NCBI Conserved Domain Search

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: 397.72 E-value: 1.41e-134

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 115 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQI 194
Cdd:cd21680     1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAHLSTFSFTKIDLGDQPLRINGVKVYTENVDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 195 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 274
Cdd:cd21680    81 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDIPGLNGLSDTI 160

                         170
                  ....*....|....*....
gi 1536901836 275 ILDIISNYLVLPNRITVPL 293
Cdd:cd21680   161 ILDIISNYLVLPNRITVPL 179

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: 370.52 E-value: 6.12e-124

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 115 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQI 194
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 195 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 274
Cdd:pfam17047  81 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 160

                         170       180
                  ....*....|....*....|
gi 1536901836 275 ILDIISNYLVLPNRITVPLV 294
Cdd:pfam17047 161 ILDIISNYLVLPNRITVPLV 180

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: 307.49 E-value: 7.46e-100

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 117 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTEnVDKRQIILDLQISF 196
Cdd:cd21679     1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTE-FDKRQIILDLHISY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 197 VGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTIIL 276
Cdd:cd21679    80 VGDVEINVEVKKYFCKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIM 159

                         170
                  ....*....|....*..
gi 1536901836 277 DIISNYLVLPNRITVPL 293
Cdd:cd21679   160 DTIASFLVLPNRLTVPL 176

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: 267.46 E-value: 1.32e-84

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 117 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQISF 196
Cdd:cd21681     1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIREKSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDRRQVILDLQICY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 197 VGNCEIDLEIKRyfCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTIIL 276
Cdd:cd21681    81 IGDCEINVEIKK--CKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGLTNLLDIPGINDMSDSLIE 158

                         170
                  ....*....|....*....
gi 1536901836 277 DIISNYLVLPNRITVPLVS 295
Cdd:cd21681   159 DLIASHLVLPNRFTVPLKK 177

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: 255.56 E-value: 3.62e-80

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 117 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVR-GANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQIS 195
Cdd:cd21670     1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSIRaLLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDIS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 196 FVGNCEIDLEIKRYFcRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTII 275
Cdd:cd21670    81 YDGDADIEVSVGTGI-KAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKII 159

                         170
                  ....*....|....*...
gi 1536901836 276 LDIISNYLVLPNRITVPL 293
Cdd:cd21670   160 VDQIASFLVLPNRITIPL 177

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: 232.95 E-value: 1.78e-72

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTYLKGLVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDPD 388
Cdd:cd08391     1 GVLRIHVIEAQDLVAKDKFVGGLVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1536901836 389 KDDFLGSLMIDLIEVEKERLLDEWFTLDEVPKGKLHLRLEW 429
Cdd:cd08391    81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

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: 226.77 E-value: 4.57e-70

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 710 PLGQIQLTIRHSSQRNKLIVVVHACRNLIAFS-EDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd04030     1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDsSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1536901836 789 VQRRTLDVAVKNSGGFLSKDKGLLGKVLVALASEELAKGWTQWYDLT 835
Cdd:cd04030    81 LKRRTLDVAVKNSKSFLSREKKLLGQVLIDLSDLDLSKGFTQWYDLT 127

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: 172.36 E-value: 1.84e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 461 LLILYLDSARNLPSgKKISSNPNPVVQMSVGHKAQESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCSLGNL 540
Cdd:cd04050     1 LLFVYLDSAKNLPL-AKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSL 79

                          90       100
                  ....*....|....*....|....*.
gi 1536901836 541 KVPLSQLLTSEDMTVSQRFQLSNSGP 566
Cdd:cd04050    80 TLPLSELLKEPDLTLDQPFPLDNSGP 105

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: 162.33 E-value: 7.76e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 108 PAWVHFPDTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAV-RGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDkr 186
Cdd:cd21677     1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLeQYKPSFISSIKFKKLTLGTVPPRIEGVKVVESDED-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 187 QIILDLQISFVGNCEIDLEIKRYFC---RAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLT-NLL 262
Cdd:cd21677    79 EVILDVDFRWAGDPDIVLAVKLLPGlslPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLKLLGgDDM 158

                         170       180       190
                  ....*....|....*....|....*....|.
gi 1536901836 263 DVPGLNGLSDTIILDIISNYLVLPNRITVPL 293
Cdd:cd21677   159 ALPGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

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: 104.26 E-value: 2.72e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLiAFSEDG---SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd08521     1 GEIEFSLSYNYKTGSLEVHIKECRNL-AYADEKkkrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1536901836 789 VQRRTLDVAVKNSGGFLSKDkgLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd08521    80 LETRTLQLSVWHHDRFGRNT--FLGEVEIPLDSWDLDSQQSEWYPL 123

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: 104.30 E-value: 2.84e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHssQRNKLIVVVHACRNLIafSEDGS--DPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFS-VSLPE 788
Cdd:cd08381     2 GQVKLSISY--KNGTLFVMVMHAKNLP--LLDGSdpDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDgLPVED 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1536901836 789 VQRRTLDVAVKNSGGFLSKDKglLGKVLVALASEELAKGWTQWYDLT 835
Cdd:cd08381    78 LQQRVLQVSVWSHDSLVENEF--LGGVCIPLKKLDLSQETEKWYPLG 122

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: 105.10 E-value: 5.35e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 137 IEKLFRETIEPAVRGA--NTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQISFVGNCEIDLEIK------R 208
Cdd:cd21669     1 LEQLIRESLQELLEEVkkPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDLQLVLDLDLEYAGDFSVVLSAKlgggglG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 209 YFCRAGVKSIQIHGTMRVILEpLIGDMPLVGALSIFFLRKPLLEINWT--GLTNLLDVPGLNGLSDTIILDIISNYLVLP 286
Cdd:cd21669    81 LPVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRplGGVDLMELPGLSSWLEKLLTDALVELLVEP 159


                  ....*.
gi 1536901836 287 NRITVP 292
Cdd:cd21669   160 NRIVID 165

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: 103.27 E-value: 6.65e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTYlkglVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDP- 387
Cdd:cd04024     1 GVLRVHVVEAKDLAAKDRS----GKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRf 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1536901836 388 DKDDFLGSLMIDL---IEVEKERLLDEWFTLD-------EVPKGKLHLRLEW 429
Cdd:cd04024    77 AGKDYLGEFDIALeevFADGKTGQSDKWITLKstrpgktSVVSGEIHLQFSW 128

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: 99.26 E-value: 1.69e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 710 PLGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRsgRRKTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd08385     1 KLGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGtSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFKVPYSE 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1536901836 789 VQRRTLDVAVKNSGGFLSKDkgLLGKVLVALASEELAKGWTQWYDLTE 836
Cdd:cd08385    79 LGNKTLVFSVYDFDRFSKHD--LIGEVRVPLLTVDLGHVTEEWRDLES 124

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 107.54 E-value: 1.24e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  115 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGA------NTHLSTFsftkvDVGQQPLRINGVKVYTeNVDKRQI 188
Cdd:COG5038    219 DYESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAipsfidALALDEF-----TLGSKPPRIDGIRSYP-STESDTV 292

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  189 ILDLQISFVG---------------NCEIDLEIKRYFcRAGVKSIQI-------HGTMRVILEpLIGDMPLVGALSIFFL 246
Cdd:COG5038    293 VMDVDFSFTPhdisdvtatsarasvNPKISLVVKKGK-SFGSFTLPIlvedlffKGRVRVRVE-LMSKYPFIKTVSFQLL 370

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  247 RKPLLEINWTGL------TNLLDVPGLNglsdTIILDIISNYL----VLPNRITVPlVSEVQIAQLRFPVpkGVLRIHFI 316
Cdd:COG5038    371 EVPEFDFILVPLggdffgVDIFAIPGLS----RFIQEIINSTLgpmlLPPNSLTID-ISQIMAGDSGTAI--GVVEVKIK 443

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  317 EAQDLQGKDtylkGLVKGKSDPYGIIRV-GNQIFQSRVIKENLSPKWNEvYEALVYEHPGQELEIELFD-EDPDKDDFLG 394
Cdd:COG5038    444 SAEGLKKSD----STINGTVDPYITVTFsDRVIGKTRVKKNTLNPVWNE-TFYILLNSFTDPLNLSLYDfNSFKSDKVVG 518

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  395 SLMIDLIEVEKERLLDEW---FTLDEVPKGKLHLRLEWLTLMPNASNLDKvltdIKADKDQANDGLSSALLIlYLDSARN 471
Cdd:COG5038    519 STQLDLALLHQNPVKKNElyeFLRNTKNVGRLTYDLRFFPVIEDKKELKG----SVEPLEDSNTGILKVTLR-EVKALDE 593

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  472 LPSGKKISSNP---NPVVQMSvghkaqeSKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCSLGNLKVPLSQLL 548
Cdd:COG5038    594 LSSKKDNKSAElytNAKEVYS-------TGKLKFTNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLI 666

