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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113   221 RLRLRLVSAEGLPRprtRPGSGGGGCCVILRLQPRVRPgAQRSRVVQSSCNPIFNEDFFFEGLRPPDlavRSLRAKVLDR 300
Cdd:smart00239   1 TLTVKIISARNLPP---KDKGGKSDPYVKVSLDGDPKE-KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDK 73

                           90       100
                   ....*....|....*....|.
gi 209870113   301 GaGLRRDVLLGECETPLIALL 321
Cdd:smart00239  74 D-RFGRDDFIGQVTIPLSDLL 93

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113   221 RLRLRLVSAEGLPRprtRPGSGGGGCCVILRLQPRVRPgAQRSRVVQSSCNPIFNEDFFFEGLRPPDlavRSLRAKVLDR 300
Cdd:smart00239   1 TLTVKIISARNLPP---KDKGGKSDPYVKVSLDGDPKE-KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDK 73

                           90       100
                   ....*....|....*....|.
gi 209870113   301 GaGLRRDVLLGECETPLIALL 321
Cdd:smart00239  74 D-RFGRDDFIGQVTIPLSDLL 93

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLPrPRTrpgSGGGGC--CVILRLQPRVRPgAQRSRVVQSSCNPIFNEDFFFEgLR 284
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLP-PRT---KDVAHCdpFVKVCLLPDERR-SLQSKVKRKTQNPNFDETFVFQ-VS 74

                         90       100       110
                 ....*....|....*....|....*....|....
gi 209870113 285 PPDLAVRSLRAKVLDRGaGLRRDVLLGECETPLI 318
Cdd:cd08390   75 FKELQRRTLRLSVYDVD-RFSRHCIIGHVLFPLK 107

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+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLPrprTRPGSGGGGCCVILRLQP-RVRPGAQRSRVVQSSCNPIFNEDFFFEGLRP 285
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLP---PRDDGSLRNPYVKVYLLPdRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRR 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 209870113 286 PDLAVRSLRAKVLDrgagLRRD---VLLGECETPL 317
Cdd:cd04031   80 ETLKERTLEVTVWD----YDRDgenDFLGEVVIDL 110

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLPRPRtrpGSGGGGCCVILRL-QPRVRPGAQRSRVVQSSCNPIFNEDFFFEgLRP 285
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPSD---GKGLSDPYVKVSLlQGGKKLKKKKTSVKKGTLNPVFNEAFSFD-VPA 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 209870113 286 PDLAVRSLRAKVLDRGaGLRRDVLLGECetpliaLLPPLAGGLG 329
Cdd:cd00276   77 EQLEEVSLVITVVDKD-SVGRNEVIGQV------VLGPDSGGEE 113

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLPRprTRPGSGGGGCCVILRLQP----RVRpgaqrSRVVQSSCNPIFNEDFFFEG 282
Cdd:cd08388    3 GTLFFSLRYNSEKKALLVNIIECRDLPA--MDEQSGTSDPYVKLQLLPekehKVK-----TRVLRKTRNPVYDETFTFYG 75

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 209870113 283 LRPPDLAVRSLRAKVL--DRgagLRRDVLLGECETPL 317
Cdd:cd08388   76 IPYNQLQDLSLHFAVLsfDR---YSRDDVIGEVVCPL 109

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLprprtRPGSGGGGC--CVILRLQPRVR-PGA--QRSRVVQSSCNPIFNEDFFF- 280
Cdd:cd04009    3 GVLTVKAYYRASEQSLRVEILNARNL-----LPLDSNGSSdpFVKVELLPRHLfPDVptPKTQVKKKTLFPLFDESFEFn 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 209870113 281 ---EGLRPPDlAVRSLRAKVLDRgagLRRDVLLGECETPLiALLPPLAGGLGPG 331
Cdd:cd04009   78 vppEQCSVEG-ALLLFTVKDYDL---LGSNDFEGEAFLPL-NDIPGVEDTSSAQ 126

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGpgRLRLRLVSAEGLPrprtrpGSGGGGCCVILRL------QPRVRpgaQRSRVVQSSCNPIFNEDFFF 280
Cdd:cd08685    1 GQLKLSIEGQNR--KLTLHVLEAKGLR------STNSGTCNSYVKIslspdkEVRFR---QKTSTVPDSANPLFHETFSF 69

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 205 RGGQLRLSTEYQAGPGRLRLRLVSAEGLPrprTRPGSGGGGCCVILRLQPRVRpgaQRSRV-VQSSCNPIFNEDFFFEGL 283
Cdd:cd08389    1 KCGDLDVAFEYDPSARKLTVTVIRAQDIP---TKDRGGASSWQVHLVLLPSKK---QRAKTkVQRGPNPVFNETFTFSRV 74

                         90       100
                 ....*....|....*....|....*....
gi 209870113 284 RPPDLAVRSLRAKVLDRGaGLRRDVLLGE 312
Cdd:cd08389   75 EPEELNNMALRFRLYGVE-RMRKERLIGE 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209870113 207 GQLRLSTEYQAGPGRLRLRLVSAEGLPRprtRPGSGGGGCCVILRL-QPRVRPGAQRSRVVQSSCNPIFNEDFFFE--GL 283
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLPK---MDVSGLADPYVKVNLyYGKKRISKKKTHVKKCTLNPVFNESFVFDipSE 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 209870113 284 RPPDLAVRSLrakVLDRGAGLRRDVlLGECE 314
Cdd:cd08404   79 ELEDISVEFL---VLDSDRVTKNEV-IGRLV 105