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: 257.09 E-value: 4.58e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  60 PSWVVFSQRQKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPAMLASLKFSKFTLGTVAPQFTGVSILESesGPN 139
Cdd:cd21677    1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLEQYKPSFISSIKFKKLTLGTVPPRIEGVKVVES--DED 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 140 GITMELEMQWDGNPKIVLDVKTLLGVSLPIEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIGGELT 219
Cdd:cd21677   79 EVILDVDFRWAGDPDIVLAVKLLPGLSLPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLKLLGGDDM 158

                        170       180       190
                 ....*....|....*....|....*....|.
gi 186522051 220 SIPGISDAIEETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21677  159 ALPGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 155.30 E-value: 1.19e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051   73 WLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPAMLASLKFSKFTLGTVAPQFTGVSileseSGPNGITMELEMQWD-- 150
Cdd:COG5038   225 WLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSFIDALALDEFTLGSKPPRIDGIR-----SYPSTESDTVVMDVDfs 299

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  151 -----------------GNPKIVLDVK--TLLGV-SLPIEVKNIGFTGVFRLIFKpLVDEFPCFGALSYSLREKKGLDFT 210
Cdd:COG5038   300 ftphdisdvtatsarasVNPKISLVVKkgKSFGSfTLPILVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEFDFI 378

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  211 LKVIGG-----ELTSIPGISDAIEETIRDAIEDSITWPvrKIIPI-LPGDYSDLELKPVGKLDVKVVQAKDLANKDMI-- 282
Cdd:COG5038   379 LVPLGGdffgvDIFAIPGLSRFIQEIINSTLGPMLLPP--NSLTIdISQIMAGDSGTAIGVVEVKIKSAEGLKKSDSTin 456

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  283 GKSDPYaIVFirPLPDRTK-KTKTISNSLNPIWNEHFeFIVEDVSTQHLTVRVFDDEGVGSSQLIGAAQVPLNELVPGKV 361
Cdd:COG5038   457 GTVDPY-ITV--TFSDRVIgKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQNPV 532

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  362 KDIWLklvkdLEIQRDTKNRGQVQLELLYCPLGKEGGLKNPfnpdysltileKVLKPESEDSdatdmkklvtskkkdviv 441
Cdd:COG5038   533 KKNEL-----YEFLRNTKNVGRLTYDLRFFPVIEDKKELKG-----------SVEPLEDSNT------------------ 578

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  442 rGVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTRvvPDSLNPVWNQTFDFVVEDALHDLLTLEVWDhDKFGKd 521
Cdd:COG5038   579 -GILKVTLREVKALDELSSKKDNKSAELYTNAKEVYSTGKL--KFTNHPSWNLQYNVLVTDRKNSSIKVVTFD-VQSGK- 653

                         490       500       510       520
                  ....*....|....*....|....*....|....*....|.
gi 186522051  522 KIGRVIMTLTRVMLEGEFQ-EWFELdGAKSGKLCVHLKWTP 561
Cdd:COG5038   654 VIATEGSTLPDLIDRTLDTfLVFPL-RNPKGRIFITNYWKP 693

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: 137.69 E-value: 7.70e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  69 QKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPAMLASLKFSKFTLGTVAPQFTGVSILESESGPNGITMELEMQ 148
Cdd:cd21670    1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSIRALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 149 WDGNPKIVLDVKTllgvSLPIEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIgGELTSIPGISDAI 228
Cdd:cd21670   81 YDGDADIEVSVGT----GIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGL-ANLLDIPGLSNLL 155

                        170       180
                 ....*....|....*....|..
gi 186522051 229 EETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21670  156 RKIIVDQIASFLVLPNRITIPL 177

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: 121.90 E-value: 6.89e-32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  70 KLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPAMLASLKFSKFTLGTVAPQFTGVSILeSESGPNGITMELEM-- 147
Cdd:cd21678    2 SVEWLNYFLQKFWLIYEPVLSETIVTNVNPVLAENCPSFLDSLRLTEFTLGTKAPRIEGVRTY-PKTEDDVVVMDWEFsf 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 148 ---------------QWdgNPKIVLDV---KTLLGVSLPIEVKNIGFTGVFRLIFKpLVDEFPCFGALSYSLREKKGLDF 209
Cdd:cd21678   81 tpndtsdltakqiknKV--NPKIVLTArvgKGVVGIDLPILVEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPPEIDF 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 186522051 210 TLKVIGG--ELTSIPGISDAIEETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21678  158 VLKPLGGgfDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDL 200

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 118.19 E-value: 8.60e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                          90       100
                  ....*....|....*....|....
gi 186522051  523 -IGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:pfam00168  81 fIGEVRIPLSELDSGEGLDGWYPL 104

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 115.88 E-value: 6.27e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRpLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSS 343
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL-DGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 186522051  344 QLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104

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: 117.42 E-value: 1.01e-30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  90 SELIKSSVEPVLEQ-YTPAMLASLKFSKFTLGTVAPQFTGVSILESESGPNGITMELEMQWDGNPKIVLDVK---TLLGV 165
Cdd:cd21669    2 EQLIRESLQELLEEvKKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDLQLVLDLDLEYAGDFSVVLSAKlggGGLGL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 166 SLPIEVKNIGFTGVFRLIFKpLVDEFPCFGALSYSLREKKGLDFTLKVIGG-ELTSIPGISDAIEETIRDAIEDSITWPV 244
Cdd:cd21669   82 PVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRPLGGvDLMELPGLSSWLEKLLTDALVELLVEPN 160


                 ....*
gi 186522051 245 RKIIP 249
Cdd:cd21669  161 RIVID 165

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: 110.27 E-value: 6.94e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051   265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQ 344
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 186522051   345 LIGAAQVPLNELVPGKVKDIW 365
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: 109.08 E-value: 1.93e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIrpLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQL 345
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSL--GGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                         90       100
                 ....*....|....*....|....
gi 186522051 346 IGAAQVPLNELV-PGKVKDIWLKL 368
Cdd:cd00030   79 LGEVEIPLSELLdSGKEGELWLPL 102

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: 103.30 E-value: 2.08e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKsKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK-I 523
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDfL 79

                         90       100
                 ....*....|....*....|...
gi 186522051 524 GRVIMTLTRVMLEGEFQE-WFEL 545
Cdd:cd00030   80 GEVEIPLSELLDSGKEGElWLPL 102

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: 99.87 E-value: 3.16e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051   444 VLSVTVVAAEDLPAVDFMGKADAFVVITL-KKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 186522051   523 -IGRVIMTLTRVMLEGEFQEW 542
Cdd:smart00239  81 fIGQVTIPLSDLLLGGRHEKL 101

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: 91.58 E-value: 4.77e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMI------GKSDPYAIVFIrplPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFdD 337
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRV---GAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELF-D 76

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186522051 338 EGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08391   77 EDPDKDDFLGRLSIDLGSVEKKGFIDEWLPL 107

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: 86.32 E-value: 4.65e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDM--IGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFD-DEGV 340
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRsgKGKSDPYAIL---SVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDkDRFA 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186522051 341 GSSQLiGAAQVPLNELVPGKVK---DIWLKLvKDLEIQRDTKNRGQVQLEL 388
Cdd:cd04024   78 GKDYL-GEFDIALEEVFADGKTgqsDKWITL-KSTRPGKTSVVSGEIHLQF 126

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: 85.81 E-value: 5.52e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFM------GKADAFVVITLkkSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHD 516
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRV--GAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 186522051 517 KFGKDKIGRVIMTLTRVMLEGEFQEWFELDGAKSGKLCVHLKW 559
Cdd:cd08391   79 PDKDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

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: 80.42 E-value: 3.60e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVsTQHLTVRVFDDEGVGSS 343
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVL---ELVNARLQTHTIYKTLNPEWNKIFTFPIKDI-HDVLEVTVYDEDKDKKP 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 186522051 344 QLIGAAQVPLNELVPGKVKdiWLKLvKDLEIQRDTKnrGQVQLELLY 390
Cdd:cd08377   77 EFLGKVAIPLLSIKNGERK--WYAL-KDKKLRTRAK--GSILLEMDV 118

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: 79.53 E-value: 6.78e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIRPlpDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQL 345
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNG--EKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDL 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 186522051 346 IGAAQVPLNELVPGKVKDIWLKLVKDLEIQRDT 378
Cdd:cd04040   79 LGSAYIDLSDLEPEETTELTLPLDGQGGGKLGA 111

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: 79.62 E-value: 9.18e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIrpLPDRTKK--TKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVFDDEG 339
Cdd:cd08385   16 NQLTVGIIQAADLPAMDMGGTSDPYVKVYL--LPDKKKKfeTKVHRKTLNPVFNETFTFKVpySELGNKTLVFSVYDFDR 93

                         90       100       110
                 ....*....|....*....|....*....|....
gi 186522051 340 VGSSQLIGAAQVPLNELVPGKVKDIWlklvKDLE 373
Cdd:cd08385   94 FSKHDLIGEVRVPLLTVDLGHVTEEW----RDLE 123

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: 79.55 E-value: 3.83e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  69 QKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPaMLASLKFSKFTLGTVAPQFTGVSILESESGPNGITMELEMQ 148
Cdd:cd21680    3 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANA-HLSTFSFTKIDLGDQPLRINGVKVYTENVDKRQIILDLQIS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 149 WDGNPKIVLDVKTLLGVSlpiEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIgGELTSIPGISDAI 228
Cdd:cd21680   82 FVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGL-TNLLDIPGLNGLS 157

                        170       180
                 ....*....|....*....|..
gi 186522051 229 EETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21680  158 DTIILDIISNYLVLPNRITVPL 179

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

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 77.08 E-value: 6.82e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFM--GKADAFVVITLkkSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKF-G 519
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRSgkGKSDPYAILSV--GAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFaG 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 186522051 520 KDKIGRVIMTLTRVMLEGE---FQEWFELDGAKSGKLCV 555
Cdd:cd04024   79 KDYLGEFDIALEEVFADGKtgqSDKWITLKSTRPGKTSV 117

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: 76.07 E-value: 1.16e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLK-----KSETKSKTrvvpdsLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFG 519
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKKT------LNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 186522051 520 K-DKIGRVIMTLTRVMLEGEFQEWFELDGAKSGKL 553
Cdd:cd04040   75 KdDLLGSAYIDLSDLEPEETTELTLPLDGQGGGKL 109

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: 75.03 E-value: 2.54e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSetKSKTRVVPDSLNPVWNQTFDFVVEDaLHDLLTLEVWDHDKFGK-D 521
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVLELVNA--RLQTHTIYKTLNPEWNKIFTFPIKD-IHDVLEVTVYDEDKDKKpE 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 186522051 522 KIGRVIMTLTRVMlEGEfQEWFELdgaKSGKLCVHLK 558
Cdd:cd08377   78 FLGKVAIPLLSIK-NGE-RKWYAL---KDKKLRTRAK 109

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: 75.36 E-value: 2.66e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 440 IVRGVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDF-VVEDalHDLL--TLEV- 512
Cdd:cd04031   13 KVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdRSEKSKRRTKTVKKTLNPEWNQTFEYsNVRR--ETLKerTLEVt 90

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 186522051 513 -WDHDKFGKDK-IGRVIMTLTRVMLEGEfQEWFEL 545
Cdd:cd04031   91 vWDYDRDGENDfLGEVVIDLADALLDDE-PHWYPL 124

