkvSLTREVISAHPRGI-DGWMNLT---EVDPDEEVQGEIHLEL 119

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 47.92 E-value: 9.29e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 281 GKSDPFAVLYVRPLP----NRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLqASELIGCAQVQLRELEP 356
Cdd:cd00275   23 SIVDPYVEVEIHGLPaddsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSG-DDDFLGQACLPLDSLRQ 101


                 .
gi 225446229 357 G 357
Cdd:cd00275  102 G 102

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

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 48.07 E-value: 9.96e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVRPlpNRMKTSKTINNQLNPVWNEHFEFIVEDASTqhLVVKIYD 334
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVDG--GQTHSTDVAKKTLDPKWNEHFDLTVGPSSI--ITIQVFD 68

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: 47.95 E-value: 1.10e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRmktSKTINNQLNPVWNEHFEFIVEDaSTQHLVVKIYDNEG------ 337
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKR---TKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDEDDdiksrl 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 225446229 338 -----LQASELIGCAQVQLRELEpGKVkDAWWKLVK 368
Cdd:cd04027   79 kqkftRESDDFLGQTIIEVRTLS-GEM-DVWYNLEK 112

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

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 47.31 E-value: 1.67e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVvdlmGKADPYVvlILKKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILEVWDHDTFGKDYMG 522
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVV--EVKLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLG 75


                 ..
gi 225446229 523 RC 524
Cdd:cd08378   76 GV 77

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in testis-expressed protein 2 (TEX2) and similar proteins; testis-expressed protein 2 (TEX2), also called transmembrane protein 96 (TMEM96), is a transmembrane protein with uncharacterized biological function. Diseases associated with TEX2 include Wernicke-Korsakoff Syndrome. This model corresponds to the SMP domain of TEX2, which may be implicated in lipid transport.

Pssm-ID: 439231 Cd Length: 186 Bit Score: 48.26 E-value: 2.18e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 105 RPMILSSLKFSRFTLGTVSPQFTGVSIIE-DGADCITLELELQWDGNPSIILDINTRLGVALPVQVKNI---------GF 174
Cdd:cd21675   36 LPSFLGEITVTDLDLGTSVPVISNPKLPSlDPDGGLWVDLDVSYRGGFSLTLETKLNLSKLKKEKVSNVplvlavevkSL 115

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 225446229 175 TGVFRLMFKPLVDEfpcfgAVCFSLRQKKKLDLTLK-VVGGDISAIPGISDAIKDTIDNAIEDSIMWPVRKVVPI 248
Cdd:cd21675  116 SGTLRLNIKPPPSN-----RLWYGFREMPKLELEIEpVVGERQVTLPHVTNWIEKKLKEEIKESLVLPNMDDFPF 185

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

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 46.52 E-value: 2.54e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDiiGKS-DPFAVLYVRPLP---NRMKTsKTINNQLNPVWNEHF---EFIVEDASTQHLVVKIYD 334
Cdd:cd08381   13 GTLFVMVMHAKNLPLLD--GSDpDPYVKTYLLPDPqktTKRKT-KVVRKTRNPTFNEMLvydGLPVEDLQQRVLQVSVWS 89

                         90       100       110
                 ....*....|....*....|....*....|..
gi 225446229 335 NEGLQASELIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd08381   90 HDSLVENEFLGGVCIPLKKLDLSQETEKWYPL 121

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

Pssm-ID: 176060 [Multi-domain] Cd Length: 126 Bit Score: 46.59 E-value: 3.22e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKdiIGKSDPFAVLYVRPLPNRMKTSKTINNQlNPVWNEHFEFIVeDASTQHLVVKIYDNEGLQASEL 343
Cdd:cd08678    1 LLVKNIKANGLSEA--AGSSNPYCVLEMDEPPQKYQSSTQKNTS-NPFWDEHFLFEL-SPNSKELLFEVYDNGKKSDSKF 76

                         90
                 ....*....|..
gi 225446229 344 IGCAQVQLRELE 355
Cdd:cd08678   77 LGLAIVPFDELR 88

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: 46.19 E-value: 4.34e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPL---PNRMKTS---KTinnqLNPVWNEHFEFIV--EDASTQHLVVKIY 333
Cdd:cd08384   13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDagkKSKHKTQvkkKT----LNPEFNEEFFYDIkhSDLAKKTLEITVW 88

