NCBI Conserved Domain Search

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: 326.01 E-value: 1.87e-106

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 120 ERVEWANKIIIQIWPYLSMIMENKIREKLEPKIREKSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNRRKVTLDLQICY 199
Cdd:cd21681    1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIREKSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDRRQVILDLQICY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 200 IGDCEISVELQKIRGGVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQINWTGLTNLLDMPGINELSDSLLEDL 279
Cdd:cd21681   81 IGDCEINVEIKKCKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGLTNLLDIPGINDMSDSLIEDL 160

                        170
                 ....*....|....*..
gi 568961591 280 IAAHLVLPNRVTVPVKK 296
Cdd:cd21681  161 IASHLVLPNRFTVPLKK 177

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: 239.70 E-value: 6.71e-74

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 120 ERVEWANKIIIQIWPYLSMIMENKIREKLEPKIREKSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKrNRRKVTLDLQICY 199
Cdd:cd21679    1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTEF-DKRQIILDLHISY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 200 IGDCEISVELQKI--RGGVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQINWTGLTNLLDMPGINELSDSLLE 277
Cdd:cd21679   80 VGDVEINVEVKKYfcKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIM 159

                        170
                 ....*....|....*..
gi 568961591 278 DLIAAHLVLPNRVTVPV 294
Cdd:cd21679  160 DTIASFLVLPNRLTVPL 176

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: 235.55 E-value: 2.46e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 118 DVERVEWANKIIIQIWPYLSMIMENKIREKLEPKIREKSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNRRKVTLDLQI 197
Cdd:cd21680    1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAHLSTFSFTKIDLGDQPLRINGVKVYTENVDKRQIILDLQI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 198 CYIGDCEISVELQK--IRGGVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQINWTGLTNLLDMPGINELSDSL 275
Cdd:cd21680   81 SFVGNCEIDLEIKRyfCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDIPGLNGLSDTI 160

                        170
                 ....*....|....*....
gi 568961591 276 LEDLIAAHLVLPNRVTVPV 294
Cdd:cd21680  161 ILDIISNYLVLPNRITVPL 179

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: 232.06 E-value: 4.22e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 120 ERVEWANKIIIQIWPYLSMIMENKIREKLEPKIR-EKSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNRRKVTLDLQIC 198
Cdd:cd21670    1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSIRaLLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDIS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 199 YIGDCEISVELQ-KIRGGVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQINWTGLTNLLDMPGINELSDSLLE 277
Cdd:cd21670   81 YDGDADIEVSVGtGIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKIIV 160

                        170
                 ....*....|....*..
gi 568961591 278 DLIAAHLVLPNRVTVPV 294
Cdd:cd21670  161 DQIASFLVLPNRITIPL 177

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: 212.20 E-value: 1.05e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  118 DVERVEWANKIIIQIWPYLSMIMENKIREKLEPKIREKSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNRRKVTLDLQI 197
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  198 CYIGDCEISVELQK--IRGGVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQINWTGLTNLLDMPGINELSDSL 275
Cdd:pfam17047  81 SFVGNCEIDLEIKRyfCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 160

                         170
                  ....*....|....*....
gi 568961591  276 LEDLIAAHLVLPNRVTVPV 294
Cdd:pfam17047 161 ILDIISNYLVLPNRITVPL 179

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: 207.13 E-value: 1.23e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 759 RLGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSS-GADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGE 837
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSdIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568961591 838 VQKRSLDVAVKNSRPLGSHRRKELGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd04030   81 LKRRTLDVAVKNSKSFLSREKKLLGQVLIDLSDLDLSKGFTQWYDLT 127

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: 189.81 E-value: 1.79e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNFLG--LGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 387
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFVGglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568961591 388 KDDFLGSLQICLGDVMKNRVVDEWFALNDTTSGRLHLRLEW 428
Cdd:cd08391   81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

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: 141.15 E-value: 3.12e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 111 PAWIHFPDVERVEWANKIIIQIWPYLSMIMENKIREKLEPKIRE-KSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNrr 189
Cdd:cd21677    1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLEQyKPSFISSIKFKKLTLGTVPPRIEGVKVVESDED-- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 190 KVTLDLQICYIGDCEISVELQKIRG-----GVSGVQLQGTLRVILEPLLVDKPFIGAVTVFFLQKPHLQIN---WTGLTN 261
Cdd:cd21677   79 EVILDVDFRWAGDPDIVLAVKLLPGlslpvQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDlklLGGDDM 158

                        170       180       190
                 ....*....|....*....|....*....|...
gi 568961591 262 LLdmPGINELSDSLLEDLIAAHLVLPNRVTVPV 294
Cdd:cd21677  159 AL--PGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

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: 126.91 E-value: 1.97e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 449 ILVVFLENACNLPrnpfdylngeyrakklsrfvKNKASRDPSSYVKLTVGKKTFTSKTCPHSKDPVWSQVFSFFVHSVAA 528
Cdd:cd04050    1 LLFVYLDSAKNLP--------------------LAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPEN 60

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568961591 529 EQLCLKVLDDELECALGVLEFPLCRILPCADLTLEQCFQLDHSG 572
Cdd:cd04050   61 QELEIEVKDDKTGKSLGSLTLPLSELLKEPDLTLDQPFPLDNSG 104

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: 110.59 E-value: 2.09e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDnfLGLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDK 388
Cdd:cd04024    1 GVLRVHVVEAKDLAAKD--RSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDrFAG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 568961591 389 DDFLGSLQICLGDVM---KNRVVDEWFALNDT-------TSGRLHLRLEW 428
Cdd:cd04024   79 KDYLGEFDIALEEVFadgKTGQSDKWITLKSTrpgktsvVSGEIHLQFSW 128

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 104.32 E-value: 1.45e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  310 GVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHC--RSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 387
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKD----GNGTSDPYVKVYLLDGKQkkKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*...
gi 568961591  388 -KDDFLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:pfam00168  77 gRDDFIGEVRIPLSELDSGEGLDGWYPL 104

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 112.16 E-value: 5.18e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591   40 YSFVARVLFYLAPVYLAGYLGLSVTWLLL-GALLWMWWRRNRRgklgrleaafEFLEHEREFISRELRGQHLPAwihfpD 118
Cdd:COG5038   155 YQSVAIVLIGSVASWIFGYLGFSFASLFFiILVTMYVYRTCIK----------RVRRNIRDLVQQELSEEKLEN-----D 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  119 VERVEWANKIIIQIWPYLSMIMENKIREKLEPKIRE------KSIHLRTFTftklyFGQKCPKVNGVKVHTdKRNRRKVT 192
Cdd:COG5038   220 YESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEaipsfiDALALDEFT-----LGSKPPRIDGIRSYP-STESDTVV 293

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  193 LDLQI----------------CYI-GDCEISVELQKIRGG------VSGVQLQGTLRVILEpLLVDKPFIGAVTVFFLQK 249
Cdd:COG5038   294 MDVDFsftphdisdvtatsarASVnPKISLVVKKGKSFGSftlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEV 372

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  250 PHLQINWTGL------TNLLDMPGINELSDSLLEDLIAAHLVLPNRVTVPVKKGL-DVTNlrvpLPCGVIRVHLLEAKKL 322
Cdd:COG5038   373 PEFDFILVPLggdffgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTIDISQIMaGDSG----TAIGVVEVKIKSAEGL 448

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  323 AQKDNFlgLGGKSDPYAKV-SIGLQHCRSRTIYKNLNPTWNEVFeFMVYEVPGQDLEVDLYD-EDTDKDDFLGSLQICLG 400
Cdd:COG5038   449 KKSDST--INGTVDPYITVtFSDRVIGKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDfNSFKSDKVVGSTQLDLA 525

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  401 DVMKNRVVDEWFA---LNDTTSGRLHLRLEW-------LSLLTDQEALTENDSGlstaILVVFLEnacnlprnpfdylng 470
Cdd:COG5038   526 LLHQNPVKKNELYeflRNTKNVGRLTYDLRFfpviedkKELKGSVEPLEDSNTG----ILKVTLR--------------- 586

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  471 eyrakKLSRFVKNKASRDPSSYVKLTVGKKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDDELECALGVLEFP 550
Cdd:COG5038   587 -----EVKALDELSSKKDNKSAELYTNAKEVYSTGKLKFTNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGST 661


                  ....*.
gi 568961591  551 LCRILP 556
Cdd:COG5038   662 LPDLID 667

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: 96.75 E-value: 7.55e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIG-LQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD-KD 389
Cdd:cd00030    1 LRVTVIEARNLPAKD----LNGKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFsKD 76

                         90       100
                 ....*....|....*....|....*.
gi 568961591 390 DFLGSLQICLGDV-MKNRVVDEWFAL 414
Cdd:cd00030   77 DFLGEVEIPLSELlDSGKEGELWLPL 102

