PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809  874 RYDVKRILLTRSYKHH-NIYNDLGVRVVGGKRQMNGELSAYVSQLHSTANNQTLGQIKIGDEVVEWNGILLRGKTFEEVE 952
Cdd:cd06714      1 DFLIGRIILQRDPKDGsVSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQ 80

                           90
                   ....*....|....*
gi 1972266809  953 RIVNKSHGEIEMVIR 967
Cdd:cd06714     81 DIISQSKGEVELVVS 95

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809  874 RYDVKRILLTRSYKHH-NIYNDLGVRVVGGKRQMNGELSAYVSQLHSTANNQTLGQIKIGDEVVEWNGILLRGKTFEEVE 952
Cdd:cd06714      1 DFLIGRIILQRDPKDGsVSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQ 80

                           90
                   ....*....|....*
gi 1972266809  953 RIVNKSHGEIEMVIR 967
Cdd:cd06714     81 DIISQSKGEVELVVS 95

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 1972266809  1038 RLVAKIIRARGLKSRDQSRSaPNPFVKVYLLPGRKvsHKRRTRFVDSSCAPEWNQVLEYQVAPHTLNtmFLEFTVCDYQR 1117
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSLDGDPK--EKKKTKVVKNTLNPVWNETFEFEVPPPELA--ELEIEVYDKDR 75

                            90
                    ....*....|....*.
gi 1972266809  1118 DVDDLPLGNVQIPLAD 1133
Cdd:smart00239   76 FGRDDFIGQVTIPLSD 91

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809  874 RYDVKRILLTRSYKHH-NIYNDLGVRVVGGKRQMNGELSAYVSQLHSTANNQTLGQIKIGDEVVEWNGILLRGKTFEEVE 952
Cdd:cd06714      1 DFLIGRIILQRDPKDGsVSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFEEVQ 80

                           90
                   ....*....|....*
gi 1972266809  953 RIVNKSHGEIEMVIR 967
Cdd:cd06714     81 DIISQSKGEVELVVS 95

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 1972266809  1038 RLVAKIIRARGLKSRDQSRSaPNPFVKVYLLPGRKvsHKRRTRFVDSSCAPEWNQVLEYQVAPHTLNtmFLEFTVCDYQR 1117
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSLDGDPK--EKKKTKVVKNTLNPVWNETFEFEVPPPELA--ELEIEVYDKDR 75

                            90
                    ....*....|....*.
gi 1972266809  1118 DVDDLPLGNVQIPLAD 1133
Cdd:smart00239   76 FGRDDFIGQVTIPLSD 91

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDG-NSRLVAKIIRARGLKSRDQSRSaPNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd04030      3 GRIQLTIRYSSqRQKLIVTVHKCRNLPPCDSSDI-PDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1972266809 1104 NTMFLEFTVCDyqrDVDDLP-----LGNVQIPLADKSAINTGPRWYPLQ 1147
Cdd:cd04030     82 KRRTLDVAVKN---SKSFLSrekklLGQVLIDLSDLDLSKGFTQWYDLT 127

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 1972266809 1025 GHIQVSLGYDGNS-RLVAKIIRARGLKSRDQSRSaPNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd00276      1 GELLLSLSYLPTAeRLTVVVLKARNLPPSDGKGL-SDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQL 79

                           90       100
                   ....*....|....*....|....
gi 1972266809 1104 NTMFLEFTVCDYQRDVDDLPLGNV 1127
Cdd:cd00276     80 EEVSLVITVVDKDSVGRNEVIGQV 103

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYD-GNSRLVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRKvsHKRRTRFVDSSCAPEWNQVLEYQVAPHT- 1102
Cdd:cd08386      3 GRIQFSVSYDfQESTLTLKILKAVELPAKDFSGTS-DPFVKIYLLPDKK--HKLETKVKRKNLNPHWNETFLFEGFPYEk 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1972266809 1103 LNTMFLEFTVCDYQRDVDDLPLGNVQIPLAD 1133
Cdd:cd08386     80 LQQRVLYLQVLDYDRFSRNDPIGEVSLPLNK 110

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDG-NSRLVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQ-VAPHT 1102
Cdd:cd04035      2 GTLEFTLLYDPaNSALHCTIIRAKGLKAMDANGLS-DPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                           90       100
                   ....*....|....*....|....*....
gi 1972266809 1103 LNTMFLEFTVCDYQRDVDDlPLGNVQIPL 1131
Cdd:cd04035     81 IQRKTLRLLVLDEDRFGND-FLGETRIPL 108

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1027 IQVSLGYDGNSR-LVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTLNT 1105
Cdd:cd08384      2 ILVSLMYNTQRRgLIVGIIRCVNLAAMDANGYS-DPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAK 80