                         90
                 ....*....|..
gi 225446229 334 DNEGLQASELIG 345
Cdd:cd08384   89 DKDIGKSNDYIG 100

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 46.42 E-value: 4.52e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDF-VVEDGLHDM-LILEVWDHDT 515
Cdd:cd08410   14 GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLvhgLKLIKTKKTSCMRGTIDPFYNESFSFkVPQEELENVsLVFTVYGHNV 93

                         90
                 ....*....|..
gi 225446229 516 FGK-DYMGRCIL 526
Cdd:cd08410   94 KSSnDFIGRIVI 105

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: 45.32 E-value: 8.90e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVrpLPNRMKTSK----TINNQLNPVWNEHFEFIV---EDASTQHLVVKIYD 334
Cdd:cd04031   16 SQLIVTVLQARDLPPRDDGSLRNPYVKVYL--LPDRSEKSKrrtkTVKKTLNPEWNQTFEYSNvrrETLKERTLEVTVWD 93

                         90
                 ....*....|.
gi 225446229 335 NEGLQASELIG 345
Cdd:cd04031   94 YDRDGENDFLG 104

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: 45.09 E-value: 1.05e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKADPY--VVLILKKSEIRnKTRVVNDSLNPVWNQTFDF-VVEDGLHDMlILEV--WDHDT 515
Cdd:cd08387   16 GILNVKLIQARNLQPRDFSGTADPYckVRLLPDRSNTK-QSKIHKKTLNPEFDESFVFeVPPQELPKR-TLEVllYDFDQ 93

                         90
                 ....*....|
gi 225446229 516 FGKDymgRCI 525
Cdd:cd08387   94 FSRD---ECI 100

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in meiotically up-regulated gene 190 protein (Mug190) and similar proteins; Meiotically up-regulated gene 190 protein (Mug190) has a role in meiosis. This model corresponds to the SMP domain of Mug190, which may be implicated in lipid transport.

Pssm-ID: 439232 Cd Length: 233 Bit Score: 46.83 E-value: 1.15e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  73 WLNHHLTKIWPYVNEAASELIRTNVEPILEQYRPMILSSLKFSRFTLGTVSPQFTGVSII-------------------- 132
Cdd:cd21676    5 WLNSLLAALWPLINPDLFTPVIDLLEDVMQASLPSFVHSVRVTDLGQGSQPLRILSMRILpdgewdesvsegghskeeee 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 133 --------EDGADCITLELELQWDGNPS------------IILDINTRL----GVALPVQVKNIGFTGV--FRLMFKPlv 186
Cdd:cd21676   85 daddeeeeEEGGDYVNLEVAFAYRARPSgkslsskaknahLLAYFGLGLkglgGVPIPVWVEVLGLVGTvrLRLQLTP-- 162

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 225446229 187 dEFPCFGAVCFSLRQKKKLDLT---LKVVGGDISAIPGISDAIKDTIDNAIED 236
Cdd:cd21676  163 -DPPFVKTVTFSFMGLPKVDISarpLSKGAFNVMNLPLISSFVNSSIDAVAAE 214

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: 44.84 E-value: 1.32e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDIIGKSDPFA-VLYVrplpNRMKTSKTINNQLNPVWNEH--FEFIVEDASTQHL-------VVKIY 333
Cdd:cd04017    3 LRAYIYQARDLLAADKSGLSDPFArVSFL----NQSQETEVIKETLSPTWDQTliFDEVELYGSPEEIaqnpplvVVELF 78

                         90
                 ....*....|..
gi 225446229 334 DNEGLQASELIG 345
Cdd:cd04017   79 DQDSVGKDEFLG 90

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

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 44.73 E-value: 1.39e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 301 SKTINNQLNPVWNEHFEFIVEdASTQHLVVKIYDNEGLQASELIGCAQVQLRELEPGKVKDAWWKLvkdLEVQRDTKNRG 380
Cdd:cd08401   38 TKTVEKSLCPFFGEDFYFEIP-RTFRHLSFYIYDRDVLRRDSVIGKVAIKKEDLHKYYGKDTWFPL---QPVDADSEVQG 113


                 ....*.
gi 225446229 381 QVHLEL 386
Cdd:cd08401  114 KVHLEL 119

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 44.13 E-value: 1.68e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 272 KEL-TNKDIIGKSDPFAVLYVrplpN--RMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDnEGLQASELIGCAQ 348
Cdd:cd04052    1 KGLdTSESKTGLLSPYAELYL----NgkLVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKD-DRDRHDPVLGSVS 75