                          490       500
                   ....*....|....*....|....
gi 1536901836  549 tSEDMTVSQRFQLSNsgPNSTIKM 572
Cdd:COG5038    667 -DRTLDTFLVFPLRN--PKGRIFI 687

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: 96.56 E-value: 1.58e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIA--FSEDGSDPYVRMYLLPDKRRSgrRKTHVSKKTLNPVFDQSFDFSVSLPEV 789
Cdd:cd08390     1 GRLWFSVQYDLEEEQLTVSLIKARNLPPrtKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQVSFKEL 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1536901836 790 QRRTLDVAVKNSGGFLSKDkgLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd08390    79 QRRTLRLSVYDVDRFSRHC--IIGHVLFPLKDLDLVKGGVVWRDL 121

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: 93.03 E-value: 3.34e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd00276     1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGlSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1536901836 791 RRTLDVAVKNSGGFLSKDKglLGKVLVALASEELAKgwTQWYDLTEDGTRPQAM 844
Cdd:cd00276    81 EVSLVITVVDKDSVGRNEV--IGQVVLGPDSGGEEL--EHWNEMLASPRKPIAR 130

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 91.61 E-value: 4.37e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRV--GNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDED 386
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKD------GNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 1536901836 387 -PDKDDFLGSLMIDLIEVEKERLLDEWFTL 415
Cdd:pfam00168  75 rFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104

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: 89.80 E-value: 3.14e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIAFSE--DGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEV 789
Cdd:cd08393     2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPkkQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1536901836 790 QRRTLDVAVKNSGGFlsKDKGLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd08393    82 PTRVLNLSVWHRDSL--GRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

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: 88.26 E-value: 1.34e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLiAFSEDG---SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd04029     2 GEILFSLSYDYKTQSLNVHVKECRNL-AYGDEAkkrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1536901836 789 VQRRTLDVAVKNSGGFlsKDKGLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd04029    81 LETRTLQLSVWHYDRF--GRNTFLGEVEIPLDSWNFDSQHEECLPL 124

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: 87.12 E-value: 1.78e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRVGN-QIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDPD- 388
Cdd:cd00030     1 LRVTVIEARNLPAKDL------NGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFs 74

                          90       100
                  ....*....|....*....|....*...
gi 1536901836 389 KDDFLGSLMIDLIEVEKERL-LDEWFTL 415
Cdd:cd00030    75 KDDFLGEVEIPLSELLDSGKeGELWLPL 102

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: 88.17 E-value: 1.91e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 713 QIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQR 791
Cdd:cd08384     1 KILVSLMYNTQRRGLIVGIIRCVNLAAMDANGySDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAK 80


                  ....*..
gi 1536901836 792 RTLDVAV 798
Cdd:cd08384    81 KTLEITV 87

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 85.83 E-value: 5.32e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 725 NKLIVVVHACRNLIA-FSEDGSDPYVRMYLLPDKRRsgrRKTHVSKKTLNPVFDQSFDFSVslPEVQRRTLDVAVKNSGG 803
Cdd:pfam00168   1 GRLTVTVIEAKNLPPkDGNGTSDPYVKVYLLDGKQK---KKTKVVKNTLNPVWNETFTFSV--PDPENAVLEIEVYDYDR 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1536901836 804 FLSKDkgLLGKVLVALASEELAKGWTQWYDL 834
Cdd:pfam00168  76 FGRDD--FIGEVRIPLSELDSGEGLDGWYPL 104

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: 85.38 E-value: 1.13e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLiAFSEDGS--DPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFS-VSLPE 788
Cdd:cd04031     3 GRIQIQLWYDKVTSQLIVTVLQARDL-PPRDDGSlrNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSnVRRET 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1536901836 789 VQRRTLDVAVKNSGgfLSKDKGLLGKVLVALASEELaKGWTQWYDL 834
Cdd:cd04031    82 LKERTLEVTVWDYD--RDGENDFLGEVVIDLADALL-DDEPHWYPL 124

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: 81.92 E-value: 2.42e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRhsSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd04026     2 GRIYLKIS--VKDNKLTVEVREAKNLIPMDPNGlSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79


                  ..
gi 1536901836 791 RR 792
Cdd:cd04026    80 RR 81

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: 79.80 E-value: 6.98e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 727 LIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRsgrrKTHVSKKTLNPVFDQSFDFSVslPEVQRRTLDVAVKNSGGFL 805
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGkSDPYVKVSLGGKQKF----KTKVVKNTLNPVWNETFEFPV--LDPESDTLTVEVWDKDRFS 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 1536901836 806 SKDkgLLGKVLVALAS-EELAKGWTQWYDL 834
Cdd:cd00030    75 KDD--FLGEVEIPLSElLDSGKEGELWLPL 102

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: 81.84 E-value: 1.55e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 117 ERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGA-NTHLSTFSFTKVDVGQQPLRINGVKVYTeNVDKRQIILDLQIS 195
Cdd:cd21678     1 ESVEWLNYFLQKFWLIYEPVLSETIVTNVNPVLAENcPSFLDSLRLTEFTLGTKAPRIEGVRTYP-KTEDDVVVMDWEFS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 196 FVG---------------NCEIDLEIKRYFCRAG------VKSIQIHGTMRVILEpLIGDMPLVGALSIFFLRKPllEIN 254
Cdd:cd21678    80 FTPndtsdltakqiknkvNPKIVLTARVGKGVVGidlpilVEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPP--EID 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1536901836 255 WT-----GLTNLLDVPGLNGLSDTIILDIISNYLVLPNRITVPL 293
Cdd:cd21678   157 FVlkplgGGFDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDL 200

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: 77.91 E-value: 2.44e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  310 VLRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRVGNQ---IFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDED 386
Cdd:smart00239   1 TLTVKIISARNLPPKDK------GGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*..
gi 1536901836  387 PD-KDDFLGSLMIDLIEVEKERLLDEW 412
Cdd:smart00239  75 RFgRDDFIGQVTIPLSDLLLGGRHEKL 101

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: 78.98 E-value: 3.03e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEV 789
Cdd:cd08402     1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGlSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1536901836 790 QRRTLDVAVKNSGGFLSKDkgLLGKVLvaLASEELAKGWTQWYDLTEDGTRPQA 843
Cdd:cd08402    81 QKVHLIVTVLDYDRIGKND--PIGKVV--LGCNATGAELRHWSDMLASPRRPIA 130

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: 76.76 E-value: 6.97e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  726 KLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRsgRRKTHVSKKTLNPVFDQSFDFSVSLPEVQRrtLDVAVKNSGGF 804
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGkSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPELAE--LEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*..
gi 1536901836  805 LSKDkgLLGKVLVALASEELAKGWTQW 831
Cdd:smart00239  77 GRDD--FIGQVTIPLSDLLLGGRHEKL 101

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: 77.32 E-value: 8.17e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDF-SVSLPE 788
Cdd:cd04035     1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGlSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYyGITEED 80

                          90
                  ....*....|
gi 1536901836 789 VQRRTLDVAV 798
Cdd:cd04035    81 IQRKTLRLLV 90

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: 76.91 E-value: 8.42e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 310 VLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDP-D 388
Cdd:cd08376     1 VVTIVLVEGKNLPPMD------DNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTgK 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1536901836 389 KDDFLGSLMIDLIEVEKERLLDEWFTLDEvPKGKLHL 425
Cdd:cd08376    75 KDEFIGRCEIDLSALPREQTHSLELELED-GEGSLLL 110

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: 77.39 E-value: 9.19e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG--SDPYVRMYLLPDKRRsgRRKTHVSKKTLNPVFDQSFDF-SVSLP 787
Cdd:cd08388     2 LGTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSgtSDPYVKLQLLPEKEH--KVKTRVLRKTRNPVYDETFTFyGIPYN 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1536901836 788 EVQRRTLDVAVknsggfLSKDK----GLLGKVLVALASEEL 824
Cdd:cd08388    80 QLQDLSLHFAV------LSFDRysrdDVIGEVVCPLAGADL 114

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

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 76.79 E-value: 1.59e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLiAFSEDGS---DPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd08392     2 GEIEFALHYNFRTSCLEITIKACRNL-AYGDEKKkkcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1536901836 789 VQRRTLDVAVKNSGGFlsKDKGLLGKVLVALASEELAKGWTQ---WYDL 834
Cdd:cd08392    81 LSSRQLQVSVWHSRTL--KRRVFLGEVLIPLADWDFEDTDSQrflWYPL 127

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 75.78 E-value: 2.85e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDtylKGlvkGKSDPYGIIRV-GNQIFQSRVIKENLSPKWNEVYEALVyEHPGQELEIELFDED-PD 388
Cdd:cd04042     2 LDIHLKEGRNLAARD---RG---GTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPI-EDVTQPLYIKVFDYDrGL 74