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: 96.94 E-value: 1.03e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG--ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKkrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 839 QKRSLDVAVKNSRPLGshRRKELGKVLIDLSKQDLIKGFSQWYEL 883
Cdd:cd08521   81 ETRTLQLSVWHHDRFG--RNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 97.01 E-value: 3.90e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 141 ENKIREKLEPKIRE--KSIHLRTFTFTKLYFGQKCPKVNGVKVHTDKRNRRKVTLDLQICYIGDCEISVELQ-------- 210
Cdd:cd21669    2 EQLIRESLQELLEEvkKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDLQLVLDLDLEYAGDFSVVLSAKlgggglgl 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 211 KIRGGVSGVQLQGTLRVILEpLLVDKPFIGAVTVFFLQKPHLQINWT--GLTNLLDMPGINELSDSLLEDLIAAHLVLPN 288
Cdd:cd21669   82 PVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRplGGVDLMELPGLSSWLEKLLTDALVELLVEPN 160


                 ....*
gi 568961591 289 RVTVP 293
Cdd:cd21669  161 RIVID 165

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: 90.18 E-value: 2.61e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG--ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKqrSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 839 QKRSLDVAVKNSRPLGshRRKELGKVLIDLSKQDLIKGFSQWYEL 883
Cdd:cd08393   82 PTRVLNLSVWHRDSLG--RNSFLGEVEVDLGSWDWSNTQPTWYPL 124

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: 87.93 E-value: 7.98e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591   311 VIRVHLLEAKKLAQKDNFlglgGKSDPYAKVSIGLQHC---RSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 387
Cdd:smart00239   1 TLTVKIISARNLPPKDKG----GKSDPYVKVSLDGDPKekkKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 568961591   388 -KDDFLGSLQICLGDVMKNRVVDEW 411
Cdd:smart00239  77 gRDDFIGQVTIPLSDLLLGGRHEKL 101

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 87.37 E-value: 1.67e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  776 LRVLVNGCRNLTPCTSSG-ADPYVRIYLLperRWASRKKTSVKQKTLEPLFDETFEFFVPmgEVQKRSLDVAVKNSRPLG 854
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGtSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVP--DPENAVLEIEVYDYDRFG 77

                          90       100
                  ....*....|....*....|....*....
gi 568961591  855 SHRRkeLGKVLIDLSKQDLIKGFSQWYEL 883
Cdd:pfam00168  78 RDDF--IGEVRIPLSELDSGEGLDGWYPL 104

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: 85.00 E-value: 1.97e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGA--DPYVRIYLLP-ERRwasRKKTSVKQKTLEPLFDETFEFFVPMGE 837
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAhcDPFVKVCLLPdERR---SLQSKVKRKTQNPNFDETFVFQVSFKE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568961591 838 VQKRSLDVAVKNSRplGSHRRKELGKVLIDLSKQDLIKGFSQW 880
Cdd:cd08390   78 LQRRTLRLSVYDVD--RFSRHCIIGHVLFPLKDLDLVKGGVVW 118

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: 83.41 E-value: 6.44e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLaqkDNfLGLGGKSDPYAKVSI-GLQHCRSRTIYKNLNPTWNEVFEFMVYEvPGQDLEVDLYDEDTD- 387
Cdd:cd04045    1 GVLRLHIRKANDL---KN-LEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEKVg 75

                         90
                 ....*....|....*..
gi 568961591 388 KDDFLGSLQICLGDVMK 404
Cdd:cd04045   76 KDRSLGSVEINVSDLIK 92

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: 82.68 E-value: 1.08e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFF-VPMGEV 838
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSlRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSnVRRETL 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 839 QKRSLDVAVKNSRPLGSHrrKELGKVLIDLSkQDLIKGFSQWYEL 883
Cdd:cd04031   83 KERTLEVTVWDYDRDGEN--DFLGEVVIDLA-DALLDDEPHWYPL 124

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: 82.34 E-value: 1.29e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVclRHCLRVLVNGCRNLTPCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEF-FVPMGEVQ 839
Cdd:cd08381    2 GQVKLSISYK--NGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYdGLPVEDLQ 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568961591 840 KRSLDVAVKNSrplGSHRRKE-LGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd08381   80 QRVLQVSVWSH---DSLVENEfLGGVCIPLKKLDLSQETEKWYPLG 122

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: 81.58 E-value: 2.37e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMV---YEVpgqdLEVDLYDEDT 386
Cdd:cd08377    1 GFLQVKVIRASGLAAAD----IGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIkdiHDV----LEVTVYDEDK 72

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568961591 387 DKD-DFLGSLQICLGDVmKNRVVDeWFALND 416
Cdd:cd08377   73 DKKpEFLGKVAIPLLSI-KNGERK-WYALKD 101

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: 80.01 E-value: 9.36e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 313 RVHLLEAKKLAQKDnflgLGGKSDPYAKVSI-GLQHCRSRTIYKNLNPTWNEVFEFMVyEVPGQDLEVDLYDED-TDKDD 390
Cdd:cd04042    3 DIHLKEGRNLAARD----RGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPI-EDVTQPLYIKVFDYDrGLTDD 77

                         90
                 ....*....|....*....
gi 568961591 391 FLGSLQICLGDVMKNRVVD 409
Cdd:cd04042   78 FMGSAFVDLSTLELNKPTE 96

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: 80.08 E-value: 1.26e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 763 IQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQKR 841
Cdd:cd08384    2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGySDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKK 81


                 ....*.
gi 568961591 842 SLDVAV 847
Cdd:cd08384   82 TLEITV 87

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: 79.37 E-value: 2.27e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd08402    1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGlSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                         90       100
                 ....*....|....*....|....*...
gi 568961591 839 QKRSLDVAVKNSRPLGSHRRkeLGKVLI 866
Cdd:cd08402   81 QKVHLIVTVLDYDRIGKNDP--IGKVVL 106

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: 78.72 E-value: 3.41e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLT--PCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLAygDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 568961591 839 QKRSLDVAVKNSRPLgsHRRKELGKVLIDLSKQDLIKGFSQ---WYEL 883
Cdd:cd08392   82 SSRQLQVSVWHSRTL--KRRVFLGEVLIPLADWDFEDTDSQrflWYPL 127

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: 77.31 E-value: 7.56e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGA-DPYVRIYLLPERRwasrKK--TSVKQKTLEPLFDETFEFFVPMG 836
Cdd:cd08385    2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTsDPYVKVYLLPDKK----KKfeTKVHRKTLNPVFNETFTFKVPYS 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568961591 837 EVQKRSLDVAVKNSRPLGSHrrKELGKVLIDLSKQDLIKGFSQWYELTA 885
Cdd:cd08385   78 ELGNKTLVFSVYDFDRFSKH--DLIGEVRVPLLTVDLGHVTEEWRDLES 124

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: 77.30 E-value: 7.94e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDT-DKD 389
Cdd:cd08376    1 VVTIVLVEGKNLPPMDD----NGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTgKKD 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568961591 390 DFLGSLQICLGDVMKNRVVDEWFALNDTTsGRLHL 424
Cdd:cd08376   77 EFIGRCEIDLSALPREQTHSLELELEDGE-GSLLL 110

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: 75.57 E-value: 2.10e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWasrkKTSVKQKTLEPLFDETFEFFVPmgEVQKRSLDVAVKNSRPLG 854
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGkSDPYVKVSLGGKQKF----KTKVVKNTLNPVWNETFEFPVL--DPESDTLTVEVWDKDRFS 74

                         90       100       110
                 ....*....|....*....|....*....|
gi 568961591 855 SHRRkeLGKVLIDLSK-QDLIKGFSQWYEL 883
Cdd:cd00030   75 KDDF--LGEVEIPLSElLDSGKEGELWLPL 102

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 74.45 E-value: 4.68e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591   776 LRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRwaSRKKTSVKQKTLEPLFDETFEFFVPmgEVQKRSLDVAVKNSRPLG 854
Cdd:smart00239   2 LTVKIISARNLPPKDKGGkSDPYVKVSLDGDPK--EKKKTKVVKNTLNPVWNETFEFEVP--PPELAELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|....*.
gi 568961591   855 SHRRkeLGKVLIDLSkqDLIKGFSQW 880
Cdd:smart00239  78 RDDF--IGQVTIPLS--DLLLGGRHE 99

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: 74.20 E-value: 1.57e-15

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568961591 764 QLTVR--YVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRW--ASRKKTSVKQKTLEPLFDETFEFFVP 834
Cdd:cd04009    4 VLTVKayYRASEQSLRVEILNARNLLPLDSNGsSDPFVKVELLPRHLFpdVPTPKTQVKKKTLFPLFDESFEFNVP 79

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: 73.92 E-value: 1.57e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTP-----CTSsgaDPYVRIYLLPERRwaSRKKTSVKQKTLEPLFDETFEFF-V 833
Cdd:cd08388    2 LGTLFFSLRYNSEKKALLVNIIECRDLPAmdeqsGTS---DPYVKLQLLPEKE--HKVKTRVLRKTRNPVYDETFTFYgI 76

                         90
                 ....*....|....
gi 568961591 834 PMGEVQKRSLDVAV 847
Cdd:cd08388   77 PYNQLQDLSLHFAV 90

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: 73.47 E-value: 1.82e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFF-VPMGE 837
Cdd:cd04035    1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGlSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568961591 838 VQKRSLDVAVKNSRPLGShrrKELGKVLIDLSK 870
Cdd:cd04035   81 IQRKTLRLLVLDEDRFGN---DFLGETRIPLKK 110

