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: 344.88 E-value: 9.03e-114

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 116 ERVEWANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQICY 195
Cdd:cd21681     1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIREKSVHLKTFTFTKLHFGEKCPRINGVKVYTKEVDRRQVILDLQICY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 196 IGDCEISVELQKIQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSLLEDL 275
Cdd:cd21681    81 IGDCEINVEIKKCKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGLTNLLDIPGINDMSDSLIEDL 160

                         170
                  ....*....|....*..
gi 1018191476 276 IATHLVLPNRVTVPVKK 292
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: 240.08 E-value: 5.18e-74

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 116 ERVEWANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTcNRRRVTVDLQICY 195
Cdd:cd21679     1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTEF-DKRQIILDLHISY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 196 IGDCEISVELQKI--QAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSLLE 273
Cdd:cd21679    80 VGDVEINVEVKKYfcKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIM 159

                         170
                  ....*....|....*..
gi 1018191476 274 DLIATHLVLPNRVTVPV 290
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: 234.01 E-value: 1.05e-71

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 114 DVERVEWANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQI 193
Cdd:cd21680     1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAHLSTFSFTKIDLGDQPLRINGVKVYTENVDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 194 CYIGDCEISVELQK--IQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSL 271
Cdd:cd21680    81 SFVGNCEIDLEIKRyfCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDIPGLNGLSDTI 160

                         170
                  ....*....|....*....
gi 1018191476 272 LEDLIATHLVLPNRVTVPV 290
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: 228.98 E-value: 5.05e-70

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 116 ERVEWANKIISQTWPYLSMIMESKFREKLEPKIR-EKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQIC 194
Cdd:cd21670     1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSIRaLLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDIS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 195 YIGDCEISVELQ-KIQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSLLE 273
Cdd:cd21670    81 YDGDADIEVSVGtGIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKIIV 160

                         170
                  ....*....|....*..
gi 1018191476 274 DLIATHLVLPNRVTVPV 290
Cdd:cd21670   161 DQIASFLVLPNRITIPL 177

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: 211.36 E-value: 3.34e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSS-GADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd04030     2 LGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSdIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1018191476 834 KKRSLDVAVKNSRPLGSHRRKELGKVLIDLSKEDLIKGFSQWYELT 879
Cdd:cd04030    82 KRRTLDVAVKNSKSFLSREKKLLGQVLIDLSDLDLSKGFTQWYDLT 127

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: 212.59 E-value: 7.12e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 114 DVERVEWANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQI 193
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 194 CYIGDCEISVELQK--IQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSL 271
Cdd:pfam17047  81 SFVGNCEIDLEIKRyfCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 160

                         170
                  ....*....|....*....
gi 1018191476 272 LEDLIATHLVLPNRVTVPV 290
Cdd:pfam17047 161 ILDIISNYLVLPNRITVPL 179

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: 188.65 E-value: 4.86e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFLG--LRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 383
Cdd:cd08391     1 GVLRIHVIEAQDLVAKDKFVGglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1018191476 384 RDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLHLRLEW 424
Cdd:cd08391    81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121

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: 146.94 E-value: 2.28e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 445 ILVVFLESACNLPRNpfdylngeyrakklsrfarnKVSKDPSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVAT 524
Cdd:cd04050     1 LLFVYLDSAKNLPLA--------------------KSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPEN 60

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1018191476 525 ERLHLKVLDDDQECALGMLEVPLCQILPYADLTLEQRFQLDHSG 568
Cdd:cd04050    61 QELEIEVKDDKTGKSLGSLTLPLSELLKEPDLTLDQPFPLDNSG 104

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: 131.90 E-value: 4.56e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 107 PAWIHFPDVERVEWANKIISQTWPYLSMIMESKFREKLEPKIRE-KSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNrr 185
Cdd:cd21677     1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLEQyKPSFISSIKFKKLTLGTVPPRIEGVKVVESDED-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 186 RVTVDLQICYIGDCEISVELQ-----KIQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQIN---WTGLTN 257
Cdd:cd21677    79 EVILDVDFRWAGDPDIVLAVKllpglSLPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDlklLGGDDM 158

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1018191476 258 LLdaPGINDVSDSLLEDLIATHLVLPNRVTVPV 290
Cdd:cd21677   159 AL--PGLKSWLDSFIRDALLDMLVWPKRIVIPI 189

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: 106.35 E-value: 6.76e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDnfLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDR 384
Cdd:cd04024     1 GVLRVHVVEAKDLAAKD--RSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDrFAG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1018191476 385 DDFLGSLQICLGDVMTN---RVVDEWFVLNDT-------TSGRLHLRLEW 424
Cdd:cd04024    79 KDYLGEFDIALEEVFADgktGQSDKWITLKSTrpgktsvVSGEIHLQFSW 128

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 102.40 E-value: 7.84e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFlglrGKSDPYAKVSIGLQH--FRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 383
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGN----GTSDPYVKVYLLDGKqkKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*...
gi 1018191476 384 -RDDFLGSLQICLGDVMTNRVVDEWFVL 410
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: 112.54 E-value: 4.13e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476   50 YLAGYLGLSITWLLL-GALLWMWWRRNRRgklgrlaaafEFLDNEREFISRELRGQHLPAwihfpDVERVEWANKIISQT 128
Cdd:COG5038    169 WIFGYLGFSFASLFFiILVTMYVYRTCIK----------RVRRNIRDLVQQELSEEKLEN-----DYESVEWLNTFLQKF 233

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  129 WPYLSMIMESKFREKLEPKIRE------KSIHLRTFTFtklyfGQKCPRVNGVKAHTNTcNRRRVTVDLQI--------- 193
Cdd:COG5038    234 WPIIEPSISQQVVDQVNQQLAEaipsfiDALALDEFTL-----GSKPPRIDGIRSYPST-ESDTVVMDVDFsftphdisd 307

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  194 -------CYI-GDCEISVELQKIQAG------VNGIQLQGTLRVILEpLLVDKPFVGAVTVFFLQKPHLQINWTGL---- 255
Cdd:COG5038    308 vtatsarASVnPKISLVVKKGKSFGSftlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEFDFILVPLggdf 386

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  256 --TNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKKGL-DLTNLrfplPCGVIRVHLLEAEQLAQKDNFLGlrGKSD 332
Cdd:COG5038    387 fgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTIDISQIMaGDSGT----AIGVVEVKIKSAEGLKKSDSTIN--GTVD 460

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  333 PYAKV-SIGLQHFRSRTIYRNLNPTWNEVFeFMVYEVPGQDLEVDLYD-EDTDRDDFLGSLQICLGDVMTNRVVDEWFV- 409
Cdd:COG5038    461 PYITVtFSDRVIGKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDfNSFKSDKVVGSTQLDLALLHQNPVKKNELYe 539

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  410 --LNDTTSGRLHLRLEW-------LSLLTDQEVLtEDhggLSTAILVVFLEsacnlprnpfdylngeyrakKLSRFARNK 480
Cdd:COG5038    540 flRNTKNVGRLTYDLRFfpviedkKELKGSVEPL-ED---SNTGILKVTLR--------------------EVKALDELS 595

                          490       500       510       520       530       540       550
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1018191476  481 vSKDPSSYVKLSV-GKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECALGMLEVPLCQILP 552
Cdd:COG5038    596 -SKKDNKSAELYTnAKEVYSTGKLKFTNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLID 667

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: 98.10 E-value: 4.04e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG--ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08521     1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKkrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 834 KKRSLDVAVKNSRPLGshRRKELGKVLIDLSKEDLIKGFSQWYEL 878
Cdd:cd08521    81 ETRTLQLSVWHHDRFG--RNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 96.37 E-value: 1.01e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDNFlglrGKSDPYAKVSIG-LQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD-RD 385
Cdd:cd00030     1 LRVTVIEARNLPAKDLN----GKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFsKD 76

                          90       100
                  ....*....|....*....|....*.
gi 1018191476 386 DFLGSLQICLGDV-MTNRVVDEWFVL 410
Cdd:cd00030    77 DFLGEVEIPLSELlDSGKEGELWLPL 102

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: 93.93 E-value: 3.97e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 137 ESKFREKLEPKIRE--KSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQICYIGDCEISVELQ-------- 206
Cdd:cd21669     2 EQLIRESLQELLEEvkKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDLQLVLDLDLEYAGDFSVVLSAKlgggglgl 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 207 KIQAGVNGIQLQGTLRVILEpLLVDKPFVGAVTVFFLQKPHLQINWT--GLTNLLDAPGINDVSDSLLEDLIATHLVLPN 284
Cdd:cd21669    82 PVPVSVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRplGGVDLMELPGLSSWLEKLLTDALVELLVEPN 160