                          90
                  ....*....|....*....
gi 1536901836 389 KDDFLGSLMIDLIEVEKER 407
Cdd:cd04042    75 TDDFMGSAFVDLSTLELNK 93

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: 75.53 E-value: 4.13e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEV 789
Cdd:cd08405     1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGtSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1536901836 790 QRRTLDVAVknsggfLSKDK----GLLGKVLVALASEELAKGwtQWYDLTEDGTRPQA 843
Cdd:cd08405    81 RETTLIITV------MDKDRlsrnDLIGKIYLGWKSGGLELK--HWKDMLSKPRQPVA 130

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: 75.82 E-value: 8.29e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 710 PLGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFS-VSLP 787
Cdd:cd04020    12 PPESEGALKSKKPSTGELHVWVKEAKNLPALKSGGtSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNHTFVYDgVSPE 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1536901836 788 EVQRRTLDVAVKNSGGFLSKDkgLLGKVLVALASEELAKGWTQWYDLTED 837
Cdd:cd04020    92 DLSQACLELTVWDHDKLSSND--FLGGVRLGLGTGKSYGQAVDWMDSTGE 139

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 71.45 E-value: 7.81e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRV-GNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDED-PD 388
Cdd:cd04040     1 LTVDVISAENLPSADR------NGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDrGG 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1536901836 389 KDDFLGSLMIDLIEVEKERLLDewFTLDEVPKGKLHLRLEWL 430
Cdd:cd04040    75 KDDLLGSAYIDLSDLEPEETTE--LTLPLDGQGGGKLGAVFL 114

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: 71.56 E-value: 8.10e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYE-ALVYEHpgQELEIELFDEDP 387
Cdd:cd08377     1 GFLQVKVIRASGLAAAD------IGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTfPIKDIH--DVLEVTVYDEDK 72

                          90
                  ....*....|....*...
gi 1536901836 388 DKD-DFLGSLMIDLIEVE 404
Cdd:cd08377    73 DKKpEFLGKVAIPLLSIK 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: 69.82 E-value: 2.97e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDED-PDK 389
Cdd:cd04025     2 LRCHVLEARDLAPKD------RNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDlVSK 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1536901836 390 DDFLGSLMIDLIEVEKERLLDEWFTL------DEVPKGKL-HLRLE 428
Cdd:cd04025    76 NDFLGKVVFSIQTLQQAKQEEGWFRLlpdpraEEESGGNLgSLRLK 121

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: 70.15 E-value: 3.30e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd08404     2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGlADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1536901836 791 RRTLDVAVKNSGGfLSKDKgLLGKVLVALASEELAKGWtqWYDLTEDGTR 840
Cdd:cd08404    82 DISVEFLVLDSDR-VTKNE-VIGRLVLGPKASGSGGHH--WKEVCNPPRR 127

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: 69.54 E-value: 3.70e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLqgKDtyLKGLvkGKSDPYGIIRVGNQI-FQSRVIKENLSPKWNEVYEALVYEhPGQELEIELFDEDP 387
Cdd:cd04045     1 GVLRLHIRKANDL--KN--LEGV--GKIDPYVRVLVNGIVkGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEK 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1536901836 388 D-KDDFLGSLMIDLIEVEKERLLDEwftldEVPKGKLHLRLEWLTL 432
Cdd:cd04045    74 VgKDRSLGSVEINVSDLIKKNEDGK-----YVEYDDEEERLKRLLS 114

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: 69.35 E-value: 4.75e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIA--FSEDgSDPYVRMYLLPDKRRSGRRKTHvsKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd08387     2 RGELHFSLEYDKDMGILNVKLIQARNLQPrdFSGT-ADPYCKVRLLPDRSNTKQSKIH--KKTLNPEFDESFVFEVPPQE 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1536901836 789 VQRRTLDVAVKNSGGFlSKDKGlLGKVLVALASEELAKGWTQW 831
Cdd:cd08387    79 LPKRTLEVLLYDFDQF-SRDEC-IGVVELPLAEVDLSEKLDLW 119

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: 69.28 E-value: 4.98e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRsgRRKTHVSKKTLNPVFDQSFDFS-VSLPE 788
Cdd:cd08386     2 LGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGtSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEgFPYEK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1536901836 789 VQRRTLDVAVKNSGGFLSKDKglLGKVLVALASEELAKGWTQWYDLT 835
Cdd:cd08386    80 LQQRVLYLQVLDYDRFSRNDP--IGEVSLPLNKVDLTEEQTFWKDLK 124

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: 66.58 E-value: 8.35e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTylkglvkGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYeALVYEHPGQELEIELFDED-P 387
Cdd:cd04038     2 GLLKVRVVRGTNLAVRDF-------TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEEL-TLSVPNPMAPLKLEVFDKDtF 73

                          90
                  ....*....|...
gi 1536901836 388 DKDDFLGSLMIDL 400
Cdd:cd04038    74 SKDDSMGEAEIDL 86

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: 65.72 E-value: 1.25e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 715 QLTIR--HSSQRNKLIVVVHACRNLIAFSEDG-SDPYVRMYLLPDKRRSG--RRKTHVSKKTLNPVFDQSFDFSVSlPEv 789
Cdd:cd04009     4 VLTVKayYRASEQSLRVEILNARNLLPLDSNGsSDPFVKVELLPRHLFPDvpTPKTQVKKKTLFPLFDESFEFNVP-PE- 81

                          90       100
                  ....*....|....*....|....*
gi 1536901836 790 QRRTLDVAVKnsggFLSKDKGLLGK 814
Cdd:cd04009    82 QCSVEGALLL----FTVKDYDLLGS 102

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. 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: 176051 [Multi-domain] Cd Length: 136 Bit Score: 65.58 E-value: 1.30e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLI-AFSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd08406     2 GEILLSLSYLPTAERLTVVVVKARNLVwDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1536901836 791 RRTLDVAVKNSGGFLSKDKglLGKVLValASEELAKGWTQWYDLTEDGTRPQAM 844
Cdd:cd08406    82 DLSLRVTVAESTEDGKTPN--VGHVII--GPAASGMGLSHWNQMLASLRKPVAM 131

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: 64.16 E-value: 2.59e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 332 VKGKSDPYGIIRVGNQ-IFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDPDKDDFLGSL---MIDLIEvEKER 407
Cdd:cd04052     9 KTGLLSPYAELYLNGKlVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVsisLNDLID-ATSV 87

                          90       100
                  ....*....|....*....|..
gi 1536901836 408 LLDeWFTLDEVPKGKLHLRLEW 429
Cdd:cd04052    88 GQQ-WFPLSGNGQGRIRISALW 108

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: 64.84 E-value: 2.69e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIA-FSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd08403     1 GELMFSLCYLPTAGRLTLTIIKARNLKAmDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80


                  ....*...
gi 1536901836 791 RRTLDVAV 798
Cdd:cd08403    81 NVSLIIAV 88

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: 63.63 E-value: 3.08e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 462 LILYLDSARNLPSgKKISSNPNPVVQMSVGHKA-QESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDE---QHQCSL 537
Cdd:cd00030     1 LRVTVIEARNLPA-KDLNGKSDPYVKVSLGGKQkFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKdrfSKDDFL 79

                          90
                  ....*....|.
gi 1536901836 538 GNLKVPLSQLL 548
Cdd:cd00030    80 GEVEIPLSELL 90

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: 63.94 E-value: 5.67e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQgkdtylKGLVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDED-- 386
Cdd:cd08375    15 GRLMVVIVEGRDLK------PCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDff 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1536901836 387 -PdkDDFLGSLMIDLIEVEKE----------RLLdewftLDEVPKGKLHLRLE 428
Cdd:cd08375    89 sP--DDFLGRTEIRVADILKEtkeskgpitkRLL-----LHEVPTGEVVVKLD 134

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: 62.66 E-value: 6.78e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTylkglVKGKSDPY---GIIRVGNQIFQSRVIKENLSPKWNEvyEALVYEHP-----GQELEI 380
Cdd:cd04041     1 GVLVVTIHRATDLPKADF-----GTGSSDPYvtaSFAKFGKPLYSTRIIRKDLNPVWEE--TWFVLVTPdevkaGERLSC 73

                          90       100
                  ....*....|....*....|.
gi 1536901836 381 ELFDED-PDKDDFLGSLMIDL 400
Cdd:cd04041    74 RLWDSDrFTADDRLGRVEIDL 94

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: 63.93 E-value: 7.40e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 307 PKGVLRIHFIEAQDLQGKDtylkglVKGKSDPY---GII---RVGNQ-----------------------IFQSRVIKEN 357
Cdd:cd08676    26 PIFVLKVTVIEAKGLLAKD------VNGFSDPYcmlGIVpasRERNSekskkrkshrkkavlkdtvpaksIKVTEVKPQT 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1536901836 358 LSPKWNEVYEALVYEHPGQELEIELFDEDpdkDDFLGSLMIDLIEVEKERlLDEWFTL 415
Cdd:cd08676   100 LNPVWNETFRFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCG-LDSWFKL 153

