NCBI Conserved Domain Search

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

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 157.95 E-value: 2.57e-47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 236 MGELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQL 311
Cdd:cd08402    1 LGDICFSLRYVPTAGKLTVVILEAKNLKKmdvgGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 312 QSVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08402   81 QKVHLIVTVLDYDRIGKNDPIGKVVLGCNATGAELRHWSDMLASPRRPIAQWHTL 135

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

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 138.17 E-value: 6.44e-40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKAE---GTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELPKA 185
Cdd:cd08385    3 GKLQFSLDYDFQSNQLTVGIIQAADLPAMdmgGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVPYSELGNK 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 553727180 186 TLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLGP 227
Cdd:cd08385   83 TLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEEWRDLES 124

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

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 123.46 E-value: 3.24e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPsdgkGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 553727180 313 SVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd00276   81 EVSLVITVVDKDSVGRNEVIGQVVLGPDSGGEELEHWNEMLASPRKPIARWHKL 134

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176051 [Multi-domain] Cd Length: 136 Bit Score: 110.65 E-value: 2.08e-29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGL----NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLvwdnGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 313 SVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHLR 367
Cdd:cd08406   82 DLSLRVTVAESTEDGKTPNVGHVIIGPAASGMGLSHWNQMLASLRKPVAMWHPLR 136

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

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 109.43 E-value: 7.32e-29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd08405    2 GELLLSLCYNPTANRITVNIIKARNLKAmdinGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERLR 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 313 SVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHLR 367
Cdd:cd08405   82 ETTLIITVMDKDRLSRNDLIGKIYLGWKSGGLELKHWKDMLSKPRQPVAQWHRLK 136

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 104.05 E-value: 6.06e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGL----NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLpkmdVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 553727180 313 --SVDLVLAVWARGlqLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHLR 367
Cdd:cd08404   82 diSVEFLVLDSDRV--TKNEVIGRLVLGPKASGSGGHHWKEVCNPPRRQIAEWHMLC 136

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

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 103.64 E-value: 6.83e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKAE---GTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELPKA 185
Cdd:cd08387    3 GELHFSLEYDKDMGILNVKLIQARNLQPRdfsGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVPPQELPKR 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 553727180 186 TLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLGP 227
Cdd:cd08387   83 TLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLWRKIQS 124

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176054 [Multi-domain] Cd Length: 137 Bit Score: 96.64 E-value: 4.34e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP---GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQS 313
Cdd:cd08409    2 GDIQISLTYNPTLNRLTVVVLRARGLRQldhAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQLDT 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 314 VDLVLAVWARGLQLRTEPVGKVLLGS--RASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08409   82 ASLSLSVMQSGGVRKSKLLGRVVLGPfmYARGKELEHWNDMLSKPKELIKRWHAL 136

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

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 94.88 E-value: 1.38e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAmditGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 553727180 313 SVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08403   81 NVSLIIAVVDYDRVGHNELIGVCRVGPNADGQGREHWNEMLANPRKPIAQWHQL 134

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 92.00 E-value: 7.34e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180  124 IRVGLRQAGNLKA---EGTADPYAWVSVsTQSGRRHETKVHRGTLSPMFEETCCFLVPPaeLPKATLKVQLWDFKRFSEH 200
Cdd:pfam00168   3 LTVTVIEAKNLPPkdgNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPD--PENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 553727180  201 EPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 92.65 E-value: 1.02e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGL----NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLlqtdMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 313 SVDLVLAVWARGLQLRTEPVGKVLLGSRASGQP-LQHWADMLAHARRPIAQWHHL 366
Cdd:cd08410   81 NVSLVFTVYGHNVKSSNDFIGRIVIGQYSSGPSeTNHWRRMLNSQRTAVEQWHSL 135

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

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 85.46 E-value: 3.14e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKAE---GTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAE-LPK 184
Cdd:cd08386    3 GRIQFSVSYDFQESTLTLKILKAVELPAKdfsGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEGFPYEkLQQ 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 553727180 185 ATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLGP 227
Cdd:cd08386   83 RVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTFWKDLKP 125