                         90
                 ....*....|....*....
gi 225446229 349 VQLREL-EPGKVKDAWWKL 366
Cdd:cd04052   76 ISLNDLiDATSVGQQWFPL 94

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: 44.08 E-value: 1.91e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 266 VKLVQAKELTNKDIIGKSDPfavlYVRpLPNRMKT----SKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQAS 341
Cdd:cd04037    4 VYVVRARNLQPKDPNGKSDP----YLK-IKLGKKKindrDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSD 78


                 ....
gi 225446229 342 ELIG 345
Cdd:cd04037   79 DLIG 82

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 44.34 E-value: 1.95e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDIIGKSDPFAVLYVRPLPNRMKTSKT--INNQLNPVWNEHFEFIVEDASTQHLVVKI--YDNEG 337
Cdd:cd08404   15 NRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKThvKKCTLNPVFNESFVFDIPSEELEDISVEFlvLDSDR 94


                 ....*...
gi 225446229 338 LQASELIG 345
Cdd:cd08404   95 VTKNEVIG 102

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

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 44.19 E-value: 2.16e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKeLTNKDIIGKSDPFAVLYVRPLPNRmKTSKtINNQLNPVWNEHFEFIVEDASTQHLvvKIYDNEGLQASEL 343
Cdd:cd04021    4 LQITVESAK-LKSNSKSFKPDPYVEVTVDGQPPK-KTEV-SKKTSNPKWNEHFTVLVTPQSTLEF--KVWSHHTLKADVL 78

                         90
                 ....*....|.
gi 225446229 344 IGCAQVQLREL 354
Cdd:cd04021   79 LGEASLDLSDI 89

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: 43.53 E-value: 5.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 261 VGTLEVKLVQAKELTNKDIIGKSDPFAVLyvrPLPNRMKTSKTINNQLNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQA 340
Cdd:cd08375   14 IGRLMVVIVEGRDLKPCNSNGKSDPYCEV---SMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSP 90

                         90
                 ....*....|....
gi 225446229 341 SELIGCAQVQLREL 354
Cdd:cd08375   91 DDFLGRTEIRVADI 104

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain] Cd Length: 158 Bit Score: 43.83 E-value: 5.55e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDI------------------------------IGKSDPFAVLYVRPlpNRMKTSKTINNQLNPV 311
Cdd:cd04015    7 GTLDVTIYEADNLPNMDMfseklrrffsklvgcseptlkrpsshrhvgKITSDPYATVDLAG--ARVARTRVIENSENPV 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 225446229 312 WNEHFE-FIVEDASTQHLVVKIYDNEGlqaSELIGCAQVQLRELEPGKVKDAW 363
Cdd:cd04015   85 WNESFHiYCAHYASHVEFTVKDNDVVG---AQLIGRAYIPVEDLLSGEPVEGW 134

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

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 42.12 E-value: 9.80e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDLMGKADPYVVLILkKSEIRNKTRVVNDSLNPVWNQTFDFVVEDGLHDMLILeVWDHDTFGK-DYM 521
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKV-DNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFY-VLDEDTLSRdDVI 79


                 ....*.
gi 225446229 522 GRCILT 527
Cdd:cd04054   80 GKVSLT 85

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: 1.26e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 442 VLSITVISAEDLPVVDL-MGKADPYVVLILKKSEIRNK-TRVVNDSLNPVWNQTFDFVV--EDGLHDMLILEVWDHDTFG 517
Cdd:cd08390   15 QLTVSLIKARNLPPRTKdVAHCDPFVKVCLLPDERRSLqSKVKRKTQNPNFDETFVFQVsfKELQRRTLRLSVYDVDRFS 94


                 ....*....
gi 225446229 518 KdymgRCIL 526
Cdd:cd08390   95 R----HCII 99

cellulose synthase-interactive protein; Provisional

Pssm-ID: 215629 [Multi-domain] Cd Length: 2102 Bit Score: 45.09 E-value: 1.45e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229  441 GVLSITVISAEDLPvvDLMGKADPYVVLILKKSEIRnKTRVVNDSLNPVWNQTFDFVVE-----DGLHdmliLEVWDHDT 515
Cdd:PLN03200 1980 GSLTVTIKRGNNLK--QSMGNTNAFCKLTLGNGPPR-QTKVVSHSSSPEWKEGFTWAFDsppkgQKLH----ISCKSKNT 2052

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 225446229  516 FGKDYMGRCILTLTRVILEGEYKETFQL--DEAKSG 549
Cdd:PLN03200 2053 FGKSSLGKVTIQIDRVVMEGTYSGEYSLnpESNKDG 2088