                  ....*
gi 1018191476 285 RVTVP 289
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: 90.57 E-value: 2.35e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG--ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08393     2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKqrSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 834 KKRSLDVAVKNSRPLGshRRKELGKVLIDLSKEDLIKGFSQWYEL 878
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: 88.31 E-value: 6.66e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  307 VIRVHLLEAEQLAQKDNFlglrGKSDPYAKVSIGLQH---FRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 383
Cdd:smart00239   1 TLTVKIISARNLPPKDKG----GKSDPYVKVSLDGDPkekKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 1018191476  384 -RDDFLGSLQICLGDVMTNRVVDEW 407
Cdd:smart00239  77 gRDDFIGQVTIPLSDLLLGGRHEKL 101

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: 88.47 E-value: 9.39e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGA--DPYVRVYLLPERKwaCRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08390     1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAhcDPFVKVCLLPDER--RSLQSKVKRKTQNPNFDETFVFQVSFKEL 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1018191476 834 KKRSLDVAVKNSRplGSHRRKELGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd08390    79 QRRTLRLSVYDVD--RFSRHCIIGHVLFPLKDLDLVKGGVVWRDLEP 123

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 86.99 E-value: 1.79e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSG-ADPYVRVYLLperKWACRKKTSVKRKTLEPLFDETFEFFVPMEEvkKRSLDVAVKNSRPLG 849
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGtSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDPE--NAVLEIEVYDYDRFG 77

                          90       100
                  ....*....|....*....|....*....
gi 1018191476 850 SHRRkeLGKVLIDLSKEDLIKGFSQWYEL 878
Cdd:pfam00168  78 RDDF--IGEVRIPLSELDSGEGLDGWYPL 104

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

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 86.15 E-value: 6.70e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFF-VPMEEV 833
Cdd:cd04031     3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSlRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSnVRRETL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 834 KKRSLDVAVKNSRPLGSHrrKELGKVLIDLSKEdLIKGFSQWYEL 878
Cdd:cd04031    83 KERTLEVTVWDYDRDGEN--DFLGEVVIDLADA-LLDDEPHWYPL 124

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: 85.78 E-value: 9.58e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 754 QLGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGA-DPYVRVYLLPERKwacrKK--TSVKRKTLEPLFDETFEFFVPM 830
Cdd:cd08385     1 KLGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTsDPYVKVYLLPDKK----KKfeTKVHRKTLNPVFNETFTFKVPY 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1018191476 831 EEVKKRSLDVAVKNSRPLGSHrrKELGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd08385    77 SELGNKTLVFSVYDFDRFSKH--DLIGEVRVPLLTVDLGHVTEEWRDLES 124

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: 82.83 E-value: 1.27e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08402     1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGlSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                          90       100
                  ....*....|....*....|....*...
gi 1018191476 834 KKRSLDVAVKNSRPLGSHRRkeLGKVLI 861
Cdd:cd08402    81 QKVHLIVTVLDYDRIGKNDP--IGKVVL 106

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: 82.63 E-value: 1.78e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd00276     1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGlSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1018191476 835 KRSLDVAVKNSRPLGSHRrkELGKVLIdlSKEDLIKGFSQWYE-LTPNGQP 884
Cdd:cd00276    81 EVSLVITVVDKDSVGRNE--VIGQVVL--GPDSGGEELEHWNEmLASPRKP 127

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: 81.96 E-value: 2.04e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVclRRCLSVLINGCRNLTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEF-FVPMEEVK 834
Cdd:cd08381     2 GQVKLSISYK--NGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYdGLPVEDLQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1018191476 835 KRSLDVAVKNSrplGSHRRKE-LGKVLIDLSKEDLIKGFSQWYELT 879
Cdd:cd08381    80 QRVLQVSVWSH---DSLVENEfLGGVCIPLKKLDLSQETEKWYPLG 122

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: 82.40 E-value: 2.09e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 758 IQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVKKR 836
Cdd:cd08384     2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGySDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKK 81


                  ....*.
gi 1018191476 837 SLDVAV 842
Cdd:cd08384    82 TLEITV 87

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: 79.63 E-value: 1.24e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 309 RVHLLEAEQLAQKDnflgLRGKSDPYAKVSI-GLQHFRSRTIYRNLNPTWNEVFEFMVyEVPGQDLEVDLYDED-TDRDD 386
Cdd:cd04042     3 DIHLKEGRNLAARD----RGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPI-EDVTQPLYIKVFDYDrGLTDD 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 1018191476 387 FLGSLQICLGDVMTNRVVDEWFVLNDTTSG 416
Cdd:cd04042    78 FMGSAFVDLSTLELNKPTEVKLKLEDPNSD 107

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: 77.11 E-value: 5.77e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWacrkKTSVKRKTLEPLFDETFEFFVPmeEVKKRSLDVAVKNSRPLG 849
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGkSDPYVKVSLGGKQKF----KTKVVKNTLNPVWNETFEFPVL--DPESDTLTVEVWDKDRFS 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 1018191476 850 SHRRkeLGKVLIDLSK-EDLIKGFSQWYEL 878
Cdd:cd00030    75 KDDF--LGEVEIPLSElLDSGKEGELWLPL 102

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: 76.86 E-value: 1.20e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLaqkDNFLGLrGKSDPYAKVSI-GLQHFRSRTIYRNLNPTWNEVFEFMVYEvPGQDLEVDLYDEDTDR 384
Cdd:cd04045     1 GVLRLHIRKANDL---KNLEGV-GKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEVMDYEKVG 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1018191476 385 DD-FLGSLQICLGDVMTNRVVDEwFVLNDTTSGRLHLRL 422
Cdd:cd04045    76 KDrSLGSVEINVSDLIKKNEDGK-YVEYDDEEERLKRLL 113

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

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 76.79 E-value: 1.66e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLT--PCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08392     2 GEIEFALHYNFRTSCLEITIKACRNLAygDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1018191476 834 KKRSLDVAVKNSRPLgsHRRKELGKVLIDLSKEDLIKGFSQ---WYEL 878
Cdd:cd08392    82 SSRQLQVSVWHSRTL--KRRVFLGEVLIPLADWDFEDTDSQrflWYPL 127

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: 74.83 E-value: 3.18e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  771 LSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKwaCRKKTSVKRKTLEPLFDETFEFFVPMEEvkKRSLDVAVKNSRPLG 849
Cdd:smart00239   2 LTVKIISARNLPPKDKGGkSDPYVKVSLDGDPK--EKKKTKVVKNTLNPVWNETFEFEVPPPE--LAELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|....*.
gi 1018191476  850 SHRRkeLGKVLIDLSkeDLIKGFSQW 875
Cdd:smart00239  78 RDDF--IGQVTIPLS--DLLLGGRHE 99

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 74.64 E-value: 6.20e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMV---YEVpgqdLEVDLYDEDT 382
Cdd:cd08377     1 GFLQVKVIRASGLAAAD----IGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIkdiHDV----LEVTVYDEDK 72

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1018191476 383 DRD-DFLGSLQICLGDVmTNRVVDeWFVLND 412
Cdd:cd08377    73 DKKpEFLGKVAIPLLSI-KNGERK-WYALKD 101

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: 1.35e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 754 QLGEIQLTVRYVCLRRCLSVLINGCRNLTP-----CTSsgaDPYVRVYLLPERKWacRKKTSVKRKTLEPLFDETFEFF- 827
Cdd:cd08388     1 KLGTLFFSLRYNSEKKALLVNIIECRDLPAmdeqsGTS---DPYVKLQLLPEKEH--KVKTRVLRKTRNPVYDETFTFYg 75

                          90
                  ....*....|....*
gi 1018191476 828 VPMEEVKKRSLDVAV 842
Cdd:cd08388    76 IPYNQLQDLSLHFAV 90

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 72.67 E-value: 2.79e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDT-DRD 385
Cdd:cd08376     1 VVTIVLVEGKNLPPMDD----NGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTgKKD 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1018191476 386 DFLGSLQICLGDVMTNRVVDEWFVLNDTTsGRLHL 420
Cdd:cd08376    77 EFIGRCEIDLSALPREQTHSLELELEDGE-GSLLL 110

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: 73.04 E-value: 3.95e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 759 QLTVR--YVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKW-ACRK-KTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd04009     4 VLTVKayYRASEQSLRVEILNARNLLPLDSNGsSDPFVKVELLPRHLFpDVPTpKTQVKKKTLFPLFDESFEFNVPPEQC 83


                  ...
gi 1018191476 834 KKR 836
Cdd:cd04009    84 SVE 86

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: 72.31 E-value: 5.37e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFF-VPMEE 832
Cdd:cd04035     1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGlSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1018191476 833 VKKRSLDVAVKNSRPLGShrrKELGKVLIDLSK 865
Cdd:cd04035    81 IQRKTLRLLVLDEDRFGN---DFLGETRIPLKK 110

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 71.45 E-value: 8.14e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKD-NflglrGKSDPYAKVSI-GLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDR 384
Cdd:cd04040     1 LTVDVISAENLPSADrN-----GKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDrGGK 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1018191476 385 DDFLGSLQICLGDVMTNRVVDewFVLNDTTSGRLHLRLEWLS 426
Cdd:cd04040    76 DDLLGSAYIDLSDLEPEETTE--LTLPLDGQGGGKLGAVFLP 115