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 81.76 E-value: 4.27e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180   124 IRVGLRQAGNLKA---EGTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELpkATLKVQLWDFKRFSEH 200
Cdd:smart00239   2 LTVKIISARNLPPkdkGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPEL--AELEIEVYDKDRFGRD 79

                           90       100
                   ....*....|....*....|..
gi 553727180   201 EPLGELQLPLGTVDLQHVLESW 222
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRHEKL 101

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 79.03 E-value: 4.36e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKAE---GTADPYAWVSVStqSGRRHETKVHRGTLSPMFEETCCFLVPPaeLPKATLKVQLWDFKRFSEH 200
Cdd:cd00030    1 LRVTVIEARNLPAKdlnGKSDPYVKVSLG--GKQKFKTKVVKNTLNPVWNETFEFPVLD--PESDTLTVEVWDKDRFSKD 76

                         90       100
                 ....*....|....*....|....*.
gi 553727180 201 EPLGELQLPLGTV-DLQHVLESWYQL 225
Cdd:cd00030   77 DFLGEVEIPLSELlDSGKEGELWLPL 102

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 77.68 E-value: 2.27e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL----KAEGTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELPK 184
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLpprtKDVAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVSFKELQR 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 553727180 185 ATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESW 222
Cdd:cd08390   81 RTLRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVVW 118

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 70.36 E-value: 7.29e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLkAEG-----TADPYAWVSV----STQSGRRheTKVHRGTLSPMFEETCCFLVPP 179
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNL-AYAdekkkRSNPYVKVYLlpdkSKQSKRK--TSVKKNTTNPVFNETLKYHISK 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 553727180 180 AELPKATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd08521   78 SQLETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176052 [Multi-domain] Cd Length: 138 Bit Score: 70.39 E-value: 1.06e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNPGLA------EAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQ 310
Cdd:cd08407    2 GEVLLSISYLPAANRLLVVVIKAKNLHSDQLklllgiDVSVKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFELPSEL 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 553727180 311 LQSVDLVLAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08407   82 LAASSVELEVLNQDSPGQSLPLGRCSLGLHTSGTERQHWEEMLDNPRRQIAMWHQL 137

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

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 66.91 E-value: 1.64e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA---EGTADPYawVSV-----STQSGRRhETKVHRGTLSPMFEETCCFLVPPA 180
Cdd:cd04030    3 GRIQLTIRYSSQRQKLIVTVHKCRNLPPcdsSDIPDPY--VRLyllpdKSKSTRR-KTSVKKDNLNPVFDETFEFPVSLE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 553727180 181 ELPKATLKVQLW-DFKRFSEHEP-LGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd04030   80 ELKRRTLDVAVKnSKSFLSREKKlLGQVLIDLSDLDLSKGFTQWYDL 126

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

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 66.99 E-value: 1.83e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 110 RLLLSLEYDFGSQEIRVGLRQAGNLK---AEGTADPYAWVSVSTQSGR--RHETKVHRGTLSPMFEETCCFLVPPAELPK 184
Cdd:cd08384    1 KILVSLMYNTQRRGLIVGIIRCVNLAamdANGYSDPFVKLYLKPDAGKksKHKTQVKKKTLNPEFNEEFFYDIKHSDLAK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 553727180 185 ATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQhvLESWYQ-LGPPGT 230
Cdd:cd08384   81 KTLEITVWDKDIGKSNDYIGGLQLGINAKGER--LRHWLDcLKNPDK 125

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 66.30 E-value: 2.54e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA----EGTADPYAWVSV----STQSGRRheTKVHRGTLSPMFEETCCFLVPPA 180
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAadpkKQRSDPYVKTYLlpdkSNRGKRK--TSVKKKTLNPVFNETLRYKVERE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 553727180 181 ELPKATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd08393   80 ELPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 65.92 E-value: 3.35e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL----KAEGTADPYAWVSV----STQSGRRheTKVHRGTLSPMFEETCCFLVPPA 180
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLaygdEAKKRSNPYVKTYLlpdkSRQSKRK--TSIKRNTTNPVYNETLKYSISHS 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 553727180 181 ELPKATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd04029   80 QLETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPL 124

