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Conserved domains on  [gi|442620926|ref|NP_001262921|]
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extended synaptotagmin-like protein 2, isoform D [Drosophila melanogaster]

Protein Classification

extended synaptotagmin( domain architecture ID 17749537)

extended synaptotagmin, including, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SMP_ESyt cd21670
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended ...
 156-332 3.80e-82

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: 260.95  E-value: 3.80e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 156 ERCEWLNKILKQVWPNANHFARTLVKETIEPNVaLALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDLDL 235
Cdd:cd21670    1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSI-RALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FYASDCDINFYLG-GMKGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLRRII 314
Cdd:cd21670   80 SYDGDADIEVSVGtGIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKII 159

                        170
                 ....*....|....*...
gi 442620926 315 VEQIGNVMVLPNKLPISL 332
Cdd:cd21670  160 VDQIASFLVLPNRITIPL 177
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 712-840 5.25e-61

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: 202.12  E-value: 5.25e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 712 GLGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAE 791
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 792 LRQTELEVTVCTQKGFLSGGSPIIGMLKIPLddAEITTQTGLNSWFDLQ 840
Cdd:cd04030   81 LKRRTLDVAVKNSKSFLSREKKLLGQVLIDL--SDLDLSKGFTQWYDLT 127
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 348-467 1.13e-47

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: 165.29  E-value: 1.13e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSD 427
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRS--GKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 442620926 428 DESLGRASIDIASVI---KKGVVDSWLTLEDA-------KHGLLHVRLQW 467
Cdd:cd04024   79 KDYLGEFDIALEEVFadgKTGQSDKWITLKSTrpgktsvVSGEIHLQFSW 128
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 496-601 1.12e-42

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: 150.41  E-value: 1.12e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGNDIGQYT 575
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                         90       100
                 ....*....|....*....|....*.
gi 442620926 576 YTLSTLLKQFNMeVIQQPFQLQKSGP 601
Cdd:cd04050   81 LPLSELLKEPDL-TLDQPFPLDNSGP 105
 
Name Accession Description Interval E-value
SMP_ESyt cd21670
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended ...
 156-332 3.80e-82

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: 260.95  E-value: 3.80e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 156 ERCEWLNKILKQVWPNANHFARTLVKETIEPNVaLALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDLDL 235
Cdd:cd21670    1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSI-RALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FYASDCDINFYLG-GMKGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLRRII 314
Cdd:cd21670   80 SYDGDADIEVSVGtGIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKII 159

                        170
                 ....*....|....*...
gi 442620926 315 VEQIGNVMVLPNKLPISL 332
Cdd:cd21670  160 VDQIASFLVLPNRITIPL 177
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 712-840 5.25e-61

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: 202.12  E-value: 5.25e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 712 GLGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAE 791
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 792 LRQTELEVTVCTQKGFLSGGSPIIGMLKIPLddAEITTQTGLNSWFDLQ 840
Cdd:cd04030   81 LKRRTLDVAVKNSKSFLSREKKLLGQVLIDL--SDLDLSKGFTQWYDLT 127
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 348-467 1.13e-47

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: 165.29  E-value: 1.13e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSD 427
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRS--GKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 442620926 428 DESLGRASIDIASVI---KKGVVDSWLTLEDA-------KHGLLHVRLQW 467
Cdd:cd04024   79 KDYLGEFDIALEEVFadgKTGQSDKWITLKSTrpgktsvVSGEIHLQFSW 128
SMP_LBD pfam17047
Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ...
 154-332 1.11e-44

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: 159.05  E-value: 1.11e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  154 DVERCEWLNKILKQVWPNANHFARTLVKETIEPnvALALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDL 233
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEP--AVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  234 DLFYASDCDINFYLGGM--KGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLR 311
Cdd:pfam17047  79 QISFVGNCEIDLEIKRYfcRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSD 158

                         170       180
                  ....*....|....*....|.
gi 442620926  312 RIIVEQIGNVMVLPNKLPISL 332
Cdd:pfam17047 159 TIILDIISNYLVLPNRITVPL 179
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 496-601 1.12e-42

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: 150.41  E-value: 1.12e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGNDIGQYT 575
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                         90       100
                 ....*....|....*....|....*.
gi 442620926 576 YTLSTLLKQFNMeVIQQPFQLQKSGP 601
Cdd:cd04050   81 LPLSELLKEPDL-TLDQPFPLDNSGP 105
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
154-677 1.68e-35

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 145.67  E-value: 1.68e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  154 DVERCEWLNKILKQVWPNANHFARTLVKETIEPNVALALANYkMHGFRFDRIILGTIPPRIGGVKIYdKNVDRNEIIMDL 233
Cdd:COG5038   219 DYESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSF-IDALALDEFTLGSKPPRIDGIRSY-PSTESDTVVMDV 296

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  234 DLFYA--SDCDIN---------------FYLGGMKGG------IKDFQIHGWVRVVMKpLIRSMPLVGGLQIFFLNNPNI 290
Cdd:COG5038   297 DFSFTphDISDVTatsarasvnpkislvVKKGKSFGSftlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEF 375

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  291 DFNLVGV------IDFMDMPGLSDLLRRIIVEQIGNVMVLPNKLPISLSEEVSAVALKmpePEGILRIHVVEAKDLMKKD 364
Cdd:COG5038   376 DFILVPLggdffgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTIDISQIMAGDSGT---AIGVVEVKIKSAEGLKKSD 452

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  365 ISVlgKGKSDPYaiINVGAQEF---KTQIIDNNVNPKWDYWCEAVVEvSQHAILVLRLFDWDRTSDDESLGRASIDIASV 441
Cdd:COG5038   453 STI--NGTVDPY--ITVTFSDRvigKTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDKVVGSTQLDLALL 527

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  442 IKKGVVDSWLT--LEDAKH-GLLHVRLQWYkltadPNDLQQILLETQLLRVTSMSSAVLSVFIDSARHLkQARSSSKPDP 518
Cdd:COG5038   528 HQNPVKKNELYefLRNTKNvGRLTYDLRFF-----PVIEDKKELKGSVEPLEDSNTGILKVTLREVKAL-DELSSKKDNK 601

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  519 YLVCSVNKQKQQTAMIMRD-DSPVWEQGFTFLVSNPDNESLNIKIYDQKTGNDIGQYTYTLSTLL--KQFNMEVIQQPfq 595
Cdd:COG5038   602 SAELYTNAKEVYSTGKLKFtNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLIdrTLDTFLVFPLR-- 679

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  596 lqksGPESKLYMSLSLRilkPGEIDKDSDaleqvaaltrSSSVKTPDVAAVsppafkasskRLSAESPISEEDPVAATKI 675
Cdd:COG5038   680 ----NPKGRIFITNYWK---PIYNAGGSS----------SKTVYDTPIGAI----------RVSVRKANDLRNEIPGGKS 732


                  ..
gi 442620926  676 SP 677
Cdd:COG5038   733 DP 734
C2 pfam00168
C2 domain;
348-453 3.64e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.77  E-value: 3.64e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  348 GILRIHVVEAKDLMKKDisvlGKGKSDPYAIINV--GAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKD----GNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*...
gi 442620926  426 SDDESLGRASIDIASVIKKGVVDSWLTL 453
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 pfam00168
C2 domain;
727-839 8.84e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 82.37  E-value: 8.84e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  727 QKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLpgrTKESKRKTSVIKDNCNPVYDASFEYliSIAELRQTELEVTVCTQKG 806
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTF--SVPDPENAVLEIEVYDYDR 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 442620926  807 FlsGGSPIIGMLKIPLDdaEITTQTGLNSWFDL 839
Cdd:pfam00168  76 F--GRDDFIGEVRIPLS--ELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 349-450 2.41e-18

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: 80.99  E-value: 2.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   349 ILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVG---AQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:smart00239   1 TLTVKIISARNLPPKDKG----GKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 442620926   426 SDDESLGRASIDIASVIKKGVVDSW 450
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 728-824 4.81e-15

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: 71.36  E-value: 4.81e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   728 KLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKesKRKTSVIKDNCNPVYDASFEYLISIAELRqtELEVTVCTQKGF 807
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPELA--ELEIEVYDKDRF 76

                           90
                   ....*....|....*..
gi 442620926   808 lsGGSPIIGMLKIPLDD 824
Cdd:smart00239  77 --GRDDFIGQVTIPLSD 91
C2 pfam00168
C2 domain;
496-596 5.92e-15

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 71.20  E-value: 5.92e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  496 VLSVFIDSARHLKQARSSSKPDPYLVCSVN--KQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKT--GND- 570
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRfgRDDf 81

                          90       100
                  ....*....|....*....|....*.
gi 442620926  571 IGQYTYTLSTLLKQfnmEVIQQPFQL 596
Cdd:pfam00168  82 IGEVRIPLSELDSG---EGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 496-589 3.58e-13

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: 66.36  E-value: 3.58e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   496 VLSVFIDSARHLKQARSSSKPDPYLVCSVN---KQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND-- 570
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRdd 80

                           90       100
                   ....*....|....*....|
gi 442620926   571 -IGQYTYTLSTLLKQFNMEV 589
Cdd:smart00239  81 fIGQVTIPLSDLLLGGRHEK 100
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
343-441 1.29e-08

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 59.00  E-value: 1.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  343 MPEPEGILRIHVVEAKDLMKKDIsvlgKGKSDPYAIINVGAQE-FKTQIIDNNVNPKWDYwcEAVVEVS--QHAILVLRL 419
Cdd:COG5038  1035 MVENSGYLTIMLRSGENLPSSDE----NGYSDPFVKLFLNEKSvYKTKVVKKTLNPVWNE--EFTIEVLnrVKDVLTINV 1108

                          90       100
                  ....*....|....*....|..
gi 442620926  420 FDWDRTSDDESLGRASIDIASV 441
Cdd:COG5038  1109 NDWDSGEKNDLLGTAEIDLSKL 1130
PLN02952 PLN02952
phosphoinositide phospholipase C
 743-799 1.15e-04

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 45.76  E-value: 1.15e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 442620926 743 DPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELRQTELEV 799
Cdd:PLN02952 492 DSYSPPDFYTKMYIVGVPADNAKKKTKIIEDNWYPAWNEEFSFPLTVPELALLRIEV 548
PLN02270 PLN02270
phospholipase D alpha
 368-475 2.34e-04

phospholipase D alpha


Pssm-ID: 165912 [Multi-domain]  Cd Length: 808  Bit Score: 44.94  E-value: 2.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 368 LGKGKSDPYAIINVG-AQEFKTQIIDNN-VNPKW----DYWCeavVEVSQHAILVLRlfdwdrtsDDESLG-----RASI 436
Cdd:PLN02270  42 VGKGESQLYATIDLEkARVGRTRKIENEpKNPRWyesfHIYC---AHMASNIIFTVK--------DDNPIGatligRAYI 110