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: 62.12 E-value: 9.14e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  461 LLILYLDSARNLPSgKKISSNPNPVVQMSVGHKAQE---SKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCS- 536
Cdd:smart00239   1 TLTVKIISARNLPP-KDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRd 79

                           90
                   ....*....|....*..
gi 1536901836  537 --LGNLKVPLSQLLTSE 551
Cdd:smart00239  80 dfIGQVTIPLSDLLLGG 96

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 61.57 E-value: 1.66e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 461 LLILYLDSARNLPSgKKISSNPNPVVQMSVGHKAQ--ESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDE---QHQC 535
Cdd:pfam00168   2 RLTVTVIEAKNLPP-KDGNGTSDPYVKVYLLDGKQkkKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYdrfGRDD 80

                          90
                  ....*....|....*.
gi 1536901836 536 SLGNLKVPLSQLLTSE 551
Cdd:pfam00168  81 FIGEVRIPLSELDSGE 96

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: 61.51 E-value: 2.35e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 310 VLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRV---GNQIFQSRVIKENLSPKWNEVYEALVyeHPGQE--LEIELFD 384
Cdd:cd04036     1 LLTVRVLRATNITKGD------LLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRI--QSQVKnvLELTVMD 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1536901836 385 EDPDKDDFLGSLMIDLIEVEKERLLDEWFTLDEVPKGKLHLRLE 428
Cdd:cd04036    73 EDYVMDDHLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFL 116

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: 61.11 E-value: 2.95e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTYlkglvkGKSDPYGIIRVGNQIFQSRVI-KENLSPKWNEVYEALVYEHPGQELEIELFDEDP 387
Cdd:cd08681     1 GTLVVVVLKARNLPNKRKL------DKQDPYCVLRIGGVTKKTKTDfRGGQHPEWDEELRFEITEDKKPILKVAVFDDDK 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1536901836 388 DKDDFLGSLMIDLIEVEKERLLDEWFTL--DEVPKGKLHLRL 427
Cdd:cd08681    75 RKPDLIGDTEVDLSPALKEGEFDDWYELtlKGRYAGEVYLEL 116

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: 60.36 E-value: 8.02e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTYLKGLVKGKS----DPYGIIRVGNQIF-QSRVIKENLSPKWNEVYEALVyeHPGQELEIELF 383
Cdd:cd04014     4 GTLKIKICEAVDLKPTDWSTRHAVPKKGsqllDPYVSIDVDDTHIgKTSTKPKTNSPVWNEEFTTEV--HNGRNLELTVF 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1536901836 384 -DEDPDKDDFLGSLMI---DLIEVEKERLlDEWFTLDevPKGKLHLRLEW 429
Cdd:cd04014    82 hDAAIGPDDFVANCTIsfeDLIQRGSGSF-DLWVDLE--PQGKLHVKIEL 128

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

Pssm-ID: 175994 [Multi-domain] Cd Length: 146 Bit Score: 60.48 E-value: 1.00e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 699 QLENGTTLGQSPLGQIQLTIRHssQRNKLIVVVHACRNLIA--FSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVF 776
Cdd:cd04028     5 QLVGRQVLASPSMGDIQLGLYD--KKGQLEVEVIRARGLVQkpGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLY 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1536901836 777 DQSFDFSVSlpeVQRRTLDVAVKNSGGFLSKdKGLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd04028    83 QQQLVFDVS---PTGKTLQVIVWGDYGRMDK-KVFMGVAQILLDDLDLSNLVIGWYKL 136

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: 57.94 E-value: 4.61e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 310 VLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRVGNQIFQSR--VIKENLSPKWNEVYEaLVYEHPG-QELEIELFDED 386
Cdd:cd04037     1 LVRVYVVRARNLQPKD------PNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFE-LEATLPGnSILKISVMDYD 73

                          90
                  ....*....|....*
gi 1536901836 387 P-DKDDFLGSLMIDL 400
Cdd:cd04037    74 LlGSDDLIGETVIDL 88

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: 57.75 E-value: 6.78e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 310 VLRIHFIEAQDLQGKDTYlkglvkGKSDPYGIIRV-----GNQI--FQSRVIKENLSPKWNEVYEALVyeHPGQ-ELEIE 381
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIF------GASDPYVKISLydpdgNGEIdsVQTKTIKKTLNPKWNEEFFFRV--NPREhRLLFE 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1536901836 382 LFDEDP-DKDDFLGSLMIDLI------EVEKERLLDEWFTLDEVP-----KGKLHLRLEWL 430
Cdd:cd04033    73 VFDENRlTRDDFLGQVEVPLNnlptetPGNERRYTFKDYLLRPRSsksrvKGHLRLYMAYL 133

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: 57.67 E-value: 7.27e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 307 PKGVLRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNevYEALVY-EHPGQELEIELFDE 385
Cdd:cd04046     1 PQVVTQVHVHSAEGLSKQDS------GGGADPYVIIKCEGESVRSPVQKDTLSPEFD--TQAIFYrKKPRSPIKIQVWNS 72


                  ....*....
gi 1536901836 386 DPDKDDFLG 394
Cdd:cd04046    73 NLLCDEFLG 81

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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: 176062 Cd Length: 124 Bit Score: 56.86 E-value: 1.00e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 713 QIQLTIRHSSQRNKLIVVVHACRNLIAFS-EDGSDPYVRMYLLP---DKRRSGRrkTHVSKKTLNPVFDQSFDFSVSLPE 788
Cdd:cd08680     2 QVQIGLRYDSGDSSLVISVEQLRNLSALSiPENSKVYVRVALLPcssSTSCLFR--TKALEDQDKPVFNEVFRVPISSTK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1536901836 789 VQRRTLDVAVKNSGGflSKDKGLLGKVLVALASEE-LAKGWTQWYDL 834
Cdd:cd08680    80 LYQKTLQVDVCSVGP--DQQEECLGGAQISLADFEsSEEMSTKWYNL 124

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: 56.79 E-value: 1.13e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDTylkglvKGKS-DPYGIIRVGNQ--IFQSRVIKENLSPKWNEVYEALVYEHpGQELEIELFDE 385
Cdd:cd04044     2 GVLAVTIKSARGLKGSDI------IGGTvDPYVTFSISNRreLARTKVKKDTSNPVWNETKYILVNSL-TEPLNLTVYDF 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1536901836 386 DPDKDD-FLGSLMIDLIEVEKERLLDE---WFTLDEVPKGKLHLRLEW 429
Cdd:cd04044    75 NDKRKDkLIGTAEFDLSSLLQNPEQENltkNLLRNGKPVGELNYDLRF 122

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: 56.69 E-value: 1.32e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIrhSSQRNKLIVVVHACRNLIAFSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQR 791
Cdd:cd08685     1 GQLKLSI--EGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1536901836 792 RTLdVAVKNSGGfLSKDKGLLGKVLVALASEELAKGWTQWYDL 834
Cdd:cd08685    79 RLL-VTVWNKLS-KSRDSGLLGCMSFGVKSIVNQKEISGWYYL 119

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: 55.87 E-value: 2.26e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 302 LRFPVPKGVLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRV---GNQIFQSRVIKENLSPKWNE--VYEALVYEHPGQ 376
Cdd:cd08387     9 LEYDKDMGILNVKLIQARNLQPRD------FSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFDEsfVFEVPPQELPKR 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1536901836 377 ELEIELFDEDP-DKDDFLGSLMIDLIEVEKERLLDEW 412
Cdd:cd08387    83 TLEVLLYDFDQfSRDECIGVVELPLAEVDLSEKLDLW 119

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: 56.04 E-value: 2.63e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYealVYE--HPGQELEIELFDEDPD 388
Cdd:cd04027     3 ISITVVCAQGLIAKDK------TGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKF---HFEchNSSDRIKVRVWDEDDD 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1536901836 389 ------------KDDFLGSLMIDLIEVEKErlLDEWFTLDE 417
Cdd:cd04027    74 iksrlkqkftreSDDFLGQTIIEVRTLSGE--MDVWYNLEK 112

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

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 55.01 E-value: 4.16e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1536901836 329 KGLVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYeALVYEH-PGQELEIELFDEDPDKDDFLGSLMIDLIEV 403
Cdd:cd08378    10 RGLPANSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVF-AFSKDRlQGSTLEVSVWDKDKAKDDFLGGVCFDLSEV 84

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: 53.88 E-value: 1.44e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFIEAQDLQGKDtYLkglvkGKSDPYGIIRVGNQIFQSRVIKE-NLSPKWNEVYEALVyEHPGQ----ELEIELF 383
Cdd:cd04049     1 GTLEVLLISAKGLQDTD-FL-----GKIDPYVIIQCRTQERKSKVAKGdGRNPEWNEKFKFTV-EYPGWggdtKLILRIM 73