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

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 64.29 E-value: 1.60e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 242 SLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQSVDLV 317
Cdd:cd08384    5 SLMYNTQRRGLIVGIIRCVNLAAmdanGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKKTLE 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 553727180 318 LAVWARGLQLRTEPVGKVLLGSRASGQPLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08384   85 ITVWDKDIGKSNDYIGGLQLGINAKGERLRHWLDCLKNPDKKIEAWHTL 133

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

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 62.27 E-value: 6.63e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKAE---GTADPYAWVSV----STQSGRRheTKVHRGTLSPMFEETCCFL-VPPA 180
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRddgSLRNPYVKVYLlpdrSEKSKRR--TKTVKKTLNPEWNQTFEYSnVRRE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 553727180 181 ELPKATLKVQLWDFKRFSEHEPLGELQLPLGTV--DLQHVlesWYQL 225
Cdd:cd04031   81 TLKERTLEVTVWDYDRDGENDFLGEVVIDLADAllDDEPH---WYPL 124

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 61.93 E-value: 7.78e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGlrQAGNLKAEGTADPYAWVSV----STQSGRRHETKVHRGTLSPMFEETCCF-LVPPAELP 183
Cdd:cd08381    2 GQVKLSISYKNGTLFVMVM--HAKNLPLLDGSDPDPYVKTyllpDPQKTTKRKTKVVRKTRNPTFNEMLVYdGLPVEDLQ 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 553727180 184 KATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLG 226
Cdd:cd08381   80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122

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

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 61.67 E-value: 1.54e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA---EGTADPYawVSVSTQSG-RRHETK---VHRGTLSPMFEETCCFLVPPAE 181
Cdd:cd08405    2 GELLLSLCYNPTANRITVNIIKARNLKAmdiNGTSDPY--VKVWLMYKdKRVEKKktvIKKRTLNPVFNESFIFNIPLER 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 553727180 182 LPKATLKVQLWDFKRFSEHEPLGELQLPL--GTVDLQH 217
Cdd:cd08405   80 LRETTLIITVMDKDRLSRNDLIGKIYLGWksGGLELKH 117

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

Pssm-ID: 176053 [Multi-domain] Cd Length: 138 Bit Score: 60.46 E-value: 3.27e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 236 MGELCFSLRYVPSSGSLTVVVLEARGL-------NPglaEAYVKIQLM-LNQRKWKKSKTSSKKGTTTPYFNEAFVFLVP 307
Cdd:cd08408    1 VPELLLGLEYNALTGRLSVEVIKGSNFknlamnkAP---DTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQVA 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 308 VSQLQSVDLVLAVWARGLQLRTEPVGKVLLGSRASGQ-PLQHWADMLAHARRPIAQWHHL 366
Cdd:cd08408   78 LFQLSEVTLMFSVYNKRKMKRKEMIGWFSLGLNSSGEeEEEHWNEMKESKGQQVCRWHTL 137

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

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 60.06 E-value: 4.46e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA----EGTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFL-VPPAELP 183
Cdd:cd08388    3 GTLFFSLRYNSEKKALLVNIIECRDLPAmdeqSGTSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFTFYgIPYNQLQ 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 553727180 184 KATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLES 221
Cdd:cd08388   83 DLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEGEL 120

C2 domain; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176059 Cd Length: 118 Bit Score: 59.15 E-value: 6.46e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 110 RLLLSLEYDFGSQEIRVGLRQAGNLKAEGTADPYAWVSVSTQSGRRH-ETKVHRGTLSPMFEETCCFLVPPAELPKATLK 188
Cdd:cd08677    2 KLHYSLSYDKQKAELHVNILEAENISVDAGCECYISGCVSVSEGQKEaQTALKKLALHTQWEEELVFPLPEEESLDGTLT 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 553727180 189 VQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd08677   82 LTLRCCDRFSRHSTLGELRLKLADVSMMLGAAQWVDL 118

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

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 58.59 E-value: 1.21e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKAE-----GTADPYAWVSVSTQsgrRHETKVHRGTLSPMFEETCCFLV--PPAELpkatLKVQLWDFKR 196
Cdd:cd04024    3 LRVHVVEAKDLAAKdrsgkGKSDPYAILSVGAQ---RFKTQTIPNTLNPKWNYWCEFPIfsAQNQL----LKLILWDKDR 75