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: 71.14 E-value: 1.46e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRrcLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd04026     2 GRIYLKISVKDNK--LTVEVREAKNLIPMDPNGlSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79


                  ..
gi 1018191476 835 KR 836
Cdd:cd04026    80 RR 81

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: 1.53e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG--ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd04029     2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAKkrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 834 KKRSLDVAVKNSRPLGshRRKELGKVLIDLSKEDLIKGFSQWYEL 878
Cdd:cd04029    82 ETRTLQLSVWHYDRFG--RNTFLGEVEIPLDSWNFDSQHEECLPL 124

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: 70.91 E-value: 1.85e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08405     1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGtSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                          90       100
                  ....*....|....*....|....*...
gi 1018191476 834 KKRSLDVAVKNSRPLGshRRKELGKVLI 861
Cdd:cd08405    81 RETTLIITVMDKDRLS--RNDLIGKIYL 106

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: 70.09 E-value: 4.62e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSGADPYVRVYLLPERKWACrKKTSVKRKTLEPLFDETFEF-------------FVPMEEVKKRS 837
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVTLNYSSKTDT-KRTKVKKKTNNPRFDEAFYFeltigfsyekksfKVEEEDLEKSE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1018191476 838 LDVAVKNSRPLGshRRKELGKVLIDLSKEDLIKGFSQWYELTPNGQPRS 886
Cdd:cd08675    80 LRVELWHASMVS--GDDFLGEVRIPLQGLQQAGSHQAWYFLQPREAPGT 126

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: 68.89 E-value: 1.34e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFlglrgKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQdLEVDLYDEDT-DR 384
Cdd:cd04038     2 GLLKVRVVRGTNLAVRDFT-----SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKDTfSK 75

                          90
                  ....*....|....*.
gi 1018191476 385 DDFLGSLQICLGDVMT 400
Cdd:cd04038    76 DDSMGEAEIDLEPLVE 91

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: 67.51 E-value: 2.59e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDnflgLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDED-TDRDD 386
Cdd:cd04025     2 LRCHVLEARDLAPKD----RNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDlVSKND 77

                          90       100
                  ....*....|....*....|....
gi 1018191476 387 FLGSLQICLGDVMTNRVVDEWFVL 410
Cdd:cd04025    78 FLGKVVFSIQTLQQAKQEEGWFRL 101

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: 67.38 E-value: 3.29e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDNFlglrGKSDPYAKVSI-------GLQHFRSRTIYRNLNPTWNEVFEFMVyeVPGQD-LEVDLY 378
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIF----GASDPYVKISLydpdgngEIDSVQTKTIKKTLNPKWNEEFFFRV--NPREHrLLFEVF 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1018191476 379 DED-TDRDDFLGSLQICL------GDVMTNRVVDEWFVLNDTTS-----GRLHLRLEWL 425
Cdd:cd04033    75 DENrLTRDDFLGQVEVPLnnlpteTPGNERRYTFKDYLLRPRSSksrvkGHLRLYMAYL 133

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

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 66.97 E-value: 3.34e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 754 QLGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWacRKKTSVKRKTLEPLFDETFEF--FvPM 830
Cdd:cd08386     1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGtSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFegF-PY 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1018191476 831 EEVKKRSLDVAVKNSRPLGshRRKELGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd08386    78 EKLQQRVLYLQVLDYDRFS--RNDPIGEVSLPLNKVDLTEEQTFWKDLKP 125

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

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 66.66 E-value: 4.26e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKwaCRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08387     2 RGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGtADPYCKVRLLPDRS--NTKQSKIHKKTLNPEFDESFVFEVPPQEL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1018191476 834 KKRSLDVAVKNSRPLGSHRRkeLGKVLIDLSKEDLIKGFSQW 875
Cdd:cd08387    80 PKRTLEVLLYDFDQFSRDEC--IGVVELPLAEVDLSEKLDLW 119

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: 66.68 E-value: 6.03e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08404     2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGlADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                          90
                  ....*....|.
gi 1018191476 835 KRSLDVAVKNS 845
Cdd:cd08404    82 DISVEFLVLDS 92

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 64.89 E-value: 1.27e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 332 DPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDRDdfLGSLQICLGDVMT--NRVVDEWFV 409
Cdd:cd04050    22 SPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS--LGSLTLPLSELLKepDLTLDQPFP 99


                  ....
gi 1018191476 410 LNDT 413
Cdd:cd04050   100 LDNS 103

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

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 65.22 E-value: 2.25e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGA-DPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08403     1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGFsDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80


                  ....*...
gi 1018191476 835 KRSLDVAV 842
Cdd:cd08403    81 NVSLIIAV 88

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 64.16 E-value: 2.65e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 326 GLRGKSDPYAKVSIGLQH-FRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDVMTNR-V 403
Cdd:cd04052     8 SKTGLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSISLNDLIDATsV 87

                          90       100
                  ....*....|....*....|.
gi 1018191476 404 VDEWFVLNDTTSGRLHLRLEW 424
Cdd:cd04052    88 GQQWFPLSGNGQGRIRISALW 108

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: 63.36 E-value: 6.89e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQdLEVDLYDEDTD---- 383
Cdd:cd04027     3 ISITVVCAQGLIAKDK----TGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDR-IKVRVWDEDDDiksr 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1018191476 384 --------RDDFLGSLQIclgDVMT-NRVVDEWFVLNDTT-----SG--RLHL 420
Cdd:cd04027    78 lkqkftreSDDFLGQTII---EVRTlSGEMDVWYNLEKRTdksavSGaiRLHI 127

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: 64.89 E-value: 1.12e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 116 ERVEWANKIISQTW----PYLS-MIMESkfrekLEPKIRE------KSIHLRTFTFtklyfGQKCPRVNGVKAHTNTcNR 184
Cdd:cd21678     1 ESVEWLNYFLQKFWliyePVLSeTIVTN-----VNPVLAEncpsflDSLRLTEFTL-----GTKAPRIEGVRTYPKT-ED 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 185 RRVTVDLQICYI-------------GDCEISVELQ-KIQAGVNGIQL---------QGTLRVILEpLLVDKPFVGAVTVF 241
Cdd:cd21678    70 DVVVMDWEFSFTpndtsdltakqikNKVNPKIVLTaRVGKGVVGIDLpilvedlsfSGKLRVRLK-LMPDFPHIKTVEVS 148

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 242 FLQKPhlQINWT-----GLTNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKK 292
Cdd:cd21678   149 FLEPP--EIDFVlkplgGGFDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDLEQ 202

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: 1.12e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSGA-DPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEF--FVPmEEVKKRSLDVAVKNSRP 847
Cdd:cd04020    29 LHVWVKEAKNLPALKSGGTsDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNHTFVYdgVSP-EDLSQACLELTVWDHDK 107


                  ....*
gi 1018191476 848 LGSHR 852
Cdd:cd04020   108 LSSND 112

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: 62.50 E-value: 1.81e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLT-PCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08406     2 GEILLSLSYLPTAERLTVVVVKARNLVwDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1018191476 835 KRSLDVAVKNSRPLGshRRKELGKVLIDLSKEDliKGFSQWYEL 878
Cdd:cd08406    82 DLSLRVTVAESTEDG--KTPNVGHVIIGPAASG--MGLSHWNQM 121

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: 61.31 E-value: 2.10e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 469 RAKKLSRFARNKVSkDPssYVKLSVG-KKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDD---QECALGMLE 544
Cdd:cd00030     7 EARNLPAKDLNGKS-DP--YVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDrfsKDDFLGEVE 83

                          90       100
                  ....*....|....*....|
gi 1018191476 545 VPLCQiLPYADLTLEQRFQL 564
Cdd:cd00030    84 IPLSE-LLDSGKEGELWLPL 102

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: 61.20 E-value: 4.54e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 310 VHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEV---PGQDLEVDLYDE--DTDR 384
Cdd:cd04022     4 VEVVDAQDLMPKDG----QGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDrrSGRR 79


                  ....*....
gi 1018191476 385 DDFLGSLQI 393
Cdd:cd04022    80 RSFLGRVRI 88

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: 61.25 E-value: 5.16e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDT-DR 384
Cdd:cd08375    15 GRLMVVIVEGRDLKPCNS----NGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFfSP 90

                          90
                  ....*....|....*...
gi 1018191476 385 DDFLGSLQICLGDVMTNR 402
Cdd:cd08375    91 DDFLGRTEIRVADILKET 108

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

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 60.72 E-value: 5.46e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFlglrGKSDPYAKVSIGLQHFRSRTIYR-NLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDR 384
Cdd:cd08681     1 GTLVVVVLKARNLPNKRKL----DKQDPYCVLRIGGVTKKTKTDFRgGQHPEWDEELRFEITEDKKPILKVAVFDDDKRK 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1018191476 385 DDFLGSLQICLGDVMTNRVVDEWFVL--NDTTSGRLHLRL 422
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: 61.62 E-value: 5.84e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 304 PCGVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSI-------------GLQHFRSRTIYRN----------------LN 354
Cdd:cd08676    26 PIFVLKVTVIEAKGLLAKD----VNGFSDPYCMLGIvpasrernsekskKRKSHRKKAVLKDtvpaksikvtevkpqtLN 101