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1972266809 1106 MFLEFTVCDYQRDVDDLPLGNVQIPLADKSA 1136
Cdd:cd08384     81 KTLEITVWDKDIGKSNDYIGGLQLGINAKGE 111

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDGNSR-LVAKIIRARGLKSRDQSRSAPNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd04029      2 GEILFSLSYDYKTQsLNVHVKECRNLAYGDEAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1972266809 1104 NTMFLEFTVCDYQRDVDDLPLGNVQIPLADKSAINTGPRWYPLQ 1147
Cdd:cd04029     82 ETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPLH 125

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1038 RLVAKIIRARGL-KSRDQSRSAPNPFVKVYLL-PGRKVSHKRRTRFV-DSSCAPEWNQVLEYQVAPHTLntMFLEFTVCD 1114
Cdd:cd00275      3 TLTIKIISGQQLpKPKGDKGSIVDPYVEVEIHgLPADDSAKFKTKVVkNNGFNPVWNETFEFDVTVPEL--AFLRFVVYD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1972266809 1115 YQRDVDDlPLGNVQIPLadkSAINTGPRWYPLQGSYDQPIP 1155
Cdd:cd00275     81 EDSGDDD-FLGQACLPL---DSLRQGYRHVPLLDSKGEPLE 117

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 1972266809 1025 GHIQVSLGYDG-NSRLVAKIIRARGLKSRDQSRSAPNPFVKVYLLPGRKvsHKRRTRFVDSSCAPEWNQVLE-YQVAPHT 1102
Cdd:cd08388      3 GTLFFSLRYNSeKKALLVNIIECRDLPAMDEQSGTSDPYVKLQLLPEKE--HKVKTRVLRKTRNPVYDETFTfYGIPYNQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1972266809 1103 LNTMFLEFTVCDYQRDVDDLPLGNVQIPLADKSAINTG 1140
Cdd:cd08388     81 LQDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEG 118

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDGNSR-LVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRkvSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd08387      3 GELHFSLEYDKDMGiLNVKLIQARNLQPRDFSGTA-DPYCKVRLLPDR--SNTKQSKIHKKTLNPEFDESFVFEVPPQEL 79

                           90       100
                   ....*....|....*....|....*....
gi 1972266809 1104 NTMFLEFTVCDYQRDVDDLPLGNVQIPLA 1132
Cdd:cd08387     80 PKRTLEVLLYDFDQFSRDECIGVVELPLA 108

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGY-DGNSRLVAKIIRARGLKSRDqsRSAPNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd08409      2 GDIQISLTYnPTLNRLTVVVLRARGLRQLD--HAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQL 79

                   ....*....
gi 1972266809 1104 NTMFLEFTV 1112
Cdd:cd08409     80 DTASLSLSV 88

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1038 RLVAKIIRARGLKSRDqSRSAPNPFVKVYLlPGRKvSHKRRTRFVDSSCAPEWNQVLEYQVAPHTLNTmfLEFTVCDYQR 1117
Cdd:cd04036      1 LLTVRVLRATNITKGD-LLSTPDCYVELWL-PTAS-DEKKRTKTIKNSINPVWNETFEFRIQSQVKNV--LELTVMDEDY 75

                           90
                   ....*....|....*.
gi 1972266809 1118 DVDDlPLGNVQIPLAD 1133
Cdd:cd04036     76 VMDD-HLGTVLFDVSK 90

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDGNS-RLVAKIIRARGLKSRDQSRSApNPFVKVYLLP-GRKVShKRRTRFVDSSCAPEWNQVLEYQVAPHT 1102
Cdd:cd08406      2 GEILLSLSYLPTAeRLTVVVVKARNLVWDNGKTTA-DPFVKVYLLQdGRKIS-KKKTSVKRDDTNPIFNEAMIFSVPAIV 79

                           90       100
                   ....*....|....*....|....*..
gi 1972266809 1103 LNTMFLEFTVCDYQRDVDDLPLGNVQI 1129
Cdd:cd08406     80 LQDLSLRVTVAESTEDGKTPNVGHVII 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1038 RLVAKIIRARGLKSRDQSRSApNPFVKVYLLpgrkvSHKRRTRFVDSSCAPEWNQVLEYQVA-PHTLNTMFLEFTVCDYQ 1116
Cdd:cd04022      1 KLVVEVVDAQDLMPKDGQGSS-SAYVELDFD-----GQKKRTRTKPKDLNPVWNEKLVFNVSdPSRLSNLVLEVYVYNDR 74

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1972266809 1117 RDVDDLP-LGNVQIPLAD-KSAINTGPRWYPLQ 1147
Cdd:cd04022     75 RSGRRRSfLGRVRISGTSfVPPSEAVVQRYPLE 107