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: 75.49 E-value: 4.70e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 259 ELKPVGKLDVKVVQAKDLANKDMIGKSDPYAIVFIRP-------------------------LP-DRTKKTKTISNSLNP 312
Cdd:cd08676   23 AEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPasrernsekskkrkshrkkavlkdtVPaKSIKVTEVKPQTLNP 102

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 186522051 313 IWNEHFEFIVEDVSTQHLTVRVFD--DEGVGSSQLigaaqvPLNELVPGKVkDIWLKL 368
Cdd:cd08676  103 VWNETFRFEVEDVSNDQLHLDIWDhdDDFLGCVNI------PLKDLPSCGL-DSWFKL 153

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: 74.60 E-value: 4.86e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 270 VVQAKDLANKdmIGKSDPYAIVFIRplpDRTKKTKTISNSLNPIWNEHFEFiveDVSTQ-----HLTVRVFDDEGVGSSQ 344
Cdd:cd08373    2 VVSLKNLPGL--KGKGDRIAKVTFR---GVKKKTRVLENELNPVWNETFEW---PLAGSpdpdeSLEIVVKDYEKVGRNR 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 186522051 345 LIGAAQVPLNELVPGKVKDIWLKLVkdleiqrDTKNR---GQVQLELLYCPL 393
Cdd:cd08373   74 LIGSATVSLQDLVSEGLLEVTEPLL-------DSNGRptgATISLEVSYQPP 118

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: 73.84 E-value: 8.75e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTISNSLNPIWNEHFEFI----VEDVstqhLTVRVFDDEGVG 341
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRiqsqVKNV----LELTVMDEDYVM 77

                         90
                 ....*....|....*....
gi 186522051 342 SSQLiGAAQVPLNELVPGK 360
Cdd:cd04036   78 DDHL-GTVLFDVSKLKLGE 95

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: 73.46 E-value: 1.25e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYaiVFIRpLPDRT-KKTKTISNSLNPIWNEHFEFIVEDVsTQHLTVRVFDDEGVGSS 343
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPY--VKFK-YGGKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDYDRGLTD 76

                         90       100
                 ....*....|....*....|....*.
gi 186522051 344 QLIGAAQVPLNELVPGKVKDIWLKLV 369
Cdd:cd04042   77 DFMGSAFVDLSTLELNKPTEVKLKLE 102

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: 73.90 E-value: 1.95e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 434 SKKKDVIVRGVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTF---DFVVEDALHDL 507
Cdd:cd04020   18 ALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLlpdKSKKSKQKTPVVKKSVNPVWNHTFvydGVSPEDLSQAC 97

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 186522051 508 LTLEVWDHDKFG-KDKIGRVIMTLTRVMLEGEFQEW 542
Cdd:cd04020   98 LELTVWDHDKLSsNDFLGGVRLGLGTGKSYGQAVDW 133

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: 72.68 E-value: 2.30e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITL-----KKSETK--SKTrvvpdsLNPVWNQTFDF-VVEDALHD-LLTLEVWDH 515
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLlpdkkKKFETKvhRKT------LNPVFNETFTFkVPYSELGNkTLVFSVYDF 91

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186522051 516 DKFGK-DKIGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08385   92 DRFSKhDLIGEVRVPLLTVDLGHVTEEWRDL 122

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: 71.18 E-value: 4.71e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVD-FMGKADAFVVITLKKSEtkSKTRVVPDSLNPVWN-QTFDFVVEDAL--HDLLTLEVWDHDKFGK 520
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTT--YKTDVVKKSLNPVWNsEWFRFEVDDEElqDEPLQIRVMDHDTYSA 78

                         90       100
                 ....*....|....*....|....*..
gi 186522051 521 -DKIGRVIMTLTRVMLEGE---FQEWF 543
Cdd:cd08688   79 nDAIGKVYIDLNPLLLKDSvsqISGWF 105

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: 71.20 E-value: 1.24e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 442 RGVLSVTVVAAEDLPAVDFMGkADAFVVITLkkSETKSKTRVVPDSLNPVWNQTFDFVVEDaLHDLLTLEVWDHDKFGKD 521
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVLTL--GNQKVKTRVIKKNLNPVWNEELTLSVPN-PMAPLKLEVFDKDTFSKD 76

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: 70.28 E-value: 1.34e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKA-DAFVVITLKKSETKSKTRVVPDSLNPVWNQTFdFVVEDALHDLLTLEVWDHDKFGKD 521
Cdd:cd04044    2 GVLAVTIKSARGLKGSDIIGGTvDPYVTFSISNRRELARTKVKKDTSNPVWNETK-YILVNSLTEPLNLTVYDFNDKRKD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 186522051 522 K-IGRVIMTLtRVMLEGEFQE---WFELDGAKS-GKLCVHLKWTP 561
Cdd:cd04044   81 KlIGTAEFDL-SSLLQNPEQEnltKNLLRNGKPvGELNYDLRFFP 124

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: 70.44 E-value: 1.42e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITL-----KKSETKSKTRvvpdSLNPVWNQTFDF---VVEDALHDLLTLEVWDH 515
Cdd:cd08386   17 TLTLKILKAVELPAKDFSGTSDPFVKIYLlpdkkHKLETKVKRK----NLNPHWNETFLFegfPYEKLQQRVLYLQVLDY 92

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186522051 516 DKFGK-DKIGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08386   93 DRFSRnDPIGEVSLPLNKVDLTEEQTFWKDL 123

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: 69.93 E-value: 1.81e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 273 AKDLANKDMIGKSDPYAIVFIRPLPDRtkKTKTISNSLNPIWNEHFEFIVEDvSTQHLTVRVFDDEGVGSSQLIGAAQVP 352
Cdd:cd04045   10 ANDLKNLEGVGKIDPYVRVLVNGIVKG--RTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEKVGKDRSLGSVEIN 86


                 ....*
gi 186522051 353 LNELV 357
Cdd:cd04045   87 VSDLI 91

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: 70.37 E-value: 1.82e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 440 IVRGVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHD-LLTLEVWDH 515
Cdd:cd04026   10 VKDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLipdPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDrRLSIEVWDW 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 186522051 516 DKFGK-DKIGRVIMTLTRVMlEGEFQEWFELDGAKSGK 552
Cdd:cd04026   90 DRTTRnDFMGSLSFGVSELI-KMPVDGWYKLLNQEEGE 126

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: 70.30 E-value: 2.22e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITL----KKSETKsKTRVVPDSLNPVWNQTFDF-VVEDALHDL-LTLEVWDHDKF 518
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSLlqggKKLKKK-KTSVKKGTLNPVFNEAFSFdVPAEQLEEVsLVITVVDKDSV 94

                         90       100
                 ....*....|....*....|....*...
gi 186522051 519 GKD-KIGRVImtLTRVMLEGEFQEWFEL 545
Cdd:cd00276   95 GRNeVIGQVV--LGPDSGGEELEHWNEM 120

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: 71.61 E-value: 2.24e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051   69 QKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTpAMLASLKFSKFTLGTVAPQFTGVSILESESGPNGITMELEMQ 148
Cdd:pfam17047   3 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGAN-THLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQIS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  149 WDGNPKIVLDVKTLLGVSlpiEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIgGELTSIPGISDAI 228
Cdd:pfam17047  82 FVGNCEIDLEIKRYFCRA---GVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGL-TNLLDVPGLNGLS 157

                         170       180
                  ....*....|....*....|...
gi 186522051  229 EETIRDAIEDSITWPVRKIIPIL 251
Cdd:pfam17047 158 DTIILDIISNYLVLPNRITVPLV 180

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: 69.51 E-value: 3.11e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 263 VGKLDVKVVQAKDLANKDMIGKS-DPYaIVFIRPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVsTQHLTVRVFDDEGVG 341
Cdd:cd04044    1 IGVLAVTIKSARGLKGSDIIGGTvDPY-VTFSISNRRELARTKVKKDTSNPVWNETKYILVNSL-TEPLNLTVYDFNDKR 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 186522051 342 SSQLIGAAQVPLNELVP-GKVKDIwlklvkDLEIQRDTKNRGQVQLELLYCP 392
Cdd:cd04044   79 KDKLIGTAEFDLSSLLQnPEQENL------TKNLLRNGKPVGELNYDLRFFP 124

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: 69.21 E-value: 4.07e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVIT-LKKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:cd04043    2 LFTIRIVRAENLKADSSNGLSDPYVTLVdTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHD 81

                         90
                 ....*....|
gi 186522051 523 -IGRVIMTLT 531
Cdd:cd04043   82 lCGRASLKLD 91

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: 69.66 E-value: 4.90e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 263 VGKLDVKVVQAKDLANKDMIGkSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQhLTVRVFDDEGVGS 342
Cdd:cd04038    1 LGLLKVRVVRGTNLAVRDFTS-SDPYVVL---TLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKDTFSK 75

                         90
                 ....*....|....*
gi 186522051 343 SQLIGAAQVPLNELV 357
Cdd:cd04038   76 DDSMGEAEIDLEPLV 90

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: 68.67 E-value: 5.51e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRplpDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQ 344
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYN---GQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKND 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 186522051 345 LIGAAQVPLNELVPGKVKDIWLKLVKDLEIQRDTK-NRGQVQLEL 388
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQEEGWFRLLPDPRAEEESGgNLGSLRLKV 122

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: 69.82 E-value: 7.32e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  69 QKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQYTPaMLASLKFSKFTLGTVAPQFTGVSIlESESGPNGITMELEMQ 148
Cdd:cd21679    1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNN-HLQTFSFTKVDLGEKPLKVVGVKA-HTEFDKRQIILDLHIS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 149 WDGNPKIVLDVKTLLgvsLPIEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIgGELTSIPGISDAI 228
Cdd:cd21679   79 YVGDVEINVEVKKYF---CKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGM-TNLLDIPGLSSMS 154

                        170       180
                 ....*....|....*....|..
gi 186522051 229 EETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21679  155 DTMIMDTIASFLVLPNRLTVPL 176

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: 68.06 E-value: 8.23e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITLKK-SETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDH 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 186522051 523 IGRVIMTLTRVMLEGEFQEWFELDGAKSGKLCV 555
Cdd:cd04036   81 LGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEV 113

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: 67.68 E-value: 1.51e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 442 RGVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVV--EDALHDLLTLEVWDHD 516
Cdd:cd04030   15 RQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLlpdKSKSTRRKTSVKKDNLNPVFDETFEFPVslEELKRRTLDVAVKNSK 94

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 517 KF---GKDKIGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd04030   95 SFlsrEKKLLGQVLIDLSDLDLSKGFTQWYDL 126

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: 67.19 E-value: 2.05e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 440 IVRgvlsVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFG 519
Cdd:cd04037    1 LVR----VYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLG 76


                 ....*..
gi 186522051 520 KD-KIGR 525
Cdd:cd04037   77 SDdLIGE 83

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: 68.69 E-value: 2.11e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  69 QKLNWLNLELEKIWPYVNEAASELIKSSVEPVLEQyTPAMLASLKFSKFTLGTVAPQFTGVSILESESGPNGITMELEMQ 148
Cdd:cd21681    1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIRE-KSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDRRQVILDLQIC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 149 WDGNPKIVLDVKTllgvsLPIEVKNIGFTGVFRLIFKPLVDEFPCFGALSYSLREKKGLDFTLKVIgGELTSIPGISDAI 228
Cdd:cd21681   80 YIGDCEINVEIKK-----CKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGL-TNLLDIPGINDMS 153