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 437 DIASVIKKGVVDSWLTLEDAK----HG--LLHVRLQWYKLTADPN 475
Cdd:PLN02270 111 PVEEILDGEEVDRWVEILDNDknpiHGgsKIHVKLQYFEVTKDRN 155
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
448-585 6.18e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 43.59  E-value: 6.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  448 DSWLTLEDAKHGLLHVRLQWYKLTADPNDLqqilletqllrVTSMSSavLSVFIDSARHLKQARSSSKPDPYLVCSVNKQ 527
Cdd:COG5038  1006 PSSLNFPGSAKVLVQVSYTPVPVKLPPVEM-----------VENSGY--LTIMLRSGENLPSSDENGYSDPFVKLFLNEK 1072

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442620926  528 K-QQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND---IGQYTYTLSTLLKQF 585
Cdd:COG5038  1073 SvYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKndlLGTAEIDLSKLEPGG 1134
 
Name Accession Description Interval E-value
SMP_ESyt cd21670
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended ...
 156-332 3.80e-82

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: 260.95  E-value: 3.80e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 156 ERCEWLNKILKQVWPNANHFARTLVKETIEPNVaLALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDLDL 235
Cdd:cd21670    1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSI-RALLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDNVDRDEIILDLDI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FYASDCDINFYLG-GMKGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLRRII 314
Cdd:cd21670   80 SYDGDADIEVSVGtGIKAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKII 159

                        170
                 ....*....|....*...
gi 442620926 315 VEQIGNVMVLPNKLPISL 332
Cdd:cd21670  160 VDQIASFLVLPNRITIPL 177
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 712-840 5.25e-61

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: 202.12  E-value: 5.25e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 712 GLGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAE 791
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 792 LRQTELEVTVCTQKGFLSGGSPIIGMLKIPLddAEITTQTGLNSWFDLQ 840
Cdd:cd04030   81 LKRRTLDVAVKNSKSFLSREKKLLGQVLIDL--SDLDLSKGFTQWYDLT 127
SMP_ESyt2 cd21680
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 154-332 1.53e-49

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: 172.76  E-value: 1.53e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 154 DVERCEWLNKILKQVWPNANHFARTLVKETIEPnvALALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDL 233
Cdd:cd21680    1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEP--AVRGANAHLSTFSFTKIDLGDQPLRINGVKVYTENVDKRQIILDL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 234 DLFYASDCDINFYLGGM--KGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLR 311
Cdd:cd21680   79 QISFVGNCEIDLEIKRYfcRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDIPGLNGLSD 158

                        170       180
                 ....*....|....*....|.
gi 442620926 312 RIIVEQIGNVMVLPNKLPISL 332
Cdd:cd21680  159 TIILDIISNYLVLPNRITVPL 179
SMP_SYT cd21677
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the synaptotagmin ...
 147-332 1.50e-48

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: 170.04  E-value: 1.50e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 147 PAWVYFPDVERCEWLNKILKQVWPNANHFARTLVKETIEPNvalaLANYK---MHGFRFDRIILGTIPPRIGGVKIYDKN 223
Cdd:cd21677    1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPL----LEQYKpsfISSIKFKKLTLGTVPPRIEGVKVVESD 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 224 VDrnEIIMDLDLFYASDCDINFYLGGMKG-----GIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNL-VGV 297
Cdd:cd21677   77 ED--EVILDVDFRWAGDPDIVLAVKLLPGlslpvQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLkLLG 154

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 442620926 298 IDFMDMPGLSDLLRRIIVEQIGNVMVLPNKLPISL 332
Cdd:cd21677  155 GDDMALPGLKSWLDSFIRDALLDMLVWPKRIVIPI 189
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 348-467 1.13e-47

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: 165.29  E-value: 1.13e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSD 427
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRS--GKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 442620926 428 DESLGRASIDIASVI---KKGVVDSWLTLEDA-------KHGLLHVRLQW 467
Cdd:cd04024   79 KDYLGEFDIALEEVFadgKTGQSDKWITLKSTrpgktsvVSGEIHLQFSW 128
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 348-467 2.47e-45

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: 158.61  E-value: 2.47e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISVLG--KGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFVGGlvKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 442620926 426 SDDEsLGRASIDIASVIKKGVVDSWLTLEDAKHGLLHVRLQW 467
Cdd:cd08391   81 KDDF-LGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLHLKLEW 121
SMP_LBD pfam17047
Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ...
 154-332 1.11e-44

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: 159.05  E-value: 1.11e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  154 DVERCEWLNKILKQVWPNANHFARTLVKETIEPnvALALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDL 233
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEP--AVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  234 DLFYASDCDINFYLGGM--KGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLR 311
Cdd:pfam17047  79 QISFVGNCEIDLEIKRYfcRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSD 158

                         170       180
                  ....*....|....*....|.
gi 442620926  312 RIIVEQIGNVMVLPNKLPISL 332
Cdd:pfam17047 159 TIILDIISNYLVLPNRITVPL 179
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 496-601 1.12e-42

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: 150.41  E-value: 1.12e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGNDIGQYT 575
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                         90       100
                 ....*....|....*....|....*.
gi 442620926 576 YTLSTLLKQFNMeVIQQPFQLQKSGP 601
Cdd:cd04050   81 LPLSELLKEPDL-TLDQPFPLDNSGP 105
SMP_ESyt3 cd21681
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 156-333 6.30e-42

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: 151.13  E-value: 6.30e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 156 ERCEWLNKILKQVWPNANHFARTLVKETIEPNVALALANYKMhgFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDLDL 235
Cdd:cd21681    1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIREKSVHLKT--FTFTKLHFGEKCPRINGVKVYTKEVDRRQVILDLQI 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FYASDCDINFYLGGMKGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLRRIIV 315
Cdd:cd21681   79 CYIGDCEINVEIKKCKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGLTNLLDIPGINDMSDSLIE 158

                        170
                 ....*....|....*...
gi 442620926 316 EQIGNVMVLPNKLPISLS 333
Cdd:cd21681  159 DLIASHLVLPNRFTVPLK 176
SMP_ESyt1 cd21679
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 156-332 1.41e-41

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: 149.94  E-value: 1.41e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 156 ERCEWLNKILKQVWPNANHFARTLVKETIEPnvALALANYKMHGFRFDRIILGTIPPRIGGVKIYdKNVDRNEIIMDLDL 235
Cdd:cd21679    1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAP--AIRASNNHLQTFSFTKVDLGEKPLKVVGVKAH-TEFDKRQIILDLHI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FYASDCDINFYLGGM--KGGIKDFQIHGWVRVVMKPLIRSMPLVGGLQIFFLNNPNIDFNLVGVIDFMDMPGLSDLLRRI 313
Cdd:cd21679   78 SYVGDVEINVEVKKYfcKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTM 157

                        170
                 ....*....|....*....
gi 442620926 314 IVEQIGNVMVLPNKLPISL 332
Cdd:cd21679  158 IMDTIASFLVLPNRLTVPL 176
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
154-677 1.68e-35

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 145.67  E-value: 1.68e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  154 DVERCEWLNKILKQVWPNANHFARTLVKETIEPNVALALANYkMHGFRFDRIILGTIPPRIGGVKIYdKNVDRNEIIMDL 233
Cdd:COG5038   219 DYESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSF-IDALALDEFTLGSKPPRIDGIRSY-PSTESDTVVMDV 296

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  234 DLFYA--SDCDIN---------------FYLGGMKGG------IKDFQIHGWVRVVMKpLIRSMPLVGGLQIFFLNNPNI 290
Cdd:COG5038   297 DFSFTphDISDVTatsarasvnpkislvVKKGKSFGSftlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEVPEF 375

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  291 DFNLVGV------IDFMDMPGLSDLLRRIIVEQIGNVMVLPNKLPISLSEEVSAVALKmpePEGILRIHVVEAKDLMKKD 364
Cdd:COG5038   376 DFILVPLggdffgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTIDISQIMAGDSGT---AIGVVEVKIKSAEGLKKSD 452

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  365 ISVlgKGKSDPYaiINVGAQEF---KTQIIDNNVNPKWDYWCEAVVEvSQHAILVLRLFDWDRTSDDESLGRASIDIASV 441
Cdd:COG5038   453 STI--NGTVDPY--ITVTFSDRvigKTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDKVVGSTQLDLALL 527

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  442 IKKGVVDSWLT--LEDAKH-GLLHVRLQWYkltadPNDLQQILLETQLLRVTSMSSAVLSVFIDSARHLkQARSSSKPDP 518
Cdd:COG5038   528 HQNPVKKNELYefLRNTKNvGRLTYDLRFF-----PVIEDKKELKGSVEPLEDSNTGILKVTLREVKAL-DELSSKKDNK 601

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  519 YLVCSVNKQKQQTAMIMRD-DSPVWEQGFTFLVSNPDNESLNIKIYDQKTGNDIGQYTYTLSTLL--KQFNMEVIQQPfq 595
Cdd:COG5038   602 SAELYTNAKEVYSTGKLKFtNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLIdrTLDTFLVFPLR-- 679

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  596 lqksGPESKLYMSLSLRilkPGEIDKDSDaleqvaaltrSSSVKTPDVAAVsppafkasskRLSAESPISEEDPVAATKI 675
Cdd:COG5038   680 ----NPKGRIFITNYWK---PIYNAGGSS----------SKTVYDTPIGAI----------RVSVRKANDLRNEIPGGKS 732


                  ..
gi 442620926  676 SP 677
Cdd:COG5038   733 DP 734
SMP_TCB cd21678
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the tricalbin ...
 159-334 8.36e-29

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: 114.19  E-value: 8.36e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 159 EWLNKILKQVWPNanhFARTLVKETIEpNVALALANYKM---HGFRFDRIILGTIPPRIGGVKIYDkNVDRNEIIMDLDL 235
Cdd:cd21678    4 EWLNYFLQKFWLI---YEPVLSETIVT-NVNPVLAENCPsflDSLRLTEFTLGTKAPRIEGVRTYP-KTEDDVVVMDWEF 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 236 FY-----------ASDCDINFY------LGGMKGGI------KDFQIHGWVRVVMKpLIRSMPLVGGLQIFFLNNPNIDF 292
Cdd:cd21678   79 SFtpndtsdltakQIKNKVNPKivltarVGKGVVGIdlpilvEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPPEIDF 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 293 NLV---GVIDFMDMPGLSDLLRRIIVEQIGNVMVLPNKLPISLSE 334
Cdd:cd21678  158 VLKplgGGFDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDLEQ 202
SMP_SF cd21669
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP ...
 179-330 2.56e-24