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: 73.77 E-value: 1.88e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGlSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568961591 840 KRSLDVAVKNSRPLGSHRrkELGKVLIDLSKQDLikGFSQWYELTA 885
Cdd:cd00276   81 EVSLVITVVDKDSVGRNE--VIGQVVLGPDSGGE--ELEHWNEMLA 122

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: 72.74 E-value: 6.68e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNFlglggKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQdLEVDLYDEDT-DK 388
Cdd:cd04038    2 GLLKVRVVRGTNLAVRDFT-----SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKDTfSK 75

                         90
                 ....*....|....*
gi 568961591 389 DDFLGSLQICLGDVM 403
Cdd:cd04038   76 DDSMGEAEIDLEPLV 90

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: 73.75 E-value: 9.27e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 120 ERVEWANKIIIQIW----PYLS-MIME--NKIREKLEPK-IreKSIHLRTFTFtklyfGQKCPKVNGVKVHtDKRNRRKV 191
Cdd:cd21678    1 ESVEWLNYFLQKFWliyePVLSeTIVTnvNPVLAENCPSfL--DSLRLTEFTL-----GTKAPRIEGVRTY-PKTEDDVV 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 192 TLDLQICYI-------------GDCEISVELQ-KIRGGVSGVQL---------QGTLRVILEpLLVDKPFIGAVTVFFLQ 248
Cdd:cd21678   73 VMDWEFSFTpndtsdltakqikNKVNPKIVLTaRVGKGVVGIDLpilvedlsfSGKLRVRLK-LMPDFPHIKTVEVSFLE 151

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568961591 249 KPhlQINWT-----GLTNLLDMPGINELSDSLLEDLIAAHLVLPNRVTVPVKK 296
Cdd:cd21678  152 PP--EIDFVlkplgGGFDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDLEQ 202

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: 70.93 E-value: 1.50e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG--ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAKkrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 839 QKRSLDVAVKNSRPLGshRRKELGKVLIDLSKQDLIKGFSQWYEL 883
Cdd:cd04029   82 ETRTLQLSVWHYDRFG--RNTFLGEVEIPLDSWNFDSQHEECLPL 124

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 69.90 E-value: 2.36e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHC-RSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDKD 389
Cdd:cd04040    1 LTVDVISAENLPSAD----RNGKSDPFVKFYLNGEKVfKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDrGGKD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568961591 390 DFLGSLQICLGDVMKNRVVDewFALNDTTSGRLHLRLEWLS 430
Cdd:cd04040   77 DLLGSAYIDLSDLEPEETTE--LTLPLDGQGGGKLGAVFLP 115

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: 70.21 E-value: 2.37e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDKDD 390
Cdd:cd04025    2 LRCHVLEARDLAPKD----RNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDlVSKND 77

                         90       100
                 ....*....|....*....|....
gi 568961591 391 FLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQEEGWFRL 101

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: 69.98 E-value: 4.35e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRhcLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd04026    2 GRIYLKISVKDNK--LTVEVREAKNLIPMDPNGlSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79


                 ..
gi 568961591 840 KR 841
Cdd:cd04026   80 RR 81

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: 68.94 E-value: 1.15e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTSSGADPYVRIYLLPERRWASrKKTSVKQKTLEPLFDETFEF-------------FVPMGEVQKRS 842
Cdd:cd08675    1 LSVRVLECRDLALKSNGTCDPFARVTLNYSSKTDT-KRTKVKKKTNNPRFDEAFYFeltigfsyekksfKVEEEDLEKSE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568961591 843 LDVAVKNSRPLGshRRKELGKVLIDLSKQDLIKGFSQWYELtadgQPRS 891
Cdd:cd08675   80 LRVELWHASMVS--GDDFLGEVRIPLQGLQQAGSHQAWYFL----QPRE 122

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: 68.20 E-value: 1.49e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 759 RLGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRwaSRKKTSVKQKTLEPLFDETFEFFVPMGE 837
Cdd:cd08387    1 TRGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGtADPYCKVRLLPDRS--NTKQSKIHKKTLNPEFDESFVFEVPPQE 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568961591 838 VQKRSLDVAVKNSRPLGSHRRkeLGKVLIDLSKQDLIKGFSQW 880
Cdd:cd08387   79 LPKRTLEVLLYDFDQFSRDEC--IGVVELPLAEVDLSEKLDLW 119

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 66.99 E-value: 5.07e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDNFlglgGKSDPYAKVSI----GLQHCRS---RTIYKNLNPTWNEVFEFMVyeVPGQD-LEVDLY 382
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIF----GASDPYVKISLydpdGNGEIDSvqtKTIKKTLNPKWNEEFFFRV--NPREHrLLFEVF 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568961591 383 DED-TDKDDFLGSLQICL------GDVMKNRVVDEWFALNDTTS-----GRLHLRLEWL 429
Cdd:cd04033   75 DENrLTRDDFLGQVEVPLnnlpteTPGNERRYTFKDYLLRPRSSksrvkGHLRLYMAYL 133

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: 66.05 E-value: 5.17e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 332 GGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDKDdfLGSLQICLGDVMK--NRVVD 409
Cdd:cd04050   18 TKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS--LGSLTLPLSELLKepDLTLD 95


                 ....*...
gi 568961591 410 EWFALNDT 417
Cdd:cd04050   96 QPFPLDNS 103

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: 64.96 E-value: 1.75e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAQKDNflglGGKSDPYAKVSIgLQHC------RSRTIYKNLNPTWNEVFEFMVyeVPGQDL-----EVDLY 382
Cdd:cd04031   20 VTVLQARDLPPRDD----GSLRNPYVKVYL-LPDRsekskrRTKTVKKTLNPEWNQTFEYSN--VRRETLkertlEVTVW 92

                         90       100
                 ....*....|....*....|.
gi 568961591 383 DEDTDK-DDFLGSLQICLGDV 402
Cdd:cd04031   93 DYDRDGeNDFLGEVVIDLADA 113

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: 64.58 E-value: 2.41e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNFlglgGKSDPYAKVSIGLQHCRSRTIYK-NLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDK 388
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKL----DKQDPYCVLRIGGVTKKTKTDFRgGQHPEWDEELRFEITEDKKPILKVAVFDDDKRK 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 568961591 389 DDFLGSLQICLGDVMKNRVVDEWFAL--NDTTSGRLHLRL 426
Cdd:cd08681   77 PDLIGDTEVDLSPALKEGEFDDWYELtlKGRYAGEVYLEL 116

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: 65.47 E-value: 2.60e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 300 VTNLRVPLPCgvIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSI----------GLQH-------------------CRS 350
Cdd:cd08676   20 VREAEPPIFV--LKVTVIEAKGLLAKD----VNGFSDPYCMLGIvpasrernseKSKKrkshrkkavlkdtvpaksiKVT 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568961591 351 RTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDtdkDDFLGSLQICLGDVMKNRvVDEWFAL 414
Cdd:cd08676   94 EVKPQTLNPVWNETFRFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCG-LDSWFKL 153

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: 64.75 E-value: 2.93e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEV 838
Cdd:cd08405    1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGtSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                         90       100
                 ....*....|....*....|....*...
gi 568961591 839 QKRSLDVAVKNSRPLGshRRKELGKVLI 866
Cdd:cd08405   81 RETTLIITVMDKDRLS--RNDLIGKIYL 106

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: 64.37 E-value: 4.04e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGlADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                         90
                 ....*....|.
gi 568961591 840 KRSLDVAVKNS 850
Cdd:cd08404   82 DISVEFLVLDS 92

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: 63.39 E-value: 5.12e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 330 GLGGKSDPYAKVSIG--LQHcRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDKDDFLGSLQICLGDVMKNR- 406
Cdd:cd04052    8 SKTGLLSPYAELYLNgkLVY-TTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATs 86

                         90       100
                 ....*....|....*....|..
gi 568961591 407 VVDEWFALNDTTSGRLHLRLEW 428
Cdd:cd04052   87 VGQQWFPLSGNGQGRIRISALW 108

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: 63.88 E-value: 9.31e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTSSGA-DPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEF--FVPmGEVQKRSLDVAVKNSRP 852
Cdd:cd04020   29 LHVWVKEAKNLPALKSGGTsDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNHTFVYdgVSP-EDLSQACLELTVWDHDK 107


                 ....*
gi 568961591 853 LGSHR 857
Cdd:cd04020  108 LSSND 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: 62.72 E-value: 1.04e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAqkdnflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDKDDFLG 393
Cdd:cd08378    4 VRVVKARGLP--------ANSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLG 75


                 ....*....
gi 568961591 394 SLQICLGDV 402
Cdd:cd08378   76 GVCFDLSEV 84

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: 62.89 E-value: 1.35e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLT-PCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLVwDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568961591 840 KRSLDVAVKNSRPLGshRRKELGKVLIDLSKQDliKGFSQWYELTA 885
Cdd:cd08406   82 DLSLRVTVAESTEDG--KTPNVGHVIIGPAASG--MGLSHWNQMLA 123

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: 61.63 E-value: 3.59e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDT-DK 388
Cdd:cd08375   15 GRLMVVIVEGRDLKPCNS----NGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFfSP 90