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1026 HIQVSLGYD-GNSRLVAKIIRARGLKS---RDQSRSapnpFVKVYLLPG-RKVSHKRRTRFVDSSCAPEWNQVLEYQVAP 1100
Cdd:cd08680      2 QVQIGLRYDsGDSSLVISVEQLRNLSAlsiPENSKV----YVRVALLPCsSSTSCLFRTKALEDQDKPVFNEVFRVPISS 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1972266809 1101 HTLNTMFLEFTVCDYQRDVDDLPLGNVQIPLAD-KSAINTGPRWYPL 1146
Cdd:cd08680     78 TKLYQKTLQVDVCSVGPDQQEECLGGAQISLADfESSEEMSTKWYNL 124

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1025 GHIQVSLGYDGNsRLVAKIIRARGLKSRDqsrsaPN----PFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAP 1100
Cdd:cd04026      2 GRIYLKISVKDN-KLTVEVREAKNLIPMD-----PNglsdPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKP 75

                           90
                   ....*....|....*..
gi 1972266809 1101 HTLNTmFLEFTVCDYQR 1117
Cdd:cd04026     76 ADKDR-RLSIEVWDWDR 91

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1042 KIIRARGLKSRDQSRSAPNPFVKVYLLPGRKVShkrRTRFVDSSCAPEWNQVLEYQVaphTLNTMFLEFTVCDYQRDVDD 1121
Cdd:cd04044      7 TIKSARGLKGSDIIGGTVDPYVTFSISNRRELA---RTKVKKDTSNPVWNETKYILV---NSLTEPLNLTVYDFNDKRKD 80

                           90
                   ....*....|..
gi 1972266809 1122 LPLGNVQIPLAD 1133
Cdd:cd04044     81 KLIGTAEFDLSS 92

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 1972266809 1025 GHIQVSLGY-DGNSRLVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd08410      1 GELLLSLNYlPSAGRLNVDIIRAKQLLQTDMSQGS-DPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEEL 79

                           90       100
                   ....*....|....*....|....*.
gi 1972266809 1104 NTMFLEFTVCDYQRDVDDLPLGNVQI 1129
Cdd:cd08410     80 ENVSLVFTVYGHNVKSSNDFIGRIVI 105

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 1972266809 1025 GHIQVSLGYDGNS-RLVAKIIRARGLKSRDQSRSApNPFVKVYLLPGRKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTL 1103
Cdd:cd08404      2 GELLLSLCYQPTTnRLTVVVLKARHLPKMDVSGLA-DPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEEL 80

                           90
                   ....*....|....
gi 1972266809 1104 NTMFLEFTVCDYQR 1117
Cdd:cd08404     81 EDISVEFLVLDSDR 94

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972266809 1038 RLVAKIIRARGLksrdqsRSAPNPFVKVYLLPgrkvSHKRRTRFVDSSCAPEWNQVleYQVAPHTLNTMFLEFTVCDYQR 1117
Cdd:cd08378      1 YLYVRVVKARGL------PANSNDPVVEVKLG----NYKGSTKAIERTSNPEWNQV--FAFSKDRLQGSTLEVSVWDKDK 68

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1972266809 1118 DVDDLpLGNVQIPLAD-------KSAIntGPRWYPLQG 1148
Cdd:cd08378     69 AKDDF-LGGVCFDLSEvptrvppDSPL--APQWYRLED 103

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 1972266809 1042 KIIRARGLKSRDQ-----SRSAPNPFVKVyllpgrKVSHKR-RTRFVDSSCAPEWNQVleYQVAPHTLNTMFLEFTVCDY 1115
Cdd:cd08391      6 HVIEAQDLVAKDKfvgglVKGKSDPYVIV------RVGAQTfKSKVIKENLNPKWNEV--YEAVVDEVPGQELEIELFDE 77

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1972266809 1116 QRDVDDlPLGNVQIPLADKSAINTGPRWYPLQGS 1149
Cdd:cd08391     78 DPDKDD-FLGRLSIDLGSVEKKGFIDEWLPLEDV 110

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.

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gi 1972266809 1027 IQVSLGYDGNS-RLVAKIIRARGLKSRDQSRsAPNPFVKVYLLPG-RKVSHKRRTRFVDSSCAPEWNQVLEYQVAPHTLN 1104
Cdd:cd08408      4 LLLGLEYNALTgRLSVEVIKGSNFKNLAMNK-APDTYVKLTLLNSdGQEISKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

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gi 1972266809 1105 TMFLEFTV 1112
Cdd:cd08408     83 EVTLMFSV 90

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.

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gi 1972266809 1047 RGLKSRDQSRSAPNPFVKVYlLPGRKVshkRRTRFVDSSCAPEWNQVLEYQVAPHTlNTMfLEFTVCDyQRDVDDLPLGN 1126
Cdd:cd04052      1 KGLDTSESKTGLLSPYAELY-LNGKLV---YTTRVKKKTNNPSWNASTEFLVTDRR-KSR-VTVVVKD-DRDRHDPVLGS 73