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 355 PTWNEVFEFMVYEVPGQDLEVDLYDEDtdrDDFLGSLQICLGDVMTNRvVDEWFVL 410
Cdd:cd08676   102 PVWNETFRFEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLPSCG-LDSWFKL 153

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 60.73 E-value: 6.62e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 323 NFLGLRGKSDPYAKVSI-GLQHfRSRTIYRNLNPTWNEVFEFMVYEVPGQD--LEVDLYD-EDTDRDDFLGSLQICLGDV 398
Cdd:cd08373     7 NLPGLKGKGDRIAKVTFrGVKK-KTRVLENELNPVWNETFEWPLAGSPDPDesLEIVVKDyEKVGRNRLIGSATVSLQDL 85


                  .
gi 1018191476 399 M 399
Cdd:cd08373    86 V 86

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: 61.25 E-value: 7.03e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYVclRRCLSVLINGCRNLT--PCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVpmeE 832
Cdd:cd04028    17 MGDIQLGLYDK--KGQLEVEVIRARGLVqkPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDV---S 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1018191476 833 VKKRSLDVAVknsrpLGSHRRKE----LGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd04028    92 PTGKTLQVIV-----WGDYGRMDkkvfMGVAQILLDDLDLSNLVIGWYKLFP 138

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: 59.58 E-value: 9.65e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFLGlrgKSDPYAKVSI---GLQHFRSRTIYRNLNPTWNEvfEFMVYEVP-----GQDLEVDL 377
Cdd:cd04041     1 GVLVVTIHRATDLPKADFGTG---SSDPYVTASFakfGKPLYSTRIIRKDLNPVWEE--TWFVLVTPdevkaGERLSCRL 75

                          90       100
                  ....*....|....*....|....*.
gi 1018191476 378 YDED-TDRDDFLGSLQICLGDVMTNR 402
Cdd:cd04041    76 WDSDrFTADDRLGRVEIDLKELIEDR 101

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: 59.18 E-value: 2.12e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 310 VHLLEAEQLAQKDNflglRGKSDPYAKVSI--GLQHF---RSRTIYRNLNPTWNEVFEFMVyeVPGQDL-----EVDLYD 379
Cdd:cd04031    20 VTVLQARDLPPRDD----GSLRNPYVKVYLlpDRSEKskrRTKTVKKTLNPEWNQTFEYSN--VRRETLkertlEVTVWD 93

                          90       100
                  ....*....|....*....|
gi 1018191476 380 EDTDR-DDFLGSLQICLGDV 398
Cdd:cd04031    94 YDRDGeNDFLGEVVIDLADA 113

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

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 58.33 E-value: 3.74e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSIGLQHF--RSRTIYRNLNPTWNEVFEFMVyEVPG-QDLEVDLYDEDT- 382
Cdd:cd04037     1 LVRVYVVRARNLQPKD----PNGKSDPYLKIKLGKKKIndRDNYIPNTLNPVFGKMFELEA-TLPGnSILKISVMDYDLl 75


                  ....*...
gi 1018191476 383 DRDDFLGS 390
Cdd:cd04037    76 GSDDLIGE 83

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: 58.09 E-value: 4.40e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 329 GKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDV 398
Cdd:cd08378    15 NSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLGGVCFDLSEV 84

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: 57.98 E-value: 7.59e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSV-LINGCRNLTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08410     1 GELLLSLNYLPSAGRLNVdIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80


                  ....*...
gi 1018191476 835 KRSLDVAV 842
Cdd:cd08410    81 NVSLVFTV 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: 57.27 E-value: 8.39e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSI---GLQHFRSRTIYRNLNPTWNEVFEFMVYevPGQD--LEVDLYDED 381
Cdd:cd04036     1 LLTVRVLRATNITKGD----LLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQ--SQVKnvLELTVMDED 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1018191476 382 TDRDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLHLRLE 423
Cdd:cd04036    75 YVMDDHLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFL 116

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: 57.30 E-value: 9.33e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 484 DPssYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQ--ECALGMLEVPL 547
Cdd:cd08391    29 DP--YVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPdkDDFLGRLSIDL 92

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: 57.35 E-value: 1.09e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 755 LGEIQLTVRYV-CLRRcLSVLINGCRNLTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEV 833
Cdd:cd08409     1 LGDIQISLTYNpTLNR-LTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQL 79

                          90       100
                  ....*....|....*....|....*...
gi 1018191476 834 KKRSLDVAVKNsrPLGSHRRKELGKVLI 861
Cdd:cd08409    80 DTASLSLSVMQ--SGGVRKSKLLGRVVL 105

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 56.17 E-value: 1.36e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 477 ARNKVSKDPSS----YVKLSVGKKTHTSKTCPHNK--DPVWSQVFSFFVHNVATERLHLKVLDDDQ---ECALGMLEVPL 547
Cdd:pfam00168  10 AKNLPPKDGNGtsdpYVKVYLLDGKQKKKTKVVKNtlNPVWNETFTFSVPDPENAVLEIEVYDYDRfgrDDFIGEVRIPL 89


                  ....*
gi 1018191476 548 CQILP 552
Cdd:pfam00168  90 SELDS 94

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: 55.57 E-value: 2.00e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  468 YRAKKLSRFARNKVSkDPssYVKLSVG---KKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECA---LG 541
Cdd:smart00239   7 ISARNLPPKDKGGKS-DP--YVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRddfIG 83

                           90
                   ....*....|
gi 1018191476  542 MLEVPLCQIL 551
Cdd:smart00239  84 QVTIPLSDLL 93

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: 56.19 E-value: 2.00e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLaQKDNFLGlrgKSDPYAKVSIGLQHFRSrTIYRNL--NPTWNEVFEFMVyEVPGQ----DLEVDLYD 379
Cdd:cd04049     1 GTLEVLLISAKGL-QDTDFLG---KIDPYVIIQCRTQERKS-KVAKGDgrNPEWNEKFKFTV-EYPGWggdtKLILRIMD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 380 EDT-DRDDFLGSLQICLGDVMT---------NRVVDEWFVLNDTT 414
Cdd:cd04049    75 KDNfSDDDFIGEATIHLKGLFEegvepgtaeLVPAKYNVVLEDDT 119

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: 56.12 E-value: 2.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 310 VHLLEAEQLAQKDnflgLRGKSDPYAKVSIgL----QHFRSRTIYRNLNPTWNEVFEFMV-Y-EVPGQDLEVDLYDEDT- 382
Cdd:cd08385    20 VGIIQAADLPAMD----MGGTSDPYVKVYL-LpdkkKKFETKVHRKTLNPVFNETFTFKVpYsELGNKTLVFSVYDFDRf 94

                          90       100
                  ....*....|....*....|....*
gi 1018191476 383 DRDDFLGSLQICLGDVMTNRVVDEW 407
Cdd:cd08385    95 SKHDLIGEVRVPLLTVDLGHVTEEW 119

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

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 56.25 E-value: 3.03e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLtPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFV-------------PMEEVKKRS 837
Cdd:cd04010     2 LSVRVIECSDL-ALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfemPEEDAEKLE 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1018191476 838 LDVAVKNSRPLGShrRKELGKVLIDLSKEDLIKG-FSQWYELtpngQPRS 886
Cdd:cd04010    81 LRVDLWHASMGGG--DVFLGEVRIPLRGLDLQAGsHQAWYFL----QPRE 124

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

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 55.73 E-value: 3.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 329 GKSDPYAKVSI-----GLQHFRSRTIYRNLNPTWNEVFefmVYEVPGQD----LEVDLYDED-TDRDDFLGSLQICLGDV 398
Cdd:cd04026    32 GLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETF---TFDLKPADkdrrLSIEVWDWDrTTRNDFMGSLSFGVSEL 108

                          90       100
                  ....*....|....*....|.
gi 1018191476 399 MtNRVVDEWFVLNDTTSGRLH 419
Cdd:cd04026   109 I-KMPVDGWYKLLNQEEGEYY 128

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

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 55.49 E-value: 3.97e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 299 LRFPLPCGVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSIgLQH----FRSRTIYRNLNPTWNEVFEFMV--YEVPGQD 372
Cdd:cd08387     9 LEYDKDMGILNVKLIQARNLQPRD----FSGTADPYCKVRL-LPDrsntKQSKIHKKTLNPEFDESFVFEVppQELPKRT 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1018191476 373 LEVDLYDEDT-DRDDFLGSLQICLGDVMTNRVVDEW 407
Cdd:cd08387    84 LEVLLYDFDQfSRDECIGVVELPLAEVDLSEKLDLW 119