                        170       180
                 ....*....|....*....|..
gi 186522051 229 EETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21681  154 DSLIEDLIASHLVLPNRFTVPL 175

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: 66.66 E-value: 2.74e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 261 KPVGKLDVKVVQAKDLANKDMIGKSDPYAIVfiRPLPDR--TKKTKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVFD 336
Cdd:cd08387   13 KDMGILNVKLIQARNLQPRDFSGTADPYCKV--RLLPDRsnTKQSKIHKKTLNPEFDESFVFEVppQELPKRTLEVLLYD 90

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 337 DEGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08387   91 FDQFSRDECIGVVELPLAEVDLSEKLDLWRKI 122

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: 66.53 E-value: 3.37e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYaiVFIRPLPDRT----KKTKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVFDDE 338
Cdd:cd04030   17 KLIVTVHKCRNLPPCDSSDIPDPY--VRLYLLPDKSkstrRKTSVKKDNLNPVFDETFEFPVslEELKRRTLDVAVKNSK 94

                         90       100
                 ....*....|....*....|....
gi 186522051 339 GVGS--SQLIGAAQVPLNELVPGK 360
Cdd:cd04030   95 SFLSreKKLLGQVLIDLSDLDLSK 118

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: 67.01 E-value: 3.87e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVI-------------TLKKSETKSK--------------TRVVPDSLNPVWNQTF 496
Cdd:cd08676   29 VLKVTVIEAKGLLAKDVNGFSDPYCMLgivpasrernsekSKKRKSHRKKavlkdtvpaksikvTEVKPQTLNPVWNETF 108

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 186522051 497 DFVVEDALHDLLTLEVWDHDkfgKDKIGRVIMTLTRVMLEGEFQeWFEL 545
Cdd:cd08676  109 RFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCGLDS-WFKL 153

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

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 66.15 E-value: 3.93e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRP--LPDRTKKTKTISNSLNPIWNEHFEFI---VEDVSTQHLTVRVFDDEG 339
Cdd:cd04035   16 ALHCTIIRAKGLKAMDANGLSDPYVKLNLLPgaSKATKLRTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDEDR 95

                         90       100
                 ....*....|....*....|....*
gi 186522051 340 VGsSQLIGAAQVPLNELVPGKVKDI 364
Cdd:cd04035   96 FG-NDFLGETRIPLKKLKPNQTKQF 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: 66.22 E-value: 5.23e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIRPlPDRTK-----KTKTISNSLNPIWNEHFEFIVeDVSTQHLTVRVFDDEGV 340
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISLYD-PDGNGeidsvQTKTIKKTLNPKWNEEFFFRV-NPREHRLLFEVFDENRL 79

                         90
                 ....*....|....*....
gi 186522051 341 GSSQLIGAAQVPLNELVPG 359
Cdd:cd04033   80 TRDDFLGQVEVPLNNLPTE 98

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: 66.07 E-value: 5.27e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDR--TKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTV--RVFDDEG 339
Cdd:cd00276   14 ERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKlkKKKTSVKKGTLNPVFNEAFSFDVPAEQLEEVSLviTVVDKDS 93


                 ....*...
gi 186522051 340 VGSSQLIG 347
Cdd:cd00276   94 VGRNEVIG 101

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: 65.99 E-value: 5.79e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 260 LKPVGKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTI--SNSLNPIWNEHFEFIV--EDVSTQHLTVRVF 335
Cdd:cd08403   10 LPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSvkKNTLNPTYNEALVFDVppENVDNVSLIIAVV 89

                         90       100       110
                 ....*....|....*....|....*....|....
gi 186522051 336 DDEGVGSSQLIGAAQVPLNelVPGKVKDIWLKLV 369
Cdd:cd08403   90 DYDRVGHNELIGVCRVGPN--ADGQGREHWNEML 121

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: 65.74 E-value: 6.43e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGK-SDPYAIVFIrpLPD--RTKKTKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVFDDEG 339
Cdd:cd08390   15 QLTVSLIKARNLPPRTKDVAhCDPFVKVCL--LPDerRSLQSKVKRKTQNPNFDETFVFQVsfKELQRRTLRLSVYDVDR 92

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186522051 340 VGSSQLIGAAQVPLNELVPGKVKDIWLKLVK 370
Cdd:cd08390   93 FSRHCIIGHVLFPLKDLDLVKGGVVWRDLEP 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: 64.98 E-value: 1.19e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYaiVFIRPLPDRT----KKTKTISNSLNPIWNEHFEFiveDVSTQH----LTVRVF 335
Cdd:cd04026   13 NKLTVEVREAKNLIPMDPNGLSDPY--VKLKLIPDPKnetkQKTKTIKKTLNPVWNETFTF---DLKPADkdrrLSIEVW 87

                         90       100       110
                 ....*....|....*....|....*....|...
gi 186522051 336 DDEGVGSSQLIGAAQVPLNELVPgKVKDIWLKL 368
Cdd:cd04026   88 DWDRTTRNDFMGSLSFGVSELIK-MPVDGWYKL 119

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: 64.56 E-value: 1.37e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLpdrtKKTKT----ISNSlNPIWNEHFEFIVEDVSTQH----LTVRVFD 336
Cdd:cd04051    1 TLEITIISAEDLKNVNLFGKMKVYAVVWIDPS----HKQSTpvdrDGGT-NPTWNETLRFPLDERLLQQgrlaLTIEVYC 75

                         90       100
                 ....*....|....*....|....
gi 186522051 337 DEGVGSSQLIGAAQVPLNELVPGK 360
Cdd:cd04051   76 ERPSLGDKLIGEVRVPLKDLLDGA 99

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: 64.67 E-value: 1.62e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVitLKKSETKSKTRVVPDSLNPVWNQTFDFVVEDA---LHDLLTLEVWDHDKFGKD 521
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVE--LDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDRRSGRR 79

                         90
                 ....*....|....*....
gi 186522051 522 K--IGRVIMTLTRVMLEGE 538
Cdd:cd04022   80 RsfLGRVRISGTSFVPPSE 98

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: 63.82 E-value: 1.72e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDF-MGKADAFVVITLKKS-ETKSKTRVVPDSLNPVWNQT-FDFVVEDAL--HDLLTLEVWDHDK 517
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVWEETwFVLVTPDEVkaGERLSCRLWDSDR 80

                         90
                 ....*....|
gi 186522051 518 F-GKDKIGRV 526
Cdd:cd04041   81 FtADDRLGRV 90

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: 64.57 E-value: 2.01e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRP---LPD-RTKKTKTISNSLNPIWNEHFEFIVEDVSTQH----LTVRVFD 336
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSSDPFVKVELLPrhlFPDvPTPKTQVKKKTLFPLFDESFEFNVPPEQCSVegalLLFTVKD 96

                         90       100
                 ....*....|....*....|...
gi 186522051 337 DEGVGSSQLIGAAQVPLNElVPG 359
Cdd:cd04009   97 YDLLGSNDFEGEAFLPLND-IPG 118

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: 64.33 E-value: 2.22e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 428 MKKLVTSKKKDVIVRgvLSVTVVAAEDLPAVDFMGKADAFVVITLKKSEtkSKTRVVPDSLNPVWNQTFDFVVEDALHDL 507
Cdd:cd08375    2 KAYLARSQRASGIGR--LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQE--HKTKVVSDTLNPKWNSSMQFFVKDLEQDV 77

                         90       100       110
                 ....*....|....*....|....*....|
gi 186522051 508 LTLEVWDHDKFGKDK-IGRVIMTLTRVMLE 536
Cdd:cd08375   78 LCITVFDRDFFSPDDfLGRTEIRVADILKE 107

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: 64.28 E-value: 2.26e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVS---TQHLTVRVFDDEGVG 341
Cdd:cd04022    1 KLVVEVVDAQDLMPKDGQGSSSAYVEL---DFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPSrlsNLVLEVYVYNDRRSG 77

                         90
                 ....*....|....*...
gi 186522051 342 -SSQLIGAAQVPLNELVP 358
Cdd:cd04022   78 rRRSFLGRVRISGTSFVP 95

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: 63.82 E-value: 3.19e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQLIG 347
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYVTLVDTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCG 84

                         90       100
                 ....*....|....*....|....
gi 186522051 348 AAQVPLNELV---PGKVKDIWLKL 368
Cdd:cd04043   85 RASLKLDPKRfgdDGLPREIWLDL 108

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: 63.42 E-value: 3.82e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLpdrTKKTKTISNS-LNPIWNEHFEF-IVEDVSTQhLTVRVFDDEGvG 341
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRIGGV---TKKTKTDFRGgQHPEWDEELRFeITEDKKPI-LKVAVFDDDK-R 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 186522051 342 SSQLIGAAQVPLNELVPGKVKDIWlklvkdLEIQRDTKNRGQVQLELLY 390
Cdd:cd08681   76 KPDLIGDTEVDLSPALKEGEFDDW------YELTLKGRYAGEVYLELTF 118

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: 63.33 E-value: 4.88e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 283 GKSDPYAIVFIR--PLPDRTK-KTKTIS-NSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSqLIGAAQVPLNELVP 358
Cdd:cd00275   23 SIVDPYVEVEIHglPADDSAKfKTKVVKnNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSGDDD-FLGQACLPLDSLRQ 101


                 .
gi 186522051 359 G 359
Cdd:cd00275  102 G 102

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: 62.58 E-value: 5.63e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 273 AKDLANKDMIGKSDPYaIVFIRPLPDRTK----KTKTISNSLNPIWNEhFEFIVEDV----STQHLTVRVFDDEGVGSSQ 344
Cdd:cd04047    9 GKKLDKKDFFGKSDPF-LEISRQSEDGTWvlvyRTEVIKNTLNPVWKP-FTIPLQKLcngdYDRPIKIEVYDYDSSGKHD 86

                         90       100
                 ....*....|....*....|
gi 186522051 345 LIGAAQVPLNELVPGKVKDI 364
Cdd:cd04047   87 LIGEFETTLDELLKSSPLEF 106

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

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 63.19 E-value: 5.66e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTI--SNSLNPIWNEHFEFIV--EDVSTQHLTVRVFDDEG 339
Cdd:cd08402   15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTikKRTLNPYYNESFSFEVpfEQIQKVHLIVTVLDYDR 94


                 ....*...
gi 186522051 340 VGSSQLIG 347
Cdd:cd08402   95 IGKNDPIG 102

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: 63.86 E-value: 6.05e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDM------------------------------IGKSDPYAIVFIRPlpDRTKKTKTISNSLNPI 313
Cdd:cd04015    7 GTLDVTIYEADNLPNMDMfseklrrffsklvgcseptlkrpsshrhvgKITSDPYATVDLAG--ARVARTRVIENSENPV 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 186522051 314 WNEHFE-FIVEDVStqHLTVRVFDDEGVGsSQLIGAAQVPLNELVPGKVKDIWLKLV 369
Cdd:cd04015   85 WNESFHiYCAHYAS--HVEFTVKDNDVVG-AQLIGRAYIPVEDLLSGEPVEGWLPIL 138

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: 62.70 E-value: 7.33e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDmiGKS-DPYAIVFIRPLPDRT--KKTKTISNSLNPIWNEHF---EFIVEDVSTQHLTVRVFDD 337
Cdd:cd08381   13 GTLFVMVMHAKNLPLLD--GSDpDPYVKTYLLPDPQKTtkRKTKVVRKTRNPTFNEMLvydGLPVEDLQQRVLQVSVWSH 90