                         90       100       110
                 ....*....|....*....|....*....|..
gi 553727180 197 FSEHEPLGELQLPLGTVDLQHVLE---SWYQL 225
Cdd:cd04024   76 FAGKDYLGEFDIALEEVFADGKTGqsdKWITL 107

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

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 57.38 E-value: 3.81e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 133 NLKAEGTADPYAWVSV-STQSGRRHETKVHRGTLSPMFEETCCFLVPPAE-------------LPKATLKVQLWDFKRFS 198
Cdd:cd08675   12 ALKSNGTCDPFARVTLnYSSKTDTKRTKVKKKTNNPRFDEAFYFELTIGFsyekksfkveeedLEKSELRVELWHASMVS 91

                         90       100
                 ....*....|....*....|....*....
gi 553727180 199 EHEPLGELQLPLGTVDLQHVLESWYQLGP 227
Cdd:cd08675   92 GDDFLGEVRIPLQGLQQAGSHQAWYFLQP 120

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

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 56.92 E-value: 4.28e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKA---------EGTADPYAWVSVSTQSGRrheTKVHRGTLSPMFEETCCFLVPPAelPKATLKVQLWDf 194
Cdd:cd08391    3 LRIHVIEAQDLVAkdkfvgglvKGKSDPYVIVRVGAQTFK---SKVIKENLNPKWNEVYEAVVDEV--PGQELEIELFD- 76

                         90       100       110
                 ....*....|....*....|....*....|.
gi 553727180 195 KRFSEHEPLGELQLPLGTVDLQHVLESWYQL 225
Cdd:cd08391   77 EDPDKDDFLGRLSIDLGSVEKKGFIDEWLPL 107

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

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 56.12 E-value: 9.41e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDfgSQEIRVGLRQAGNL---KAEGTADPYA--WVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELP 183
Cdd:cd04026    2 GRIYLKISVK--DNKLTVEVREAKNLipmDPNGLSDPYVklKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 553727180 184 KaTLKVQLWDFKRFSEHEPLGELQLPLGT-VDLQHvlESWYQL 225
Cdd:cd04026   80 R-RLSIEVWDWDRTTRNDFMGSLSFGVSElIKMPV--DGWYKL 119

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 55.35 E-value: 1.21e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKA----EGTADPYAWVSVSTQSGRRHETKVHRGTLSPMFEETCCFLVPPAELP-KATLKVQLWDFKRFS 198
Cdd:cd04041    3 LVVTIHRATDLPKadfgTGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEETWFVLVTPDEVKaGERLSCRLWDSDRFT 82

                         90
                 ....*....|..
gi 553727180 199 EHEPLGELQLPL 210
Cdd:cd04041   83 ADDRLGRVEIDL 94

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 53.48 E-value: 4.47e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180  250 GSLTVVVLEARGLNP----GLAEAYVKIQLM--------------LNqrkwkksktsskkgtttPYFNEAFVFLVPVSQL 311
Cdd:pfam00168   1 GRLTVTVIEAKNLPPkdgnGTSDPYVKVYLLdgkqkkktkvvkntLN-----------------PVWNETFTFSVPDPEN 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 553727180  312 QSvdLVLAVWARGLQLRTEPVGKVL--LGSRASGQPLQHWADM 352
Cdd:pfam00168  64 AV--LEIEVYDYDRFGRDDFIGEVRipLSELDSGEGLDGWYPL 104

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 54.36 E-value: 4.61e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL---KAEGTADPYAWVSVSTQSGR--RHETKVHRGTLSPMFEETCCFLVPPAELP 183
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLpkmDVSGLADPYVKVNLYYGKKRisKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 553727180 184 KATLKVQLWDFKRFSEHEPLGELQL--PLGTVDLQHVLE 220
Cdd:cd08404   82 DISVEFLVLDSDRVTKNEVIGRLVLgpKASGSGGHHWKE 120

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

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 53.56 E-value: 1.11e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 138 GTADPYAWVSVSTQSGRR--HETKVHRGTLSPMFEETCCFLV-------------PPAELPKATLKVQLWDFKRFSEHEP 202
Cdd:cd04010   17 GTCDPYASVTLIYSNKKQdtKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfemPEEDAEKLELRVDLWHASMGGGDVF 96