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: 55.84 E-value: 4.44e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDNflglrGKSDPYAKVSIGLQHF----RSRTIYRNLNPTWNEVFEFMVYE----------VPGQDL 373
Cdd:cd08675     1 LSVRVLECRDLALKSN-----GTCDPFARVTLNYSSKtdtkRTKVKKKTNNPRFDEAFYFELTIgfsyekksfkVEEEDL 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1018191476 374 E-----VDLYDEDT-DRDDFLGSLQICLGDVMTNRVVDEWFVL 410
Cdd:cd08675    76 EkselrVELWHASMvSGDDFLGEVRIPLQGLQQAGSHQAWYFL 118

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: 54.53 E-value: 6.31e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 791 PYVRVYLLPERKwacrKKTSVKRKTLEPLFDETFEFFVPmeEVKKRSLDVAVKNSRplgSHRRKELGKVLIDLSkeDLIK 870
Cdd:cd04052    15 PYAELYLNGKLV----YTTRVKKKTNNPSWNASTEFLVT--DRRKSRVTVVVKDDR---DRHDPVLGSVSISLN--DLID 83

                          90
                  ....*....|....*...
gi 1018191476 871 GFSQ---WYELTPNGQPR 885
Cdd:cd04052    84 ATSVgqqWFPLSGNGQGR 101

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: 1.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 304 PCGVIRVHLLEAEQLAQKDNFlglrGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEvPGQDLEVDLYDEDTD 383
Cdd:cd04046     1 PQVVTQVHVHSAEGLSKQDSG----GGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKK-PRSPIKIQVWNSNLL 75


                  ....*.
gi 1018191476 384 RDDFLG 389
Cdd:cd04046    76 CDEFLG 81

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: 53.03 E-value: 3.10e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 326 GLRG----KSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEF-MVYEVPGQDLEVDLYDED--TDrDDFLGSLQIclgdV 398
Cdd:cd04032    39 GLWGdyftSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDngWD-DDLLGTCSV----V 113

                          90
                  ....*....|....
gi 1018191476 399 MTNRVVDEWFVLND 412
Cdd:cd04032   114 PEAGVHEDSCQLNH 127

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: 52.56 E-value: 3.37e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 305 CGVIRVHLLEAEQLaQKDNFLGlrGKSDPYAKVSIGLQ--HFRSRTIYRNLNPTWNEVFEFMVYEVpGQDLEVDLYDEDT 382
Cdd:cd04044     1 IGVLAVTIKSARGL-KGSDIIG--GTVDPYVTFSISNRreLARTKVKKDTSNPVWNETKYILVNSL-TEPLNLTVYDFND 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1018191476 383 DRDD-FLGSLQICLGDVMTNRVVDE---WFVLNDTTSGRLHLRLEW 424
Cdd:cd04044    77 KRKDkLIGTAEFDLSSLLQNPEQENltkNLLRNGKPVGELNYDLRF 122

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: 7.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSigLQHFRSR-------TIYRNLNPTWNEVFEFmvyEVPGQDL----- 373
Cdd:cd08405    15 NRITVNIIKARNLKAMD----INGTSDPYVKVW--LMYKDKRvekkktvIKKRTLNPVFNESFIF---NIPLERLrettl 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1018191476 374 EVDLYDEDT-DRDDFLGslQICLG------------DVMTN--RVVDEWFVL 410
Cdd:cd08405    86 IITVMDKDRlSRNDLIG--KIYLGwksgglelkhwkDMLSKprQPVAQWHRL 135

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: 51.03 E-value: 9.50e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLlEAEQLAQKDNFlglrGKSDPYAKVSIGLQHFRSRTIYR------NLNPTWNEvFEFMVYEVPGQD----LEV 375
Cdd:cd04047     1 DVVELQF-SGKKLDKKDFF----GKSDPFLEISRQSEDGTWVLVYRteviknTLNPVWKP-FTIPLQKLCNGDydrpIKI 74

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1018191476 376 DLYDEDTD-RDDFLGSLQICLGDVMTNRVVdEWFVLN 411
Cdd:cd04047    75 EVYDYDSSgKHDLIGEFETTLDELLKSSPL-EFELIN 110

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

Pssm-ID: 176067 [Multi-domain] Cd Length: 119 Bit Score: 51.30 E-value: 9.93e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVclRRCLSVLINGCRNLtPCTSSGA-DPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08685     1 GQLKLSIEGQ--NRKLTLHVLEAKGL-RSTNSGTcNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQ 77

                          90
                  ....*....|.
gi 1018191476 835 KRSLdVAVKNS 845
Cdd:cd08685    78 KRLL-VTVWNK 87

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: 49.11 E-value: 3.95e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQkdnflglrGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPG--QD--LEVDLYDEDT- 382
Cdd:cd04011     6 VRVRVIEARQLVG--------GNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDelFDkiIKISVYDSRSl 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1018191476 383 DRDDFLGSLQICLGDVMTN---RVVDEWFVLND 412
Cdd:cd04011    78 RSDTLIGSFKLDVGTVYDQpdhAFLRKWLLLTD 110

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: 49.59 E-value: 4.19e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 329 GKSDPYAKVSI-----GLQHFRSRTIYRNLNPTWNEVFEFmvYEVPGQD-----LEVDLYDEDTDRDDFLGSLQICLGDV 398
Cdd:cd04035    34 GLSDPYVKLNLlpgasKATKLRTKTVHKTRNPEFNETLTY--YGITEEDiqrktLRLLVLDEDRFGNDFLGETRIPLKKL 111


                  ....*
gi 1018191476 399 MTNRV 403
Cdd:cd04035   112 KPNQT 116

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

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 49.85 E-value: 4.32e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 309 RVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPG--QDLE-------VDLYD 379
Cdd:cd04017     4 RAYIYQARDLLAADK----SGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGspEEIAqnpplvvVELFD 79

                          90
                  ....*....|..
gi 1018191476 380 EDTDR-DDFLGS 390
Cdd:cd04017    80 QDSVGkDEFLGR 91

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: 4.37e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 295 DLTNLRFPL----PCGVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSI---GLQHFRSRTIYRNLNPTWNEVFEFMVY- 366
Cdd:cd08386     1 NLGRIQFSVsydfQESTLTLKILKAVELPAKD----FSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFEGFp 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1018191476 367 --EVPGQDLEVDLYDEDT-DRDDFLGSLQICLGDV 398
Cdd:cd08386    77 yeKLQQRVLYLQVLDYDRfSRNDPIGEVSLPLNKV 111

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 49.20 E-value: 5.43e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1018191476 482 SKDPssYVKLSVGKKT-HTSKTCPHNKDPVWSQVFSFFVHNVaTERLHLKVLDDD 535
Cdd:cd04042    20 TSDP--YVKFKYGGKTvYKSKTIYKNLNPVWDEKFTLPIEDV-TQPLYIKVFDYD 71

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 49.97 E-value: 5.70e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 309 RVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQHFRSRT-IYRNLNPTWNEVFEFMVYEvPGQD---LEVDlYDEDTDR 384
Cdd:cd04019     3 RVTVIEAQDLVPSDK----NRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWNEELMFVAAE-PFEDhliLSVE-DRVGPNK 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1018191476 385 DDFLGSLQICLGDVMtNRVVDE-----WFVLNDTT-----------SGRLHLRL 422
Cdd:cd04019    77 DEPLGRAVIPLNDIE-RRVDDRpvpsrWFSLERPGgameqkkkrkfASRIHLRL 129

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: 49.05 E-value: 6.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 310 VHLLEAEQLAQKDnflgLRGKSDPYAKVSIGLQHF-RSRTIYRNLNPTWNEvfEFMVYEVPG-QDLEVDLYDEDT-DRDD 386
Cdd:cd04054     4 IRIVEGKNLPAKD----ITGSSDPYCIVKVDNEVIiRTATVWKTLNPFWGE--EYTVHLPPGfHTVSFYVLDEDTlSRDD 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1018191476 387 FLGSLQICLGDVMTN-RVVDEWFVL-----NDTTSGRLHLRLE 423
Cdd:cd04054    78 VIGKVSLTREVISAHpRGIDGWMNLtevdpDEEVQGEIHLELS 120

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: 49.10 E-value: 6.04e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1018191476 477 ARNKV-SKDPssYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNvATERLHLKVLDDDQE 537
Cdd:cd04027    15 AKDKTgTSDP--YVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDEDDD 73

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

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 49.19 E-value: 6.18e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLA----QKDNFLGLRGKS--DPYAKVSIGLQHF-RSRTIYRNLNPTWNEVFEFMVYEvpGQDLEVDLY 378
Cdd:cd04014     4 GTLKIKICEAVDLKptdwSTRHAVPKKGSQllDPYVSIDVDDTHIgKTSTKPKTNSPVWNEEFTTEVHN--GRNLELTVF 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1018191476 379 -DEDTDRDDFLGSLQICLGDVMTN--RVVDEWFVLNDTtsGRLHLRLEW 424
Cdd:cd04014    82 hDAAIGPDDFVANCTISFEDLIQRgsGSFDLWVDLEPQ--GKLHVKIEL 128