                          90       100
                  ....*....|....*....|.
gi 1536901836 384 DEDP-DKDDFLGSLMIDLIEV 403
Cdd:cd04049    74 DKDNfSDDDFIGEATIHLKGL 94

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: 52.95 E-value: 1.68e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 309 GVLRIHFiEAQDLQGKDTYlkglvkGKSDPYGII-RVG-----NQIFQSRVIKENLSPKWNEV---YEALVYEHPGQELE 379
Cdd:cd04047     1 DVVELQF-SGKKLDKKDFF------GKSDPFLEIsRQSedgtwVLVYRTEVIKNTLNPVWKPFtipLQKLCNGDYDRPIK 73

                          90
                  ....*....|....*..
gi 1536901836 380 IELFDEDPD-KDDFLGS 395
Cdd:cd04047    74 IEVYDYDSSgKHDLIGE 90

C2 domain second repeat present in Synaptotagmin 15; 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. 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: 176054 [Multi-domain] Cd Length: 137 Bit Score: 53.11 E-value: 2.89e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 711 LGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQ 790
Cdd:cd08409     1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQLD 80

                          90       100
                  ....*....|....*....|....*..
gi 1536901836 791 RRTLDVAVKNSGGflSKDKGLLGKVLV 817
Cdd:cd08409    81 TASLSLSVMQSGG--VRKSKLLGRVVL 105

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: 52.16 E-value: 6.70e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvKGKSDPYgiIRV--GNQIFQSRVIKENLSPKWNEV---YEALVYEHPGQELE------ 379
Cdd:cd04017     3 LRAYIYQARDLLAADK------SGLSDPF--ARVsfLNQSQETEVIKETLSPTWDQTlifDEVELYGSPEEIAQnpplvv 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1536901836 380 IELFDEDPD-KDDFLGSLMIdlieVEKERLLDEWftlDEVPKgklhlrLEWLTLM 433
Cdd:cd04017    75 VELFDQDSVgKDEFLGRSVA----KPLVKLDLEE---DFPPK------LQWFPIY 116

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176035 [Multi-domain] Cd Length: 124 Bit Score: 51.47 E-value: 8.74e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 712 GQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDGSDPY-VRMYLLPDKRRsgRRKTHVSKKTlNPVFDQSFDFS-VSLPEV 789
Cdd:cd08389     3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWqVHLVLLPSKKQ--RAKTKVQRGP-NPVFNETFTFSrVEPEEL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1536901836 790 QRRTLDVAVKNSGGFlSKDKgLLGKVLVALASEELAKGWTQW 831
Cdd:cd08389    80 NNMALRFRLYGVERM-RKER-LIGEKVVPLSQLNLEGETTVW 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: 51.90 E-value: 1.09e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDtylKGLVKgksDPYGIIRVGNQIFQSRVIK-ENLSPKWNEVYEALVYEHPGQELEIELFD-EDPD 388
Cdd:cd04019     2 LRVTVIEAQDLVPSD---KNRVP---EVFVKAQLGNQVLRTRPSQtRNGNPSWNEELMFVAAEPFEDHLILSVEDrVGPN 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1536901836 389 KDDFLGSLMIDLIEVEKeRLLDE-----WFTL----------DEVP-KGKLHLRL 427
Cdd:cd04019    76 KDEPLGRAVIPLNDIER-RVDDRpvpsrWFSLerpggameqkKKRKfASRIHLRL 129

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 55.15 E-value: 2.04e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  181 ENVDKRQI-ILDLQISFVGNCEIDLEIKRYFCRA------------GVKSIQI-------HGT-MRVILE----PLIGDM 235
Cdd:COG5038    869 SALDEKTIsLVDKEDSVEESIEVEELTDMYSLKPkldlnealqyksGVLGIQIlsgelpdPGQyLQIFFDdashPQIVSS 948

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  236 --PLVGALSIFFLRKPLLEINWTGLT-----NLLDVPGLNGLSDTIILDIISNYLVLPNRITVPLVSEVQIAQLRFPVPK 308
Cdd:COG5038    949 kaPTRGERNGESGDTFIRELEYSETTfrvtkNAKKSDKVVCEVTLPTLDLVSNAYEKPSSLNFPGSAKVLVQVSYTPVPV 1028

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836  309 -----------GVLRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRV-GNQIFQSRVIKENLSPKWNEVYEALVYEHPGQ 376
Cdd:COG5038   1029 klppvemvensGYLTIMLRSGENLPSSDE------NGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKD 1102

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1536901836  377 ELEIELFDEDPD-KDDFLGSLMIDL--IEVEKERLLDEWFTLDEVPKGKLHLRLEWlTLMP----NASNLDKVLTDI 446
Cdd:COG5038   1103 VLTINVNDWDSGeKNDLLGTAEIDLskLEPGGTTNSNIPLDGKTFIVLDGTLHPGF-NFRSkyalNVSRKEGILGDI 1178

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: 48.87 E-value: 8.17e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 468 SARNL-PSGKKISSNPNPVVQMSvGHKaQESKIRYKTNEPVWEENFTFFIHNPKR---QDLEVEV----RDEQHQCSLGN 539
Cdd:cd04022     8 DAQDLmPKDGQGSSSAYVELDFD-GQK-KRTRTKPKDLNPVWNEKLVFNVSDPSRlsnLVLEVYVyndrRSGRRRSFLGR 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1536901836 540 LKVPLSQLLtSEDMTVSQRFQLSNSGPNSTIKMKIALRVL 579
Cdd:cd04022    86 VRISGTSFV-PPSEAVVQRYPLEKRGLFSRVRGEIGLKVY 124

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

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 48.91 E-value: 9.95e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvkGKSDPYGIIRVGNQIFQ----SRVIKENLSPKWNEVYE------------ALVYEHP 374
Cdd:cd08675     1 LSVRVLECRDLALKSN-------GTCDPFARVTLNYSSKTdtkrTKVKKKTNNPRFDEAFYfeltigfsyekkSFKVEEE 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1536901836 375 G---QELEIELFDEDP-DKDDFLGSLMIDLIEVEKERLLDEWFTL--DEVPKGKLH 424
Cdd:cd08675    74 DlekSELRVELWHASMvSGDDFLGEVRIPLQGLQQAGSHQAWYFLqpREAPGTRSS 129

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: 48.93 E-value: 1.05e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 726 KLIVVVHACRNLiAFSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLP-------------EVQRR 792
Cdd:cd04010     1 KLSVRVIECSDL-ALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDsspekkqfempeeDAEKL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1536901836 793 TLDVAVKN-SGGFlskDKGLLGKVLVALASEELAKGWTQ-WYDL 834
Cdd:cd04010    80 ELRVDLWHaSMGG---GDVFLGEVRIPLRGLDLQAGSHQaWYFL 120

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: 48.52 E-value: 1.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 727 LIVVVHACRNLIAFSEDGSDPYVRM-YLLPDKRRSgrRKTHVSKKTLNPVFDQSFDFSVSLPE-------------VQRR 792
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVtLNYSSKTDT--KRTKVKKKTNNPRFDEAFYFELTIGFsyekksfkveeedLEKS 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1536901836 793 TLDVAVKNSGGfLSKDKgLLGKVLVALASEELAKGWTQWYDLTEDGTRPQ 842
Cdd:cd08675    79 ELRVELWHASM-VSGDD-FLGEVRIPLQGLQQAGSHQAWYFLQPREAPGT 126

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: 47.95 E-value: 1.41e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 730 VVHAcRNLIAFSEDG-SDPYVRMYLlpdkrrSGRR--KTHVSKKTLNPVFDQSFDFSVslPEVQRRTLDVAVK--NSGGf 804
Cdd:cd04040     5 VISA-ENLPSADRNGkSDPFVKFYL------NGEKvfKTKTIKKTLNPVWNESFEVPV--PSRVRAVLKVEVYdwDRGG- 74

                          90
                  ....*....|....*..
gi 1536901836 805 lsKDKgLLGKVLVALAS 821
Cdd:cd04040    75 --KDD-LLGSAYIDLSD 88

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: 47.63 E-value: 1.91e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 295 SEVQIaQLRFPVPKGVLRIHFIEAQDLQGKDTylkglvKGKSDPYGII-----RVGNQIFQSRVIKENLSPKWNEVyeaL 369
Cdd:cd04031     3 GRIQI-QLWYDKVTSQLIVTVLQARDLPPRDD------GSLRNPYVKVyllpdRSEKSKRRTKTVKKTLNPEWNQT---F 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1536901836 370 VYEHPGQE------LEIELFDEDPDK-DDFLGSLMIDLievEKERLLDE--WFTL 415
Cdd:cd04031    73 EYSNVRREtlkertLEVTVWDYDRDGeNDFLGEVVIDL---ADALLDDEphWYPL 124