                         90       100
                 ....*....|....*....|....*.
gi 553727180 203 LGELQLPLGTVDLQHVL-ESWYQLGP 227
Cdd:cd04010   97 LGEVRIPLRGLDLQAGShQAWYFLQP 122

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

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 52.65 E-value: 1.34e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLM---------------LNqrkwkksktsskkgtttPY 297
Cdd:cd08385    3 GKLQFSLDYDFQSNQLTVGIIQAADLPAmdmgGTSDPYVKVYLLpdkkkkfetkvhrktLN-----------------PV 65

                         90       100
                 ....*....|....*....|....
gi 553727180 298 FNEAFVFLVPVSQLQSVDLVLAVW 321
Cdd:cd08385   66 FNETFTFKVPYSELGNKTLVFSVY 89

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

Pssm-ID: 176035 [Multi-domain] Cd Length: 124 Bit Score: 52.24 E-value: 1.75e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL--KAEGTADPYAWVSVSTQSGR-RHETKVHRGTlSPMFEETCCFL-VPPAELPK 184
Cdd:cd08389    3 GDLDVAFEYDPSARKLTVTVIRAQDIptKDRGGASSWQVHLVLLPSKKqRAKTKVQRGP-NPVFNETFTFSrVEPEELNN 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 553727180 185 ATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLGP 227
Cdd:cd08389   82 MALRFRLYGVERMRKERLIGEKVVPLSQLNLEGETTVWLTLEP 124

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

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 51.51 E-value: 3.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA---EGTADPYA---WVSVSTQSgRRHETKVHRGTLSPMFEETCCFL-VPPAE 181
Cdd:cd04035    2 GTLEFTLLYDPANSALHCTIIRAKGLKAmdaNGLSDPYVklnLLPGASKA-TKLRTKTVHKTRNPEFNETLTYYgITEED 80

                         90       100
                 ....*....|....*....|....*....
gi 553727180 182 LPKATLKVQLWDFKRFSeHEPLGELQLPL 210
Cdd:cd04035   81 IQRKTLRLLVLDEDRFG-NDFLGETRIPL 108

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 50.33 E-value: 7.99e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNPGLAEA-----YVKIQLMLNQRKWKKSKTSSKKGTttPYFNEAFVFLVPVSQL 311
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVahcdpFVKVCLLPDERRSLQSKVKRKTQN--PNFDETFVFQVSFKEL 78

                         90       100
                 ....*....|....*....|....*.
gi 553727180 312 QSVDLVLAVWARGLQLRTEPVGKVLL 337
Cdd:cd08390   79 QRRTLRLSVYDVDRFSRHCIIGHVLF 104

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 50.78 E-value: 1.22e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQ------------EIRVGLRQAGNL---KAEGTADPY--AWVSVSTQSGRRHETKVHRGTLSPMFEE 171
Cdd:cd04020    2 GELKVALKYVPPESegalkskkpstgELHVWVKEAKNLpalKSGGTSDSFvkCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 553727180 172 TCCF-LVPPAELPKATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQHVLESW 222
Cdd:cd04020   82 TFVYdGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDW 133

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

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 50.40 E-value: 1.89e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVP------------SSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNE 300
Cdd:cd04020    2 GELKVALKYVPpesegalkskkpSTGELHVWVKEAKNLPAlksgGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 301 AFVF-LVPVSQLQSVDLVLAVWARGLQLRTEPVGKVLLGS---RASGQPlQHWADMLAharRPIAQWHH-LRSPRE-VDR 374
Cdd:cd04020   82 TFVYdGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLgtgKSYGQA-VDWMDSTG---EEILLWQKmLDNPNSwVEG 157


                 ....
gi 553727180 375 VLAL 378
Cdd:cd04020  158 TLPL 161

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

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 49.41 E-value: 1.94e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 138 GTADPYAWVSVSTQSgrrHETKVHRGTLSPMFEETCCFLVPPAELPKatLKVQLWDFKRFSEHEPLGELQLPLGTVDLQH 217
Cdd:cd04025   19 GTSDPFVRVFYNGQT---LETSVVKKSCYPRWNEVFEFELMEGADSP--LSVEVWDWDLVSKNDFLGKVVFSIQTLQQAK 93