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: 49.08 E-value: 6.58e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 328 RGKSDPYAKVSI-GL-----QHFRSRTIYRN-LNPTWNEVFEFMVYeVPgqDL-----EVdlYDEDTDRDDFLGslQICL 395
Cdd:cd00275    22 GSIVDPYVEVEIhGLpaddsAKFKTKVVKNNgFNPVWNETFEFDVT-VP--ELaflrfVV--YDEDSGDDDFLG--QACL 94

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: 49.16 E-value: 6.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 756 GEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGADPY-VRVYLLPERKWacRKKTSVKRKTlEPLFDETFEFF-VPMEEV 833
Cdd:cd08389     3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWqVHLVLLPSKKQ--RAKTKVQRGP-NPVFNETFTFSrVEPEEL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1018191476 834 KKRSLDVavknsRPLGSHR-RKE--LGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd08389    80 NNMALRF-----RLYGVERmRKErlIGEKVVPLSQLNLEGETTVWLTLEP 124

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: 48.41 E-value: 9.57e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 309 RVHLLEAEQLAqkdnflgLRGKSDPYAKVSIGLQH-FRSRTIYRnLNPTWNEVFEFmvyEVPGQD-----LEVDLYDEDT 382
Cdd:cd08383     3 RLRILEAKNLP-------SKGTRDPYCTVSLDQVEvARTKTVEK-LNPFWGEEFVF---DDPPPDvtfftLSFYNKDKRS 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1018191476 383 -DRDDFLGSLQIclgDVMTN-RVVDEWFVLNDTTS-----GRLHLRL 422
Cdd:cd08383    72 kDRDIVIGKVAL---SKLDLgQGKDEWFPLTPVDPdsevqGSVRLRA 115

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 48.88 E-value: 1.05e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1018191476 329 GKSDPYAKVSI----GLQHFRSRTI-YRNLNPTWNEVFEFMV--YEVPGQDLEVDLYDEDTDR-DDFLGSLQI 393
Cdd:cd08384    32 GYSDPFVKLYLkpdaGKKSKHKTQVkKKTLNPEFNEEFFYDIkhSDLAKKTLEITVWDKDIGKsNDYIGGLQL 104

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 47.56 E-value: 1.27e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 770 CLSVLINGCRNL-TPCTSSGADPYVRVyLLPERKwacrKKTSVKRKTLEPLFDETFEFFVPmeEVKKRSLDVAVKNsrpl 848
Cdd:cd04050     1 LLFVYLDSAKNLpLAKSTKEPSPYVEL-TVGKTT----QKSKVKERTNNPVWEEGFTFLVR--NPENQELEIEVKD---- 69

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1018191476 849 gSHRRKELGKVLIDLS----KEDLIkgFSQWYELTPNG 882
Cdd:cd04050    70 -DKTGKSLGSLTLPLSellkEPDLT--LDQPFPLDNSG 104

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: 47.64 E-value: 1.49e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 770 CLSVLINGCRNLTPCTSSgaDPYVRVYLLPERkwACRKKTsvkRKTLEPLFDETFEFFVPMEEVKKRSLDVAVKNSRPLG 849
Cdd:cd08383     1 SLRLRILEAKNLPSKGTR--DPYCTVSLDQVE--VARTKT---VEKLNPFWGEEFVFDDPPPDVTFFTLSFYNKDKRSKD 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1018191476 850 ShrrkELGKVLIDLSKEDLIKGFSQWYELTP 880
Cdd:cd08383    74 R----DIVIGKVALSKLDLGQGKDEWFPLTP 100

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

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 48.07 E-value: 1.51e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDnFLGLRgksDPYAKVSI-GLQHFRSRTIYRNLNPTWNEVFEFMVyeVPGQDLEVDLYDEDT--DR 384
Cdd:cd08382     2 VRLTVLCADGLAKRD-LFRLP---DPFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTV--GPSSIITIQVFDQKKfkKK 75

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1018191476 385 DD-FLGslqicLGDVMTNRVVDewfvLNDTTSGRLHLR 421
Cdd:cd08382    76 DQgFLG-----CVRIRANAVLP----LKDTGYQRLDLR 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: 1.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVhlLEAEQL-AQKDNflglrGKSDPYAKVS---IGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTD 383
Cdd:cd04043     5 IRI--VRAENLkADSSN-----GLSDPYVTLVdtnGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFV 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1018191476 384 RD-DFLGSLQICL------GDVMTNrvvDEWFVLNdtTSGRLHLRLE 423
Cdd:cd04043    78 GKhDLCGRASLKLdpkrfgDDGLPR---EIWLDLD--TQGRLLLRVS 119

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: 48.13 E-value: 2.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 757 EIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGA-DPYVRVYLL-PERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVK 834
Cdd:cd08408     3 ELLLGLEYNALTGRLSVEVIKGSNFKNLAMNKApDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

                          90       100
                  ....*....|....*....|..
gi 1018191476 835 KRSLDVAVKNSRplgSHRRKEL 856
Cdd:cd08408    83 EVTLMFSVYNKR---KMKRKEM 101

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: 47.18 E-value: 2.42e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 313 LEAEQLAQKDNFlglrGKSDPYAKVSI---GLQHFR--SRT--IYRNLNPTWNE--VFEFMVYEVpgQDLEVDLYDED-- 381
Cdd:cd04048     7 ISCRNLLDKDVL----SKSDPFVVVYVktgGSGQWVeiGRTevIKNNLNPDFVTtfTVDYYFEEV--QKLRFEVYDVDsk 80

                          90       100
                  ....*....|....*....|....
gi 1018191476 382 ---TDRDDFLGSLQICLGDVMTNR 402
Cdd:cd04048    81 skdLSDHDFLGEAECTLGEIVSSP 104

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 50.91 E-value: 3.34e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  268 SDSLLE-DLIATHLVLPNRVTVPVKKGLDLTNLRFPLPC-----------GVIRVHLLEAEQLAQKDnflgLRGKSDPYa 335
Cdd:COG5038    990 EVTLPTlDLVSNAYEKPSSLNFPGSAKVLVQVSYTPVPVklppvemvensGYLTIMLRSGENLPSSD----ENGYSDPF- 1064

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  336 kVSIGLQH---FRSRTIYRNLNPTWNEVFEFmvyEVPGQD---LEVDLYD-EDTDRDDFLGSLQICL------GDVMTNR 402
Cdd:COG5038   1065 -VKLFLNEksvYKTKVVKKTLNPVWNEEFTI---EVLNRVkdvLTINVNDwDSGEKNDLLGTAEIDLsklepgGTTNSNI 1140

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1018191476  403 VVD-EWF-VLNDTTSGRLHLRLEWLSLLTDQE 432
Cdd:COG5038   1141 PLDgKTFiVLDGTLHPGFNFRSKYALNVSRKE 1172

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 50.91 E-value: 4.27e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476  272 LEDLIATHLVLPNRVTVPVKKG-LDLTNLRFPL--------------PCGVIRVHLLEAEQLAQKDNFlglrGKSDPYAK 336
Cdd:COG5038    662 LPDLIDRTLDTFLVFPLRNPKGrIFITNYWKPIynaggsssktvydtPIGAIRVSVRKANDLRNEIPG----GKSDPYAT 737

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476  337 VSI-GLQHFRSRTIYRNLNPTWNEV-FEFMVYEVPGQDLEVDLYDEDTDrDDFLGSLQICLGDVMT 400
Cdd:COG5038    738 VLVnNLVKYRTIYGSSTLNPIWNEIlYVPVTSKNQRLTLECMDYEESGD-DRNLGEVNINVSNVSK 802

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: 46.81 E-value: 5.55e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 328 RGKSDPYAKVSI-----GLQHFRSRTIYRNLNPTWNEVFEFMV--YEVPGQDLEVDLYDEDTD-RDDFLGslQICLG--- 396
Cdd:cd00276    32 KGLSDPYVKVSLlqggkKLKKKKTSVKKGTLNPVFNEAFSFDVpaEQLEEVSLVITVVDKDSVgRNEVIG--QVVLGpds 109

                          90       100
                  ....*....|....*....|....*
gi 1018191476 397 ---------DVMTN--RVVDEWFVL 410
Cdd:cd00276   110 ggeelehwnEMLASprKPIARWHKL 134

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: 45.64 E-value: 7.00e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1018191476 790 DPYVRVYLLPERKwacrkKTSVKRKTLEPLFDET--FEFFVPMEEVKKRSLDVAVKNSRPLGS 850
Cdd:cd04011    22 DPVVKVEVGGQKK-----YTSVKKGTNCPFYNEYffFNFHESPDELFDKIIKISVYDSRSLRS 79

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: 46.93 E-value: 7.09e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 306 GVIRVHLLEAEQLAQKDNflglRGKSDPYAKVSIgLQH------FRSRTIYRNLNPTWNEVfefMVYE-VPGQDL----- 373
Cdd:cd04020    27 GELHVWVKEAKNLPALKS----GGTSDSFVKCYL-LPDkskkskQKTPVVKKSVNPVWNHT---FVYDgVSPEDLsqacl 98