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: 46.80 E-value: 2.47e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1536901836 469 ARNLPSGkkissNPNPVVQMSVGHKAQESKIRYKTNEPVWEENFTFFIHNPKrqdleVEVRDE 531
Cdd:cd04011    13 ARQLVGG-----NIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESP-----DELFDK 65

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

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 47.45 E-value: 2.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 331 LVKGKS---DPYGIIRVGNQIFQSRVIKENLSPKWNEvyEA-----LVYEHPGQELEIELFDEDPDK---DDFLGSLMID 399
Cdd:cd08682    12 LCKGKSgtnDAYVIIQLGKEKYSTSVKEKTTSPVWKE--ECsfelpGLLSGNGNRATLQLTVMHRNLlglDKFLGQVSIP 89

                          90       100
                  ....*....|....*....|....*
gi 1536901836 400 LIEVE--KERLLDEWFTLDEVPKGK 422
Cdd:cd08682    90 LNDLDedKGRRRTRWFKLESKPGKD 114

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: 47.24 E-value: 2.71e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 462 LILYLDSARNLPSGKKISSNpNPVVQMSVGHKAQESKIRYKT-NEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCS--LG 538
Cdd:cd08681     3 LVVVVLKARNLPNKRKLDKQ-DPYCVLRIGGVTKKTKTDFRGgQHPEWDEELRFEITEDKKPILKVAVFDDDKRKPdlIG 81

                          90       100
                  ....*....|....*....|....*..
gi 1536901836 539 NLKVPLSQLLTSEDmtVSQRFQLSNSG 565
Cdd:cd08681    82 DTEVDLSPALKEGE--FDDWYELTLKG 106

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: 46.79 E-value: 2.72e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 468 SARNLPS----GKkisSNPNPVVQMSvGHKAQESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRD----EQHQcSLGN 539
Cdd:cd04040     7 SAENLPSadrnGK---SDPFVKFYLN-GEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDwdrgGKDD-LLGS 81


                  ....*...
gi 1536901836 540 LKVPLSQL 547
Cdd:cd04040    82 AYIDLSDL 89

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: 46.15 E-value: 6.99e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1536901836 337 DPYGIIRV-GNQIFQSRVIKENLSPKWNEVYEalVYEHPGQELEIELFDE---DPDKDDFLG 394
Cdd:cd08382    22 DPFAVITVdGGQTHSTDVAKKTLDPKWNEHFD--LTVGPSSIITIQVFDQkkfKKKDQGFLG 81

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: 44.94 E-value: 1.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 466 LDSARNLPSGKKiSSNPNPVVQMSVGHKAQESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDE---QHQCSLGNLKV 542
Cdd:cd08376     6 LVEGKNLPPMDD-NGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKdtgKKDEFIGRCEI 84


                  ....*
gi 1536901836 543 PLSQL 547
Cdd:cd08376    85 DLSAL 89

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: 45.02 E-value: 1.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 726 KLIVVVHACRNLiaFSEDG---SDPYVRMYLLPDKRRsgrrkTHVSKKTLNPVFDQSFDFSVSLPEV-QRRTLDVAVKNS 801
Cdd:cd04022     1 KLVVEVVDAQDL--MPKDGqgsSSAYVELDFDGQKKR-----TRTKPKDLNPVWNEKLVFNVSDPSRlSNLVLEVYVYND 73

                          90       100
                  ....*....|....*....|
gi 1536901836 802 gGFLSKDKGLLGKVLVALAS 821
Cdd:cd04022    74 -RRSGRRRSFLGRVRISGTS 92

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 44.94 E-value: 1.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 326 TYLKGLvKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYE--HPGQELEIELFD-EDPDKDDFLGSLMIDLIE 402
Cdd:cd08373     6 KNLPGL-KGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGspDPDESLEIVVKDyEKVGRNRLIGSATVSLQD 84


                  ....*..
gi 1536901836 403 VEKERLL 409
Cdd:cd08373    85 LVSEGLL 91

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: 44.17 E-value: 3.71e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 305 PVPKGV--LRIHFIEAQDLQGkDTYlkglvkGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYE-ALVYEHPGQELEIE 381
Cdd:cd04032    22 PTRRGLatLTVTVLRATGLWG-DYF------TSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDfGSVELSPGGKLRFE 94

                          90
                  ....*....|....*.
gi 1536901836 382 LFDEDpDK--DDFLGS 395
Cdd:cd04032    95 VWDRD-NGwdDDLLGT 109

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: 43.33 E-value: 4.21e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 312 RIHFIEAQDLQGkdtylkglvkGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEhPGQEL-----EIELFDED 386
Cdd:cd04011     7 RVRVIEARQLVG----------GNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHE-SPDELfdkiiKISVYDSR 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1536901836 387 -PDKDDFLGSLMIDLIEVEKE---RLLDEWFTL 415
Cdd:cd04011    76 sLRSDTLIGSFKLDVGTVYDQpdhAFLRKWLLL 108

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: 43.40 E-value: 5.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 462 LILYLDSARNLPSGKKISSNPNPVVQMSV---GHKAQESKIRYKTNEPVWEENFTFFIHNP--KRQDLEVEVRD---EQH 533
Cdd:cd08390    16 LTVSLIKARNLPPRTKDVAHCDPFVKVCLlpdERRSLQSKVKRKTQNPNFDETFVFQVSFKelQRRTLRLSVYDvdrFSR 95

                          90       100
                  ....*....|....*....|..
gi 1536901836 534 QCSLGNLKVPLSQLLTSEDMTV 555
Cdd:cd08390    96 HCIIGHVLFPLKDLDLVKGGVV 117

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: 43.02 E-value: 8.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 302 LRFPVPKGVLRIHFIEAQDLQGKDtylkglVKGKSDPYGIIRVGN---QIFQSRVIKENLSPKWNE--VYEALVYEHPGQ 376
Cdd:cd08385     9 LDYDFQSNQLTVGIIQAADLPAMD------MGGTSDPYVKVYLLPdkkKKFETKVHRKTLNPVFNEtfTFKVPYSELGNK 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1536901836 377 ELEIELFDEDP-DKDDFLGSLMIDLIEVEKERLLDEW 412
Cdd:cd08385    83 TLVFSVYDFDRfSKHDLIGEVRVPLLTVDLGHVTEEW 119

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: 42.17 E-value: 9.24e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 727 LIVVVHACRNLIAFSEDGS-DPYVRMyLLPDKRRsgrrKTHVSKKTLNPVFDQSFDFSVSLPEVQrrTLDVAVKNsggfl 805
Cdd:cd04050     2 LFVYLDSAKNLPLAKSTKEpSPYVEL-TVGKTTQ----KSKVKERTNNPVWEEGFTFLVRNPENQ--ELEIEVKD----- 69

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1536901836 806 SKDKGLLGKVLVALASEELAKGWT--QWYDLTEDG 838
Cdd:cd04050    70 DKTGKSLGSLTLPLSELLKEPDLTldQPFPLDNSG 104

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: 42.71 E-value: 1.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYE---HPGQELEIELFDE-- 385
Cdd:cd04022     2 LVVEVVDAQDLMPKDG------QGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDpsrLSNLVLEVYVYNDrr 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1536901836 386 DPDKDDFLGSLMIDLIEV--EKERLLdEWFTLD 416
Cdd:cd04022    76 SGRRRSFLGRVRISGTSFvpPSEAVV-QRYPLE 107

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: 42.15 E-value: 1.46e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1536901836 734 CRNLIAFSEDG-SDPYVRMYLLpdKRRSGRRKTHVsKKTLNPVFDQSFDFSVSLPEVQrrTLDVAVKNSgGFLSKD 808
Cdd:cd04037     9 ARNLQPKDPNGkSDPYLKIKLG--KKKINDRDNYI-PNTLNPVFGKMFELEATLPGNS--ILKISVMDY-DLLGSD 78

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: 42.25 E-value: 1.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 301 QLRFPVPKGVLRIHFIEAQDLQGKDTylkglvKGKSDPYGIIRV----GNQIFQ-SRVIKENLSPKWNEVYealVYE-HP 374
Cdd:cd04026     5 YLKISVKDNKLTVEVREAKNLIPMDP------NGLSDPYVKLKLipdpKNETKQkTKTIKKTLNPVWNETF---TFDlKP 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1536901836 375 GQE---LEIELFDED-PDKDDFLGSLMIDLIEVEKERlLDEWFTL 415
Cdd:cd04026    76 ADKdrrLSIEVWDWDrTTRNDFMGSLSFGVSELIKMP-VDGWYKL 119

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 41.76 E-value: 2.35e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1536901836 741 SEDGSDPYVRMYLL-PDKRRSGRRKTHVSKK-TLNPVFDQSFDFSVSLPEV 789
Cdd:cd00275    21 KGSIVDPYVEVEIHgLPADDSAKFKTKVVKNnGFNPVWNETFEFDVTVPEL 71