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186522051 338 EGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08381   91 DSLVENEFLGGVCIPLKKLDLSQETEKWYPL 121

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: 62.27 E-value: 7.56e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKtrVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK- 522
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSK--VCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEf 78

                         90       100
                 ....*....|....*....|....
gi 186522051 523 IGRVIMTLTRVMLEGEFQEWFELD 546
Cdd:cd08376   79 IGRCEIDLSALPREQTHSLELELE 102

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: 62.59 E-value: 8.80e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVviTLKKSETKSKTRVVPDSLNPVWNQTFDFVVEDAlHDLLTLEVWDHD-------- 516
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYV--TVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNS-SDRIKVRVWDEDddiksrlk 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 186522051 517 -KFGK---DKIGRVIMTLTrvMLEGEFQEWFELD-----GAKSGKLCVHL 557
Cdd:cd04027   80 qKFTResdDFLGQTIIEVR--TLSGEMDVWYNLEkrtdkSAVSGAIRLHI 127

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

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 62.79 E-value: 9.93e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 263 VGKLDVKVVQAKDLANKDMIGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGS 342
Cdd:cd08375   14 IGRLMVVIVEGRDLKPCNSNGKSDPYCEV---SMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSP 90

                         90
                 ....*....|....
gi 186522051 343 SQLIGAAQVPLNEL 356
Cdd:cd08375   91 DDFLGRTEIRVADI 104

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 61.43 E-value: 1.10e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITLKKseTKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKfgKDKI 523
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGK--TTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKT--GKSL 76

                         90       100
                 ....*....|....*....|....*..
gi 186522051 524 GRVIMTLTRVMLEGE--FQEWFELDGA 548
Cdd:cd04050   77 GSLTLPLSELLKEPDltLDQPFPLDNS 103

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: 62.42 E-value: 1.16e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVV--EDALHDLLTLEVWDHDK 517
Cdd:cd08402   15 GKLTVVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESFSFEVpfEQIQKVHLIVTVLDYDR 94

                         90
                 ....*....|..
gi 186522051 518 FGK-DKIGRVIM 528
Cdd:cd08402   95 IGKnDPIGKVVL 106

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: 61.88 E-value: 1.50e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIrpLPDRTKK----TKTISNSLNPIWNEHFEFIV---EDVSTQHLTVRVFDDE 338
Cdd:cd04031   18 LIVTVLQARDLPPRDDGSLRNPYVKVYL--LPDRSEKskrrTKTVKKTLNPEWNQTFEYSNvrrETLKERTLEVTVWDYD 95

                         90
                 ....*....|....*
gi 186522051 339 GVGSSQLIGAAQVPL 353
Cdd:cd04031   96 RDGENDFLGEVVIDL 110

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: 61.58 E-value: 1.67e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIrpLPDRTKK--TKTISNSLNPIWNE--HFE-FIVEDVSTQHLTVRVFDDEGV 340
Cdd:cd08386   18 LTLKILKAVELPAKDFSGTSDPFVKIYL--LPDKKHKleTKVKRKNLNPHWNEtfLFEgFPYEKLQQRVLYLQVLDYDRF 95

                         90       100
                 ....*....|....*....|....*...
gi 186522051 341 GSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08386   96 SRNDPIGEVSLPLNKVDLTEEQTFWKDL 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: 61.04 E-value: 1.95e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 450 VAAEDLPAVDFMGKADAFVVITlKKSETKS-----KTRVVPDSLNPVWNqTFDFVVEDA----LHDLLTLEVWDHDKFGK 520
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEIS-RQSEDGTwvlvyRTEVIKNTLNPVWK-PFTIPLQKLcngdYDRPIKIEVYDYDSSGK 84

                         90       100
                 ....*....|....*....|...
gi 186522051 521 DK-IGRVIMTLtRVMLEGEFQEW 542
Cdd:cd04047   85 HDlIGEFETTL-DELLKSSPLEF 106

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: 61.17 E-value: 2.06e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSkTRVVPDSLNPVWNQTFDFVVEDalHDLLTLEVWDHDKFGK 520
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLPDPFAVITVDGGQTHS-TDVAKKTLDPKWNEHFDLTVGP--SSIITIQVFDQKKFKK 74

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: 61.19 E-value: 2.07e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTRVVPDSlNPVWNQTFDFVVED----ALHDLLtLEVWDHDKF 518
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGR-NPEWNEKFKFTVEYpgwgGDTKLI-LRIMDKDNF 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 519 -GKDKIGRVIMTLTRVMLEGEFQEWFELDGAK 549
Cdd:cd04049   79 sDDDFIGEATIHLKGLFEEGVEPGTAELVPAK 110

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: 61.17 E-value: 2.18e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRPlpDRTKKTKTISNSLNPIWNEHFEFIVEDVSTqhLTVRVFD 336
Cdd:cd08382    1 KVRLTVLCADGLAKRDLFRLPDPFAVITVDG--GQTHSTDVAKKTLDPKWNEHFDLTVGPSSI--ITIQVFD 68

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: 61.59 E-value: 2.42e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 442 RGVLSVTVVAAEDLPAVDFMGKADAFVVITLK---KSETKSKTRVVPDSLNPVWNQTFDFVVedALHDL----LTLEVWD 514
Cdd:cd08384   12 RRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKpdaGKKSKHKTQVKKKTLNPEFNEEFFYDI--KHSDLakktLEITVWD 89

                         90       100       110
                 ....*....|....*....|....*....|...
gi 186522051 515 HDkFGK--DKIGRVIMTLTRvmlEGE-FQEWFE 544
Cdd:cd08384   90 KD-IGKsnDYIGGLQLGINA---KGErLRHWLD 118

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: 59.65 E-value: 7.90e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRplpDRTKKTKTISNS-LNPIWNEHFEFIVED---VSTQHLTVRVFDDEG 339
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVIIQCR---TQERKSKVAKGDgRNPEWNEKFKFTVEYpgwGGDTKLILRIMDKDN 77

                         90
                 ....*....|....*...
gi 186522051 340 VGSSQLIGAAQVPLNELV 357
Cdd:cd04049   78 FSDDDFIGEATIHLKGLF 95

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: 59.11 E-value: 8.40e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEgvgSSQL 345
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVEL---TVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDK---TGKS 75

                         90       100
                 ....*....|....*....|....*
gi 186522051 346 IGAAQVPLNEL--VPGKVKDIWLKL 368
Cdd:cd04050   76 LGSLTLPLSELlkEPDLTLDQPFPL 100

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: 59.22 E-value: 1.02e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITL----KKSeTKSKTRVVPDSLNPVWNQTFDFV---VEDALHDLLTLEVWDHDK 517
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpgaSKA-TKLRTKTVHKTRNPEFNETLTYYgitEEDIQRKTLRLLVLDEDR 95


                 ....*..
gi 186522051 518 FGKDKIG 524
Cdd:cd04035   96 FGNDFLG 102

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: 59.04 E-value: 1.19e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKkSETKsKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGK-DKI 523
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYN-GQTL-ETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKnDFL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 186522051 524 GRVIMTLTRVMLEGEFQEWFEL---------DGAKSGKLCVHLK 558
Cdd:cd04025   80 GKVVFSIQTLQQAKQEEGWFRLlpdpraeeeSGGNLGSLRLKVR 123

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: 59.19 E-value: 1.20e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGK-SDPYAIVFIrpLPDRTK----KTKTISNSLNPIWNEHFEFIVE--DVSTQHLTVRVFD 336
Cdd:cd08521   14 GSLEVHIKECRNLAYADEKKKrSNPYVKVYL--LPDKSKqskrKTSVKKNTTNPVFNETLKYHISksQLETRTLQLSVWH 91

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 337 DEGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08521   92 HDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 58.81 E-value: 1.45e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 442 RGVLSVTVVAAEDLPAvDFMGKADAFVVITLKKSEtkSKTRVVPDSLNPVWNQTFDF-VVEDALHDLLTLEVWDHDKFGK 520
Cdd:cd04032   27 LATLTVTVLRATGLWG-DYFTSTDGYVKVFFGGQE--KRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDNGWD 103


                 .
gi 186522051 521 D 521
Cdd:cd04032  104 D 104

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: 58.80 E-value: 1.54e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTrVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKT-DFRGGQHPEWDEELRFEITEDKKPILKVAVFDDDKRKPDL 79

                         90       100
                 ....*....|....*....|....
gi 186522051 523 IGRVIMTLTRVMLEGEFQEWFELD 546
Cdd:cd08681   80 IGDTEVDLSPALKEGEFDDWYELT 103

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: 58.73 E-value: 1.83e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIrplpDRTKK-TKTISNSLNPIWNEHFEFIVEDvSTQHLTVRVFDDE 338
Cdd:cd04027    2 KISITVVCAQGLIAKDKTGTSDPYVTVQV----GKTKKrTKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDED 71

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: 58.97 E-value: 2.06e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRT--KKTKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVFDDEG 339
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVekKKTVIKKRTLNPVFNESFIFNIplERLRETTLIITVMDKDR 94

                         90
                 ....*....|....*.
gi 186522051 340 VGSSQLIGAAQVPLNE 355
Cdd:cd08405   95 LSRNDLIGKIYLGWKS 110

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: 58.33 E-value: 2.53e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKDMIGKSDPYAIVFIRplpdRTK---KTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQ 344
Cdd:cd04037    4 VYVVRARNLQPKDPNGKSDPYLKIKLG----KKKindRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDD 79


                 ...
gi 186522051 345 LIG 347
Cdd:cd04037   80 LIG 82

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: 57.65 E-value: 4.47e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 448 TVVAAEDLPAvdFMGKADAFVVITLKksETKSKTRVVPDSLNPVWNQTFDFVVEDALH--DLLTLEVWDHDKFGKDK-IG 524
Cdd:cd08373    1 LVVSLKNLPG--LKGKGDRIAKVTFR--GVKKKTRVLENELNPVWNETFEWPLAGSPDpdESLEIVVKDYEKVGRNRlIG 76

                         90
                 ....*....|....*.
gi 186522051 525 RVIMTLTRVMLEGEFQ 540
Cdd:cd08373   77 SATVSLQDLVSEGLLE 92

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 62.85 E-value: 4.69e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKkSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:COG5038  1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFLN-EKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKND 1118

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 186522051  523 -IGRVIMTLTRVMLEGEFQEWFELDGAKSGKL--CVHLKW 559
Cdd:COG5038  1119 lLGTAEIDLSKLEPGGTTNSNIPLDGKTFIVLdgTLHPGF 1158

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: 57.81 E-value: 5.10e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITL----KKSEtKSKTRVVPDSLNPVWNQTFDFVVE-DALHDL-LTLEVWDHD 516
Cdd:cd08405   15 NRITVNIIKARNLKAMDINGTSDPYVKVWLmykdKRVE-KKKTVIKKRTLNPVFNESFIFNIPlERLRETtLIITVMDKD 93

                         90       100       110
                 ....*....|....*....|....*....|
gi 186522051 517 KFGK-DKIGRVImtLTRVMLEGEFQEWFEL 545
Cdd:cd08405   94 RLSRnDLIGKIY--LGWKSGGLELKHWKDM 121

