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 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTNFRTTTCRDGGRNPIFQEKFVFSLIEGI-REINVTVWNSNTVTYDDFIG 140
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPEsDTLTVEVWDKDRFSKDDFLG 80

                          90
                  ....*....|....*....
gi 2047916339 141 NGKIQLAKVLAEGYDDSTW 159
Cdd:cd00030    81 EVEIPLSELLDSGKEGELW 99

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 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTNFRTTTCRDGGRNPIFQEKFVFSLIEGI-REINVTVWNSNTVTYDDFIG 140
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPEsDTLTVEVWDKDRFSKDDFLG 80

                          90
                  ....*....|....*....
gi 2047916339 141 NGKIQLAKVLAEGYDDSTW 159
Cdd:cd00030    81 EVEIPLSELLDSGKEGELW 99

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGS-TNFRTTTCRDGGRNPIFQEKFVFSLIEGI-REINVTVWNSNTVTYDDFI 139
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLLDgKQKKKTKVVKNTLNPVWNETFTFSVPDPEnAVLEIEVYDYDRFGRDDFI 82

                          90
                  ....*....|.
gi 2047916339 140 GNGKIQLAKVL 150
Cdd:pfam00168  83 GEVRIPLSELD 93

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 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTNFRTTTCRDGGRNPIFQEKFVFSLIEGI-REINVTVWNSNTVTYDDFIG 140
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPEsDTLTVEVWDKDRFSKDDFLG 80

                          90
                  ....*....|....*....
gi 2047916339 141 NGKIQLAKVLAEGYDDSTW 159
Cdd:cd00030    81 EVEIPLSELLDSGKEGELW 99

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 2047916339   62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTN---FRTTTCRDGGrNPIFQEKFVFSLIE-GIREINVTVWNSNTVTYDD 137
Cdd:smart00239   2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPkekKKTKVVKNTL-NPVWNETFEFEVPPpELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|....*....
gi 2047916339  138 FIGNGKIQLAKVLAEGYDD 156
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHE 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTNFRTTTCRDGGRNPIFQEKFVFSLIEGIREI-NVTVWNSNTVTyDDFIG 140
Cdd:cd08681     3 LVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRGGQHPEWDEELRFEITEDKKPIlKVAVFDDDKRK-PDLIG 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2047916339 141 NGKIQLAKVLAEG-YDDstWSLQTKTGRHAGEVRLILHF 178
Cdd:cd08681    82 DTEVDLSPALKEGeFDD--WYELTLKGRYAGEVYLELTF 118

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  78 ISRQDPYVCLEYGSTNFRTTTCRDGGRNPIFQEKFVFSLIEGIREINVTVWNSNTVTYDDFIGNGKIQLAKVLAEGYD-D 156
Cdd:cd04016    19 LTRMDPYCRIRVGHAVYETPTAYNGAKNPRWNKTIQCTLPEGVDSIYIEIFDERAFTMDERIAWTHITIPESVFNGETlD 98

                          90       100
                  ....*....|....*....|...
gi 2047916339 157 STWSLQTKTGRH-AGEVRLILHF 178
Cdd:cd04016    99 DWYSLSGKQGEDkEGMINLVFSY 121

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLE-YGSTNFRTTTCRDGGRNPIFQEKFVFSL-----IEGIREINVTVWNSNTVTY 135
Cdd:cd04051     2 LEITIISAEDLKNVNLFGKMKVYAVVWiDPSHKQSTPVDRDGGTNPTWNETLRFPLderllQQGRLALTIEVYCERPSLG 81

                          90
                  ....*....|....*...
gi 2047916339 136 DDFIGNGKIQLAKVLAEG 153
Cdd:cd04051    82 DKLIGEVRVPLKDLLDGA 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYV--CLEYGSTNF--RTTTCRDGGRNPIFQEKFVFSL-IEGIRE--INVTVWNSNTVT 134
Cdd:cd08405    17 ITVNIIKARNLKAMDINGTSDPYVkvWLMYKDKRVekKKTVIKKRTLNPVFNESFIFNIpLERLREttLIITVMDKDRLS 96

                          90
                  ....*....|...
gi 2047916339 135 YDDFIgnGKIQLA 147
Cdd:cd08405    97 RNDLI--GKIYLG 107

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  82 DPYVCLEYGSTNFRTTTCRDgGRNPIFQEKF--VFSLIEGiREINVTVWNSNtVTYDDFIGNGKIQLAKVLAEGYDDSTW 159
Cdd:cd08391    29 DPYVIVRVGAQTFKSKVIKE-NLNPKWNEVYeaVVDEVPG-QELEIELFDED-PDKDDFLGRLSIDLGSVEKKGFIDEWL 105