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

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 41.62 E-value: 2.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 333 KGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEhPGQELEIELFD-------EDPDKDDFLGSLMIDLIEVEK 405
Cdd:cd08379    21 RGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYD-PCTVLTVGVFDnsqshwkEAVQPDVLIGKVRIRLSTLED 99


                  ..
gi 1536901836 406 ER 407
Cdd:cd08379   100 DR 101

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: 41.09 E-value: 3.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 728 IVVVHAcRNLIAFSEDG-SDPYVRMYLlpdkrRSGRRKTHVSKKTLNPVFDQSFDFsvSLPEVQRRTLDVAV--KNSGgf 804
Cdd:cd08376     4 IVLVEG-KNLPPMDDNGlSDPYVKFRL-----GNEKYKSKVCSKTLNPQWLEQFDL--HLFDDQSQILEIEVwdKDTG-- 73

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1536901836 805 lsKDKGLLGKVLVALASEELAKGWTQWYDLtEDGT 839
Cdd:cd08376    74 --KKDEFIGRCEIDLSALPREQTHSLELEL-EDGE 105

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: 41.56 E-value: 3.49e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 334 GKSDPYgiIRV-------GNQIFQSRVIKENLSPKWNE--VYEALVYEHPGQELEIELFDEDPDK-DDFLGSLMIDlIEV 403
Cdd:cd08384    32 GYSDPF--VKLylkpdagKKSKHKTQVKKKTLNPEFNEefFYDIKHSDLAKKTLEITVWDKDIGKsNDYIGGLQLG-INA 108

                          90       100
                  ....*....|....*....|....*....
gi 1536901836 404 EKERlLDEWFtldEVPKGKLHLRLEWLTL 432
Cdd:cd08384   109 KGER-LRHWL---DCLKNPDKKIEAWHTL 133

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: 41.16 E-value: 3.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 302 LRFPVPKGVLRIHFIEAQDLQGKDtylkglVKGKSDPYgiIRV-----GNQIFQSRVIKENLSPKWNEV--YEALVYEHP 374
Cdd:cd08386     9 VSYDFQESTLTLKILKAVELPAKD------FSGTSDPF--VKIyllpdKKHKLETKVKRKNLNPHWNETflFEGFPYEKL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1536901836 375 GQE-LEIELFDEDP-DKDDFLGSLMIDLIEVE 404
Cdd:cd08386    81 QQRvLYLQVLDYDRfSRNDPIGEVSLPLNKVD 112

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: 41.00 E-value: 4.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 466 LDSARNLPSGKKISSNPNPVVQMSVGHKAQE--SKIRYKTNEPVWEE-------------NFTFFIHNPKRQDLEvevrd 530
Cdd:cd04044     8 IKSARGLKGSDIIGGTVDPYVTFSISNRRELarTKVKKDTSNPVWNEtkyilvnslteplNLTVYDFNDKRKDKL----- 82

                          90       100
                  ....*....|....*....|....*..
gi 1536901836 531 eqhqcsLGNLKVPLSQLL---TSEDMT 554
Cdd:cd04044    83 ------IGTAEFDLSSLLqnpEQENLT 103

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: 40.28 E-value: 4.71e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 470 RNLPSGKKISSNPNPVVQMSVGHKA--QESKIRyKTNEPVWEENFTFFIHNPKRQDLEVEVRDEQ--HQCSLGNLKVPLS 545
Cdd:cd04052     1 KGLDTSESKTGLLSPYAELYLNGKLvyTTRVKK-KTNNPSWNASTEFLVTDRRKSRVTVVVKDDRdrHDPVLGSVSISLN 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1536901836 546 QLLTSEDMtVSQRFQLSnSGPNSTIKMKIALR 577
Cdd:cd04052    80 DLIDATSV-GQQWFPLS-GNGQGRIRISALWK 109

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 41.54 E-value: 4.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 305 PVPKGVLRIHFIEAQDL------QGKDTYLKGLV----KGKSdpygiirvgnqIFQSRVIKENLSPKWNE--VYEALVYE 372
Cdd:cd04020    23 KPSTGELHVWVKEAKNLpalksgGTSDSFVKCYLlpdkSKKS-----------KQKTPVVKKSVNPVWNHtfVYDGVSPE 91

                          90       100
                  ....*....|....*....|....
gi 1536901836 373 HPGQE-LEIELFDEDPDK-DDFLG 394
Cdd:cd04020    92 DLSQAcLELTVWDHDKLSsNDFLG 115

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: 40.26 E-value: 8.82e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1536901836 744 GSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQRRTLDVAV 798
Cdd:cd08410    34 GSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELENVSLVFTV 88

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: 40.10 E-value: 9.55e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 728 IVVVHAcRNLIAFSEDG---SDPYVRMYLlpdkrRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQrrTLDVAVKNSGGF 804
Cdd:cd04024     5 VHVVEA-KDLAAKDRSGkgkSDPYAILSV-----GAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQ--LLKLILWDKDRF 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1536901836 805 LSKDKglLGKVLVALAS---EELAKGWTQWYDLteDGTRPQAM 844
Cdd:cd04024    77 AGKDY--LGEFDIALEEvfaDGKTGQSDKWITL--KSTRPGKT 115

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: 39.83 E-value: 9.95e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1536901836 468 SARNLP-SGKKISSNPNPVVQMSV-GHKAQESKiRYKTN-------EPVWEENFTFFIHNP 519
Cdd:cd00275    10 SGQQLPkPKGDKGSIVDPYVEVEIhGLPADDSA-KFKTKvvknngfNPVWNETFEFDVTVP 69

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: 39.86 E-value: 1.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 733 ACRNLI---AFSEdgSDPYVRMYLLPDKRRS----GRrkTHVSKKTLNPVFDQSFDFSVSLPEVQRRTLDV-AVKNSGGF 804
Cdd:cd04048     8 SCRNLLdkdVLSK--SDPFVVVYVKTGGSGQwveiGR--TEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVyDVDSKSKD 83

                          90
                  ....*....|.
gi 1536901836 805 LSKDKgLLGKV 815
Cdd:cd04048    84 LSDHD-FLGEA 93

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: 39.62 E-value: 1.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 337 DPYGIIRVGNQIFQSRV-IKENLSPKWNEVYEALVyeHPG-QELEIELFDEDPDK-DDFLGSLMIDLIE-VEKERLLDEW 412
Cdd:cd04016    23 DPYCRIRVGHAVYETPTaYNGAKNPRWNKTIQCTL--PEGvDSIYIEIFDERAFTmDERIAWTHITIPEsVFNGETLDDW 100


                  ...
gi 1536901836 413 FTL 415
Cdd:cd04016   101 YSL 103

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: 39.83 E-value: 1.30e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 731 VHACRNLIAFSEDG-SDPYVRMYLLpdkRRSgrRKTHVSKKTLNPVFDQSFDF-SVSLPE 788
Cdd:cd04017     7 IYQARDLLAADKSGlSDPFARVSFL---NQS--QETEVIKETLSPTWDQTLIFdEVELYG 61

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: 39.45 E-value: 1.39e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 311 LRIHFIEAQDLqgkdTYLKGLVKGKSDPY------GIIRVGNQIFQSRVIKEN-LSPKWNEVYEALVYEHpgqEL---EI 380
Cdd:cd00275     4 LTIKIISGQQL----PKPKGDKGSIVDPYveveihGLPADDSAKFKTKVVKNNgFNPVWNETFEFDVTVP---ELaflRF 76

                          90
                  ....*....|....
gi 1536901836 381 ELFDEDPDKDDFLG 394
Cdd:cd00275    77 VVYDEDSGDDDFLG 90

C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 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: 176072 [Multi-domain] Cd Length: 155 Bit Score: 39.98 E-value: 1.57e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 746 DPYVRmYLLP---DKRRSGRrkTHVSKKTLNPVFDQSFDFSV-----SLPEV-QRRTLDVAVKNSGGFLSKDKgLLGKVL 816
Cdd:cd08690    26 DTYVK-FEFPypnEEPQSGK--TSTIKDTNSPEYNESFKLNInrkhrSFQRVfKRHGLKFEVYHKGGFLRSDK-LLGTAQ 101


                  ...
gi 1536901836 817 VAL 819
Cdd:cd08690   102 VKL 104

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: 39.09 E-value: 1.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 315 FIEAQDLQGKDtylkglVKGKSDPYGIIRVGNQ-----IFQSR--VIKENLSPKWNEV------YEALvyehpgQELEIE 381
Cdd:cd04048     6 SISCRNLLDKD------VLSKSDPFVVVYVKTGgsgqwVEIGRteVIKNNLNPDFVTTftvdyyFEEV------QKLRFE 73

                          90       100
                  ....*....|....*....|....
gi 1536901836 382 LFDED-----PDKDDFLGSLMIDL 400
Cdd:cd04048    74 VYDVDskskdLSDHDFLGEAECTL 97