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: 57.55 E-value: 5.19e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLP--AVDFMGKADAFVVITL----KKSETKSKTRVVPD-SLNPVWNQTFDFVVEDalHDL--LTLEVWDH 515
Cdd:cd00275    4 LTIKIISGQQLPkpKGDKGSIVDPYVEVEIhglpADDSAKFKTKVVKNnGFNPVWNETFEFDVTV--PELafLRFVVYDE 81


                 ....*....
gi 186522051 516 DKFGKDKIG 524
Cdd:cd00275   82 DSGDDDFLG 90

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: 56.83 E-value: 6.30e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSEtKSKTRVVPDSLNPVWNQTFdFVVEDALHDLLTLEVWDHDKFGKDK 522
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLVNGIV-KGRTVTISNTLNPVWDEVL-YVPVTSPNQKITLEVMDYEKVGKDR 78


                 ....*
gi 186522051 523 -IGRV 526
Cdd:cd04045   79 sLGSV 83

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 61.70 E-value: 9.91e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  260 LKPVGKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPlpDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEG 339
Cdd:COG5038  1036 VENSGYLTIMLRSGENLPSSDENGYSDPFVKLFLNE--KSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDS 1113

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 186522051  340 VGSSQLIGAAQVPLNELVPGKvkdiwlklVKDLEIQRDTKNRGQVQLEL 388
Cdd:COG5038  1114 GEKNDLLGTAEIDLSKLEPGG--------TTNSNIPLDGKTFIVLDGTL 1154

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: 57.00 E-value: 1.07e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMiGKSDPYAIVF-IRPLPDRTKKTKTISNSLNPIWNEHFEFIV---------------EDVSTQH 329
Cdd:cd08675    1 LSVRVLECRDLALKSN-GTCDPFARVTlNYSSKTDTKRTKVKKKTNNPRFDEAFYFELtigfsyekksfkveeEDLEKSE 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 186522051 330 LTVRVFDDEGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08675   80 LRVELWHASMVSGDDFLGEVRIPLQGLQQAGSHQAWYFL 118

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: 56.09 E-value: 1.51e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKkSETKSKTRVVPD-SLNPVWNQTFDFVVEDAL----HDLLTLEVWDHDKFG 519
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWID-PSHKQSTPVDRDgGTNPTWNETLRFPLDERLlqqgRLALTIEVYCERPSL 80

                         90
                 ....*....|....*.
gi 186522051 520 KDK-IGRVIMTLTRVM 534
Cdd:cd04051   81 GDKlIGEVRVPLKDLL 96

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: 56.40 E-value: 1.55e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 272 QAKDLANKDMIGKSDPYAIVFIRplpDRTKKTKTISNSLNPIWNEhfEFIVEDV----STQHLT-------VRVFDDEGV 340
Cdd:cd04017    9 QARDLLAADKSGLSDPFARVSFL---NQSQETEVIKETLSPTWDQ--TLIFDEVelygSPEEIAqnpplvvVELFDQDSV 83

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 186522051 341 GSSQLIGAAQVP------LNELVPGKVKdiWLKLVKD 371
Cdd:cd04017   84 GKDEFLGRSVAKplvkldLEEDFPPKLQ--WFPIYKG 118

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: 55.75 E-value: 1.91e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVItlkKSETKS-KTRVVPDSLNPVWNQTFDFVVEDaLHDLLTLEVWDHDKFGKDK 522
Cdd:cd04046    4 VTQVHVHSAEGLSKQDSGGGADPYVII---KCEGESvRSPVQKDTLSPEFDTQAIFYRKK-PRSPIKIQVWNSNLLCDEF 79


                 ....*..
gi 186522051 523 IGRVIMT 529
Cdd:cd04046   80 LGQATLS 86

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: 55.38 E-value: 2.17e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 430 KLVTSKKKdvivrGVLSVTVVAAEDLPAVDfmGKA-DAFVVITLK---KSETKSKTRVVPDSLNPVWNQTF---DFVVED 502
Cdd:cd08381    5 KLSISYKN-----GTLFVMVMHAKNLPLLD--GSDpDPYVKTYLLpdpQKTTKRKTKVVRKTRNPTFNEMLvydGLPVED 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 186522051 503 ALHDLLTLEVWDHDKFG-KDKIGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08381   78 LQQRVLQVSVWSHDSLVeNEFLGGVCIPLKKLDLSQETEKWYPL 121

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: 56.73 E-value: 2.66e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 105 TPAMLASLKFSKFTLGTVAPQFTGVSILESeSGPNGITMELEMQWDGNPKIVLDVKTLLGVSLPIEVKNI---------G 175
Cdd:cd21675   36 LPSFLGEITVTDLDLGTSVPVISNPKLPSL-DPDGGLWVDLDVSYRGGFSLTLETKLNLSKLKKEKVSNVplvlavevkS 114

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 186522051 176 FTGVFRLIFKPlvdefPCFGALSYSLREKKGLDFTLK-VIGGELTSIPGISDAIEETIRDAIEDSITWPVRKIIPI 250
Cdd:cd21675  115 LSGTLRLNIKP-----PPSNRLWYGFREMPKLELEIEpVVGERQVTLPHVTNWIEKKLKEEIKESLVLPNMDDFPF 185

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: 55.67 E-value: 2.81e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 260 LKPVGKLDVKVVQAKDLANKDMIGKSDPYA-IVFIRPLP-DRTKKTKTISNSLNPIWNEHFEFIV--EDVSTQHLTVRVF 335
Cdd:cd08410   10 LPSAGRLNVDIIRAKQLLQTDMSQGSDPFVkIQLVHGLKlIKTKKTSCMRGTIDPFYNESFSFKVpqEELENVSLVFTVY 89

                         90
                 ....*....|..
gi 186522051 336 DDEGVGSSQLIG 347
Cdd:cd08410   90 GHNVKSSNDFIG 101

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: 54.18 E-value: 5.56e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGK-ADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVVEDalHDLLT----LEVWD 514
Cdd:cd08521   14 GSLEVHIKECRNLAYADEKKKrSNPYVKVYLlpdKSKQSKRKTSVKKNTTNPVFNETLKYHISK--SQLETrtlqLSVWH 91

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 515 HDKFG-KDKIGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08521   92 HDRFGrNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 53.80 E-value: 8.20e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKDMIGKSDPYaiVFIRpLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQLIG 347
Cdd:cd08376    4 IVLVEGKNLPPMDDNGLSDPY--VKFR-LGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDEFIG 80

                         90       100
                 ....*....|....*....|.
gi 186522051 348 AAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08376   81 RCEIDLSALPREQTHSLELEL 101

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: 54.09 E-value: 8.34e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 452 AEDLPAVDFMGKADAFV-VITLKKSETkskTRVVPDSLNPVWNQTFDF---VVEDALHDLLT------LEVWDHDKFGKD 521
Cdd:cd04017   10 ARDLLAADKSGLSDPFArVSFLNQSQE---TEVIKETLSPTWDQTLIFdevELYGSPEEIAQnpplvvVELFDQDSVGKD 86


                 ....*..
gi 186522051 522 K-IGRVI 527
Cdd:cd04017   87 EfLGRSV 93

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: 54.17 E-value: 8.99e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITLKKSE-----TKSKTRVVPDSLNPVWNQTFDFVV--EDALHD--LLTLEVWD 514
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSSDPFVKVELLPRHlfpdvPTPKTQVKKKTLFPLFDESFEFNVppEQCSVEgaLLLFTVKD 96

                         90       100
                 ....*....|....*....|.
gi 186522051 515 HDKFGKDK-IGRVIMTLTRVM 534
Cdd:cd04009   97 YDLLGSNDfEGEAFLPLNDIP 117

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: 53.03 E-value: 1.04e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKA----DAFVVITLKKSetKSKTRVVPDSLNPVWNQTFDF-VVEDALHDLLTLEVWDHDK 517
Cdd:cd04039    1 GVVFMEIKSITDLPPLKNMTRTgfdmDPFVIISFGRR--VFRTSWRRHTLNPVFNERLAFeVYPHEKNFDIQFKVLDKDK 78

                         90       100
                 ....*....|....*....|
gi 186522051 518 F-GKDKIGRVIMTLTRVMLE 536
Cdd:cd04039   79 FsFNDYVATGSLSVQELLNA 98

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: 53.05 E-value: 1.43e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKdLANKDMIGKSDPYAIVFIRPLPdrTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLtvRVFDDEGVGSSQ 344
Cdd:cd04021    3 QLQITVESAK-LKSNSKSFKPDPYVEVTVDGQP--PKKTEVSKKTSNPKWNEHFTVLVTPQSTLEF--KVWSHHTLKADV 77

                         90
                 ....*....|..
gi 186522051 345 LIGAAQVPLNEL 356
Cdd:cd04021   78 LLGEASLDLSDI 89

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: 52.22 E-value: 2.07e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 462 GKADAFVVITLKKSETKsKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDKIGRVIMTLTRVMLEGEF-Q 540
Cdd:cd04052   11 GLLSPYAELYLNGKLVY-TTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATSVgQ 89

                         90       100
                 ....*....|....*....|.
gi 186522051 541 EWFELDGAKSGKLCVHLKWTP 561
Cdd:cd04052   90 QWFPLSGNGQGRIRISALWKP 110

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 53.20 E-value: 2.08e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLE--VWDHDKFG 519
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLyygKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELEDISVEflVLDSDRVT 96


                 ....*..
gi 186522051 520 KDK-IGR 525
Cdd:cd08404   97 KNEvIGR 103

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: 52.24 E-value: 2.81e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDfMGKADAF----VVITLKKSETKSKTRVVPdslNPVWNQTFDF--VVEDALHDL-LTLEVWDHDK 517
Cdd:cd08389   18 LTVTVIRAQDIPTKD-RGGASSWqvhlVLLPSKKQRAKTKVQRGP---NPVFNETFTFsrVEPEELNNMaLRFRLYGVER 93

                         90       100       110
                 ....*....|....*....|....*....|
gi 186522051 518 FGKDK-IGRVIMTLTRVMLEGEFQEWFELD 546
Cdd:cd08389   94 MRKERlIGEKVVPLSQLNLEGETTVWLTLE 123

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: 52.13 E-value: 3.23e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPdrTKKTKTISNSLNPIWNEhfEFIVEDVSTQH-LTVRVFDDEGVGSSQ 344
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNEV--IIRTATVWKTLNPFWGE--EYTVHLPPGFHtVSFYVLDEDTLSRDD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 186522051 345 LIGAAQVPlNELVPGKVK--DIWLKLVkdlEIQRDTKNRGQVQLEL 388
Cdd:cd04054   78 VIGKVSLT-REVISAHPRgiDGWMNLT---EVDPDEEVQGEIHLEL 119

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: 52.19 E-value: 3.37e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 271 VQAKDLANKDMIGKSDPYAIVFIRPlPDRTK-----KTKTISNSLNPIWNE--HFEFIVEDVstQHLTVRVFDDEG---- 339
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKT-GGSGQwveigRTEVIKNNLNPDFVTtfTVDYYFEEV--QKLRFEVYDVDSkskd 83

                         90
                 ....*....|....*...
gi 186522051 340 VGSSQLIGAAQVPLNELV 357
Cdd:cd04048   84 LSDHDFLGEAECTLGEIV 101

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: 52.29 E-value: 4.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRTKKTKTisNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDEGVGSSQ 344
Cdd:cd04019    1 YLRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQT--RNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDE 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 186522051 345 LIGAAQVPLNE----LVPGKVKDIWLKLVKDLEIQRDTKNR 381
Cdd:cd04019   79 PLGRAVIPLNDierrVDDRPVPSRWFSLERPGGAMEQKKKR 119