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: 100.09  E-value: 2.56e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 179 LVKETIEPNVALALANYKMHGFRFDRIILGTIPPRIGGVKIYDKNVDRNEIIMDLDLFYASD--CDINFYLGGMKGG--- 253
Cdd:cd21669    4 LIRESLQELLEEVKKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSSDLQLVLDLDLEYAGDfsVVLSAKLGGGGLGlpv 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 254 ---IKDFQIHGWVRVVMKpLIRSMPLVGGLQIFFLNNPNIDFNLV--GVIDFMDMPGLSDLLRRIIVEQIGNVMVLPNKL 328
Cdd:cd21669   84 pvsVSDLSLEGRLRVRLT-LLPEFPYVGALSISFVEPPDIDFSIRplGGVDLMELPGLSSWLEKLLTDALVELLVEPNRI 162


                 ..
gi 442620926 329 PI 330
Cdd:cd21669  163 VI 164
C2 pfam00168
C2 domain;
348-453 3.64e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.77  E-value: 3.64e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  348 GILRIHVVEAKDLMKKDisvlGKGKSDPYAIINV--GAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKD----GNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*...
gi 442620926  426 SDDESLGRASIDIASVIKKGVVDSWLTL 453
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 714-831 2.36e-23

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: 95.78  E-value: 2.36e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPS-NIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 442620926 793 RQTELEVTVCTQKGFlsGGSPIIGMLKIPLDDAEITTQT 831
Cdd:cd08521   81 ETRTLQLSVWHHDRF--GRNTFLGEVEIPLDSWDLDSQQ 117
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 714-840 3.30e-23

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: 95.78  E-value: 3.30e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYL-ISIAEL 792
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSnVRRETL 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 442620926 793 RQTELEVTVCTQKgfLSGGSPIIGMLKIPLDDAEITTQTglnSWFDLQ 840
Cdd:cd04031   83 KERTLEVTVWDYD--RDGENDFLGEVVIDLADALLDDEP---HWYPLQ 125
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 714-839 6.86e-22

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: 91.59  E-value: 6.86e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYsaQRQKLDVTIHKIQKIPLRDpSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEY-LISIAEL 792
Cdd:cd08381    2 GQVKLSISY--KNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYdGLPVEDL 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 442620926 793 RQTELEVTVCTQKGFLSggSPIIGMLKIPLDDAEITTQTglNSWFDL 839
Cdd:cd08381   79 QQRVLQVSVWSHDSLVE--NEFLGGVCIPLKKLDLSQET--EKWYPL 121
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 350-453 1.65e-21

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: 89.82  E-value: 1.65e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVG-AQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSDD 428
Cdd:cd00030    1 LRVTVIEARNLPAKDLN----GKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKD 76

                         90       100
                 ....*....|....*....|....*.
gi 442620926 429 ESLGRASIDIASVIKKG-VVDSWLTL 453
Cdd:cd00030   77 DFLGEVEIPLSELLDSGkEGELWLPL 102
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 714-816 2.32e-19

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: 84.94  E-value: 2.32e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELR 793
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                         90       100
                 ....*....|....*....|...
gi 442620926 794 QTELEVTVCTQKGFlsGGSPIIG 816
Cdd:cd00276   81 EVSLVITVVDKDSV--GRNEVIG 101
C2 pfam00168
C2 domain;
727-839 8.84e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 82.37  E-value: 8.84e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  727 QKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLpgrTKESKRKTSVIKDNCNPVYDASFEYliSIAELRQTELEVTVCTQKG 806
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTF--SVPDPENAVLEIEVYDYDR 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 442620926  807 FlsGGSPIIGMLKIPLDdaEITTQTGLNSWFDL 839
Cdd:pfam00168  76 F--GRDDFIGEVRIPLS--ELDSGEGLDGWYPL 104
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 714-841 1.49e-18

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: 82.30  E-value: 1.49e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIP-DPYVKLYLLP--GRTKESKrktsVIKDNCNPVYDASFEYLISIA 790
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAHcDPFVKVCLLPdeRRSLQSK----VKRKTQNPNFDETFVFQVSFK 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 442620926 791 ELRQTELEVTV--CTQKGFLSggspIIGMLKIPLddAEITTQTGLNSWFDLQP 841
Cdd:cd08390   77 ELQRRTLRLSVydVDRFSRHC----IIGHVLFPL--KDLDLVKGGVVWRDLEP 123
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 349-450 2.41e-18

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: 80.99  E-value: 2.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   349 ILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVG---AQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:smart00239   1 TLTVKIISARNLPPKDKG----GKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 442620926   426 SDDESLGRASIDIASVIKKGVVDSW 450
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 713-822 3.02e-18

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: 81.56  E-value: 3.02e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYL-ISIAE 791
Cdd:cd04035    1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 442620926 792 LRQTELEVTVCTQKGFlsgGSPIIGMLKIPL 822
Cdd:cd04035   81 IQRKTLRLLVLDEDRF---GNDFLGETRIPL 108
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 714-840 4.26e-18

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: 80.95  E-value: 4.26e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPS-NIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAkKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 442620926 793 RQTELEVTVCTQKGFlsGGSPIIGMLKIPLDDAEITTQTglNSWFDLQ 840
Cdd:cd04029   82 ETRTLQLSVWHYDRF--GRNTFLGEVEIPLDSWNFDSQH--EECLPLH 125
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 713-841 6.14e-18

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: 80.39  E-value: 6.14e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKesKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08385    2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFKVPYSEL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 793 RQTELEVTVCTQKGFLSggSPIIGMLKIPLddAEITTQTGLNSWFDLQP 841
Cdd:cd08385   80 GNKTLVFSVYDFDRFSK--HDLIGEVRVPL--LTVDLGHVTEEWRDLES 124
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 714-840 3.16e-17

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: 78.63  E-value: 3.16e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNI-PDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQrSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 442620926 793 RQTELEVTVCTQKGFlsGGSPIIGMLKIPLDDAEItTQTGLNsWFDLQ 840
Cdd:cd08393   82 PTRVLNLSVWHRDSL--GRNSFLGEVEVDLGSWDW-SNTQPT-WYPLQ 125
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 350-441 3.27e-17

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: 77.99  E-value: 3.27e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQE-FKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSDD 428
Cdd:cd04040    1 LTVDVISAENLPSADRN----GKSDPFVKFYLNGEKvFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKD 76

                         90
                 ....*....|...
gi 442620926 429 ESLGRASIDIASV 441
Cdd:cd04040   77 DLLGSAYIDLSDL 89
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 348-445 4.52e-16

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: 74.93  E-value: 4.52e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLmkkdISVLGKGKSDPYAIINV-GAQEFKTQIIDNNVNPKWDYWCEAVVeVSQHAILVLRLFDWDRTS 426
Cdd:cd04045    1 GVLRLHIRKANDL----KNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPV-TSPNQKITLEVMDYEKVG 75

                         90
                 ....*....|....*....
gi 442620926 427 DDESLGRASIDIASVIKKG 445
Cdd:cd04045   76 KDRSLGSVEINVSDLIKKN 94
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 348-465 6.00e-16

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: 75.11  E-value: 6.00e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDisvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSD 427
Cdd:cd08375   15 GRLMVVIVEGRDLKPCN----SNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSP 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 442620926 428 DESLGRASIDIASVIK-----KGVVDSWLTLEDAKHGLLHVRL 465
Cdd:cd08375   91 DDFLGRTEIRVADILKetkesKGPITKRLLLHEVPTGEVVVKL 133
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 714-801 4.23e-15

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


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 73.51  E-value: 4.23e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRY--SAQRQK----------LDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDA 781
Cdd:cd04020    2 GELKVALKYvpPESEGAlkskkpstgeLHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                         90       100
                 ....*....|....*....|.
gi 442620926 782 SFEY-LISIAELRQTELEVTV 801
Cdd:cd04020   82 TFVYdGVSPEDLSQACLELTV 102
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 715-801 4.39e-15

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: 72.77  E-value: 4.39e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 715 RMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELRQ 794
Cdd:cd08384    1 KILVSLMYNTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAK 80


                 ....*..
gi 442620926 795 TELEVTV 801
Cdd:cd08384   81 KTLEITV 87
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 728-824 4.81e-15

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: 71.36  E-value: 4.81e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   728 KLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKesKRKTSVIKDNCNPVYDASFEYLISIAELRqtELEVTVCTQKGF 807
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPELA--ELEIEVYDKDRF 76

                           90
                   ....*....|....*..
gi 442620926   808 lsGGSPIIGMLKIPLDD 824
Cdd:smart00239  77 --GRDDFIGQVTIPLSD 91
C2 pfam00168
C2 domain;
496-596 5.92e-15

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 71.20  E-value: 5.92e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  496 VLSVFIDSARHLKQARSSSKPDPYLVCSVN--KQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKT--GND- 570
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRfgRDDf 81

                          90       100
                  ....*....|....*....|....*.
gi 442620926  571 IGQYTYTLSTLLKQfnmEVIQQPFQL 596
Cdd:pfam00168  82 IGEVRIPLSELDSG---EGLDGWYPL 104
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 348-438 6.12e-15

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 72.74  E-value: 6.12e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDIsvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYwcEAVVEV-SQHAILVLRLFDWDRTS 426
Cdd:cd04038    2 GLLKVRVVRGTNLAVRDF-----TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNE--ELTLSVpNPMAPLKLEVFDKDTFS 74

                         90
                 ....*....|..
gi 442620926 427 DDESLGRASIDI 438
Cdd:cd04038   75 KDDSMGEAEIDL 86
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 729-839 7.92e-15

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: 70.94  E-value: 7.92e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 729 LDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRtkesKRKTSVIKDNCNPVYDASFEylISIAELRQTELEVTVCTQKGFl 808
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFE--FPVLDPESDTLTVEVWDKDRF- 73

                         90       100       110
                 ....*....|....*....|....*....|.
gi 442620926 809 sGGSPIIGMLKIPLDDAEITTQTGlNSWFDL 839
Cdd:cd00030   74 -SKDDFLGEVEIPLSELLDSGKEG-ELWLPL 102
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 497-584 4.18e-14

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: 69.02  E-value: 4.18e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSV-NKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND---IG 572
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLgGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKddfLG 80

                         90
                 ....*....|..
gi 442620926 573 QYTYTLSTLLKQ 584
Cdd:cd00030   81 EVEIPLSELLDS 92
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 713-801 7.42e-14

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: 69.37  E-value: 7.42e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08405    1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80


                 ....*....
gi 442620926 793 RQTELEVTV 801
Cdd:cd08405   81 RETTLIITV 89
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 714-799 7.94e-14

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: 68.83  E-value: 7.94e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYsaQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIA-EL 792
Cdd:cd04026    2 GRIYLKISV--KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPAdKD 79


                 ....*..
gi 442620926 793 RQTELEV 799
Cdd:cd04026   80 RRLSIEV 86
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 496-589 3.58e-13