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 374 EVDLYDEDTD-RDDFLGSLQICLGDVMTNRVVDEWFvlnDTTSGRLHLrleWLSLL 428
Cdd:cd04020    99 ELTVWDHDKLsSNDFLGGVRLGLGTGKSYGQAVDWM---DSTGEEILL---WQKML 148

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: 46.08 E-value: 9.42e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDNflglRGKSDPYAKVSIGLQH-F------RSRTIYRNLNPTWNEVFEFMV----YEVPGQDLEV 375
Cdd:cd04009    17 SLRVEILNARNLLPLDS----NGSSDPFVKVELLPRHlFpdvptpKTQVKKKTLFPLFDESFEFNVppeqCSVEGALLLF 92

                          90       100
                  ....*....|....*....|....*
gi 1018191476 376 DLYDEDT-DRDDFLGSLQICLGDVM 399
Cdd:cd04009    93 TVKDYDLlGSNDFEGEAFLPLNDIP 117

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

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 44.94 E-value: 1.44e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1018191476 306 GVIRVHLLEAEQLAQKDNFLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYE 367
Cdd:cd04039     1 GVVFMEIKSITDLPPLKNMTRTGFDMDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYP 62

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: 45.44 E-value: 1.87e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 469 RAKKLSRFARNKVSKDPSSyvklsvGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKV--LDDDqecALGMLEVP 546
Cdd:cd08676    68 KSKKRKSHRKKAVLKDTVP------AKSIKVTEVKPQTLNPVWNETFRFEVEDVSNDQLHLDIwdHDDD---FLGCVNIP 138

                          90
                  ....*....|....*...
gi 1018191476 547 LCQILPyadLTLEQRFQL 564
Cdd:cd08676   139 LKDLPS---CGLDSWFKL 153

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: 44.55 E-value: 2.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 790 DPYVRVYLLPERKwacrKKTSVKRKTLEPLFDETFEFfvPMEEVKKRSLDVAVKNSRPlgsHRRKELGKVLIDLSKEdLI 869
Cdd:cd08681    23 DPYCVLRIGGVTK----KTKTDFRGGQHPEWDEELRF--EITEDKKPILKVAVFDDDK---RKPDLIGDTEVDLSPA-LK 92

                          90
                  ....*....|....*
gi 1018191476 870 KG-FSQWYELTPNGQ 883
Cdd:cd08681    93 EGeFDDWYELTLKGR 107

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 44.13 E-value: 2.52e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 480 KVSKDPSSYVKLSV-GKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDD 534
Cdd:cd04052     8 SKTGLLSPYAELYLnGKLVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDD 63

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: 44.17 E-value: 3.16e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 298 NLRFPLPCGVIRVHLLEAEQLAQKDNflgLRGKSDPYAKVSIgL----QHFRSRTIYRN--LNPTWNEVFEfmvYEVPGQ 371
Cdd:cd08521     6 SLSYNYKTGSLEVHIKECRNLAYADE---KKKRSNPYVKVYL-LpdksKQSKRKTSVKKntTNPVFNETLK---YHISKS 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 372 DLE-----VDLYDEDT-DRDDFLGSLQICLGDVMTNRVVDEWFVL 410
Cdd:cd08521    79 QLEtrtlqLSVWHHDRfGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 44.10 E-value: 3.20e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKWacrkKTSVKRKTLEPLFDETFEFFVP 829
Cdd:cd04040     1 LTVDVISAENLPSADRNGkSDPFVKFYLNGEKVF----KTKTIKKTLNPVWNESFEVPVP 56

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: 43.80 E-value: 4.31e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHllEAEQLAQKDNflglRGKSDPYakVSIGL---QHFRSR----TIYRNLNPTWNEVFEFMVY--EVPGQDLEVDL 377
Cdd:cd04030    19 IVTVH--KCRNLPPCDS----SDIPDPY--VRLYLlpdKSKSTRrktsVKKDNLNPVFDETFEFPVSleELKRRTLDVAV 90

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1018191476 378 YDE----DTDRdDFLGSLQICLGDVMTNRVVDEWFVL 410
Cdd:cd04030    91 KNSksflSREK-KLLGQVLIDLSDLDLSKGFTQWYDL 126

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: 42.68 E-value: 7.65e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 332 DPYAKVSIGLQHFRSRTIYRNLNPTWN-EVFEFMVYEVPGQD--LEVDLYDEDT-DRDDFLGSLQICLGDVMT---NRVV 404
Cdd:cd08688    22 DAFVEVKFGSTTYKTDVVKKSLNPVWNsEWFRFEVDDEELQDepLQIRVMDHDTySANDAIGKVYIDLNPLLLkdsVSQI 101


                  ....*....
gi 1018191476 405 DEWFVLNDT 413
Cdd:cd08688   102 SGWFPIYDT 110

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: 43.09 E-value: 8.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 477 ARNKVSKD----PSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNvaTERLHLKVLD----DDQECA-----LGML 543
Cdd:cd04022     9 AQDLMPKDgqgsSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSD--PSRLSNLVLEvyvyNDRRSGrrrsfLGRV 86

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1018191476 544 EVPLCQILPYADLTLeQRFQLDHSGLDSLISMRLVLRFL 582
Cdd:cd04022    87 RISGTSFVPPSEAVV-QRYPLEKRGLFSRVRGEIGLKVY 124

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: 41.65 E-value: 2.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 307 VIRVHLLEAEQLAQKDNFLGLRgksDPYAKVSIGLQH-FRSRTIYRNLNPTWNEVFEFmvyEVPG--QDLEVDLYDEDT- 382
Cdd:cd08401     1 SLKIKIGEAKNLPPRSGPNKMR---DCYCTVNLDQEEvFRTKTVEKSLCPFFGEDFYF---EIPRtfRHLSFYIYDRDVl 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1018191476 383 DRDDFLGSLQICLGDVMTNRVVDEWFVL-----NDTTSGRLHLRL 422
Cdd:cd08401    75 RRDSVIGKVAIKKEDLHKYYGKDTWFPLqpvdaDSEVQGKVHLEL 119

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 41.66 E-value: 2.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 296 LTNLRFPLPCGVIRVHLLEAEQLAQKDNflgLRGKSDPYAKVSI----GLQHFRSRTIYRN-LNPTWNEVFEfmvYEVPG 370
Cdd:cd04029     5 LFSLSYDYKTQSLNVHVKECRNLAYGDE---AKKRSNPYVKTYLlpdkSRQSKRKTSIKRNtTNPVYNETLK---YSISH 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1018191476 371 QDLE-------VDLYDEdTDRDDFLGSLQICLGDVMTNRVVDEWFVL 410
Cdd:cd04029    79 SQLEtrtlqlsVWHYDR-FGRNTFLGEVEIPLDSWNFDSQHEECLPL 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: 41.12 E-value: 3.89e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 332 DPYAKVSI--GLQHFRSR---TIYRNLNPTWNEVF---EFMVYEVPGQDLEVDLYDEDTDR-DDFLGSLQICLGDVMTNR 402
Cdd:cd08381    34 DPYVKTYLlpDPQKTTKRktkVVRKTRNPTFNEMLvydGLPVEDLQQRVLQVSVWSHDSLVeNEFLGGVCIPLKKLDLSQ 113


                  ....*....
gi 1018191476 403 VVDEWFVLN 411
Cdd:cd08381   114 ETEKWYPLG 122

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: 41.23 E-value: 4.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 299 LRFPLPCGVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSigLQHFRSR------TI-YRNLNPTWNEVFEFmvyEVPGQ 371
Cdd:cd08402     8 LRYVPTAGKLTVVILEAKNLKKMD----VGGLSDPYVKIH--LMQNGKRlkkkktTIkKRTLNPYYNESFSF---EVPFE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1018191476 372 -----DLEVDLYDED-TDRDDFLGslQICLG------------DVMTN--RVVDEWFVL 410
Cdd:cd08402    79 qiqkvHLIVTVLDYDrIGKNDPIG--KVVLGcnatgaelrhwsDMLASprRPIAQWHTL 135

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: 40.78 E-value: 5.26e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 332 DPYAKVSIGLQHFRSRTIYRNL-NPTWNEVFEFMVYevPGQD-LEVDLYDEDT-DRDDFLGSLQICLGD-VMTNRVVDEW 407
Cdd:cd04016    23 DPYCRIRVGHAVYETPTAYNGAkNPRWNKTIQCTLP--EGVDsIYIEIFDERAfTMDERIAWTHITIPEsVFNGETLDDW 100


                  ....
gi 1018191476 408 FVLN 411
Cdd:cd04016   101 YSLS 104

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: 40.32 E-value: 5.89e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 447 VVFLE--SACNLPRnpfdylngeyrakkLSRFARNKVSKDPssYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHnvAT 524
Cdd:cd04039     2 VVFMEikSITDLPP--------------LKNMTRTGFDMDP--FVIISFGRRVFRTSWRRHTLNPVFNERLAFEVY--PH 63