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: 51.74 E-value: 5.78e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQT--FDFVVEDALHDLLTLEVWDHDK 517
Cdd:cd08403   14 GRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKNTLNPTYNEAlvFDVPPENVDNVSLIIAVVDYDR 93


                 ....*.
gi 186522051 518 FGKDKI 523
Cdd:cd08403   94 VGHNEL 99

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: 52.31 E-value: 5.93e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLP--------AVDFMGKADAFVVITLKKSETKS---------------------KTRVVPDSLNPVWN 493
Cdd:cd04015    7 GTLDVTIYEADNLPnmdmfsekLRRFFSKLVGCSEPTLKRPSSHRhvgkitsdpyatvdlagarvaRTRVIENSENPVWN 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 186522051 494 QTFD-FVVEDALHdlLTLEVWDHDKFGKDKIGRVIMTLTRVMLEGEFQEWFELDGAkSGKLCVHlkwTPRLKLR 566
Cdd:cd04015   87 ESFHiYCAHYASH--VEFTVKDNDVVGAQLIGRAYIPVEDLLSGEPVEGWLPILDS-NGKPPKP---GAKIRVS 154

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: 51.21 E-value: 6.63e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKdmIGKSDPYAIVFIRPLPDRTKkTKTISNSLNPIWNEHFEFiveDVS--TQHLTVRVFDDEGVGSSQL 345
Cdd:cd08678    3 VKNIKANGLSEA--AGSSNPYCVLEMDEPPQKYQ-SSTQKNTSNPFWDEHFLF---ELSpnSKELLFEVYDNGKKSDSKF 76

                         90
                 ....*....|.
gi 186522051 346 IGAAQVPLNEL 356
Cdd:cd08678   77 LGLAIVPFDEL 87

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: 50.68 E-value: 7.33e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 186522051 280 DMIGKSDPYAIVFIRPlpDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFDDeGVGSSQLIGAAQVPLNELV 357
Cdd:cd04052    8 SKTGLLSPYAELYLNG--KLVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDD-RDRHDPVLGSVSISLNDLI 82

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: 51.20 E-value: 7.72e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 442 RGVLSVTVVAAEDLPAVDF-MGKADAFVVIT-LKKSETKSKTRVVPDSLNPVWNQTFDF--VVEDALHDL-LTLEVWDHD 516
Cdd:cd08388   15 KKALLVNIIECRDLPAMDEqSGTSDPYVKLQlLPEKEHKVKTRVLRKTRNPVYDETFTFygIPYNQLQDLsLHFAVLSFD 94

                         90       100       110
                 ....*....|....*....|....*....|....
gi 186522051 517 KFGKDK-IGRVIMTLTRVML--EGEFQEWFELDG 547
Cdd:cd08388   95 RYSRDDvIGEVVCPLAGADLlnEGELLVSREIQP 128

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 51.94 E-value: 7.86e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 250 ILPGDYSDLELKPV--GKLDVKVVQAKDLANKDMIGKSDPYAIVFIrpLPDRTK----KTKTISNSLNPIWNEHFEF--- 320
Cdd:cd04020   11 VPPESEGALKSKKPstGELHVWVKEAKNLPALKSGGTSDSFVKCYL--LPDKSKkskqKTPVVKKSVNPVWNHTFVYdgv 88

                         90       100
                 ....*....|....*....|....*..
gi 186522051 321 IVEDVSTQHLTVRVFDDEGVGSSQLIG 347
Cdd:cd04020   89 SPEDLSQACLELTVWDHDKLSSNDFLG 115

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: 50.34 E-value: 1.12e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKDMigkSDPYAIVFIrplpDRTK--KTKTISnSLNPIWNEHFEF--IVEDVSTQHLTVRVFDDEGVG 341
Cdd:cd08383    2 LRLRILEAKNLPSKGT---RDPYCTVSL----DQVEvaRTKTVE-KLNPFWGEEFVFddPPPDVTFFTLSFYNKDKRSKD 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 186522051 342 SSQLIGaaQVPLNELVPGKVKDIWLKLVkdlEIQRDTKNRGQVQLELLY 390
Cdd:cd08383   74 RDIVIG--KVALSKLDLGQGKDEWFPLT---PVDPDSEVQGSVRLRARY 117

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: 50.00 E-value: 1.75e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFmgkaDAFVVITLkkSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDKIG 524
Cdd:cd08378    2 LYVRVVKARGLPANSN----DPVVEVKL--GNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLG 75


                 ..
gi 186522051 525 RV 526
Cdd:cd08378   76 GV 77

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: 50.12 E-value: 1.76e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDM-IGKSDPYAIVFIrpLPDRT----KKTKTISNSLNPIWNEHFEFIVE--DVSTQHLTVRVFD 336
Cdd:cd08393   15 RELHVHVIQCQDLAAADPkKQRSDPYVKTYL--LPDKSnrgkRKTSVKKKTLNPVFNETLRYKVEreELPTRVLNLSVWH 92

                         90       100       110
                 ....*....|....*....|....*....|..
gi 186522051 337 DEGVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08393   93 RDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

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: 49.58 E-value: 2.78e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKKSET-KSKTrvVPDSLNPVWNQTFDFVVEDaLHDLLTLEVWDHDKFGKDK- 522
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTVyKSKT--IYKNLNPVWDEKFTLPIED-VTQPLYIKVFDYDRGLTDDf 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 186522051 523 IGRVIMTLTRvmLEGEFQEWFELD------GAKSGKLCVHLKWTP 561
Cdd:cd04042   79 MGSAFVDLST--LELNKPTEVKLKledpnsDEDLGYISLVVTLTP 121

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

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 49.58 E-value: 2.85e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDL-----ANKDMIGKS-----DPYAIVFIrplpDRTK--KTKTISNSLNPIWNEhfEFIVEDVSTQHLT 331
Cdd:cd04014    4 GTLKIKICEAVDLkptdwSTRHAVPKKgsqllDPYVSIDV----DDTHigKTSTKPKTNSPVWNE--EFTTEVHNGRNLE 77

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 186522051 332 VRVFDDEGVGSSQLIGAAQVPLNELV--PGKVKDIWLKL 368
Cdd:cd04014   78 LTVFHDAAIGPDDFVANCTISFEDLIqrGSGSFDLWVDL 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: 49.32 E-value: 3.20e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSK-TRVVPDSLNPVWNQTFDF-VVEDALHDlLTLEV--WDHDKF 518
Cdd:cd08387   16 GILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKqSKIHKKTLNPEFDESFVFeVPPQELPK-RTLEVllYDFDQF 94

                         90       100
                 ....*....|....*....|....*
gi 186522051 519 GKDK-IGRVIMTLTRVMLEGEFQEW 542
Cdd:cd08387   95 SRDEcIGVVELPLAEVDLSEKLDLW 119

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: 49.97 E-value: 3.38e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKKSETKSKTRVVPdSLNPVWNQTFDFVVEDALHDLLTLEVWDHDKFGKDK-I 523
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTR-NGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEpL 80

                         90
                 ....*....|.
gi 186522051 524 GRVIMTLTRVM 534
Cdd:cd04019   81 GRAVIPLNDIE 91

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

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 49.37 E-value: 3.56e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKDMIGKSDPYAIVFIrplpDRTK-KTKTISNSLNPIWNEHFEF----IVEDVSTQH-LTVRVFDDEGVG 341
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQL----GKEKySTSVKEKTTSPVWKEECSFelpgLLSGNGNRAtLQLTVMHRNLLG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 186522051 342 SSQLIGAAQVPLNEL--VPGKVKDIWLKLvkDLEIQRDTKNRGQVQL 386
Cdd:cd08682   79 LDKFLGQVSIPLNDLdeDKGRRRTRWFKL--ESKPGKDDKERGEIEV 123

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: 49.50 E-value: 3.60e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAEDLPAVDFMGKADAFVVITL----KKSETKsKTRVVPDSLNPVWNQTFDF-VVEDALHDL-LTLEVWDHD 516
Cdd:cd08410   14 GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLvhglKLIKTK-KTSCMRGTIDPFYNESFSFkVPQEELENVsLVFTVYGHN 92

                         90
                 ....*....|...
gi 186522051 517 -KFGKDKIGRVIM 528
Cdd:cd08410   93 vKSSNDFIGRIVI 105

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: 49.27 E-value: 3.65e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDFMGKADAFVVITLKKSE-----TKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLtLEVWDHDKF 518
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDgngeiDSVQTKTIKKTLNPKWNEEFFFRVNPREHRLL-FEVFDENRL 79


                 ...
gi 186522051 519 GKD 521
Cdd:cd04033   80 TRD 82

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: 49.10 E-value: 3.80e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 450 VAAEDLPAVDFMGKADAFVVITLKKSETKS-----KTRVVPDSLNPVWNQTF--DFVVEDALHdlLTLEVWDHDKFGK-- 520
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQwveigRTEVIKNNLNPDFVTTFtvDYYFEEVQK--LRFEVYDVDSKSKdl 84

                         90
                 ....*....|...
gi 186522051 521 ---DKIGRVIMTL 530
Cdd:cd04048   85 sdhDFLGEAECTL 97

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: 48.88 E-value: 5.93e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRplPDRTKKTKTISN----SLNPIWNEHFEFIV--EDVSTQHLTVRVFDD 337
Cdd:cd08384   13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLK--PDAGKKSKHKTQvkkkTLNPEFNEEFFYDIkhSDLAKKTLEITVWDK 90

                         90
                 ....*....|....*..
gi 186522051 338 EGVGSSQLIGAAQVPLN 354
Cdd:cd08384   91 DIGKSNDYIGGLQLGIN 107

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

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 47.83 E-value: 1.02e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 446 SVTVVAAEDLPAVDFMGKADAFVVITLKKSetKSKTRVVPDSLNPVWNQTFDF-----VVEDALHDLLTLEVWDHDKFGK 520
Cdd:cd08682    2 QVTVLQARGLLCKGKSGTNDAYVIIQLGKE--KYSTSVKEKTTSPVWKEECSFelpglLSGNGNRATLQLTVMHRNLLGL 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 186522051 521 DK-IGRVIMTLTRVML--EGEFQEWFELDGAKSGK 552
Cdd:cd08682   80 DKfLGQVSIPLNDLDEdkGRRRTRWFKLESKPGKD 114

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: 47.75 E-value: 1.70e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDfMGKADAFVVITL---KKSETKsKTRVVPDSLNPVWNQTFDFVV---------------EDALHD 506
Cdd:cd08675    1 LSVRVLECRDLALKS-NGTCDPFARVTLnysSKTDTK-RTKVKKKTNNPRFDEAFYFELtigfsyekksfkveeEDLEKS 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 186522051 507 LLTLEVWDHDKFGKDK-IGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08675   79 ELRVELWHASMVSGDDfLGEVRIPLQGLQQAGSHQAWYFL 118

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: 46.87 E-value: 2.12e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 444 VLSVTVVAAEDLPAVDF-MGKADAFVVITLKKSETKSK-TRVVPDSLNPVWNQTFDFVV--EDALHDLLTLEVWDHDKFG 519
Cdd:cd08390   15 QLTVSLIKARNLPPRTKdVAHCDPFVKVCLLPDERRSLqSKVKRKTQNPNFDETFVFQVsfKELQRRTLRLSVYDVDRFS 94