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: 66.36  E-value: 3.58e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926   496 VLSVFIDSARHLKQARSSSKPDPYLVCSVN---KQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND-- 570
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRdd 80

                           90       100
                   ....*....|....*....|
gi 442620926   571 -IGQYTYTLSTLLKQFNMEV 589
Cdd:smart00239  81 fIGQVTIPLSDLLLGGRHEK 100
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 712-841 6.29e-13

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: 66.22  E-value: 6.29e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 712 GLGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDP-SNIPDPYVKLYLLPgrTKESKRKTSVIKDNCNPVYDASFE-YLISI 789
Cdd:cd08388    1 KLGTLFFSLRYNSEKKALLVNIIECRDLPAMDEqSGTSDPYVKLQLLP--EKEHKVKTRVLRKTRNPVYDETFTfYGIPY 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 442620926 790 AELRQTELEVTVCTQKGFlsGGSPIIGMLKIPLDDAEITTQTGLNSWFDLQP 841
Cdd:cd08388   79 NQLQDLSLHFAVLSFDRY--SRDDVIGEVVCPLAGADLLNEGELLVSREIQP 128
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 714-801 8.44e-13

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: 66.30  E-value: 8.44e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELR 793
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81


                 ....*...
gi 442620926 794 QTELEVTV 801
Cdd:cd08404   82 DISVEFLV 89
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 350-455 1.24e-12

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: 65.38  E-value: 1.24e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQE-FKTQIIDNNVNPKWD-YWCEAVVEVSQHaiLVLRLFDWDRTSD 427
Cdd:cd04042    2 LDIHLKEGRNLAARDRG----GTSDPYVKFKYGGKTvYKSKTIYKNLNPVWDeKFTLPIEDVTQP--LYIKVFDYDRGLT 75

                         90       100
                 ....*....|....*....|....*...
gi 442620926 428 DESLGRASIDIASVIKKGVVDSWLTLED 455
Cdd:cd04042   76 DDFMGSAFVDLSTLELNKPTEVKLKLED 103
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 350-453 2.20e-12

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: 64.81  E-value: 2.20e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSDDE 429
Cdd:cd04025    2 LRCHVLEARDLAPKDRN----GTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKND 77

                         90       100
                 ....*....|....*....|....
gi 442620926 430 SLGRASIDIASVIKKGVVDSWLTL 453
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQEEGWFRL 101
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 714-801 3.42e-12

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: 64.08  E-value: 3.42e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIP-DPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81


                 ....*....
gi 442620926 793 RQTELEVTV 801
Cdd:cd08392   82 SSRQLQVSV 90
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 713-801 5.04e-12

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


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 63.96  E-value: 5.04e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08402    1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80


                 ....*....
gi 442620926 793 RQTELEVTV 801
Cdd:cd08402   81 QKVHLIVTV 89
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 348-444 2.10e-11

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: 61.51  E-value: 2.10e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDIsvlGKGKSDPYaiINVGAQEFK-----TQIIDNNVNPKWDywCEAVVEVSQHAI-----LVL 417
Cdd:cd04041    1 GVLVVTIHRATDLPKADF---GTGSSDPY--VTASFAKFGkplysTRIIRKDLNPVWE--ETWFVLVTPDEVkagerLSC 73

                         90       100
                 ....*....|....*....|....*..
gi 442620926 418 RLFDWDRTSDDESLGRASIDIASVIKK 444
Cdd:cd04041   74 RLWDSDRFTADDRLGRVEIDLKELIED 100
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 713-841 3.09e-11

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


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 61.58  E-value: 3.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPgrTKESKRKTSVIKDNCNPVYDASFEYL-ISIAE 791
Cdd:cd08386    2 LGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLP--DKKHKLETKVKRKNLNPHWNETFLFEgFPYEK 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 442620926 792 LRQTELEVTVCTQKGFlSGGSPiIGMLKIPLDDAEIT-TQTglnSWFDLQP 841
Cdd:cd08386   80 LQQRVLYLQVLDYDRF-SRNDP-IGEVSLPLNKVDLTeEQT---FWKDLKP 125
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 348-457 3.81e-11

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: 60.78  E-value: 3.81e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEvSQHAILVLRLFDWDRTSD 427
Cdd:cd08377    1 GFLQVKVIRASGLAAADIG----GKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIK-DIHDVLEVTVYDEDKDKK 75

                         90       100       110
                 ....*....|....*....|....*....|
gi 442620926 428 DESLGRASIDIASvIKKGVVDsWLTLEDAK 457
Cdd:cd08377   76 PEFLGKVAIPLLS-IKNGERK-WYALKDKK 103
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 717-796 9.56e-11

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: 60.33  E-value: 9.56e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 717 QLSIR--YSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRT--KESKRKTSVIKDNCNPVYDASFEYLISiAEL 792
Cdd:cd04009    4 VLTVKayYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLFPLFDESFEFNVP-PEQ 82


                 ....
gi 442620926 793 RQTE 796
Cdd:cd04009   83 CSVE 86
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 349-438 3.11e-10

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: 3.11e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 349 ILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEF--KTQIIDNNVNPKWdYWC-EAVVEVSQHAILVLRLFDWDRT 425
Cdd:cd04037    1 LVRVYVVRARNLQPKDPN----GKSDPYLKIKLGKKKIndRDNYIPNTLNPVF-GKMfELEATLPGNSILKISVMDYDLL 75

                         90
                 ....*....|...
gi 442620926 426 SDDESLGRASIDI 438
Cdd:cd04037   76 GSDDLIGETVIDL 88
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 348-458 2.88e-09

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: 55.80  E-value: 2.88e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFKTQII-DNNVNPKWDYWCEAVVEVSQHAI---LVLRLFDWD 423
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFL----GKIDPYVIIQCRTQERKSKVAkGDGRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKD 76

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 442620926 424 RTSDDESLGRASIDIASVIKKGVVDSWLTLEDAKH 458
Cdd:cd04049   77 NFSDDDFIGEATIHLKGLFEEGVEPGTAELVPAKY 111
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 349-436 4.47e-09

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: 55.44  E-value: 4.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 349 ILRIHVVEAKDLMKKDISvlgkGKSDPYAII-------NVGAQEFKTQIIDNNVNPKWDywCEAVVEV--SQHAiLVLRL 419
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIF----GASDPYVKIslydpdgNGEIDSVQTKTIKKTLNPKWN--EEFFFRVnpREHR-LLFEV 73

                         90
                 ....*....|....*..
gi 442620926 420 FDWDRTSDDESLGRASI 436
Cdd:cd04033   74 FDENRLTRDDFLGQVEV 90
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
343-441 1.29e-08

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 59.00  E-value: 1.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  343 MPEPEGILRIHVVEAKDLMKKDIsvlgKGKSDPYAIINVGAQE-FKTQIIDNNVNPKWDYwcEAVVEVS--QHAILVLRL 419
Cdd:COG5038  1035 MVENSGYLTIMLRSGENLPSSDE----NGYSDPFVKLFLNEKSvYKTKVVKKTLNPVWNE--EFTIEVLnrVKDVLTINV 1108

                          90       100
                  ....*....|....*....|..
gi 442620926  420 FDWDRTSDDESLGRASIDIASV 441
Cdd:COG5038  1109 NDWDSGEKNDLLGTAEIDLSKL 1130
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 748-844 1.43e-08

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


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 53.37  E-value: 1.43e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 748 PDPYVKLYLlpgrTKESKRKTSVIKDNCNPVYDASFEYLisIAELRQTELEVTVCTQKGFlsgGSPIIGMLKIPLDDAEI 827
Cdd:cd04052   13 LSPYAELYL----NGKLVYTTRVKKKTNNPSWNASTEFL--VTDRRKSRVTVVVKDDRDR---HDPVLGSVSISLNDLID 83

                         90       100
                 ....*....|....*....|.
gi 442620926 828 TTQTGLnSWFDLQP----EIR 844
Cdd:cd04052   84 ATSVGQ-QWFPLSGngqgRIR 103
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 714-801 1.64e-08

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: 54.03  E-value: 1.64e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELR 793
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81


                 ....*...
gi 442620926 794 QTELEVTV 801
Cdd:cd08406   82 DLSLRVTV 89
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 350-490 2.09e-08

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: 53.70  E-value: 2.09e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISVLgkgkSDPYAIINVGAQEFKTQIIDNNVNPKWD--------YWCEAVVEVSQHA-ILVLRLF 420
Cdd:cd04017    3 LRAYIYQARDLLAADKSGL----SDPFARVSFLNQSQETEVIKETLSPTWDqtlifdevELYGSPEEIAQNPpLVVVELF 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 421 DWDRTSDDESLGRasidiaSVIKKGVvdsWLTLEDAKHGllhvRLQWYKLTADPNDLQQILLETQLLRVT 490
Cdd:cd04017   79 DQDSVGKDEFLGR------SVAKPLV---KLDLEEDFPP----KLQWFPIYKGGQSAGELLAAFELIEVT 135
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 713-799 2.24e-08

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: 53.18  E-value: 2.24e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKEskRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08387    2 RGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDESFVFEVPPQEL 79


                 ....*..
gi 442620926 793 RQTELEV 799
Cdd:cd08387   80 PKRTLEV 86
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
329-784 2.30e-08

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 58.23  E-value: 2.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  329 PISLSEEVSAVALKMPePEGILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQE-FKTQIIDNNVNPKWDYWCEAVV 407
Cdd:COG5038   693 PIYNAGGSSSKTVYDT-PIGAIRVSVRKANDLRNEIPG----GKSDPYATVLVNNLVkYRTIYGSSTLNPIWNEILYVPV 767

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  408 eVSQHAILVLRLFDWDRTSDDESLGRASIDIASVIKKGVVDSwltledakhgllhvrlqwYKLTADPNdlqqilLETQLL 487
Cdd:COG5038   768 -TSKNQRLTLECMDYEESGDDRNLGEVNINVSNVSKKDEDSA------------------LMETIDGA------EETGKL 822

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  488 RVT-SMSSAVLSVFIDSarhLKQARSSSKPDPYLVCSVNKQKQQTamiMRDDSPVWEQGfTFLVSNPDNESLNIKIYDQK 566
Cdd:COG5038   823 SLTgKKVKGTITYKCRF---YPAVIVLSLEEVRYVDKVSSEKRKS---EKRKSALDEKT-ISLVDKEDSVEESIEVEELT 895

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  567 TgndigQYTYTLSTLLKqfnmEVIQqpfqlQKSGpeSKLYMSLSLRILKPG---EIDKDSDALEQVaaltrsssvktpdV 643
Cdd:COG5038   896 D-----MYSLKPKLDLN----EALQ-----YKSG--VLGIQILSGELPDPGqylQIFFDDASHPQI-------------V 946