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: 38.77 E-value: 1.96e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1536901836 309 GVLRIHFIEAQDLQGkdtyLKGLVKGK--SDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEH 373
Cdd:cd04039     1 GVVFMEIKSITDLPP----LKNMTRTGfdMDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPH 63

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: 38.78 E-value: 2.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 469 ARNLPSGKKISSnPNPVVQMSVgHKAQESKIRYKT----NEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCS--LGNLKV 542
Cdd:cd04036     9 ATNITKGDLLST-PDCYVELWL-PTASDEKKRTKTiknsINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDdhLGTVLF 86

                          90       100
                  ....*....|....*....|....
gi 1536901836 543 PLSQLLTSEdmTVSQRFQLSNSGP 566
Cdd:cd04036    87 DVSKLKLGE--KVRVTFSLNPQGK 108

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: 38.79 E-value: 2.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 467 DSARNLPSGKKISSNPNPVVQMSVGHKA-QESKIRYKTNEPVWEENFTFFIHNPkrQDLEVEVRdeqHQCSLG------N 539
Cdd:cd04014    20 DWSTRHAVPKKGSQLLDPYVSIDVDDTHiGKTSTKPKTNSPVWNEEFTTEVHNG--RNLELTVF---HDAAIGpddfvaN 94

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1536901836 540 LKVPLSQLLTSEDMTVSQRFQLSnsgPNSTIKMKIALR 577
Cdd:cd04014    95 CTISFEDLIQRGSGSFDLWVDLE---PQGKLHVKIELK 129

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: 38.05 E-value: 3.65e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 461 LLILYLDSARNLPSgKKISSNPNPVVQMSVGHKAQESKIRYKTNEPVWEENFTFF---IHnpkrQDLEVEVRDEQHQCS- 536
Cdd:cd08377     2 FLQVKVIRASGLAA-ADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPikdIH----DVLEVTVYDEDKDKKp 76

                          90
                  ....*....|...
gi 1536901836 537 --LGNLKVPLSQL 547
Cdd:cd08377    77 efLGKVAIPLLSI 89

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: 38.54 E-value: 3.86e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 468 SARNLPSGkkISSNPNPVVQMSV-----------GHKAQE--SKIRYKTNEPVWE-ENFTFFIHnpkRQD-LEVEVRDEQ 532
Cdd:cd08691     9 QARNLKKG--MFFNPDPYVKISIqpgkrhifpalPHHGQEcrTSIVENTINPVWHrEQFVFVGL---PTDvLEIEVKDKF 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1536901836 533 HQCS------LGNLKVPLSQLLTSE---DMTVSQRfqLSNSGPNSTIKMKIALRVL 579
Cdd:cd08691    84 AKSRpiirrfLGKLSIPVQRLLERHaigDQELSYT--LGRRTPTDHVSGQLTFRFE 137

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: 38.20 E-value: 4.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 729 VVVHACRNLIAFSEDGS-DPYVRMYLLPDKRRsgrrkTHVSKKTLNPVFDQ--SFDFS---VSLPEVQRRTLDVAVKNSG 802
Cdd:cd08682     3 VTVLQARGLLCKGKSGTnDAYVIIQLGKEKYS-----TSVKEKTTSPVWKEecSFELPgllSGNGNRATLQLTVMHRNLL 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1536901836 803 GFlskDKgLLGKVLVALASEELAKGW--TQWYDL 834
Cdd:cd08682    78 GL---DK-FLGQVSIPLNDLDEDKGRrrTRWFKL 107

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

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 38.02 E-value: 4.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 462 LILYLDSARNLPSGKKiSSNPNPVVQM------SVGHKaQESKIRYKTNEPVWEENFTFFIH--NPKRQDLEVEVRDE-- 531
Cdd:cd04030    18 LIVTVHKCRNLPPCDS-SDIPDPYVRLyllpdkSKSTR-RKTSVKKDNLNPVFDETFEFPVSleELKRRTLDVAVKNSks 95

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1536901836 532 ---QHQCSLGNLKVPLSQLLTSEdmTVSQRFQLS 562
Cdd:cd04030    96 flsREKKLLGQVLIDLSDLDLSK--GFTQWYDLT 127

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: 37.63 E-value: 4.81e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 745 SDPYVRMYLlpDKRRSGRrkTHVSKKtLNPVFDQSFDFSVSLPEVQRRTLdvavknsgGFLSKDKGLLGK----VLVALA 820
Cdd:cd08383    18 RDPYCTVSL--DQVEVAR--TKTVEK-LNPFWGEEFVFDDPPPDVTFFTL--------SFYNKDKRSKDRdiviGKVALS 84

                          90
                  ....*....|....*.
gi 1536901836 821 SEELAKGWTQWYDLTE 836
Cdd:cd08383    85 KLDLGQGKDEWFPLTP 100

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: 37.64 E-value: 5.20e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 483 NPVVQMSVGHKA-QESKIRYKTNEPVWEENFTFFIHNPkRQDLEVEVRDEQHQCS---LGNLKVPLSQLLTSEdmtvSQR 558
Cdd:cd04042    22 DPYVKFKYGGKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDYDRGLTddfMGSAFVDLSTLELNK----PTE 96

                          90       100
                  ....*....|....*....|...
gi 1536901836 559 FQLSNSGPNSTIKMKIALRVLHL 581
Cdd:cd04042    97 VKLKLEDPNSDEDLGYISLVVTL 119

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: 37.29 E-value: 5.44e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 337 DPYGIIRVGNQIFQSRVIKENLSPKWNEvyEALVYEHPGQEL-----EIELFDEDP-DKDDFLGSLMIDL 400
Cdd:cd08688    22 DAFVEVKFGSTTYKTDVVKKSLNPVWNS--EWFRFEVDDEELqdeplQIRVMDHDTySANDAIGKVYIDL 89

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: 38.12 E-value: 6.70e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 726 KLIVVVHACRNLIAFSEDG-SDPYVRMYLLPD---------KRRSGRRK---------------THVSKKTLNPVFDQSF 780
Cdd:cd08676    29 VLKVTVIEAKGLLAKDVNGfSDPYCMLGIVPAsrernseksKKRKSHRKkavlkdtvpaksikvTEVKPQTLNPVWNETF 108

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1536901836 781 DFSVSlpEVQRRTLDVAVKNSggflskDKGLLGKVLVALaSEELAKGWTQWYDL 834
Cdd:cd08676   109 RFEVE--DVSNDQLHLDIWDH------DDDFLGCVNIPL-KDLPSCGLDSWFKL 153

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: 37.18 E-value: 7.09e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1536901836 745 SDPYVRMYLlpdkRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEvQRRTLDVAVKNSGGflsKDKgLLGKVLVALA 820
Cdd:cd04045    22 IDPYVRVLV----NGIVKGRTVTISNTLNPVWDEVLYVPVTSPN-QKITLEVMDYEKVG---KDR-SLGSVEINVS 88

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: 36.90 E-value: 7.57e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 729 VVVHACRNLIAF--SEDGSDPYVRMYLLpdkrrSGRRKTHVSKKTLNPVF-DQSFDFSVSLPEVQRRTLDVAVKNSGGFL 805
Cdd:cd08688     3 VRVVAARDLPVMdrSSDLTDAFVEVKFG-----STTYKTDVVKKSLNPVWnSEWFRFEVDDEELQDEPLQIRVMDHDTYS 77

                          90
                  ....*....|....
gi 1536901836 806 SKDkgLLGKVLVAL 819
Cdd:cd08688    78 AND--AIGKVYIDL 89

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: 37.27 E-value: 8.24e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1536901836 728 IVVVHAcRNLIA-------FSEDGSDPYVrmyllpdKRRSGRR--KTHVSKKTLNPVFDQSFDfsVSLPEVQRRTLDVAV 798
Cdd:cd08391     5 IHVIEA-QDLVAkdkfvggLVKGKSDPYV-------IVRVGAQtfKSKVIKENLNPKWNEVYE--AVVDEVPGQELEIEL 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1536901836 799 knsggfLSKDKG---LLGKVLVALASEELAKGWTQWYDLTE 836
Cdd:cd08391    75 ------FDEDPDkddFLGRLSIDLGSVEKKGFIDEWLPLED 109

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: 36.79 E-value: 8.61e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1536901836 745 SDPYVRMYLLPDKRRsgrrkTHVSKKTLNPVFDQS--FDFSVSLPEVQRRTLDVAVKNSGGFLS 806
Cdd:cd04011    21 IDPVVKVEVGGQKKY-----TSVKKGTNCPFYNEYffFNFHESPDELFDKIIKISVYDSRSLRS 79

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: 37.35 E-value: 9.59e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1536901836 469 ARNLPsgKKISSNPNPVVQMSVGH----KAQESKIRYKTNEPVWEENFTF---FIHNPKRQDLEVEVRD 530
Cdd:cd08675     8 CRDLA--LKSNGTCDPFARVTLNYssktDTKRTKVKKKTNNPRFDEAFYFeltIGFSYEKKSFKVEEED 74