                         90
                 ....*....|....*...
gi 568961591 389 DDFLGSLQICLGDVMKNR 406
Cdd:cd08375   91 DDFLGRTEIRVADILKET 108

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: 61.12 E-value: 4.48e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 327 NFLGLGGKSDPYAKVSI-GLQHcRSRTIYKNLNPTWNEVFEFMVYEVPGQD--LEVDLYD-EDTDKDDFLGSLQICLGDV 402
Cdd:cd08373    7 NLPGLKGKGDRIAKVTFrGVKK-KTRVLENELNPVWNETFEWPLAGSPDPDesLEIVVKDyEKVGRNRLIGSATVSLQDL 85

                         90
                 ....*....|....*
gi 568961591 403 MKNRVVDEWFALNDT 417
Cdd:cd08373   86 VSEGLLEVTEPLLDS 100

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: 60.66 E-value: 5.73e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQdLEVDLYDEDTD---- 387
Cdd:cd04027    3 ISITVVCAQGLIAKDK----TGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDR-IKVRVWDEDDDiksr 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568961591 388 --------KDDFLGSLQIclgDVMK-NRVVDEWFALNDTT-----SG--RLHL 424
Cdd:cd04027   78 lkqkftreSDDFLGQTII---EVRTlSGEMDVWYNLEKRTdksavSGaiRLHI 127

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: 60.74 E-value: 7.44e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 302 NLRVPLPCGVIRVHLLEAKKLAQKD-NflglgGKSDPYAKVSI-----GLQHCRSRTIYKNLNPTWNEVFefmVYEVPGQ 375
Cdd:cd04026    5 YLKISVKDNKLTVEVREAKNLIPMDpN-----GLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETF---TFDLKPA 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568961591 376 D----LEVDLYDED-TDKDDFLGSLQICLGDVMKnRVVDEWFALNDTTSGRLH 423
Cdd:cd04026   77 DkdrrLSIEVWDWDrTTRNDFMGSLSFGVSELIK-MPVDGWYKLLNQEEGEYY 128

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: 60.60 E-value: 8.85e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGA-DPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGFsDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80


                 ....*...
gi 568961591 840 KRSLDVAV 847
Cdd:cd08403   81 NVSLIIAV 88

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: 59.58 E-value: 1.10e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDnFLGlggKSDPYAKVSI---GLQHCRSRTIYKNLNPTWNEVFEFMVYevPGQD--LEVDLYDED 385
Cdd:cd04036    1 LLTVRVLRATNITKGD-LLS---TPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQ--SQVKnvLELTVMDED 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568961591 386 TDKDDFLGSLQICLGDVMKNRVVDEWFALNDTTSGRLHLRLE 427
Cdd:cd04036   75 YVMDDHLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFL 116

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: 59.65 E-value: 1.45e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 759 RLGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRwaSRKKTSVKQKTLEPLFDETFEF--FvPM 835
Cdd:cd08386    1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGtSDPFVKIYLLPDKK--HKLETKVKRKNLNPHWNETFLFegF-PY 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568961591 836 GEVQKRSLDVAVKNSRPLGshRRKELGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd08386   78 EKLQQRVLYLQVLDYDRFS--RNDPIGEVSLPLNKVDLTEEQTFWKDLK 124

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: 58.73 E-value: 1.83e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLlEAKKLAQKDNFlglgGKSDPYAKVSIG------LQHCRSRTIYKNLNPTWNEvFEFMVYEVPGQD----LEV 379
Cdd:cd04047    1 DVVELQF-SGKKLDKKDFF----GKSDPFLEISRQsedgtwVLVYRTEVIKNTLNPVWKP-FTIPLQKLCNGDydrpIKI 74

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568961591 380 DLYDEDTD-KDDFLGSLQICLGDVMKNRVVD 409
Cdd:cd04047   75 EVYDYDSSgKHDLIGEFETTLDELLKSSPLE 105

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 58.89 E-value: 2.56e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEV---PGQDLEVDLYDE--DTDK 388
Cdd:cd04022    4 VEVVDAQDLMPKDG----QGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDrrSGRR 79


                 ....*....
gi 568961591 389 DDFLGSLQI 397
Cdd:cd04022   80 RSFLGRVRI 88

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: 59.09 E-value: 2.86e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 313 RVHLLEAKKL--AQKDNFlglggkSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPG--QDLE-------VDL 381
Cdd:cd04017    4 RAYIYQARDLlaADKSGL------SDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGspEEIAqnpplvvVEL 77

                         90
                 ....*....|....
gi 568961591 382 YDEDTD-KDDFLGS 394
Cdd:cd04017   78 FDQDSVgKDEFLGR 91

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: 58.50 E-value: 4.43e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08409    1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQLD 80

                         90       100
                 ....*....|....*....|....*..
gi 568961591 840 KRSLDVAVKNsrPLGSHRRKELGKVLI 866
Cdd:cd08409   81 TASLSLSVMQ--SGGVRKSKLLGRVVL 105

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: 58.15 E-value: 6.05e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNflglgGKSDPYAKVSIGLQHC----RSRTIYKNLNPTWNEVFEFMVYE----------VPGQDL 377
Cdd:cd08675    1 LSVRVLECRDLALKSN-----GTCDPFARVTLNYSSKtdtkRTKVKKKTNNPRFDEAFYFELTIgfsyekksfkVEEEDL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568961591 378 E-----VDLYDEDT-DKDDFLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:cd08675   76 EkselrVELWHASMvSGDDFLGEVRIPLQGLQQAGSHQAWYFL 118

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: 57.27 E-value: 7.47e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNFLGlggKSDPYAKVSI---GLQHCRSRTIYKNLNPTWNEvfEFMVYEVP-----GQDLEVDL 381
Cdd:cd04041    1 GVLVVTIHRATDLPKADFGTG---SSDPYVTASFakfGKPLYSTRIIRKDLNPVWEE--TWFVLVTPdevkaGERLSCRL 75

                         90       100
                 ....*....|....*....|....*.
gi 568961591 382 YDED-TDKDDFLGSLQICLGDVMKNR 406
Cdd:cd04041   76 WDSDrFTADDRLGRVEIDLKELIEDR 101

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: 57.56 E-value: 7.56e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHC--RSRTIYKNLNPTWNEVFEFMVyEVPG-QDLEVDLYDEDT- 386
Cdd:cd04037    1 LVRVYVVRARNLQPKD----PNGKSDPYLKIKLGKKKIndRDNYIPNTLNPVFGKMFELEA-TLPGnSILKISVMDYDLl 75


                 ....*...
gi 568961591 387 DKDDFLGS 394
Cdd:cd04037   76 GSDDLIGE 83

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 56.57 E-value: 1.47e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLaQKDNFLGlggKSDPYAKVSIGLQHCRSrTIYKNL--NPTWNEVFEFMVyEVPGQ----DLEVDLYD 383
Cdd:cd04049    1 GTLEVLLISAKGL-QDTDFLG---KIDPYVIIQCRTQERKS-KVAKGDgrNPEWNEKFKFTV-EYPGWggdtKLILRIMD 74

                         90       100
                 ....*....|....*....|
gi 568961591 384 EDT-DKDDFLGSLQICLGDV 402
Cdd:cd04049   75 KDNfSDDDFIGEATIHLKGL 94

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: 56.50 E-value: 1.58e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAQKDnflgLGGKSDPYAKVSigLQHCRSRTI-----YKNLNPTWNEVFEFMV-Y-EVPGQDLEVDLYDEDT 386
Cdd:cd08385   20 VGIIQAADLPAMD----MGGTSDPYVKVY--LLPDKKKKFetkvhRKTLNPVFNETFTFKVpYsELGNKTLVFSVYDFDR 93

                         90       100
                 ....*....|....*....|....*.
gi 568961591 387 -DKDDFLGSLQICLGDVMKNRVVDEW 411
Cdd:cd08385   94 fSKHDLIGEVRVPLLTVDLGHVTEEW 119

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: 57.01 E-value: 1.80e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 760 LGEIQLTVRYVclRHCLRVLVNGCRNLT--PCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVpmgE 837
Cdd:cd04028   17 MGDIQLGLYDK--KGQLEVEVIRARGLVqkPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDV---S 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 568961591 838 VQKRSLDVAVknsrpLGSHRRKE----LGKVLIDLSKQDLIKGFSQWYEL 883
Cdd:cd04028   92 PTGKTLQVIV-----WGDYGRMDkkvfMGVAQILLDDLDLSNLVIGWYKL 136

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: 56.02 E-value: 2.79e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 309 CGVIRVHLLEAKKLAQKDnflGLGGKSDPYAKVSIGLQ--HCRSRTIYKNLNPTWNEVFEFMVYEVpGQDLEVDLYDE-D 385
Cdd:cd04044    1 IGVLAVTIKSARGLKGSD---IIGGTVDPYVTFSISNRreLARTKVKKDTSNPVWNETKYILVNSL-TEPLNLTVYDFnD 76

                         90       100
                 ....*....|....*....|
gi 568961591 386 TDKDDFLGSLQICLGDVMKN 405
Cdd:cd04044   77 KRKDKLIGTAEFDLSSLLQN 96

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: 54.72 E-value: 6.49e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIgLQHC----RSRTIYKNLNPTWNEVFEFMV--YEVPGQDLEVDLYD 383
Cdd:cd08387   16 GILNVKLIQARNLQPRD----FSGTADPYCKVRL-LPDRsntkQSKIHKKTLNPEFDESFVFEVppQELPKRTLEVLLYD 90