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  644 AAVSPPAFKASSKrlSAESPISE----EDPVAATKISPamsastSSEKPISE--LATSVLTHRFPDSTSSPGEHGLGRMQ 717
Cdd:COG5038   947 SSKAPTRGERNGE--SGDTFIREleysETTFRVTKNAK------KSDKVVCEvtLPTLDLVSNAYEKPSSLNFPGSAKVL 1018

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442620926  718 LSIRYSAQRQK------------LDVTIHKIQKIPLRDPSNIPDPYVKLYLlpgrTKESKRKTSVIKDNCNPVYDASFE 784
Cdd:COG5038  1019 VQVSYTPVPVKlppvemvensgyLTIMLRSGENLPSSDENGYSDPFVKLFL----NEKSVYKTKVVKKTLNPVWNEEFT 1093
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 349-461 2.57e-08

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: 52.64  E-value: 2.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 349 ILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKW----DYwceAVVEVSQHaILVLRLFDWDR 424
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDN----GLSDPYVKFRLGNEKYKSKVCSKTLNPQWleqfDL---HLFDDQSQ-ILEIEVWDKDT 72

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442620926 425 TSDDESLGRASIDIASVIKKGVVDSWLTLEDAKHGLL 461
Cdd:cd08376   73 GKKDEFIGRCEIDLSALPREQTHSLELELEDGEGSLL 109
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 496-601 2.72e-08

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: 52.94  E-value: 2.72e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLK-QARSSSKPDPYLVCSVNKQKQ--QTAMIMRDDSPVWEQGFTFLVSNpDNESLNIKIYD---QKTGN 569
Cdd:cd04044    3 VLAVTIKSARGLKgSDIIGGTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETKYILVNS-LTEPLNLTVYDfndKRKDK 81

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442620926 570 DIGQYTYTLSTLLkqfnmeviQQPFQLQKSGP 601
Cdd:cd04044   82 LIGTAEFDLSSLL--------QNPEQENLTKN 105
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 348-453 3.20e-08

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: 52.64  E-value: 3.20e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLmkKDISVLGKgkSDPYAIINVGAQEFKTQ-IIDNNVNPKWDYWCE-AVVEVSQHaILVLRLFDwDRT 425
Cdd:cd08681    1 GTLVVVVLKARNL--PNKRKLDK--QDPYCVLRIGGVTKKTKtDFRGGQHPEWDEELRfEITEDKKP-ILKVAVFD-DDK 74

                         90       100
                 ....*....|....*....|....*...
gi 442620926 426 SDDESLGRASIDIASVIKKGVVDSWLTL 453
Cdd:cd08681   75 RKPDLIGDTEVDLSPALKEGEFDDWYEL 102
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 714-841 1.01e-07

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


Pssm-ID: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 51.47  E-value: 1.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPgrTKESKRKTSVIKDNCnPVYDASFEYL-ISIAEL 792
Cdd:cd08389    3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLP--SKKQRAKTKVQRGPN-PVFNETFTFSrVEPEEL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 793 RQTELEVTVCTQKGFlsGGSPIIGMLKIPLDDAEITTQTGLnsWFDLQP 841
Cdd:cd08389   80 NNMALRFRLYGVERM--RKERLIGEKVVPLSQLNLEGETTV--WLTLEP 124
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 351-476 1.48e-07

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: 50.91  E-value: 1.48e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 351 RIHVVEAKDLMKKdisvlGK-GKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCE-----AVVEVSQHAILVLRLFDWDR 424
Cdd:cd08682    2 QVTVLQARGLLCK-----GKsGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSfelpgLLSGNGNRATLQLTVMHRNL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 442620926 425 TSDDESLGRASIDIASVikkgvvdswltleDAKHGllHVRLQWYKLTADPND 476
Cdd:cd08682   77 LGLDKFLGQVSIPLNDL-------------DEDKG--RRRTRWFKLESKPGK 113
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 339-450 1.59e-07

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: 50.86  E-value: 1.59e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 339 VALKMPEPEGILRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFK---TQIIDNNVNPKWDYwcEAVVEVSQHAI- 414
Cdd:cd08387    7 FSLEYDKDMGILNVKLIQARNLQPRDFS----GTADPYCKVRLLPDRSNtkqSKIHKKTLNPEFDE--SFVFEVPPQELp 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 442620926 415 ---LVLRLFDWDRTSDDESLGRASIDIASVIKKGVVDSW 450
Cdd:cd08387   81 krtLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLW 119
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 341-459 1.93e-07

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: 50.72  E-value: 1.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 341 LKMPEPEGILRIHVVEAKDLMKKDISvlgkGKSDPYAIINV-----GAQEFKTQIIDNNVNPKWDywcEA-VVEVSQ--- 411
Cdd:cd04026    6 LKISVKDNKLTVEVREAKNLIPMDPN----GLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWN---ETfTFDLKPadk 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 442620926 412 HAILVLRLFDWDRTSDDESLGRASIDIASVIKKGvVDSWLTLEDAKHG 459
Cdd:cd04026   79 DRRLSIEVWDWDRTTRNDFMGSLSFGVSELIKMP-VDGWYKLLNQEEG 125
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 714-801 4.06e-07

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: 49.81  E-value: 4.06e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELR 793
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80


                 ....*...
gi 442620926 794 QTELEVTV 801
Cdd:cd08403   81 NVSLIIAV 88
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 514-597 5.32e-07

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: 49.21  E-value: 5.32e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 514 SKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND--IGQYTYTLSTllkQFNMEVIQ 591
Cdd:cd08391   26 GKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPDKDdfLGRLSIDLGS---VEKKGFID 102


                 ....*.
gi 442620926 592 QPFQLQ 597
Cdd:cd08391  103 EWLPLE 108
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 496-602 6.93e-07

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: 48.80  E-value: 6.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSV---NKQKQQTAMIMRDDSPVWEQGFTFLV-SNPDNeSLNIKIYDQKTGND- 570
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIqSQVKN-VLELTVMDEDYVMDd 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 442620926 571 -IGQYTYTLSTLLKQfnmEVIQQPFQLQKSGPE 602
Cdd:cd04036   80 hLGTVLFDVSKLKLG---EKVRVTFSLNPQGKE 109
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 350-464 7.01e-07

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 48.87  E-value: 7.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDisvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCE-AVVEVSQHAILVLRLFDWDRTSDD 428
Cdd:cd04022    2 LVVEVVDAQDLMPKD----GQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVfNVSDPSRLSNLVLEVYVYNDRRSG 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 442620926 429 ES---LGRASIDIASVIKKG-VVDSWLTLEdaKHGLL-HVR 464
Cdd:cd04022   78 RRrsfLGRVRISGTSFVPPSeAVVQRYPLE--KRGLFsRVR 116
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 350-442 9.10e-07

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: 48.46  E-value: 9.10e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISVLgkgkSDPYAIINV-GAQEFKTQIIDNNVNPKWDYwcEAVVEVSQHAILVLRLFDWDRT--S 426
Cdd:cd08382    2 VRLTVLCADGLAKRDLFRL----PDPFAVITVdGGQTHSTDVAKKTLDPKWNE--HFDLTVGPSSIITIQVFDQKKFkkK 75

                         90
                 ....*....|....*.
gi 442620926 427 DDESLGRASIDIASVI 442
Cdd:cd08382   76 DQGFLGCVRIRANAVL 91
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 714-801 1.02e-06

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: 48.73  E-value: 1.02e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 714 GRMQLSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELR 793
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80


                 ....*...
gi 442620926 794 QTELEVTV 801
Cdd:cd08410   81 NVSLVFTV 88
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 497-583 2.11e-06

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


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 47.24  E-value: 2.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMR-DDSPVWEQGFTFLVSNPDNESLNIKIYDQ--KTGNDIGQ 573
Cdd:cd08681    3 LVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRgGQHPEWDEELRFEITEDKKPILKVAVFDDdkRKPDLIGD 82

                         90
                 ....*....|
gi 442620926 574 YTYTLSTLLK 583
Cdd:cd08681   83 TEVDLSPALK 92
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 505-612 2.27e-06

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: 47.21  E-value: 2.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 505 RHLKQARSSS-KPDPYLVCSVNKQK-QQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND--IGQYTYTLST 580
Cdd:cd04052    1 KGLDTSESKTgLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDpvLGSVSISLND 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442620926 581 LLkqFNMEVIQQPFQLQkSGPESKLYMSLSLR 612
Cdd:cd04052   81 LI--DATSVGQQWFPLS-GNGQGRIRISALWK 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 728-823 4.31e-06

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: 46.77  E-value: 4.31e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 728 KLDVTIHKI--QKIPL--RDPSNIPDPYVKLYLL-PGRTKESKRKTSVIKDN-CNPVYDASFEYLISIAELrqTELEVTV 801
Cdd:cd00275    1 PLTLTIKIIsgQQLPKpkGDKGSIVDPYVEVEIHgLPADDSAKFKTKVVKNNgFNPVWNETFEFDVTVPEL--AFLRFVV 78

                         90       100
                 ....*....|....*....|..
gi 442620926 802 CTQKgflSGGSPIIGMLKIPLD 823
Cdd:cd00275   79 YDED---SGDDDFLGQACLPLD 97
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 346-401 4.88e-06

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: 46.50  E-value: 4.88e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 442620926 346 PEGILRIHVVEAKDLMKKDisvlGKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDY 401
Cdd:cd04046    1 PQVVTQVHVHSAEGLSKQD----SGGGADPYVIIKCEGESVRSPVQKDTLSPEFDT 52
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 348-442 5.45e-06

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: 46.09  E-value: 5.45e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMK-KDISVLGKgKSDPYAIINVGAQEFKTQIIDNNVNPKWDYwcEAVVEV---SQHAILVLRLFDWD 423
Cdd:cd04039    1 GVVFMEIKSITDLPPlKNMTRTGF-DMDPFVIISFGRRVFRTSWRRHTLNPVFNE--RLAFEVyphEKNFDIQFKVLDKD 77

                         90
                 ....*....|....*....
gi 442620926 424 RTSDDESLGRASIDIASVI 442
Cdd:cd04039   78 KFSFNDYVATGSLSVQELL 96
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 729-802 7.58e-06

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: 45.72  E-value: 7.58e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442620926 729 LDVTIHKIQKIPLRDPSNIPDPYVKLYLlpgRTKESKRK-TSVIKDNCNPVYDASFEYLISiaelRQTE--LEVTVC 802
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWL---PTASDEKKrTKTIKNSINPVWNETFEFRIQ----SQVKnvLELTVM 71
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 358-467 1.22e-05

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: 44.90  E-value: 1.22e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 358 KDLmkkDISVLGKGKSDPYAIINVGAQE-FKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDwDRTSDDESLGRASI 436
Cdd:cd04052    1 KGL---DTSESKTGLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKD-DRDRHDPVLGSVSI 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442620926 437 DIASVIK-KGVVDSWLTLEDAKHGLLHVRLQW 467
Cdd:cd04052   77 SLNDLIDaTSVGQQWFPLSGNGQGRIRISALW 108
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 729-840 1.69e-05