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 42.27 E-value: 1.54e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 297 RMKTSKTINNqlNPVWNEHFEFIVEDASTQHLVVKIYDNEGLQASELIGCAQVQLRELE----PGKVKDAWWKLVKDLEV 372
Cdd:cd04019   35 RTRPSQTRNG--NPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPLGRAVIPLNDIErrvdDRPVPSRWFSLERPGGA 112

                         90
                 ....*....|....*..
gi 225446229 373 QRD---TKNRGQVHLEL 386
Cdd:cd04019  113 MEQkkkRKFASRIHLRL 129

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 41.27 E-value: 1.88e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVD-LMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDFVV-EDGLHD-MLILEVWDHD 514
Cdd:cd04029   15 QSLNVHVKECRNLAYGDeAKKRSNPYVKTYLlpdKSRQSKRKTSIKRNTTNPVYNETLKYSIsHSQLETrTLQLSVWHYD 94

                         90       100       110
                 ....*....|....*....|....*....|
gi 225446229 515 TFGKD-YMGRCILTLTRVILEGEYKETFQL 543
Cdd:cd04029   95 RFGRNtFLGEVEIPLDSWNFDSQHEECLPL 124

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

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 41.59 E-value: 1.93e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 443 LSITVISAEDLPVVDlMGKADPYVVLIL--------KKSEIRNKTRvvndslNPVWNQTFDFVV---------------E 499
Cdd:cd08675    1 LSVRVLECRDLALKS-NGTCDPFARVTLnyssktdtKRTKVKKKTN------NPRFDEAFYFELtigfsyekksfkveeE 73

                         90       100
                 ....*....|....*....|....*
gi 225446229 500 DGLHDMLILEVWDHDT-FGKDYMGR 523
Cdd:cd08675   74 DLEKSELRVELWHASMvSGDDFLGE 98

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 41.92 E-value: 2.67e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 248 ILPGDYSDLELKPV--GTLEVKLVQAKELTNKDIIGKSDPFAVLYVrpLPNRMKTSK----TINNQLNPVWNEHFEF--- 318
Cdd:cd04020   11 VPPESEGALKSKKPstGELHVWVKEAKNLPALKSGGTSDSFVKCYL--LPDKSKKSKqktpVVKKSVNPVWNHTFVYdgv 88

                         90       100
                 ....*....|....*....|....*...
gi 225446229 319 IVEDASTQHLVVKIYDNEGLQASELIGC 346
Cdd:cd04020   89 SPEDLSQACLELTVWDHDKLSSNDFLGG 116

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176035 [Multi-domain] Cd Length: 124 Bit Score: 40.69 E-value: 3.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 422 EVAENGNAVMQKkrevivrgvLSITVISAEDLPVVDlMGKADPY----VVLILKKSeiRNKTRVVNDSlNPVWNQTFDF- 496
Cdd:cd08389    6 DVAFEYDPSARK---------LTVTVIRAQDIPTKD-RGGASSWqvhlVLLPSKKQ--RAKTKVQRGP-NPVFNETFTFs 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 225446229 497 -VVEDGLHDM-LILEVWDHDTFGKDYM-GRCILTLTRVILEGEYKETFQLD 544
Cdd:cd08389   73 rVEPEELNNMaLRFRLYGVERMRKERLiGEKVVPLSQLNLEGETTVWLTLE 123

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain] Cd Length: 158 Bit Score: 41.14 E-value: 4.10e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 441 GVLSITVISAEDLPVVDLMGKA------------------------------DPYVVLILKKSEIrNKTRVVNDSLNPVW 490
Cdd:cd04015    7 GTLDVTIYEADNLPNMDMFSEKlrrffsklvgcseptlkrpsshrhvgkitsDPYATVDLAGARV-ARTRVIENSENPVW 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 225446229 491 NQTFDFVVEdglHDM--LILEVWDHDTFGKDYMGRCILTLTRvILEGEYKE 539
Cdd:cd04015   86 NESFHIYCA---HYAshVEFTVKDNDVVGAQLIGRAYIPVED-LLSGEPVE 132

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

Pssm-ID: 176067 [Multi-domain] Cd Length: 119 Bit Score: 39.74 E-value: 6.73e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 432 QKKREVIVRG-VLSITVISAEDLPVVDlMGKADPYVVLIL---KKSEIRNKTRVVNDSLNPVWNQTFDF-VVEDGLHDML 506
Cdd:cd08685    2 QLKLSIEGQNrKLTLHVLEAKGLRSTN-SGTCNSYVKISLspdKEVRFRQKTSTVPDSANPLFHETFSFdVNERDYQKRL 80