                         90       100
                 ....*....|....*....|....*...
gi 186522051 520 K-DKIGRVIMTLTRVMLEGEFQEWFELD 546
Cdd:cd08390   95 RhCIIGHVLFPLKDLDLVKGGVVWRDLE 122

cellulose synthase-interactive protein; Provisional

Pssm-ID: 215629 [Multi-domain] Cd Length: 2102 Bit Score: 50.87 E-value: 2.51e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  443 GVLSVTVVAAEDLPAVdfMGKADAFVVITLKKSETKsKTRVVPDSLNPVWNQTFDFVVEDA-----LHdlltLEVWDHDK 517
Cdd:PLN03200 1980 GSLTVTIKRGNNLKQS--MGNTNAFCKLTLGNGPPR-QTKVVSHSSSPEWKEGFTWAFDSPpkgqkLH----ISCKSKNT 2052

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 186522051  518 FGKDKIGRVIMTLTRVMLEGEFQEWFEL--DGAKSGK---LCVHLKWTPR 562
Cdd:PLN03200 2053 FGKSSLGKVTIQIDRVVMEGTYSGEYSLnpESNKDGSsrtLEIEFQWSNR 2102

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in maintenance of mitochondrial morphology protein 1 (Mmm1) and similar proteins; Maintenance of mitochondrial morphology protein 1 (Mmm1), also called mitochondrial outer membrane protein Mmm1, or yeast mitochondrial escape protein 6 (YME6), is a mitochondrial outer membrane protein essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids. It is a component of the ER-mitochondrion encounter structure/ mitochondrial distribution and morphology (ERMES/Mdm) complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. Components of this complex are involved in the control of mitochondrial shape and protein biogenesis, and function in nonvesicular lipid trafficking between the ER and mitochondria. The Mdm12-Mmm1 subcomplex functions in the major beta-barrel assembly pathway that is responsible for biogenesis of all outer membrane beta-barrel proteins, and acts in a late step after the SAM complex. The Mdm10-Mdm12-Mmm1 subcomplex further acts in the TOM40-specific pathway after the action of the Mdm12-Mmm1 complex. This model corresponds to the SMP domain of Mmm1, which may be implicated in lipid transport.

Pssm-ID: 439227 Cd Length: 216 Bit Score: 47.90 E-value: 4.66e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  71 LNWLNLELEKIW-PYVNEAA-SELIKSSVEPVL-EQYTPAMLASLKFSKFTLGTVAPQFTGVSILESESGPNgitMELEM 147
Cdd:cd21671   21 LDWLNVLLAQILaQYRSDAEgDDNLLRKLEEALnGERKPSFLDPIKVTDLDLGDDFPRFSNARIRPSDDSGG---LRAEI 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 148 Q--WDGNPKIVLDVKTLLGV------SLPIE--VKNIGFTGVFRLifkplvdEFPCFGA----LSYSLREKKGLDFTLK- 212
Cdd:cd21671   98 DidYSDTISLGIDTSLLLNYpkprfaSLPVSlsVSLVRFSGTLTI-------ELPSPSSpgptLSFSLLPDFRLDLKVSs 170

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 186522051 213 VIGGE--LTSIPGISDAIEETIRDAIEDSITWPVRKIIPiLPG 253
Cdd:cd21671  171 LIGSRakLQDVPKLHSLIESRLRRWFADRCVEPNFWKIV-LPS 212

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: 47.60 E-value: 6.80e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051  73 WLNLELEKIWPYVNeaaSELIKSSV---EPVLEQYTPAMLASLKFSKFTLGTVAPQFTGVSIL----------------- 132
Cdd:cd21676    5 WLNSLLAALWPLIN---PDLFTPVIdllEDVMQASLPSFVHSVRVTDLGQGSQPLRILSMRILpdgewdesvsegghske 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 133 ---------ESESGPNGITMELEMQWDGNPK----------------IVLDVKTLLGVSLPIEVKNIGFTGV--FRLIFK 185
Cdd:cd21676   82 eeedaddeeEEEEGGDYVNLEVAFAYRARPSgkslsskaknahllayFGLGLKGLGGVPIPVWVEVLGLVGTvrLRLQLT 161

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 186522051 186 PlvdEFPCFGALSYSLREKKGLDFT---LKVIGGELTSIPGISDAIEETIRDAIED 238
Cdd:cd21676  162 P---DPPFVKTVTFSFMGLPKVDISarpLSKGAFNVMNLPLISSFVNSSIDAVAAE 214

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: 44.73 E-value: 1.18e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDF-MGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVVE--DALHDLLTLEVWDHDKF 518
Cdd:cd08393   17 LHVHVIQCQDLAAADPkKQRSDPYVKTYLlpdKSNRGKRKTSVKKKTLNPVFNETLRYKVEreELPTRVLNLSVWHRDSL 96


                 ...
gi 186522051 519 GKD 521
Cdd:cd08393   97 GRN 99

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: 44.74 E-value: 1.52e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 463 KADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLTLE--VWDHDKFGKDK-IGRVIMTLTRVMLE 536
Cdd:cd04029   36 RSNPYVKTYLlpdKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQLETRTLQlsVWHYDRFGRNTfLGEVEIPLDSWNFD 115


                 ....*....
gi 186522051 537 GEFQEWFEL 545
Cdd:cd04029  116 SQHEECLPL 124

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176041 [Multi-domain] Cd Length: 120 Bit Score: 43.92 E-value: 2.03e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLaNKDMIGKSDPYA-IVFIRP-LPDRTKK--TKTISNSLNPIWNEHFEFIV---EDVSTQHLTVRVFDD 337
Cdd:cd08395    1 KVTVKVVAANDL-KWQTTGMFRPFVeVNLIGPhLSDKKRKfaTKSKNNNWSPKYNETFQFILgneDDPESYELHICVKDY 79

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 186522051 338 EGVGSSQLIGAAQVPLNELVPGKVKDIWLKLVKDLEI 374
Cdd:cd08395   80 CFARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHM 116

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: 2.32e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 186522051 445 LSVTVVAAEdLPAVDFMGKADAFVVITLKKSETKsKTRVVPDSLNPVWNQTFDFVVEDalHDLLTLEVWDHDKFGKD 521
Cdd:cd04021    4 LQITVESAK-LKSNSKSFKPDPYVEVTVDGQPPK-KTEVSKKTSNPKWNEHFTVLVTP--QSTLEFKVWSHHTLKAD 76

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: 43.96 E-value: 2.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDMIGKSDPYAIVFIRPLPDRT--KKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVR--VFDDEG 339
Cdd:cd08404   15 NRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRIskKKTHVKKCTLNPVFNESFVFDIPSEELEDISVEflVLDSDR 94


                 ....*...
gi 186522051 340 VGSSQLIG 347
Cdd:cd08404   95 VTKNEVIG 102

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: 43.38 E-value: 3.71e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDMiGKSDPYAiVFIRPLPDRTKKTKT-ISNSLNPIWNEHFEFI---VEDVSTQHLTVRVFDDEGV 340
Cdd:cd08389   17 KLTVTVIRAQDIPTKDR-GGASSWQ-VHLVLLPSKKQRAKTkVQRGPNPVFNETFTFSrvePEELNNMALRFRLYGVERM 94

                         90       100
                 ....*....|....*....|....*...
gi 186522051 341 GSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08389   95 RKERLIGEKVVPLSQLNLEGETTVWLTL 122

Phospholipase D delta

Pssm-ID: 178585 [Multi-domain] Cd Length: 868 Bit Score: 46.63 E-value: 4.42e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 252 PGDYSDLELKPVGKLDvkvvqAKDLANKDMIGKSDPYAIVFIrplPDRT-KKTKTISNSLNPIWNEHFefiveDVSTQH- 329
Cdd:PLN03008  49 PTDTDDVDPRDKGEFG-----DKNIRSHRKVITSDPYVTVVV---PQATlARTRVLKNSQEPLWDEKF-----NISIAHp 115

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 186522051 330 ---LTVRVFDDEGVGSsQLIGAAQVPLNELVPGKVKDIWLKLV 369
Cdd:PLN03008 116 fayLEFQVKDDDVFGA-QIIGTAKIPVRDIASGERISGWFPVL 157

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: 43.16 E-value: 4.46e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 276 LANKDMIGKSDPYAIVFIRPLPDRTKktkTISNSLNPIWNEHFEFIVEDVSTQhLTVRVFD------DEGVGSSQLIGAA 349
Cdd:cd08379   15 LRAKDGRGSTDAYCVAKYGPKWVRTR---TVEDSSNPRWNEQYTWPVYDPCTV-LTVGVFDnsqshwKEAVQPDVLIGKV 90

                         90
                 ....*....|..
gi 186522051 350 QVPLNELVPGKV 361
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: 43.09 E-value: 4.78e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 263 VGKLDVKVVQAKDLANKDMIgKSDPYaiVFIRpLPDRTKKTKTISN-SLNPIWNEHFE-FIVEDVStqHLTVRVFDDEGV 340
Cdd:cd04016    1 VGRLSITVVQAKLVKNYGLT-RMDPY--CRIR-VGHAVYETPTAYNgAKNPRWNKTIQcTLPEGVD--SIYIEIFDERAF 74

                         90       100
                 ....*....|....*....|....*....
gi 186522051 341 GSSQLIGAAQVPLNE-LVPGKVKDIWLKL 368
Cdd:cd04016   75 TMDERIAWTHITIPEsVFNGETLDDWYSL 103

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: 42.81 E-value: 5.09e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 302 KTKTISNSLNPIWNEHFEFIVEdVSTQHLTVRVFDDEGVGSSQLIGAAQVPLNELVPGKVKDIWLKLvkdLEIQRDTKNR 381
Cdd:cd08401   37 RTKTVEKSLCPFFGEDFYFEIP-RTFRHLSFYIYDRDVLRRDSVIGKVAIKKEDLHKYYGKDTWFPL---QPVDADSEVQ 112


                 ....*..
gi 186522051 382 GQVQLEL 388
Cdd:cd08401  113 GKVHLEL 119

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

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 43.15 E-value: 7.44e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 265 KLDVKVVQAKDLANKDmiGKSDPYAIVFIRPLPDR--TKKTKTISNSLNPIWNEHFEFIV---------------EDVST 327
Cdd:cd04010    1 KLSVRVIECSDLALKN--GTCDPYASVTLIYSNKKqdTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfempeEDAEK 78

                         90       100
                 ....*....|....*....|....*....
gi 186522051 328 QHLTVRVFDDEGVGSSQLIGAAQVPLNEL 356
Cdd:cd04010   79 LELRVDLWHASMGGGDVFLGEVRIPLRGL 107

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: 42.25 E-value: 8.66e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFmgkADAFVVITLKKSETkSKTRVVPDsLNPVWNQtfDFVVEDALHDL----LTLEVWDHDKFGK 520
Cdd:cd08383    2 LRLRILEAKNLPSKGT---RDPYCTVSLDQVEV-ARTKTVEK-LNPFWGE--EFVFDDPPPDVtfftLSFYNKDKRSKDR 74

                         90       100
                 ....*....|....*....|....*.
gi 186522051 521 DK-IGRVimTLTRVMLEGEFQEWFEL 545
Cdd:cd08383   75 DIvIGKV--ALSKLDLGQGKDEWFPL 98