                         90       100
                 ....*....|....*....|....*....
gi 568961591 384 EDT-DKDDFLGSLQICLGDVMKNRVVDEW 411
Cdd:cd08387   91 FDQfSRDECIGVVELPLAEVDLSEKLDLW 119

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: 54.00 E-value: 7.71e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 473 RAKKLSRFVKNKASrDPssYVKLTVG-KKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDDEL---ECALGVLE 548
Cdd:cd00030    7 EARNLPAKDLNGKS-DP--YVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRfskDDFLGEVE 83

                         90       100
                 ....*....|....*....|
gi 568961591 549 FPLCRILPcADLTLEQCFQL 568
Cdd:cd00030   84 IPLSELLD-SGKEGELWLPL 102

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: 54.19 E-value: 8.48e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 313 RVHLLEAKKLAQKdnflglgGKSDPYAKVSIGLQH-CRSRTIYKnLNPTWNEVFEFmvyEVPGQD-----LEVDLYDEDT 386
Cdd:cd08383    3 RLRILEAKNLPSK-------GTRDPYCTVSLDQVEvARTKTVEK-LNPFWGEEFVF---DDPPPDvtfftLSFYNKDKRS 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568961591 387 -DKDDFLGSLQICLGDvmKNRVVDEWFALNDTTS-----GRLHLRL 426
Cdd:cd08383   72 kDRDIVIGKVALSKLD--LGQGKDEWFPLTPVDPdsevqGSVRLRA 115

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: 54.21 E-value: 9.82e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 308 PCGVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEvPGQDLEVDLYDEDTD 387
Cdd:cd04046    1 PQVVTQVHVHSAEGLSKQD----SGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKK-PRSPIKIQVWNSNLL 75


                 ....*.
gi 568961591 388 KDDFLG 393
Cdd:cd04046   76 CDEFLG 81

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: 54.28 E-value: 1.19e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 333 GKSDPYAKVSI----GLQHCRSRTIYK-NLNPTWNEVFEFMV--YEVPGQDLEVDLYDEDTDK-DDFLGSLQICLG---- 400
Cdd:cd08384   32 GYSDPFVKLYLkpdaGKKSKHKTQVKKkTLNPEFNEEFFYDIkhSDLAKKTLEITVWDKDIGKsNDYIGGLQLGINakge 111

                         90       100
                 ....*....|....*....|..
gi 568961591 401 ------DVMK--NRVVDEWFAL 414
Cdd:cd08384  112 rlrhwlDCLKnpDKKIEAWHTL 133

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 52.60 E-value: 2.75e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 796 PYVRIYLLPErrwaSRKKTSVKQKTLEPLFDETFEFFVPmgevQKRS--LDVAVKNSRplgSHRRKELGKVLIDLSkqDL 873
Cdd:cd04052   15 PYAELYLNGK----LVYTTRVKKKTNNPSWNASTEFLVT----DRRKsrVTVVVKDDR---DRHDPVLGSVSISLN--DL 81

                         90       100
                 ....*....|....*....|
gi 568961591 874 IKGFSQ---WYELTADGQPR 890
Cdd:cd04052   82 IDATSVgqqWFPLSGNGQGR 101

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

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 52.29 E-value: 4.66e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568961591 475 KKLSRFVKNKAsrDPssYVKLTVGKKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDD 538
Cdd:cd08391   18 KFVGGLVKGKS--DP--YVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDE 77

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 52.58 E-value: 5.71e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPC-TSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTdMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80


                 ....*...
gi 568961591 840 KRSLDVAV 847
Cdd:cd08410   81 NVSLVFTV 88

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: 51.51 E-value: 8.97e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 307 LPCGVIRvhlleAKKLAQKDNflglGGKSDPYAKVSI-----GLQHCRSRTIYKNLNPTWNEVFEFmvYEVPGQD----- 376
Cdd:cd04035   17 LHCTIIR-----AKGLKAMDA----NGLSDPYVKLNLlpgasKATKLRTKTVHKTRNPEFNETLTY--YGITEEDiqrkt 85

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568961591 377 LEVDLYDEDTDKDDFLGSLQICLGDVMKNRV 407
Cdd:cd04035   86 LRLLVLDEDRFGNDFLGETRIPLKKLKPNQT 116

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

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 52.04 E-value: 9.00e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSigLQHCRSR-------TIYKNLNPTWNEVFEFmvyEVPGQDL----- 377
Cdd:cd08405   15 NRITVNIIKARNLKAMD----INGTSDPYVKVW--LMYKDKRvekkktvIKKRTLNPVFNESFIF---NIPLERLrettl 85

                         90       100
                 ....*....|....*....|....
gi 568961591 378 EVDLYDEDT-DKDDFLGslQICLG 400
Cdd:cd08405   86 IITVMDKDRlSRNDLIG--KIYLG 107

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: 50.92 E-value: 1.32e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVclRHCLRVLVNGCRNLtPCTSSGA-DPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08685    1 GQLKLSIEGQ--NRKLTLHVLEAKGL-RSTNSGTcNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQ 77

                         90
                 ....*....|.
gi 568961591 840 KRSLdVAVKNS 850
Cdd:cd08685   78 KRLL-VTVWNK 87

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: 51.24 E-value: 1.72e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLtPCTSSGADPYVRIYLLPERRWASRKKTSVKQKTLEPLFDETFEFFV-------------PMGEVQKRS 842
Cdd:cd04010    2 LSVRVIECSDL-ALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfemPEEDAEKLE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 568961591 843 LDVAVKNSRPLGShrRKELGKVLIDLSKQDLIKG-FSQWYELtadgQPRS 891
Cdd:cd04010   81 LRVDLWHASMGGG--DVFLGEVRIPLRGLDLQAGsHQAWYFL----QPRE 124

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

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 50.21 E-value: 2.37e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQH-CRSRTIYKNLNPTWNEvfEFMVYEVPG-QDLEVDLYDEDT-DKDD 390
Cdd:cd04054    4 IRIVEGKNLPAKD----ITGSSDPYCIVKVDNEViIRTATVWKTLNPFWGE--EYTVHLPPGfHTVSFYVLDEDTlSRDD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 568961591 391 FLGSLQICLGDV-MKNRVVDEWFAL-----NDTTSGRLHLRLE 427
Cdd:cd04054   78 VIGKVSLTREVIsAHPRGIDGWMNLtevdpDEEVQGEIHLELS 120

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: 50.35 E-value: 2.54e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEA---KKLAQKDNFLGLGGKS---DPYakVSIGLQHC---RSRTIYKNLNPTWNEVFEFMVYEvpGQDLEVD 380
Cdd:cd04014    4 GTLKIKICEAvdlKPTDWSTRHAVPKKGSqllDPY--VSIDVDDThigKTSTKPKTNSPVWNEEFTTEVHN--GRNLELT 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568961591 381 LY-DEDTDKDDFLGSLQICLGDVMKN--RVVDEWFALNDTtsGRLHLRLEW 428
Cdd:cd04014   80 VFhDAAIGPDDFVANCTISFEDLIQRgsGSFDLWVDLEPQ--GKLHVKIEL 128

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: 49.41 E-value: 2.59e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591   472 YRAKKLSRFVKNKASrDPssYVKLTVG---KKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDDELECA---LG 545
Cdd:smart00239   7 ISARNLPPKDKGGKS-DP--YVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRddfIG 83

                           90
                   ....*....|
gi 568961591   546 VLEFPLCRIL 555
Cdd:smart00239  84 QVTIPLSDLL 93

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: 49.50 E-value: 3.06e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAqkdnflglGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPG--QD--LEVDLYDEDT- 386
Cdd:cd04011    6 VRVRVIEARQLV--------GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDelFDkiIKISVYDSRSl 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568961591 387 DKDDFLGSLQICLGDVMKN---RVVDEWFALND 416
Cdd:cd04011   78 RSDTLIGSFKLDVGTVYDQpdhAFLRKWLLLTD 110

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: 50.75 E-value: 3.23e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 313 RVHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHCRSRT-IYKNLNPTWNEVFEFMVYEvPGQD---LEVDlYDEDTDK 388
Cdd:cd04019    3 RVTVIEAQDLVPSDK----NRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWNEELMFVAAE-PFEDhliLSVE-DRVGPNK 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568961591 389 DDFLGSLQICLGDVMKnRVVDE-----WFALNDTT-----------SGRLHLRL 426
Cdd:cd04019   77 DEPLGRAVIPLNDIER-RVDDRpvpsrWFSLERPGgameqkkkrkfASRIHLRL 129

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: 49.64 E-value: 3.73e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568961591 308 PCGVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSI---GLQHCRSRTIYKNLNPTWNEVFEF 367
Cdd:cd08386   14 QESTLTLKILKAVELPAKD----FSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLF 72

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 53.99 E-value: 3.90e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  276 LEDLIAAHLVLPNRVTVPVKKG-LDVTNLRVPL--------------PCGVIRVHLLEAKKLAQKDnflgLGGKSDPYAK 340
Cdd:COG5038   662 LPDLIDRTLDTFLVFPLRNPKGrIFITNYWKPIynaggsssktvydtPIGAIRVSVRKANDLRNEI----PGGKSDPYAT 737