                         90       100
                 ....*....|....*....|....*..
gi 553727180 218 VLESWYQLGPPGTTEPEQMGELCfSLR 244
Cdd:cd04025   94 QEEGWFRLLPDPRAEEESGGNLG-SLR 119

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

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 49.43 E-value: 2.32e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKAE---GTADPYAWVSVSTQsGRR---HETKVHRGTLSPMFEETCCFLVPPAEL 182
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAMditGFSDPYVKVSLMCE-GRRlkkKKTSVKKNTLNPTYNEALVFDVPPENV 79

                         90       100
                 ....*....|....*....|..
gi 553727180 183 PKATLKVQLWDFKRFSEHEPLG 204
Cdd:cd08403   80 DNVSLIIAVVDYDRVGHNELIG 101

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176051 [Multi-domain] Cd Length: 136 Bit Score: 47.86 E-value: 7.96e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 108 WGRLLLSLEYDFGSQEIRVGLRQAGNL---KAEGTADPYAWVSVsTQSGRR---HETKVHRGTLSPMFEETCCFLVPPAE 181
Cdd:cd08406    1 VGEILLSLSYLPTAERLTVVVVKARNLvwdNGKTTADPFVKVYL-LQDGRKiskKKTSVKRDDTNPIFNEAMIFSVPAIV 79

                         90       100
                 ....*....|....*....|...
gi 553727180 182 LPKATLKVQLWDFKRFSEHEPLG 204
Cdd:cd08406   80 LQDLSLRVTVAESTEDGKTPNVG 102

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 47.82 E-value: 8.17e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNPG-----LAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQL 311
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGdeakkRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 553727180 312 QSVDLVLAVWARGLQLRTEPVGKV--LLGSRASGQPLQHW 349
Cdd:cd04029   82 ETRTLQLSVWHYDRFGRNTFLGEVeiPLDSWNFDSQHEEC 121

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 46.40 E-value: 1.31e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 128 LRQAGNL---KAEGTADPYAWVSVSTQSgrrHETKVHRGTLSPMFEETCCFLVPPAElpKATLKVQLWDFKRFSEhepLG 204
Cdd:cd04050    6 LDSAKNLplaKSTKEPSPYVELTVGKTT---QKSKVKERTNNPVWEEGFTFLVRNPE--NQELEIEVKDDKTGKS---LG 77

                         90       100
                 ....*....|....*....|....*...
gi 553727180 205 ELQLPLGTVdLQH---VLESWYQLGPPG 229
Cdd:cd04050   78 SLTLPLSEL-LKEpdlTLDQPFPLDNSG 104

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176054 [Multi-domain] Cd Length: 137 Bit Score: 45.79 E-value: 4.19e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLK--AEGTADPYAWVSVS--TQSGRRHETKVHRGTLSPMFEETCCFLVPPAELPK 184
Cdd:cd08409    2 GDIQISLTYNPTLNRLTVVVLRARGLRqlDHAHTSVYVKVSLMihNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQLDT 81


                 ....*...
gi 553727180 185 ATLKVQLW 192
Cdd:cd08409   82 ASLSLSVM 89

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

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 44.57 E-value: 8.72e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGL----NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQ 312
Cdd:cd04030    3 GRIQLTIRYSSQRQKLIVTVHKCRNLppcdSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEELK 82

                         90       100
                 ....*....|....*....|....*..
gi 553727180 313 SVDLVLAVWARG--LQLRTEPVGKVLL 337
Cdd:cd04030   83 RRTLDVAVKNSKsfLSREKKLLGQVLI 109

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 44.50 E-value: 1.48e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL---KAEGTADPYawVSVSTQSGRR----HETKVHRGTLSPMFEETCCFLVPPAE 181
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLlqtDMSQGSDPF--VKIQLVHGLKliktKKTSCMRGTIDPFYNESFSFKVPQEE 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 553727180 182 LPKATLKVQLWDFKRFSEHEPLGelQLPLGTvdlqhvleswYQLGPPGTTEPEQM 236
Cdd:cd08410   79 LENVSLVFTVYGHNVKSSNDFIG--RIVIGQ----------YSSGPSETNHWRRM 121