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: 44.48  E-value: 1.69e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 729 LDVTIHKIQKIPLRDPSNIPDPYVKLYLlpGRTKeskRKTSVIKDNCNPVYDASFEYLISIAElRQtELEVTVCTQKGFL 808
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVELTV--GKTT---QKSKVKERTNNPVWEEGFTFLVRNPE-NQ-ELEIEVKDDKTGK 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 442620926 809 SggspiIGMLKIPLddAEITTQTGL--NSWFDLQ 840
Cdd:cd04050   75 S-----LGSLTLPL--SELLKEPDLtlDQPFPLD 101
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 497-581 2.31e-05

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: 44.45  E-value: 2.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHL--KQARSSSKPDPYLVCSV------NKQKQQTAMIMRD-DSPVWEQGFTFLVSNPDNESLNIKIYDQKT 567
Cdd:cd00275    4 LTIKIISGQQLpkPKGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKNNgFNPVWNETFEFDVTVPELAFLRFVVYDEDS 83

                         90
                 ....*....|....*.
gi 442620926 568 GND--IGQYTYTLSTL 581
Cdd:cd00275   84 GDDdfLGQACLPLDSL 99
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 350-454 3.24e-05

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: 44.10  E-value: 3.24e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVlRLFDWD------ 423
Cdd:cd04027    3 ISITVVCAQGLIAKDKT----GTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKV-RVWDEDddiksr 77

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 442620926 424 ------RTSDDeSLGRASIDIASVikKGVVDSWLTLE 454
Cdd:cd04027   78 lkqkftRESDD-FLGQTIIEVRTL--SGEMDVWYNLE 111
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 348-448 4.03e-05

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: 43.32  E-value: 4.03e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVvEAKDLMKKDISvlgkGKSDPYAII---NVGAQE---FKTQIIDNNVNPKW-------------DYWCEAVVE 408
Cdd:cd04047    1 DVVELQF-SGKKLDKKDFF----GKSDPFLEIsrqSEDGTWvlvYRTEVIKNTLNPVWkpftiplqklcngDYDRPIKIE 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442620926 409 VsqhailvlrlFDWDRTSDDESLGRASIDIASVIKKGVVD 448
Cdd:cd04047   76 V----------YDYDSSGKHDLIGEFETTLDELLKSSPLE 105
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 749-840 4.25e-05

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: 43.82  E-value: 4.25e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 749 DPYVKLyllpgRTKESKRKTSVIKDNCNPVYDASFEYLISIAElrQTELEVTVCTQKGflsGGSPIIGMLKIPLddAEIT 828
Cdd:cd08391   29 DPYVIV-----RVGAQTFKSKVIKENLNPKWNEVYEAVVDEVP--GQELEIELFDEDP---DKDDFLGRLSIDL--GSVE 96

                         90
                 ....*....|..
gi 442620926 829 TQTGLNSWFDLQ 840
Cdd:cd08391   97 KKGFIDEWLPLE 108
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 713-816 5.31e-05

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: 43.86  E-value: 5.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYSAQRQKLDVTIHKIQKIPLRDpSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAEL 792
Cdd:cd08409    1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLD-HAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQL 79

                         90       100
                 ....*....|....*....|....
gi 442620926 793 RQTELEVTVCTQKGflSGGSPIIG 816
Cdd:cd08409   80 DTASLSLSVMQSGG--VRKSKLLG 101
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 354-463 5.99e-05

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: 43.40  E-value: 5.99e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 354 VVEAKDLMKKdisvlgKGKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHA--ILVLRLFDWDRTSDDESL 431
Cdd:cd08373    2 VVSLKNLPGL------KGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDPdeSLEIVVKDYEKVGRNRLI 75

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442620926 432 GRASIDIASVIKKGVVDSWLTLEDAKHGLLHV 463
Cdd:cd08373   76 GSATVSLQDLVSEGLLEVTEPLLDSNGRPTGA 107
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 350-441 6.37e-05

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: 43.02  E-value: 6.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKD-ISvlgkgKSDPYAIINV---GAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRT 425
Cdd:cd04036    2 LTVRVLRATNITKGDlLS-----TPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV 76

                         90
                 ....*....|....*.
gi 442620926 426 SDDEsLGRASIDIASV 441
Cdd:cd04036   77 MDDH-LGTVLFDVSKL 91
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 350-444 8.49e-05

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


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 43.03  E-value: 8.49e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKdlmKKDISVLGKGksDPYAIINVGAQE-FKTQIIDNNVNPKWDYwcEAVVEVSQHAILVLRLFDWDRTSDD 428
Cdd:cd04021    4 LQITVESAK---LKSNSKSFKP--DPYVEVTVDGQPpKKTEVSKKTSNPKWNE--HFTVLVTPQSTLEFKVWSHHTLKAD 76

                         90
                 ....*....|....*.
gi 442620926 429 ESLGRASIDIASVIKK 444
Cdd:cd04021   77 VLLGEASLDLSDILKN 92
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 352-465 8.83e-05

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: 43.02  E-value: 8.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 352 IHVVEAKDLMKKDisvlGKGKSDPY-AIINVGAQE--FKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSDD 428
Cdd:cd04043    5 IRIVRAENLKADS----SNGLSDPYvTLVDTNGKRriAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 442620926 429 ESLGRASIDIASVIKKGVV---DSWLTLEDAKHGLLHVRL 465
Cdd:cd04043   81 DLCGRASLKLDPKRFGDDGlprEIWLDLDTQGRLLLRVSM 120
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 350-450 9.20e-05

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: 43.13  E-value: 9.20e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDisvlgKGKSDPYAI---INVGAQEFK-TQIIDNNVNPKWDywcEA----------------VVEV 409
Cdd:cd08675    1 LSVRVLECRDLALKS-----NGTCDPFARvtlNYSSKTDTKrTKVKKKTNNPRFD---EAfyfeltigfsyekksfKVEE 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 442620926 410 SQHAILVLR--LFDWDRTSDDESLGRASIDIASVIKKGVVDSW 450
Cdd:cd08675   73 EDLEKSELRveLWHASMVSGDDFLGEVRIPLQGLQQAGSHQAW 115
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 496-593 1.06e-04

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: 42.80  E-value: 1.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHL--KQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQ---KTGND 570
Cdd:cd04024    2 VLRVHVVEAKDLaaKDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKdrfAGKDY 81

                         90       100
                 ....*....|....*....|...
gi 442620926 571 IGQYTYTLSTLlkqFNMEVIQQP 593
Cdd:cd04024   82 LGEFDIALEEV---FADGKTGQS 101
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 496-582 1.08e-04

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: 42.70  E-value: 1.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDS-PVWEQGFTFLVSNPDNES---LNIKIYDQKTGND- 570
Cdd:cd04049    2 TLEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGRnPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFSDd 81

                         90
                 ....*....|....
gi 442620926 571 --IGQYTYTLSTLL 582
Cdd:cd04049   82 dfIGEATIHLKGLF 95
PLN02952 PLN02952
phosphoinositide phospholipase C
 743-799 1.15e-04

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 45.76  E-value: 1.15e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 442620926 743 DPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIAELRQTELEV 799
Cdd:PLN02952 492 DSYSPPDFYTKMYIVGVPADNAKKKTKIIEDNWYPAWNEEFSFPLTVPELALLRIEV 548
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 350-455 1.21e-04

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: 43.04  E-value: 1.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLmkkdISVLGKGKSDPYAIINVGAQEFKTQI-IDNNVNPKWDywcEAVVEV-----SQHAILVLRlfdwD 423
Cdd:cd04019    2 LRVTVIEAQDL----VPSDKNRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWN---EELMFVaaepfEDHLILSVE----D 70

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442620926 424 RTSD--DESLGRASIDIASVIK----KGVVDSWLTLED 455
Cdd:cd04019   71 RVGPnkDEPLGRAVIPLNDIERrvddRPVPSRWFSLER 108
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 497-573 1.70e-04

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: 42.19  E-value: 1.70e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPY----LVCSVNKQKQ-QTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKI----YDQKT 567
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYvkvsLLQGGKKLKKkKTSVKKGTLNPVFNEAFSFDVPAEQLEEVSLVItvvdKDSVG 95


                 ....*..
gi 442620926 568 GND-IGQ 573
Cdd:cd00276   96 RNEvIGQ 102
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 355-445 1.70e-04

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: 41.79  E-value: 1.70e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 355 VEAKDLMKKDIsvlgKGKSDPYAIINVGAQEFK-------TQIIDNNVNPKW------DYwceaVVEVSQHaiLVLRLFD 421
Cdd:cd04048    7 ISCRNLLDKDV----LSKSDPFVVVYVKTGGSGqwveigrTEVIKNNLNPDFvttftvDY----YFEEVQK--LRFEVYD 76

                         90       100
                 ....*....|....*....|....*...
gi 442620926 422 WD-RTSDDES---LGRASIDIASVIKKG 445
Cdd:cd04048   77 VDsKSKDLSDhdfLGEAECTLGEIVSSP 104
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 496-584 1.76e-04

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: 41.81  E-value: 1.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 496 VLSVFIDSARHLKQARSSSKPDPYLVCSVN-KQKQQTAMIMRDDSPVWEQGFTFLVSNPdNESLNIKIYD-QKTGND--I 571
Cdd:cd04045    2 VLRLHIRKANDLKNLEGVGKIDPYVRVLVNgIVKGRTVTISNTLNPVWDEVLYVPVTSP-NQKITLEVMDyEKVGKDrsL 80

                         90
                 ....*....|...
gi 442620926 572 GQYTYTLSTLLKQ 584
Cdd:cd04045   81 GSVEINVSDLIKK 93
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 507-597 1.79e-04

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


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 41.97  E-value: 1.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 507 LKQARSSSkpDPYLVCSVNK--QKQQTAMIMRDDSPVWEQGFTFLVSNPDNEsLNIKIYDQKTGND---IGQYTYTLSTL 581
Cdd:cd08678   11 LSEAAGSS--NPYCVLEMDEppQKYQSSTQKNTSNPFWDEHFLFELSPNSKE-LLFEVYDNGKKSDskfLGLAIVPFDEL 87

                         90
                 ....*....|....*.
gi 442620926 582 LKQFNMeviQQPFQLQ 597
Cdd:cd08678   88 RKNPSG---RQIFPLQ 100
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 497-589 2.29e-04

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


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 41.88  E-value: 2.29e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSArHLKQARSSSKPDPYL-VCSVNKQKQQTAMIMRDDSPVWEQGFTFLVsNPdNESLNIKIYD-QKTGND--IG 572
Cdd:cd04021    4 LQITVESA-KLKSNSKSFKPDPYVeVTVDGQPPKKTEVSKKTSNPKWNEHFTVLV-TP-QSTLEFKVWShHTLKADvlLG 80