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568961591  341 VSIGlQHCRSRTIYK--NLNPTWNEV-FEFMVYEVPGQDLEVDLYDEDTDkDDFLGSLQICLGDVMK 404
Cdd:COG5038   738 VLVN-NLVKYRTIYGssTLNPIWNEIlYVPVTSKNQRLTLECMDYEESGD-DRNLGEVNINVSNVSK 802

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: 49.57 E-value: 4.05e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 334 KSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEF-MVYEVPGQDLEVDLYDED-TDKDDFLGSLQIclgdVMKNRVVDEW 411
Cdd:cd04032   47 STDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDnGWDDDLLGTCSV----VPEAGVHEDS 122


                 ....*
gi 568961591 412 FALND 416
Cdd:cd04032  123 CQLNH 127

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: 50.40 E-value: 5.01e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNflglGGKSDPYAKVSI------GLQHcRSRTIYKNLNPTWNEVfefMVYE-VPGQDL----- 377
Cdd:cd04020   27 GELHVWVKEAKNLPALKS----GGTSDSFVKCYLlpdkskKSKQ-KTPVVKKSVNPVWNHT---FVYDgVSPEDLsqacl 98

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568961591 378 EVDLYDEDTDK-DDFLGSLQICLGDVMKNRVVDEWFalnDTTSGRLHLrleWLSLL 432
Cdd:cd04020   99 ELTVWDHDKLSsNDFLGGVRLGLGTGKSYGQAVDWM---DSTGEEILL---WQKML 148

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: 48.69 E-value: 8.34e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 332 GGKSDPYAKVSI-GL-----QHCRSRTIYKN-LNPTWNEVFEFMVYeVPgqDL-----EVdlYDEDTDKDDFLGslQICL 399
Cdd:cd00275   22 GSIVDPYVEVEIhGLpaddsAKFKTKVVKNNgFNPVWNETFEFDVT-VP--ELaflrfVV--YDEDSGDDDFLG--QACL 94

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: 47.95 E-value: 1.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 317 LEAKKLAQKDNFlglgGKSDPYAKVSIG-------LQHCRSRTIYKNLNPTWNE--VFEFMVYEVpgQDLEVDLYDED-- 385
Cdd:cd04048    7 ISCRNLLDKDVL----SKSDPFVVVYVKtggsgqwVEIGRTEVIKNNLNPDFVTtfTVDYYFEEV--QKLRFEVYDVDsk 80

                         90       100
                 ....*....|....*....|....
gi 568961591 386 ---TDKDDFLGSLQICLGDVMKNR 406
Cdd:cd04048   81 skdLSDHDFLGEAECTLGEIVSSP 104

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

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 48.03 E-value: 1.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 330 GLGGKSDPYAKVS---IGLQHCRSRTIYKNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDKDDFLGSLQICL------ 399
Cdd:cd04043   17 SSNGLSDPYVTLVdtnGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSfVGKHDLCGRASLKLdpkrfg 96

                         90       100
                 ....*....|....*....|....*...
gi 568961591 400 GDVMKNrvvDEWFALNdtTSGRLHLRLE 427
Cdd:cd04043   97 DDGLPR---EIWLDLD--TQGRLLLRVS 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: 46.79 E-value: 2.55e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 775 CLRVLVNGCRNL-TPCTSSGADPYVRIYLLPERRwasrkKTSVKQKTLEPLFDETFEFFVPMGEVQkrSLDVAVKNsrpl 853
Cdd:cd04050    1 LLFVYLDSAKNLpLAKSTKEPSPYVELTVGKTTQ-----KSKVKERTNNPVWEEGFTFLVRNPENQ--ELEIEVKD---- 69

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568961591 854 gSHRRKELGKVLIDLS----KQDLIkgFSQWYELTADG 887
Cdd:cd04050   70 -DKTGKSLGSLTLPLSellkEPDLT--LDQPFPLDNSG 104

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: 47.30 E-value: 2.98e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNFLGLggksDPYAKVSIGLQHCRSRTIYKN-LNPTWNEVFEFMVyeVPGQDLEVDLYDEDT--DK 388
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRLP----DPFAVITVDGGQTHSTDVAKKtLDPKWNEHFDLTV--GPSSIITIQVFDQKKfkKK 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568961591 389 DD-FLGslqicLGDVMKNRVVDewfaLNDTTSGRLHLRlewlslltdqeALTENDSGLSTAILVVFLE 455
Cdd:cd08382   76 DQgFLG-----CVRIRANAVLP----LKDTGYQRLDLR-----------KLKKSDNLSVRGKIVVSLS 123

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: 47.23 E-value: 3.22e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDNflglGGKSDPYAKVSIGLQHC-------RSRTIYKNLNPTWNEVFEFMV----YEVPGQDLEV 379
Cdd:cd04009   17 SLRVEILNARNLLPLDS----NGSSDPFVKVELLPRHLfpdvptpKTQVKKKTLFPLFDESFEFNVppeqCSVEGALLLF 92

                         90       100
                 ....*....|....*....|....*
gi 568961591 380 DLYDEDT-DKDDFLGSLQICLGDVM 403
Cdd:cd04009   93 TVKDYDLlGSNDFEGEAFLPLNDIP 117

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: 46.63 E-value: 5.56e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSigLQHCRSR------TI-YKNLNPTWNEVFEFmvyEVPGQ-----DL 377
Cdd:cd08402   15 GKLTVVILEAKNLKKMD----VGGLSDPYVKIH--LMQNGKRlkkkktTIkKRTLNPYYNESFSF---EVPFEqiqkvHL 85

                         90       100
                 ....*....|....*....|....
gi 568961591 378 EVDLYDED-TDKDDFLGslQICLG 400
Cdd:cd08402   86 IVTVLDYDrIGKNDPIG--KVVLG 107

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: 46.32 E-value: 6.06e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 775 CLRVLVNGCRNLTPCTSSGA-DPYVRIyllperRWASR-KKTSVKQKTLEPLFDETFEFFVPMGEVQKRSL-----DVAV 847
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTsDPFVRV------FYNGQtLETSVVKKSCYPRWNEVFEFELMEGADSPLSVevwdwDLVS 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568961591 848 KNSRplgshrrkeLGKVLIDLSKQDLIKGFSQWYELTADGQPRS 891
Cdd:cd04025   75 KNDF---------LGKVVFSIQTLQQAKQEEGWFRLLPDPRAEE 109

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 45.77 E-value: 6.71e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  472 YRAKKLsrfVKNKASRDPSSYVKLTV--GKKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDDEL---ECALGV 546
Cdd:pfam00168   8 IEAKNL---PPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRfgrDDFIGE 84

                          90
                  ....*....|
gi 568961591  547 LEFPLCRILP 556
Cdd:pfam00168  85 VRIPLSELDS 94

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

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 46.04 E-value: 9.47e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 314 VHLLEAKKLAQKDNflglGGKSDPYAKVSIgLQHCR------SRTIYKNLNPTWNEVFEFMV--YEVPGQDLEVDLYDED 385
Cdd:cd00276   18 VVVLKARNLPPSDG----KGLSDPYVKVSL-LQGGKklkkkkTSVKKGTLNPVFNEAFSFDVpaEQLEEVSLVITVVDKD 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568961591 386 TD-KDDFLGslQICLG------------DVMKN--RVVDEW 411
Cdd:cd00276   93 SVgRNEVIG--QVVLGpdsggeelehwnEMLASprKPIARW 131

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: 44.87 E-value: 1.30e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568961591 795 DPYVRIYLLPERrwasrKKTSVKQKTLEPLFDET--FEFFVPMGEVQKRSLDVAVKNSRPLGS 855
Cdd:cd04011   22 DPVVKVEVGGQK-----KYTSVKKGTNCPFYNEYffFNFHESPDELFDKIIKISVYDSRSLRS 79

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: 45.34 E-value: 1.59e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHllEAKKLAQKDNflglGGKSDPYAKVSIGLQH---CRSRT--IYKNLNPTWNEVFEFMVY--EVPGQDLEVDLYD 383
Cdd:cd04030   19 IVTVH--KCRNLPPCDS----SDIPDPYVRLYLLPDKsksTRRKTsvKKDNLNPVFDETFEFPVSleELKRRTLDVAVKN 92

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568961591 384 E----DTDKdDFLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:cd04030   93 SksflSREK-KLLGQVLIDLSDLDLSKGFTQWYDL 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: 44.87 E-value: 1.60e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTSSG-ADPYVRIYLLPERRWasrkKTSVKQKTLEPLFDETFEFFVP 834
Cdd:cd04040    1 LTVDVISAENLPSADRNGkSDPFVKFYLNGEKVF----KTKTIKKTLNPVWNESFEVPVP 56

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: 44.21 E-value: 3.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 332 GGKSDPYAKVSI--GLQHCRSR---TIYKNLNPTWNEVF---EFMVYEVPGQDLEVDLYDEDT-DKDDFLGSLQICLGDV 402
Cdd:cd08381   30 GSDPDPYVKTYLlpDPQKTTKRktkVVRKTRNPTFNEMLvydGLPVEDLQQRVLQVSVWSHDSlVENEFLGGVCIPLKKL 109