                          90
                  ....*....|....
gi 1018191476 525 ER---LHLKVLDDD 535
Cdd:cd04039    64 EKnfdIQFKVLDKD 77

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: 40.47 E-value: 7.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 326 GLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEvPGQDLEVDLYD-------EDTDRDDFLGSLQICLGDV 398
Cdd:cd08379    19 DGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYD-PCTVLTVGVFDnsqshwkEAVQPDVLIGKVRIRLSTL 97


                  ....*
gi 1018191476 399 MTNRV 403
Cdd:cd08379    98 EDDRV 102

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: 40.77 E-value: 8.15e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1018191476 477 ARNKVSKDPssYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATErLHLKVLDDD 535
Cdd:cd04038    16 VRDFTSSDP--YVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEVFDKD 71

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: 40.11 E-value: 9.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKDNflgLRGKSDPYAKVSI----GLQHFRSRTIY-RNLNPTWNEVFEFMV--YEVPGQDLEVDLYDE 380
Cdd:cd08393    17 LHVHVIQCQDLAAADP---KKQRSDPYVKTYLlpdkSNRGKRKTSVKkKTLNPVFNETLRYKVerEELPTRVLNLSVWHR 93

                          90
                  ....*....|....*..
gi 1018191476 381 DT-DRDDFLGSLQICLG 396
Cdd:cd08393    94 DSlGRNSFLGEVEVDLG 110

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: 40.43 E-value: 1.01e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1018191476 807 KKTSVKRKTLEPLFDETFEFFVpmEEVKKRSLDVavknsrPLGSHRRKELGKVLIDLsKEDLIKGFSQWYEL 878
Cdd:cd08676    91 KVTEVKPQTLNPVWNETFRFEV--EDVSNDQLHL------DIWDHDDDFLGCVNIPL-KDLPSCGLDSWFKL 153

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: 39.73 E-value: 1.03e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1018191476 808 KTSVKRKTLEPLFDETFEFFVPMEevkKRSLDVAVKNSRPLGshRRKELGKVLIdlSKEDLIK--GFSQWYELTP 880
Cdd:cd08401    37 RTKTVEKSLCPFFGEDFYFEIPRT---FRHLSFYIYDRDVLR--RDSVIGKVAI--KKEDLHKyyGKDTWFPLQP 104

104 kDa microneme/rhoptry antigen; Provisional

Pssm-ID: 185628 [Multi-domain] Cd Length: 943 Bit Score: 42.75 E-value: 1.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 585 EERELGSPYTGPEAL---KKGPllIKKVATNQGPKAQPQEEGPTDLPCPPDPASDTKDVSrstttttsaTTVATEPTSQE 661
Cdd:PTZ00449  542 EPKEGGKPGETKEGEvgkKPGP--AKEHKPSKIPTLSKKPEFPKDPKHPKDPEEPKKPKR---------PRSAQRPTRPK 610

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1018191476 662 TGPEPKGKD---SAKRFCEPIGEKKSPATIFLTVPG-PHSPGPIKSPRPMKCPASPF 714
Cdd:PTZ00449  611 SPKLPELLDipkSPKRPESPKSPKRPPPPQRPSSPErPEGPKIIKSPKPPKSPKPPF 667

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: 39.74 E-value: 1.09e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 308 IRVHLLEAEQLAQKdnflGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFmvyEVPGQDLEVDLYDEDT----- 382
Cdd:cd08682     1 VQVTVLQARGLLCK----GKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSF---ELPGLLSGNGNRATLQltvmh 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1018191476 383 ----DRDDFLGSLQICLGDV--MTNRVVDEWFVLNDTTSGR 417
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: 39.52 E-value: 1.33e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 327 LRGKSDPYAKVSIGLQHFRSRTI--YRNLNPTWNEVFEFMVYEVPGQD----LEVDLYDEDTD-RDDFLGSLQICLGDVM 399
Cdd:cd04051    17 LFGKMKVYAVVWIDPSHKQSTPVdrDGGTNPTWNETLRFPLDERLLQQgrlaLTIEVYCERPSlGDKLIGEVRVPLKDLL 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: 39.16 E-value: 1.64e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 773 VLINGcRNLTPCTSSG-ADPYVRVYLLPERKwacrkKTSVKRKTLEPLFDETFEFFVPMEEvkKRSLDVAVKNSRPlgsh 851
Cdd:cd08376     5 VLVEG-KNLPPMDDNGlSDPYVKFRLGNEKY-----KSKVCSKTLNPQWLEQFDLHLFDDQ--SQILEIEVWDKDT---- 72

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1018191476 852 RRKE--LGKVLIDLSKEDLIKGFSQWYELTPNG 882
Cdd:cd08376    73 GKKDefIGRCEIDLSALPREQTHSLELELEDGE 105

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: 38.78 E-value: 2.09e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1018191476 470 AKKLSRFARNKVSkDPssYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDD 535
Cdd:cd08376     9 GKNLPPMDDNGLS-DP--YVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKD 71

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: 38.90 E-value: 2.56e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1018191476 487 SYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECA---LGMLEVPLCQIL 551
Cdd:cd08375    38 PYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPddfLGRTEIRVADIL 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: 38.86 E-value: 2.61e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 771 LSVLINGCRNLTPCTSSG-ADPYVRVYLLPERKwacrkKTSVKRKTLEPLFDETFEFFVP-MEEVKKRSLDVAVKNSRPL 848
Cdd:cd04022     2 LVVEVVDAQDLMPKDGQGsSSAYVELDFDGQKK-----RTRTKPKDLNPVWNEKLVFNVSdPSRLSNLVLEVYVYNDRRS 76

                          90
                  ....*....|....*.
gi 1018191476 849 GsHRRKELGKVLIDLS 864
Cdd:cd04022    77 G-RRRSFLGRVRISGT 91

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: 38.64 E-value: 3.21e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1018191476 303 LP-CGVIRVHLLEAEQLAQKDnflgLRGKSDPYAKVSIGLQHFRSR----TIYRN-LNPTWNEVfefMVYEVPGQDLE 374
Cdd:cd08403    10 LPtAGRLTLTIIKARNLKAMD----ITGFSDPYVKVSLMCEGRRLKkkktSVKKNtLNPTYNEA---LVFDVPPENVD 80

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: 38.46 E-value: 3.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 482 SKDPssYVK---LSVGKKTHTSKTCPHNKDPVWSQVFSF--FVHNVATER-LHLKVLDDDQ---ECALGMLEVPLCQIlp 552
Cdd:cd08386    36 TSDP--FVKiylLPDKKHKLETKVKRKNLNPHWNETFLFegFPYEKLQQRvLYLQVLDYDRfsrNDPIGEVSLPLNKV-- 111

                          90
                  ....*....|
gi 1018191476 553 yaDLTLEQRF 562
Cdd:cd08386   112 --DLTEEQTF 119

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 38.38 E-value: 4.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 315 AEQLAQKDNFLGLRGK----------SDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVP-GQDLEVDLYDEDT- 382
Cdd:cd04018     9 AEDLPQMDSGIMANVKkaflgekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPlCERIKIQIRDWDRv 88


                  ....*...
gi 1018191476 383 DRDDFLGS 390
Cdd:cd04018    89 GNDDVIGT 96

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: 37.67 E-value: 5.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 477 ARNKVSKDPSSYVKLSV-GKKTHTSKTCPHNKDPVWSQVFSFFVHN--VATERL--HLKVLDDDQEcALGMLEVPLCQIL 551
Cdd:cd08382    13 AKRDLFRLPDPFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGPssIITIQVfdQKKFKKKDQG-FLGCVRIRANAVL 91

                          90
                  ....*....|...
gi 1018191476 552 PYADlTLEQRFQL 564
Cdd:cd08382    92 PLKD-TGYQRLDL 103

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 37.46 E-value: 6.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 779 RNLTPCTSSGA-DPYVRVYllperkWACR-KKTSVKRKTLEPLFDETFEFFVPmeEVKKRSLDVAVKNSRPLGshRRKEL 856
Cdd:cd04025    10 RDLAPKDRNGTsDPFVRVF------YNGQtLETSVVKKSCYPRWNEVFEFELM--EGADSPLSVEVWDWDLVS--KNDFL 79

                          90       100       110
                  ....*....|....*....|....*....|
gi 1018191476 857 GKVLIDLSKEDLIKGFSQWYELTPNGQPRS 886
Cdd:cd04025    80 GKVVFSIQTLQQAKQEEGWFRLLPDPRAEE 109

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: 37.15 E-value: 7.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1018191476 468 YRAKKLSRfaRNKVSKDPSSYVKLSVGKKTHT--SKTCPHNKDPVWSQVFsFFVHNVATERLHLKVLD-----DDQEcaL 540
Cdd:cd04044     9 KSARGLKG--SDIIGGTVDPYVTFSISNRRELarTKVKKDTSNPVWNETK-YILVNSLTEPLNLTVYDfndkrKDKL--I 83


                  ....*..
gi 1018191476 541 GMLEVPL 547
Cdd:cd04044    84 GTAEFDL 90