                         90
                 ....*....|....*..
gi 442620926 573 QYTYTLSTLLKQFNMEV 589
Cdd:cd04021   81 EASLDLSDILKNHNGKL 97
PLN02270 PLN02270
phospholipase D alpha
 368-475 2.34e-04

phospholipase D alpha


Pssm-ID: 165912 [Multi-domain]  Cd Length: 808  Bit Score: 44.94  E-value: 2.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 368 LGKGKSDPYAIINVG-AQEFKTQIIDNN-VNPKW----DYWCeavVEVSQHAILVLRlfdwdrtsDDESLG-----RASI 436
Cdd:PLN02270  42 VGKGESQLYATIDLEkARVGRTRKIENEpKNPRWyesfHIYC---AHMASNIIFTVK--------DDNPIGatligRAYI 110

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 437 DIASVIKKGVVDSWLTLEDAK----HG--LLHVRLQWYKLTADPN 475
Cdd:PLN02270 111 PVEEILDGEEVDRWVEILDNDknpiHGgsKIHVKLQYFEVTKDRN 155
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 350-466 2.44e-04

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: 41.73  E-value: 2.44e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINVGAQEF-KTQIIDNNVNPKWDYWCEAVVEVSQHAiLVLRLFDWDRTSDD 428
Cdd:cd04054    2 LYIRIVEGKNLPAKDIT----GSSDPYCIVKVDNEVIiRTATVWKTLNPFWGEEYTVHLPPGFHT-VSFYVLDEDTLSRD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 429 ESLGRASI--DIASVIKKGvVDSWLTL-----EDAKHGLLHVRLQ 466
Cdd:cd04054   77 DVIGKVSLtrEVISAHPRG-IDGWMNLtevdpDEEVQGEIHLELS 120
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 713-841 2.50e-04

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: 41.99  E-value: 2.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 713 LGRMQLSIRYsaQRQKLDVTIHKIQK-IPLRDPSNIPDPYVKLYLLPGRTKESKRKTSVIKDNCNPVYDASFEYLISIae 791
Cdd:cd04028   17 MGDIQLGLYD--KKGQLEVEVIRARGlVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSP-- 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 442620926 792 lRQTELEVTVCTQKGFLSGGSpIIGMLKIPLDDAEITTQTglNSWFDLQP 841
Cdd:cd04028   93 -TGKTLQVIVWGDYGRMDKKV-FMGVAQILLDDLDLSNLV--IGWYKLFP 138
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 717-803 2.79e-04

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176062  Cd Length: 124  Bit Score: 41.45  E-value: 2.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 717 QLSIRYSAQRQKLdvTIHKIQkipLRDPS--NIPDP---YVKLYLLPG--------RTKeskrktsVIKDNCNPVYDASF 783
Cdd:cd08680    4 QIGLRYDSGDSSL--VISVEQ---LRNLSalSIPENskvYVRVALLPCssstsclfRTK-------ALEDQDKPVFNEVF 71

                         90       100
                 ....*....|....*....|
gi 442620926 784 EYLISIAELRQTELEVTVCT 803
Cdd:cd08680   72 RVPISSTKLYQKTLQVDVCS 91
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 350-466 2.84e-04

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: 41.10  E-value: 2.84e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLmkkdisvLGKGKSDPYAIINVGAQE-FKTQIIDnNVNPKW--DYWCEAV-VEVSQHAILvlrLFDWDRT 425
Cdd:cd08383    2 LRLRILEAKNL-------PSKGTRDPYCTVSLDQVEvARTKTVE-KLNPFWgeEFVFDDPpPDVTFFTLS---FYNKDKR 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 442620926 426 SDDESLGRASIDIASVIKKGVVDSWLTL--EDAK---HGLLHVRLQ 466
Cdd:cd08383   71 SKDRDIVIGKVALSKLDLGQGKDEWFPLtpVDPDsevQGSVRLRAR 116
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 483-548 2.90e-04

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: 42.31  E-value: 2.90e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442620926 483 ETQLLRVTSMSSAVLSVFIDSARHLKQARSSSKPDPYLVCSV-----NKQKQQTAMIMRDDSPVWEQGFTF 548
Cdd:cd04020   15 SEGALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFVY 85
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 350-441 2.91e-04

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: 41.45  E-value: 2.91e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISvlgkGKSDPYAIINV-------GAQEFKTQIIDNNVNPKWDywcEA-VVEVSQH------AIL 415
Cdd:cd04009   18 LRVEILNARNLLPLDSN----GSSDPFVKVELlprhlfpDVPTPKTQVKKKTLFPLFD---ESfEFNVPPEqcsvegALL 90

                         90       100
                 ....*....|....*....|....*.
gi 442620926 416 VLRLFDWDRTSDDESLGRASIDIASV 441
Cdd:cd04009   91 LFTVKDYDLLGSNDFEGEAFLPLNDI 116
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 497-614 3.56e-04

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: 41.17  E-value: 3.56e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNP---DNESLNIKIYDQK----TGN 569
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDRrsgrRRS 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 570 DIGQYTYTLSTLLKQfnMEVIQQPFQLQKSGPESKLYMSLSLRIL 614
Cdd:cd04022   82 FLGRVRISGTSFVPP--SEAVVQRYPLEKRGLFSRVRGEIGLKVY 124
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 348-467 3.57e-04

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: 41.49  E-value: 3.57e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDIS----VLGKGKS--DPYAIINVGAQEF-KTQIIDNNVNPKWDYwcEAVVEVSQHAILVLRLF 420
Cdd:cd04014    4 GTLKIKICEAVDLKPTDWStrhaVPKKGSQllDPYVSIDVDDTHIgKTSTKPKTNSPVWNE--EFTTEVHNGRNLELTVF 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 442620926 421 DWDRTSDDESLGRASIDIASVIK--KGVVDSWLTLEdaKHGLLHVRLQW 467
Cdd:cd04014   82 HDAAIGPDDFVANCTISFEDLIQrgSGSFDLWVDLE--PQGKLHVKIEL 128
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 349-441 3.87e-04

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: 41.46  E-value: 3.87e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 349 ILRIHvvEAKDLMKKDISVLGKGK----------SDPYAIINVGAQEFKTQIIDNNVNPKWDywcEAVVEVSQHAILV-- 416
Cdd:cd04018    3 IFKIY--RAEDLPQMDSGIMANVKkaflgekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWN---EQIVFPEMFPPLCer 77

                         90       100
                 ....*....|....*....|....*..
gi 442620926 417 --LRLFDWDRTSDDESLGRASIDIASV 441
Cdd:cd04018   78 ikIQIRDWDRVGNDDVIGTHFIDLSKI 104
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 497-565 4.15e-04

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: 41.22  E-value: 4.15e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQ 565
Cdd:cd08375   17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDR 85
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 503-588 4.26e-04

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: 40.63  E-value: 4.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 503 SARHLKQARSSSKPDPYLV---CSVNKQKQ---QTAMIMRDDSPVWEqgfTFLVS-------NPDNEsLNIKIYDQ-KTG 568
Cdd:cd04047    8 SGKKLDKKDFFGKSDPFLEisrQSEDGTWVlvyRTEVIKNTLNPVWK---PFTIPlqklcngDYDRP-IKIEVYDYdSSG 83

                         90       100
                 ....*....|....*....|..
gi 442620926 569 ND--IGQYTYTLSTLLKQFNME 588
Cdd:cd04047   84 KHdlIGEFETTLDELLKSSPLE 105
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 718-801 4.43e-04

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: 41.20  E-value: 4.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 718 LSIRYSAQRQKLDVTIHKIQKIPLRDPSNIPDPYVKLYLLPGRTKE-SKRKTSVIKDNCNPVYDASFEYLISIAELRQTE 796
Cdd:cd08408    6 LGLEYNALTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLNSDGQEiSKSKTSIRRGQPDPEFKETFVFQVALFQLSEVT 85


                 ....*
gi 442620926 797 LEVTV 801
Cdd:cd08408   86 LMFSV 90
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 350-455 5.32e-04

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


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 40.37  E-value: 5.32e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDL--MKKDIsvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDywCEAVV-----EVSQHAILVLRLFDW 422
Cdd:cd08688    1 LKVRVVAARDLpvMDRSS-----DLTDAFVEVKFGSTTYKTDVVKKSLNPVWN--SEWFRfevddEELQDEPLQIRVMDH 73

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 442620926 423 DRTSDDESLGRASIDIASVIKKG---VVDSWLTLED 455
Cdd:cd08688   74 DTYSANDAIGKVYIDLNPLLLKDsvsQISGWFPIYD 109
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 729-788 5.39e-04

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: 40.62  E-value: 5.39e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442620926 729 LDVTIHKIQKIPLRD-PSNIPDPYVKLYLlpGRTKESKRkTSVIKDNCNPVYDASFEYLIS 788
Cdd:cd04044    4 LAVTIKSARGLKGSDiIGGTVDPYVTFSI--SNRRELAR-TKVKKDTSNPVWNETKYILVN 61
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 348-468 5.46e-04

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 41.52  E-value: 5.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDI--------------------------SVLGKGKSDPYAIINV-GAQEFKTQIIDNNVNPKWD 400
Cdd:cd04015    7 GTLDVTIYEADNLPNMDMfseklrrffsklvgcseptlkrpsshRHVGKITSDPYATVDLaGARVARTRVIENSENPVWN 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 401 -----YWCEAVVEVsqhAILVlrlfdwdrtSDDESL-----GRASIDIASVIKKGVVDSWLTLED-----AKHGL-LHVR 464
Cdd:cd04015   87 esfhiYCAHYASHV---EFTV---------KDNDVVgaqliGRAYIPVEDLLSGEPVEGWLPILDsngkpPKPGAkIRVS 154


                 ....
gi 442620926 465 LQWY 468
Cdd:cd04015  155 LQFT 158
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
448-585 6.18e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 43.59  E-value: 6.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926  448 DSWLTLEDAKHGLLHVRLQWYKLTADPNDLqqilletqllrVTSMSSavLSVFIDSARHLKQARSSSKPDPYLVCSVNKQ 527
Cdd:COG5038  1006 PSSLNFPGSAKVLVQVSYTPVPVKLPPVEM-----------VENSGY--LTIMLRSGENLPSSDENGYSDPFVKLFLNEK 1072

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442620926  528 K-QQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND---IGQYTYTLSTLLKQF 585
Cdd:COG5038  1073 SvYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKndlLGTAEIDLSKLEPGG 1134
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 497-565 6.26e-04

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: 40.36  E-value: 6.26e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSnpDNES-LNIKIYDQ 565
Cdd:cd08377    3 LQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIK--DIHDvLEVTVYDE 70
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 497-600 6.96e-04