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: 41.79 E-value: 1.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANkdmiGKSDPYAIVFIRplpDRTKKTKTISNSLNPIWNEHFEFIV----EDVSTQHLTVRVFDDEGVGSS 343
Cdd:cd04011    8 VRVIEARQLVG----GNIDPVVKVEVG---GQKKYTSVKKGTNCPFYNEYFFFNFhespDELFDKIIKISVYDSRSLRSD 80


                 ....*...
gi 186522051 344 QLIGAAQV 351
Cdd:cd04011   81 TLIGSFKL 88

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: 40.71 E-value: 2.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 264 GKLDVKVVQAKDLANKDM-IGKSDPYAIVFIRPLPDRTKKTKTISNSLNPIWNE-HFEFIV-EDVSTQ-HLTVRVFDDEG 339
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEEtWFVLVTpDEVKAGeRLSCRLWDSDR 80

                         90
                 ....*....|....*..
gi 186522051 340 VGSSQLIGAAQVPLNEL 356
Cdd:cd04041   81 FTADDRLGRVEIDLKEL 97

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: 40.37 E-value: 3.02e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKD-MIGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEH-FEFIVEDVSTQH--LTVRVFDDEGVG 341
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEV---KFGSTTYKTDVVKKSLNPVWNSEwFRFEVDDEELQDepLQIRVMDHDTYS 77

                         90
                 ....*....|....*.
gi 186522051 342 SSQLIGAAQVPLNELV 357
Cdd:cd08688   78 ANDAIGKVYIDLNPLL 93

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: 40.89 E-value: 3.06e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 262 PVGKLDVKVVQAKDLANKDMIGK-SDPYAIVFIRPLPDRTKKTKTI--SNSLNPIWNEHFEFIVED--VSTQHLTVRVFD 336
Cdd:cd04029   13 KTQSLNVHVKECRNLAYGDEAKKrSNPYVKTYLLPDKSRQSKRKTSikRNTTNPVYNETLKYSISHsqLETRTLQLSVWH 92

                         90
                 ....*....|....*...
gi 186522051 337 DEGVGSSQLIGAAQVPLN 354
Cdd:cd04029   93 YDRFGRNTFLGEVEIPLD 110

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: 40.13 E-value: 4.13e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 436 KKDVIVRG-VLSVTVVAAEDLPAVDfMGKADAFVVITL---KKSETKSKTRVVPDSLNPVWNQTFDF-VVEDALHDLLTL 510
Cdd:cd08685    4 KLSIEGQNrKLTLHVLEAKGLRSTN-SGTCNSYVKISLspdKEVRFRQKTSTVPDSANPLFHETFSFdVNERDYQKRLLV 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 186522051 511 EVWDHDKFGKDK--IGRVIMTLTRVMLEGEFQEWFEL 545
Cdd:cd08685   83 TVWNKLSKSRDSglLGCMSFGVKSIVNQKEISGWYYL 119

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: 39.81 E-value: 5.59e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFMGKADAFVVITLKkSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDlLTLEVWDHDKFGKDK-I 523
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVD-NEVIIRTATVWKTLNPFWGEEYTVHLPPGFHT-VSFYVLDEDTLSRDDvI 79


                 ....*.
gi 186522051 524 GRVIMT 529
Cdd:cd04054   80 GKVSLT 85

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: 39.54 E-value: 5.65e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDL--------ANKDMigksDPYAIV-FIRplpdRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTV-RVFDD 337
Cdd:cd04039    5 MEIKSITDLpplknmtrTGFDM----DPFVIIsFGR----RVFRTSWRRHTLNPVFNERLAFEVYPHEKNFDIQfKVLDK 76

                         90       100
                 ....*....|....*....|....*.
gi 186522051 338 EGVGSSQLIGAAQVPLNELVPGKVKD 363
Cdd:cd04039   77 DKFSFNDYVATGSLSVQELLNAAPQP 102

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: 39.99 E-value: 5.74e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 186522051 266 LDVKVVQAKDLANkdmiGKSDPYAIVfirPLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQHLTVRVFD 336
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVVEV---KLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWD 65

phospholipase D alpha

Pssm-ID: 165912 [Multi-domain] Cd Length: 808 Bit Score: 42.24 E-value: 8.52e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 283 GKSDPYAIVFIRPLpdRTKKTKTISN-SLNPIWNEHFEFIVEDVSTqHLTVRVFDDEGVGSSqLIGAAQVPLNELVPGKV 361
Cdd:PLN02270  45 GESQLYATIDLEKA--RVGRTRKIENePKNPRWYESFHIYCAHMAS-NIIFTVKDDNPIGAT-LIGRAYIPVEEILDGEE 120


                 ....*...
gi 186522051 362 KDIWLKLV 369
Cdd:PLN02270 121 VDRWVEIL 128

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: 39.18 E-value: 1.11e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 186522051 268 VKVVQAKDLANKDMIGKSDPYAIVFIRplpDRTKKTKTISNSLNPIWNEHFEF 320
Cdd:cd04046    7 VHVHSAEGLSKQDSGGGADPYVIIKCE---GESVRSPVQKDTLSPEFDTQAIF 56

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: 39.17 E-value: 1.20e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186522051 263 VGKLDVKVVQAKDLaNKDMIGKSDPYAIVFirpLPDRTKKTKTISNSLNPIWNEHFEFIVEDVSTQH-LTVRVFD 336
Cdd:cd04032   27 LATLTVTVLRATGL-WGDYFTSTDGYVKVF---FGGQEKRTEVIWNNNNPRWNATFDFGSVELSPGGkLRFEVWD 97

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: 38.89 E-value: 1.32e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 462 GKADAFVVITLKKSETKSKTRVVPDSLNPVWNQTFDFVVEDALHDLLtLEVWDHDKFGKDK-IGRVIMTLTRVMLEGEFQ 540
Cdd:cd08678   16 GSSNPYCVLEMDEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKELL-FEVYDNGKKSDSKfLGLAIVPFDELRKNPSGR 94

                         90
                 ....*....|..
gi 186522051 541 EWFELDGAKSGK 552
Cdd:cd08678   95 QIFPLQGRPYEG 106

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: 38.89 E-value: 1.57e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVDFmgkADAFVVITLKKSET-KSKTRVVPdslNPVWNQtfDFVVEDALHDLLTLEVWDHDKFGKDK- 522
Cdd:cd08400    6 LQLNVLEAHKLPVKHV---PHPYCVISLNEVKVaRTKVREGP---NPVWSE--EFVFDDLPPDVNSFTISLSNKAKRSKd 77

                         90       100
                 ....*....|....*....|....*...
gi 186522051 523 --IGRVIMTLTRVMLEGEFQEWFELDGA 548
Cdd:cd08400   78 seIAEVTVQLSKLQNGQETDEWYPLSSA 105

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 39.15 E-value: 1.60e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 445 LSVTVVAAEDLPAVD----------FMGKA----DAFVVITLkkSETKSKTRVVPDSLNPVWNQTFDFVVE-DALHDLLT 509
Cdd:cd04018    2 FIFKIYRAEDLPQMDsgimanvkkaFLGEKkelvDPYVEVSF--AGQKVKTSVKKNSYNPEWNEQIVFPEMfPPLCERIK 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 186522051 510 LEVWDHDKFGKDK-IGRVIMTLTRVMLEGE 538
Cdd:cd04018   80 IQIRDWDRVGNDDvIGTHFIDLSKISNSGD 109

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: 38.57 E-value: 1.74e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 186522051 465 DAFVVITLKKSETkSKTRVVPDSLNPVWNQTFDFVVEDALHdLLTLEVWDHDKFGKDK-IGRV 526
Cdd:cd08401   23 DCYCTVNLDQEEV-FRTKTVEKSLCPFFGEDFYFEIPRTFR-HLSFYIYDRDVLRRDSvIGKV 83

Phospholipase D delta

Pssm-ID: 178585 [Multi-domain] Cd Length: 868 Bit Score: 40.85 E-value: 2.38e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 464 ADAFVVITLKKSeTKSKTRVVPDSLNPVWNQTFDFVVEDALHdLLTLEVWDHDKFGKDKIGRVIMTLTRVMLEGEFQEWF 543
Cdd:PLN03008  77 SDPYVTVVVPQA-TLARTRVLKNSQEPLWDEKFNISIAHPFA-YLEFQVKDDDVFGAQIIGTAKIPVRDIASGERISGWF 154

                         90       100
                 ....*....|....*....|....*
gi 186522051 544 ELDGAkSGK-------LCVHLKWTP 561
Cdd:PLN03008 155 PVLGA-SGKppkaetaIFIDMKFTP 178

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 38.00 E-value: 3.87e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 268 VKVVQAKDLANKD--MIGKSDPYAIVFIRPLPD---------RTKKTKTISNSLNPIWNEHFEFIVEDVS-TQHLTVRVF 335
Cdd:cd04018    4 FKIYRAEDLPQMDsgIMANVKKAFLGEKKELVDpyvevsfagQKVKTSVKKNSYNPEWNEQIVFPEMFPPlCERIKIQIR 83

                         90
                 ....*....|..
gi 186522051 336 DDEGVGSSQLIG 347
Cdd:cd04018   84 DWDRVGNDDVIG 95

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

Pssm-ID: 176073 [Multi-domain] Cd Length: 137 Bit Score: 37.77 E-value: 4.04e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 186522051 272 QAKDLaNKDMIGKSDPYAIVFIRPLPDRT----------KKTKTISNSLNPIW-NEHFEFIV 322
Cdd:cd08691    9 QARNL-KKGMFFNPDPYVKISIQPGKRHIfpalphhgqeCRTSIVENTINPVWhREQFVFVG 69

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: 37.72 E-value: 4.35e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 266 LDVKVVQAKDLANKD-MIGKSDPYaiVFIRPLPDRTKKTKT--ISNSLNPIWNEHFEFI------VEDVSTqHLTVRVFD 336
Cdd:cd08388   18 LLVNIIECRDLPAMDeQSGTSDPY--VKLQLLPEKEHKVKTrvLRKTRNPVYDETFTFYgipynqLQDLSL-HFAVLSFD 94

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: 37.35 E-value: 5.64e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 261 KPVGKLDVKVVQAKDLANKDMigkSDPYAIVFIRPLpdRTKKTKtISNSLNPIWNEhfEFIVEDVSTQ--HLTVRVFDDE 338
Cdd:cd08400    1 RQVRSLQLNVLEAHKLPVKHV---PHPYCVISLNEV--KVARTK-VREGPNPVWSE--EFVFDDLPPDvnSFTISLSNKA 72

                         90       100       110
                 ....*....|....*....|....*....|
gi 186522051 339 GVGSSQLIGAAQVPLNELVPGKVKDIWLKL 368
Cdd:cd08400   73 KRSKDSEIAEVTVQLSKLQNGQETDEWYPL 102

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: 37.39 E-value: 5.65e-03

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186522051 443 GVLSVTVVAAedLPAVDFMGKADAFVVItlKKSETKSKTRVVPDSLNPVWNQTFDFVVEDALhDLLTLEVWDHDKFGKDK 522
Cdd:cd08379    5 GILGAQGLDV--LRAKDGRGSTDAYCVA--KYGPKWVRTRTVEDSSNPRWNEQYTWPVYDPC-TVLTVGVFDNSQSHWKE 79

                         90
                 ....*....|....*...
gi 186522051 523 -------IGRVIMTLTRV 533
Cdd:cd08379   80 avqpdvlIGKVRIRLSTL 97