                  ....*....
gi 2047916339 160 SLQ-TKTGR 167
Cdd:cd08391   106 PLEdVKSGR 114

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2047916339  82 DPYVCLEYGSTNFRTTTCrDGGRNPIFQEKFVFSLIE---GIREInvTVWNSNTVTYDDFIGNGKIQLAKVLAE 152
Cdd:cd08376    22 DPYVKFRLGNEKYKSKVC-SKTLNPQWLEQFDLHLFDdqsQILEI--EVWDKDTGKKDEFIGRCEIDLSALPRE 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGSTNFRTTTCRDgGRNPIFQEKFVFsLIEGIRE--INVTVWNSNTVTYDDFI 139
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSD-TLNPKWNSSMQF-FVKDLEQdvLCITVFDRDFFSPDDFL 94

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2047916339 140 GNGKIQLAKVLAEgyddstwslqTKTGRHAGEVRLILH 177
Cdd:cd08375    95 GRTEIRVADILKE----------TKESKGPITKRLLLH 122

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2047916339  82 DPYVCLEY-----GSTNFRTTTCRdGGRNPIFQEKFVFSLIEG--IREINVTVWNSNTVTYDDFIG 140
Cdd:cd04026    35 DPYVKLKLipdpkNETKQKTKTIK-KTLNPVWNETFTFDLKPAdkDRRLSIEVWDWDRTTRNDFMG 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  62 LEVIVIGCTKLKDTEWISRQDPYVCLEYGS----TNFRTTTCRDGGRNPIFQEKFVFSLI-EGIREIN--VTVWNSNTVT 134
Cdd:cd08410    16 LNVDIIRAKQLLQTDMSQGSDPFVKIQLVHglklIKTKKTSCMRGTIDPFYNESFSFKVPqEELENVSlvFTVYGHNVKS 95

                  ....*.
gi 2047916339 135 YDDFIG 140
Cdd:cd08410    96 SNDFIG 101

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  60 QPLEVIVIGCTKL------KDtewisRQDPYV---CLEYGSTNF-RTTTCRDGGRNPIFQEKFVF----SLIEGiREINV 125
Cdd:cd08521    14 GSLEVHIKECRNLayadekKK-----RSNPYVkvyLLPDKSKQSkRKTSVKKNTTNPVFNETLKYhiskSQLET-RTLQL 87

                          90       100
                  ....*....|....*....|..
gi 2047916339 126 TVWNSNTVTYDDFIGNGKIQLA 147
Cdd:cd08521    88 SVWHHDRFGRNTFLGEVEIPLD 109

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  48 LERRLLFLIFNGQpLEVIVIGCTKLKDTEWISRQDPYVCL-----EYGSTNFRTTTCRdGGRNPIFQEKFVFsliEGIRE 122
Cdd:cd04035     4 LEFTLLYDPANSA-LHCTIIRAKGLKAMDANGLSDPYVKLnllpgASKATKLRTKTVH-KTRNPEFNETLTY---YGITE 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2047916339 123 -------INVTVWNSNTVtYDDFIGNGKIQLAKV 149
Cdd:cd04035    79 ediqrktLRLLVLDEDRF-GNDFLGETRIPLKKL 111

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2047916339  83 PYVCLEYGSTNFRTTTcRDGGRNPIFQEKFVFSLIEGIR----EINVTVWNSNTVTY-DDFIGNGKIQLAKVLAEG 153
Cdd:cd04022    23 AYVELDFDGQKKRTRT-KPKDLNPVWNEKLVFNVSDPSRlsnlVLEVYVYNDRRSGRrRSFLGRVRISGTSFVPPS 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2047916339  82 DPYVCLEYGSTNFRTTTCRDGgRNPIFQEKFVFSLI--EGIREINVTVWNSNTVTYDDFIGNGKIQLAKVLAEGY-DDST 158
Cdd:cd04039    27 DPFVIISFGRRVFRTSWRRHT-LNPVFNERLAFEVYphEKNFDIQFKVLDKDKFSFNDYVATGSLSVQELLNAAPqPDPE 105

                  ...
gi 2047916339 159 WSL 161
Cdd:cd04039   106 TGL 108

biotin carboxyl carrier protein of acetyl-CoA carboxylase

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2047916339 189 APSAPPFHAPPPSQLAMyatMPSAHPTAYPHPHTPYAFSSPFPSYPPNNGAYQTS 243
Cdd:PLN02983  145 PPPAPVVMMQPPPPHAM---PPASPPAAQPAPSAPASSPPPTPASPPPAKAPKSS 196

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2047916339  82 DPYVCL----EYGSTNFRTTTCRDGGRNPIFQEKFVFS------LIEgiREINVTVWNSNTVTYDDFIGNGKIQLAKVL 150
Cdd:cd04031    38 NPYVKVyllpDRSEKSKRRTKTVKKTLNPEWNQTFEYSnvrretLKE--RTLEVTVWDYDRDGENDFLGEVVIDLADAL 114