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: 40.24  E-value: 6.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 497 LSVFIDSARHLKQARSSSKPDPYLVCSVNKQK-QQTAMIMRDDSPVWEQGFTFLVSNPDNESLNIKIYDQKTGND---IG 572
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNGEKvFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKddlLG 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 442620926 573 QYTYTLSTL--LKQFNMEViqqPFQLQKSG 600
Cdd:cd04040   81 SAYIDLSDLepEETTELTL---PLDGQGGG 107
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 350-459 7.60e-04

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


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 39.99  E-value: 7.60e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKkdisvlgkGKSDPYAIINVGAQEFKTQIIDNNVNPKWDywceAVVEVSQHAIL--VLRLFDWDR-TS 426
Cdd:cd08378    2 LYVRVVKARGLPA--------NSNDPVVEVKLGNYKGSTKAIERTSNPEWN----QVFAFSKDRLQgsTLEVSVWDKdKA 69

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 442620926 427 DDESLGRASIDIASVIKKGVVDS-----WLTLEDAKHG 459
Cdd:cd08378   70 KDDFLGGVCFDLSEVPTRVPPDSplapqWYRLEDKKGG 107
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 517-586 8.15e-04

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: 40.32  E-value: 8.15e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442620926 517 DPYLVCSV-----NKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNES-LNIKI--YDQKTGND-IGQYTYTLSTLLKQFN 586
Cdd:cd04026   35 DPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRrLSIEVwdWDRTTRNDfMGSLSFGVSELIKMPV 113
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 495-565 1.08e-03

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: 39.86  E-value: 1.08e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 442620926 495 AVLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNpDNESLNIKIYDQ 565
Cdd:cd04027    1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHN-SSDRIKVRVWDE 70
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 360-443 1.41e-03

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


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 39.66  E-value: 1.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 360 LMKKDISVLGK----GKSDPYAII--NVGAQEFKTQIIDNNVNPKWDYwcEAVVEVSQH-AILVLRLFDWDRTSDDESLG 432
Cdd:cd08678    1 LLVKNIKANGLseaaGSSNPYCVLemDEPPQKYQSSTQKNTSNPFWDE--HFLFELSPNsKELLFEVYDNGKKSDSKFLG 78

                         90
                 ....*....|.
gi 442620926 433 RASIDIASVIK 443
Cdd:cd08678   79 LAIVPFDELRK 89
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 350-466 1.54e-03

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: 39.34  E-value: 1.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLMKKDISVlgkGKSDPYAIINVGAQE-FKTQIIDNNVNPKW--DYWCEAVVEVSQhaiLVLRLFDWDRTS 426
Cdd:cd08401    2 LKIKIGEAKNLPPRSGPN---KMRDCYCTVNLDQEEvFRTKTVEKSLCPFFgeDFYFEIPRTFRH---LSFYIYDRDVLR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442620926 427 DDESLGRASIDIASVIKKGVVDSWLTLE--DAK---HGLLHVRLQ 466
Cdd:cd08401   76 RDSVIGKVAIKKEDLHKYYGKDTWFPLQpvDADsevQGKVHLELR 120
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 503-597 1.70e-03

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: 39.14  E-value: 1.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 503 SARHLKQARSSSKPDPYLVCSVN-KQKQQTAMimrDDS----PVWEQGFTFLV----SNPDNESLNIKIYDQKTG---ND 570
Cdd:cd04051    8 SAEDLKNVNLFGKMKVYAVVWIDpSHKQSTPV---DRDggtnPTWNETLRFPLderlLQQGRLALTIEVYCERPSlgdKL 84

                         90       100
                 ....*....|....*....|....*..
gi 442620926 571 IGQYTYTLSTLLKQFNMEVIQQPFQLQ 597
Cdd:cd04051   85 IGEVRVPLKDLLDGASPAGELRFLSYQ 111
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 350-450 3.02e-03

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: 38.40  E-value: 3.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 350 LRIHVVEAKDLmKKDISVlgkgKSDPYAIINVGAQEFKTQIIDNNVNPKWDywcEAV----VEVSQHAILVLRLFDWDRT 425
Cdd:cd04032   30 LTVTVLRATGL-WGDYFT----STDGYVKVFFGGQEKRTEVIWNNNNPRWN---ATFdfgsVELSPGGKLRFEVWDRDNG 101

                         90       100
                 ....*....|....*....|....*
gi 442620926 426 SDDESLGRASIdiasVIKKGVVDSW 450
Cdd:cd04032  102 WDDDLLGTCSV----VPEAGVHEDS 122
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 506-607 3.06e-03

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: 38.41  E-value: 3.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 506 HLKQAR------SSSKPDPYLVCSVN-KQKQQTAMIMRDDSPVWEQGFTFLVSNPDnESLNIKIYD-QKTGND--IGQYT 575
Cdd:cd04042    5 HLKEGRnlaardRGGTSDPYVKFKYGgKTVYKSKTIYKNLNPVWDEKFTLPIEDVT-QPLYIKVFDyDRGLTDdfMGSAF 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 442620926 576 YTLSTLLKQFnmeviQQPFQLQKSGPESKLYM 607
Cdd:cd04042   84 VDLSTLELNK-----PTEVKLKLEDPNSDEDL 110
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 491-551 4.24e-03

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


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 38.02  E-value: 4.24e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 442620926 491 SMSSAVLSVFIDSARHLKQARSSSKPDPY----LVCSVNKQ-KQQTAMIMRDDSPVWEQGFTFLVS 551
Cdd:cd04030   12 SSQRQKLIVTVHKCRNLPPCDSSDIPDPYvrlyLLPDKSKStRRKTSVKKDNLNPVFDETFEFPVS 77
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 515-589 4.25e-03

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: 38.00  E-value: 4.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 515 KPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTF-LVSNPD-NESLNIKIYD-QKTGND--IGQYTYTLSTLLKQFNMEV 589
Cdd:cd08373   14 KGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWpLAGSPDpDESLEIVVKDyEKVGRNrlIGSATVSLQDLVSEGLLEV 93
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 749-841 4.92e-03

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: 38.12  E-value: 4.92e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 749 DPYVKLYLLPGRTKESKRkTSVIKDNCNPVYDASFE---YLISIAELRQT----------ELEVTVCTQKgfLSGGSPII 815
Cdd:cd08675   20 DPFARVTLNYSSKTDTKR-TKVKKKTNNPRFDEAFYfelTIGFSYEKKSFkveeedleksELRVELWHAS--MVSGDDFL 96

                         90       100
                 ....*....|....*....|....*.
gi 442620926 816 GMLKIPLDdaEITTQTGLNSWFDLQP 841
Cdd:cd08675   97 GEVRIPLQ--GLQQAGSHQAWYFLQP 120
C2_Tollip cd04016
C2 domain present in Toll-interacting protein (Tollip); Tollip is a part of the Interleukin-1 ...
 348-462 5.21e-03

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: 37.70  E-value: 5.21e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKdLMKKdisvLGKGKSDPYAIINVGAQEFKTQIIDNNV-NPKWD--YWCEAVVEVSQhaiLVLRLFDWDR 424
Cdd:cd04016    2 GRLSITVVQAK-LVKN----YGLTRMDPYCRIRVGHAVYETPTAYNGAkNPRWNktIQCTLPEGVDS---IYIEIFDERA 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 442620926 425 TSDDESLGRASIDIASVIKKGV-VDSWLTLE----DAKHGLLH 462
Cdd:cd04016   74 FTMDERIAWTHITIPESVFNGEtLDDWYSLSgkqgEDKEGMIN 116
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
 748-824 6.92e-03

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


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 37.77  E-value: 6.92e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 748 PDPYVKLYLLPGRTKE--------SKRKTSVIKDNCNPVYDASFEYLISiaeLRQTELEVTVCTQkgfLSGGSPII---- 815
Cdd:cd08691   21 PDPYVKISIQPGKRHIfpalphhgQECRTSIVENTINPVWHREQFVFVG---LPTDVLEIEVKDK---FAKSRPIIrrfl 94


                 ....*....
gi 442620926 816 GMLKIPLDD 824
Cdd:cd08691   95 GKLSIPVQR 103
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 349-445 7.41e-03

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: 37.52  E-value: 7.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 349 ILRIHVVEAKDLMKKDISvlGKGKSDPYAIINV-GA-----QEFKTQIIDNN-VNPKWDYWCEAVVEVSQHAILVLRLFD 421
Cdd:cd00275    3 TLTIKIISGQQLPKPKGD--KGSIVDPYVEVEIhGLpaddsAKFKTKVVKNNgFNPVWNETFEFDVTVPELAFLRFVVYD 80

                         90       100
                 ....*....|....*....|....
gi 442620926 422 WDrTSDDESLGRASIDIASvIKKG 445
Cdd:cd00275   81 ED-SGDDDFLGQACLPLDS-LRQG 102
PLN02964 PLN02964
phosphatidylserine decarboxylase
 348-442 8.76e-03

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 39.84  E-value: 8.76e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAkdLMKKdisvlgkgKSDPYAIINVGAQEFKTQIIDNNVNPKWDYWCEAVVEVSQHAILVLRLFDWDRTSD 427
Cdd:PLN02964  54 GIALLTLVGA--EMKF--------KDKWLACVSFGEQTFRTETSDSTDKPVWNSEKKLLLEKNGPHLARISVFETNRLSK 123

                         90
                 ....*....|....*
gi 442620926 428 DESLGRASIDIASVI 442
Cdd:PLN02964 124 NTLVGYCELDLFDFV 138
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 348-440 9.12e-03

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: 9.12e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 348 GILRIHVVEAKDLMKKDIsvlGKGKSDPYAIINVGAQEF--KTQIIDNNVNPKWDywcEA----VVEVSQHaiLVLRLFD 421
Cdd:cd04044    2 GVLAVTIKSARGLKGSDI---IGGTVDPYVTFSISNRRElaRTKVKKDTSNPVWN---ETkyilVNSLTEP--LNLTVYD 73

                         90
                 ....*....|....*....
gi 442620926 422 WDRTSDDESLGRASIDIAS 440
Cdd:cd04044   74 FNDKRKDKLIGTAEFDLSS 92
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 493-614 9.65e-03

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: 36.87  E-value: 9.65e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620926 493 SSAVLSVFIDSARHLKQARSSSKPDPYLVCSVNKQKQQTAMIMRDDSPVWEQGFTFLVSNPDNeSLNIKIYDQKTGND-- 570
Cdd:cd04046    1 PQVVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRS-PIKIQVWNSNLLCDef 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 442620926 571 IGQYTYTLSTLLKQfnmEVIQQPFQLQKSGPESKLYMSLSLRIL 614
Cdd:cd04046   80 LGQATLSADPNDSQ---TLRTLPLRKRGRDAAGEVPGTISVKVT 120
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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