                         90
                 ....*....|...
gi 568961591 403 MKNRVVDEWFALN 415
Cdd:cd08381  110 DLSQETEKWYPLG 122

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 43.45 E-value: 3.98e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNFLGLggkSDPYAKVSIGLQHCRSRTIYKNLNPTWN-EVFEFMVYEVPGQD--LEVDLYDEDT-D 387
Cdd:cd08688    1 LKVRVVAARDLPVMDRSSDL---TDAFVEVKFGSTTYKTDVVKKSLNPVWNsEWFRFEVDDEELQDepLQIRVMDHDTyS 77

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568961591 388 KDDFLGSLQICLGDVMK---NRVVDEWFALNDT 417
Cdd:cd08688   78 ANDAIGKVYIDLNPLLLkdsVSQISGWFPIYDT 110

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: 43.41 E-value: 5.31e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 775 CLRVLVNGCRNLTPCTSSgaDPYVRIYLLPERRWasrkKTSVKQKtLEPLFDETFEFFVPMGEVQKRSLDVAVKNSRPLG 854
Cdd:cd08383    1 SLRLRILEAKNLPSKGTR--DPYCTVSLDQVEVA----RTKTVEK-LNPFWGEEFVFDDPPPDVTFFTLSFYNKDKRSKD 73

                         90       100       110
                 ....*....|....*....|....*....|
gi 568961591 855 ShrrkELGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd08383   74 R----DIVIGKVALSKLDLGQGKDEWFPLT 99

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

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 43.58 E-value: 5.94e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 311 VIRVHLLEAKKLAQKDnflGLGGKSDPYAKVSIGLQH-CRSRTIYKNLNPTWNEVFEFmvyEVPG--QDLEVDLYDEDT- 386
Cdd:cd08401    1 SLKIKIGEAKNLPPRS---GPNKMRDCYCTVNLDQEEvFRTKTVEKSLCPFFGEDFYF---EIPRtfRHLSFYIYDRDVl 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 387 DKDDFLGSLQICLGDVMKNRVVDEWFAL-----NDTTSGRLHLRL 426
Cdd:cd08401   75 RRDSVIGKVAIKKEDLHKYYGKDTWFPLqpvdaDSEVQGKVHLEL 119

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: 42.63 E-value: 7.27e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568961591 310 GVIRVHLLEAKKLAQKDNFLGLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYE 371
Cdd:cd04039    1 GVVFMEIKSITDLPPLKNMTRTGFDMDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYP 62

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: 42.61 E-value: 1.09e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 761 GEIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGADPY-VRIYLLPERRwaSRKKTSVKQKTlEPLFDETFEFF-VPMGEV 838
Cdd:cd08389    3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWqVHLVLLPSKK--QRAKTKVQRGP-NPVFNETFTFSrVEPEEL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568961591 839 QKRSLDVavknsRPLGSHR-RKE--LGKVLIDLSKQDLIKGFSQW 880
Cdd:cd08389   80 NNMALRF-----RLYGVERmRKErlIGEKVVPLSQLNLEGETTVW 119

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: 42.63 E-value: 1.19e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 488 DPssYVKL---TVGKKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDDELEC--ALGVLEFPLCRILPcaDLTL 562
Cdd:cd04036   22 DC--YVELwlpTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMddHLGTVLFDVSKLKL--GEKV 97

                         90
                 ....*....|....
gi 568961591 563 EQCFQLDHSGLDSL 576
Cdd:cd04036   98 RVTFSLNPQGKEEL 111

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 45.91 E-value: 1.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591  333 GKSDPYakVSIGLQH---CRSRTIYKNLNPTWNEVFEFmvyEVPGQD---LEVDLYD-EDTDKDDFLGSLQICL------ 399
Cdd:COG5038  1059 GYSDPF--VKLFLNEksvYKTKVVKKTLNPVWNEEFTI---EVLNRVkdvLTINVNDwDSGEKNDLLGTAEIDLsklepg 1133

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 568961591  400 GDVMKNRVVD-EWFALNDTT-SGRLHLRLEWLSLLTDQEA 437
Cdd:COG5038  1134 GTTNSNIPLDgKTFIVLDGTlHPGFNFRSKYALNVSRKEG 1173

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: 42.05 E-value: 1.69e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKdnflGLGGKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFmvyEVPGQDLEVDLYDEDT----- 386
Cdd:cd08682    1 VQVTVLQARGLLCK----GKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSF---ELPGLLSGNGNRATLQltvmh 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 568961591 387 ----DKDDFLGSLQICLGDV--MKNRVVDEWFALNDTTSGR 421
Cdd:cd08682   74 rnllGLDKFLGQVSIPLNDLdeDKGRRRTRWFKLESKPGKD 114

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176016 [Multi-domain] Cd Length: 125 Bit Score: 41.83 E-value: 1.99e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 331 LGGKSDPYAKVSI-GLQHCRSRTIYK-NLNPTWNEVFEFMVYEVPGQD----LEVDLYDEDTDK-DDFLGSLQICLGDVM 403
Cdd:cd04051   17 LFGKMKVYAVVWIdPSHKQSTPVDRDgGTNPTWNETLRFPLDERLLQQgrlaLTIEVYCERPSLgDKLIGEVRVPLKDLL 96


                 ..
gi 568961591 404 KN 405
Cdd:cd04051   97 DG 98

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: 41.67 E-value: 2.36e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 777 RVLVNGCRNLTPCTSSGA-DPYVRIYLLPERRwasrkKTSVKQKTLEPLFDETFEFFVPMGEVQKRSLDVAVKNSRplgs 855
Cdd:cd08682    2 QVTVLQARGLLCKGKSGTnDAYVIIQLGKEKY-----STSVKEKTTSPVWKEECSFELPGLLSGNGNRATLQLTVM---- 72

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568961591 856 HRR-----KELGKVLIDLSKQDLIKGF--SQWYEL 883
Cdd:cd08682   73 HRNllgldKFLGQVSIPLNDLDEDKGRrrTRWFKL 107

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: 41.49 E-value: 2.88e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 482 KNKASRDPSS----YVKLTVGKKT-FTSKTCPHSKDPVWSQVFSFFVHSVaAEQLCLKVLDDELECA---LGVLEFPLCr 553
Cdd:cd04042   10 RNLAARDRGGtsdpYVKFKYGGKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDYDRGLTddfMGSAFVDLS- 87

                         90
                 ....*....|....*..
gi 568961591 554 ilpcadlTLEQCFQLDH 570
Cdd:cd04042   88 -------TLELNKPTEV 97

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: 41.09 E-value: 4.35e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 783 CRNLTPCTSSGaDPYVRIyllpERRWASrKKTSVKQKTLEPLFDETFEFFVPMGEVQKRSLDVAVKNSRPLGSHRRkeLG 862
Cdd:cd08373    5 LKNLPGLKGKG-DRIAKV----TFRGVK-KKTRVLENELNPVWNETFEWPLAGSPDPDESLEIVVKDYEKVGRNRL--IG 76

                         90       100
                 ....*....|....*....|..
gi 568961591 863 KVLIDLskQDLIKGFSQWYELT 884
Cdd:cd08373   77 SATVSL--QDLVSEGLLEVTEP 96

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: 40.70 E-value: 4.44e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 778 VLVNGcRNLTPCTSSG-ADPYVRIYLLPERRwasrkKTSVKQKTLEPLFDETFEFFvpMGEVQKRSLDVAVKNSRPlgsh 856
Cdd:cd08376    5 VLVEG-KNLPPMDDNGlSDPYVKFRLGNEKY-----KSKVCSKTLNPQWLEQFDLH--LFDDQSQILEIEVWDKDT---- 72

                         90       100       110
                 ....*....|....*....|....*....|
gi 568961591 857 RRKE--LGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd08376   73 GKKDefIGRCEIDLSALPREQTHSLELELE 102

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

Pssm-ID: 439231 Cd Length: 186 Bit Score: 42.09 E-value: 5.06e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 140 MENKIREKLEPKIreKSIHLRTF----TFTKLYFGQKCPKVNGVKVHTDKRNRrKVTLDLQICYIGDCEISVE----LQK 211
Cdd:cd21675   19 WKEFIKEKIQKKL--SKIKLPSFlgeiTVTDLDLGTSVPVISNPKLPSLDPDG-GLWVDLDVSYRGGFSLTLEtklnLSK 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 212 I-RGGVSGV---------QLQGTLRVILEPLLVDKPFIGavtvfFLQKPHLQINWT--GLTNLLDMPGINELSDSLLEDL 279
Cdd:cd21675   96 LkKEKVSNVplvlavevkSLSGTLRLNIKPPPSNRLWYG-----FREMPKLELEIEpvVGERQVTLPHVTNWIEKKLKEE 170

                        170
                 ....*....|
gi 568961591 280 IAAHLVLPNR 289
Cdd:cd21675  171 IKESLVLPNM 180

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: 40.32 E-value: 7.17e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 310 GVIRVHLLEAKKLAQKDNflgLGGKSDPYAKVSIGLQHCRS---RTIYKN--LNPTWNEVFEfmvYEVPGQDLE-----V 379
Cdd:cd08521   14 GSLEVHIKECRNLAYADE---KKKRSNPYVKVYLLPDKSKQskrKTSVKKntTNPVFNETLK---YHISKSQLEtrtlqL 87