                 ....*
gi 225446229 507 ILEVW 511
Cdd:cd08685   81 LVTVW 85

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

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 38.93 E-value: 1.54e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 274 LTNKDIIGKSDPFAVlyVRPLPNRMKTSkTINNQLNPVWNEHFEFIVEDASTQhLVVKIYDN------EGLQASELIGCA 347
Cdd:cd08379   15 LRAKDGRGSTDAYCV--AKYGPKWVRTR-TVEDSSNPRWNEQYTWPVYDPCTV-LTVGVFDNsqshwkEAVQPDVLIGKV 90

                         90
                 ....*....|..
gi 225446229 348 QVQLRELEPGKV 359
Cdd:cd08379   91 RIRLSTLEDDRV 102

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. 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: 175983 [Multi-domain] Cd Length: 121 Bit Score: 38.47 E-value: 1.87e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 440 RGVLSITVISAEdLPVVDLMGKADPYVVLILKKSEIRNKTrVVNDSLNPVWNQTFDFVVEDGLhDMLILEVWDHDTFGKD 519
Cdd:cd04016    1 VGRLSITVVQAK-LVKNYGLTRMDPYCRIRVGHAVYETPT-AYNGAKNPRWNKTIQCTLPEGV-DSIYIEIFDERAFTMD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 225446229 520 -YMGRCILTLTRVILEGE-----YKETFQLDEAKSGRLNLHL 555
Cdd:cd04016   78 eRIAWTHITIPESVFNGEtlddwYSLSGKQGEDKEGMINLVF 119

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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: 176045 [Multi-domain] Cd Length: 126 Bit Score: 38.50 E-value: 1.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 259 KPVGTLEVKLVQAKELTNKDIigkSDPFAVLYVrplpNRMKTSKT-INNQLNPVWNEhfEFIVEDASTQ--HLVVKIYdN 335
Cdd:cd08400    1 RQVRSLQLNVLEAHKLPVKHV---PHPYCVISL----NEVKVARTkVREGPNPVWSE--EFVFDDLPPDvnSFTISLS-N 70

                         90       100       110
                 ....*....|....*....|....*....|..
gi 225446229 336 EGLQASE-LIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd08400   71 KAKRSKDsEIAEVTVQLSKLQNGQETDEWYPL 102

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: 37.94 E-value: 2.55e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 444 SITVISAEDLPVVDLmgkaDPYVVLIL---KKSeirnkTRVVNDSLNPVWNQTFDFVVEDGLHDM----LILEVWDHDTF 516
Cdd:cd04011    7 RVRVIEARQLVGGNI----DPVVKVEVggqKKY-----TSVKKGTNCPFYNEYFFFNFHESPDELfdkiIKISVYDSRSL 77


                 ...
gi 225446229 517 GKD 519
Cdd:cd04011   78 RSD 80

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 37.80 E-value: 3.39e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 264 LEVKLVQAKELTNKDI-IGKSDPFAVLYVRPLPNRMKTSKTI--NNQLNPVWNEHFEFIVEDAS--TQHLVVKIYDNEGL 338
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSvkKKTLNPVFNETLRYKVEREElpTRVLNLSVWHRDSL 96

                         90       100
                 ....*....|....*....|....*...
gi 225446229 339 QASELIGCAQVQLRELEPGKVKDAWWKL 366
Cdd:cd08393   97 GRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

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

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 37.62 E-value: 4.00e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 225446229 262 GTLEVKLVQAKELTNKDIIGK-SDPFAVLYVRPLPNRMKTSKTI--NNQLNPVWNEHFEFIVE 321
Cdd:cd08521   14 GSLEVHIKECRNLAYADEKKKrSNPYVKVYLLPDKSKQSKRKTSvkKNTTNPVFNETLKYHIS 76

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: 36.47 E-value: 6.84e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225446229 262 GTLEVKLVQAKELTNKDI-IGKSDPFAVLYVRPLPNRMKTSKTINNQLNPVWNE-HFEFIVEDASTQH--LVVKIYDNEG 337
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEEtWFVLVTPDEVKAGerLSCRLWDSDR 80

                         90
                 ....*....|....*..
gi 225446229 338 LQASELIGCAQVQLREL 354
Cdd:cd04041   81 FTADDRLGRVEIDLKEL 97