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 568961591 380 DLYDEDTDK-DDFLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:cd08521   88 SVWHHDRFGrNTFLGEVEIPLDSWDLDSQQSEWYPL 123

C2 domain second 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176053 [Multi-domain] Cd Length: 138 Bit Score: 40.43 E-value: 8.65e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 762 EIQLTVRYVCLRHCLRVLVNGCRNLTPCTSSGA-DPYVRIYLL-PERRWASRKKTSVKQKTLEPLFDETFEFFVPMGEVQ 839
Cdd:cd08408    3 ELLLGLEYNALTGRLSVEVIKGSNFKNLAMNKApDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

                         90       100
                 ....*....|....*....|..
gi 568961591 840 KRSLDVAVKNSRplgSHRRKEL 861
Cdd:cd08408   83 EVTLMFSVYNKR---KMKRKEM 101

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: 40.82 E-value: 9.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 775 CLRVLVNGCRNLTPCTSSG-ADPYVRIYLLP----------ERRWASRKK--------------TSVKQKTLEPLFDETF 829
Cdd:cd08676   29 VLKVTVIEAKGLLAKDVNGfSDPYCMLGIVPasrernseksKKRKSHRKKavlkdtvpaksikvTEVKPQTLNPVWNETF 108

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568961591 830 EFFVpmGEVQKRSLDVavknsrPLGSHRRKELGKVLIDLsKQDLIKGFSQWYEL 883
Cdd:cd08676  109 RFEV--EDVSNDQLHL------DIWDHDDDFLGCVNIPL-KDLPSCGLDSWFKL 153

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: 39.80 E-value: 1.24e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568961591 307 LP-CGVIRVHLLEAKKLAQKDnflgLGGKSDPYAKVSIGLQHCRSR----TIYKN-LNPTWNEVfefMVYEVPGQDLE 378
Cdd:cd08403   10 LPtAGRLTLTIIKARNLKAMD----ITGFSDPYVKVSLMCEGRRLKkkktSVKKNtLNPTYNEA---LVFDVPPENVD 80

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: 39.72 E-value: 1.57e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNflglGGKSDPYAKVSI---GLQHCRSRTIYK--NLNPTWNEVFefmVYEVP---GQDLEVDLYD 383
Cdd:cd08404   17 LTVVVLKARHLPKMDV----SGLADPYVKVNLyygKKRISKKKTHVKkcTLNPVFNESF---VFDIPseeLEDISVEFLV 89

                         90
                 ....*....|....*..
gi 568961591 384 EDTD---KDDFLGSLQI 397
Cdd:cd08404   90 LDSDrvtKNEVIGRLVL 106

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: 39.24 E-value: 1.72e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTSSG-ADPYVRIYLLperrwASRKKTSVKQKTLEPLFDETFEFFVPMGEV-QKRSLDVAVKNSRPL 853
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGsSSAYVELDFD-----GQKKRTRTKPKDLNPVWNEKLVFNVSDPSRlSNLVLEVYVYNDRRS 76

                         90
                 ....*....|....*.
gi 568961591 854 GsHRRKELGKVLIDLS 869
Cdd:cd04022   77 G-RRRSFLGRVRISGT 91

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: 39.15 E-value: 1.91e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 795 DPYVRIYLLPERrwasrKKTSVKQKT-LEPLFDETFEFfvPMGEVQKRSLDVAVKNSRPlgsHRRKELGKVLIDLSKQdL 873
Cdd:cd08681   23 DPYCVLRIGGVT-----KKTKTDFRGgQHPEWDEELRF--EITEDKKPILKVAVFDDDK---RKPDLIGDTEVDLSPA-L 91

                         90
                 ....*....|....*.
gi 568961591 874 IKG-FSQWYELTADGQ 888
Cdd:cd08681   92 KEGeFDDWYELTLKGR 107

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 39.54 E-value: 1.91e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568961591 336 DPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEVP-GQDLEVDLYDEDT-DKDDFLGS 394
Cdd:cd04018   36 DPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPlCERIKIQIRDWDRvGNDDVIGT 96

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176045 [Multi-domain] Cd Length: 126 Bit Score: 39.27 E-value: 1.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDnflglggKSDPYAKVSIG-LQHCRSRtIYKNLNPTWNEvfEFMVYEVPGQ--DLEVDLYDEDT-D 387
Cdd:cd08400    6 LQLNVLEAHKLPVKH-------VPHPYCVISLNeVKVARTK-VREGPNPVWSE--EFVFDDLPPDvnSFTISLSNKAKrS 75

                         90       100
                 ....*....|....*....|....*..
gi 568961591 388 KDDFLGSLQICLGDVMKNRVVDEWFAL 414
Cdd:cd08400   76 KDSEIAEVTVQLSKLQNGQETDEWYPL 102

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: 38.95 E-value: 2.13e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 312 IRVHLLEAKKLAQKDNflgLGGKSDPYAKVSI----GLQHCRSRTIYK-NLNPTWNEVFEFMV--YEVPGQDLEVDLYDE 384
Cdd:cd08393   17 LHVHVIQCQDLAAADP---KKQRSDPYVKTYLlpdkSNRGKRKTSVKKkTLNPVFNETLRYKVerEELPTRVLNLSVWHR 93

                         90       100       110
                 ....*....|....*....|....*....|...
gi 568961591 385 DT-DKDDFLGSLQICLG--DVMKNRVvdEWFAL 414
Cdd:cd08393   94 DSlGRNSFLGEVEVDLGswDWSNTQP--TWYPL 124

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: 38.35 E-value: 2.64e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568961591 484 KASRDPSSYVKLTV-GKKTFTSKTCPHSKDPVWSQVFSFFVHSVAAEQLCLKVLDD 538
Cdd:cd04052    8 SKTGLLSPYAELYLnGKLVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDD 63

C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 receptor (IL-1R) signaling pathway. Tollip is proposed to link serine/threonine kinase IRAK to IL-1Rs as well as inhibiting phosphorylation of IRAK. There is a single C2 domain present in Tollip. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175983 [Multi-domain] Cd Length: 121 Bit Score: 38.47 E-value: 3.47e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 336 DPYAKVSIGLQHCRSRTIYKNL-NPTWNEVFEFMVYevPGQD-LEVDLYDEDTDK-DDFLGSLQICLGD-VMKNRVVDEW 411
Cdd:cd04016   23 DPYCRIRVGHAVYETPTAYNGAkNPRWNKTIQCTLP--EGVDsIYIEIFDERAFTmDERIAWTHITIPEsVFNGETLDDW 100


                 ....
gi 568961591 412 FALN 415
Cdd:cd04016  101 YSLS 104

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: 37.24 E-value: 6.74e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 776 LRVLVNGCRNLTPCTS-SGADPYVRIYLlperRWAS--RKKTSVKQKTLEPLFDETFEFFVPMGevQKRSLDVAVKNSRP 852
Cdd:cd04036    2 LTVRVLRATNITKGDLlSTPDCYVELWL----PTASdeKKRTKTIKNSINPVWNETFEFRIQSQ--VKNVLELTVMDEDY 75

                         90
                 ....*....|....*...
gi 568961591 853 LGShrrKELGKVLIDLSK 870
Cdd:cd04036   76 VMD---DHLGTVLFDVSK 90

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

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 37.18 E-value: 7.58e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 775 CLRVLVNGCRNLTPCTSSG-ADPYVRIyLLPERrwaSRKKTSVKQKTLEPLFDETfeFFVP-MGEVQKRSLDV----AVK 848
Cdd:cd04045    2 VLRLHIRKANDLKNLEGVGkIDPYVRV-LVNGI---VKGRTVTISNTLNPVWDEV--LYVPvTSPNQKITLEVmdyeKVG 75

                         90       100
                 ....*....|....*....|....*..
gi 568961591 849 NSRPLGShrrkelgkvlIDLSKQDLIK 875
Cdd:cd04045   76 KDRSLGS----------VEINVSDLIK 92

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: 8.48e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 779 LVNGCRNLTPCTSSGADPYVRIyllperRWASRK-KTSVKQKTLEPLFDETFEFFVPmgEVQKRSLDVAVKNSRPlgsHR 857
Cdd:cd08391   13 LVAKDKFVGGLVKGKSDPYVIV------RVGAQTfKSKVIKENLNPKWNEVYEAVVD--EVPGQELEIELFDEDP---DK 81

                         90       100
                 ....*....|....*....|....*..
gi 568961591 858 RKELGKVLIDLSKQDLIKGFSQWYELT 884
Cdd:cd08391   82 DDFLGRLSIDLGSVEKKGFIDEWLPLE 108

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

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 37.39 E-value: 8.99e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568961591 333 GKSDPYAKVSIGLQHCRSRTIYKNLNPTWNEVFEFMVYEvPGQDLEVDLYD-------EDTDKDDFLGSLQICLGDVMKN 405
Cdd:cd08379   22 GSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYD-PCTVLTVGVFDnsqshwkEAVQPDVLIGKVRIRLSTLEDD 100


                 ..
gi 568961591 406 RV 407
Cdd:cd08379  101 RV 102