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

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 43.41 E-value: 2.30e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 121 SQEIRVGlrQAGNLKAEGTADPYAWVSV-STQSGRrheTKVHRGtLSPMFEETCCFLVPPAELPKATLKVQLWDfKRfSE 199
Cdd:cd08383    1 SLRLRIL--EAKNLPSKGTRDPYCTVSLdQVEVAR---TKTVEK-LNPFWGEEFVFDDPPPDVTFFTLSFYNKD-KR-SK 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 553727180 200 HEPLGELQLPLGTVDLQHVLESWYQLGPPGTTEPEQmGELCFSLRY 245
Cdd:cd08383   73 DRDIVIGKVALSKLDLGQGKDEWFPLTPVDPDSEVQ-GSVRLRARY 117

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 42.86 E-value: 2.45e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180   251 SLTVVVLEARGLNP----GLAEAYVKIQLmlNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQLQSvdLVLAVWARGLQ 326
Cdd:smart00239   1 TLTVKIISARNLPPkdkgGKSDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAE--LEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 553727180   327 LRTEPVGKVL--LGSRASGQPLQHW 349
Cdd:smart00239  77 GRDDFIGQVTipLSDLLLGGRHEKL 101

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 42.93 E-value: 4.06e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKAE----GTADPYawVSVSTQSGRRHE-TKVHRGTLSPMFEETCCFLVPPAELPkatLKVQLWDFKRFS 198
Cdd:cd04044    4 LAVTIKSARGLKGSdiigGTVDPY--VTFSISNRRELArTKVKKDTSNPVWNETKYILVNSLTEP---LNLTVYDFNDKR 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 553727180 199 EHEPLGELQLPLGTVDLQHVLEswyqlgppGTTEPEQM-----GELCFSLRYVP 247
Cdd:cd04044   79 KDKLIGTAEFDLSSLLQNPEQE--------NLTKNLLRngkpvGELNYDLRFFP 124

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 45.91 E-value: 4.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180  124 IRVGLRQAGNLK-----AEGTADPYAWVSVSTQSGRRheTKVHRGTLSPMFEETCCFLVPPAELPkatLKVQLWDFKRFS 198
Cdd:COG5038   438 VEVKIKSAEGLKksdstINGTVDPYITVTFSDRVIGK--TRVKKNTLNPVWNETFYILLNSFTDP---LNLSLYDFNSFK 512

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 553727180  199 EHEPLGELQLPLGTVDLQHVLESWYqLGPPGTTEPeqMGELCFSLRYVPS---SGSLTVVVLEARGLNPGLA 267
Cdd:COG5038   513 SDKVVGSTQLDLALLHQNPVKKNEL-YEFLRNTKN--VGRLTYDLRFFPViedKKELKGSVEPLEDSNTGIL 581

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

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 42.39 E-value: 4.80e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQrkWKKSKTSSKKGTTTPYFNEAFVFLVPVSQL 311
Cdd:cd08387    3 GELHFSLEYDKDMGILNVKLIQARNLQPrdfsGTADPYCKVRLLPDR--SNTKQSKIHKKTLNPEFDESFVFEVPPQEL 79

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 41.84 E-value: 8.96e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNLKA---EGTADPYAWVS---------VSTQSgrrheTKVHRGTLSPMFEETCCFL 176
Cdd:cd04009    3 GVLTVKAYYRASEQSLRVEILNARNLLPldsNGSSDPFVKVEllprhlfpdVPTPK-----TQVKKKTLFPLFDESFEFN 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 553727180 177 VPPAELPKA------TLKVQlwDFKRFSEHEplGELQLPLGTV 213
Cdd:cd04009   78 VPPEQCSVEgalllfTVKDY--DLLGSNDFE--GEAFLPLNDI 116

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

Pssm-ID: 175994 [Multi-domain] Cd Length: 146 Bit Score: 42.37 E-value: 9.11e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVgLRqAGNLKAEGTAD--PYAWVSVSTQSGRR----HETKVHRGTLSPMFEETCCFLVPPAel 182
Cdd:cd04028   18 GDIQLGLYDKKGQLEVEV-IR-ARGLVQKPGSKvlPAPYVKVYLLEGKKciakKKTKIARKTLDPLYQQQLVFDVSPT-- 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 553727180 183 pKATLKVQLW-DFKRFSEHEPLGELQLPLGTVDLQHVLESWYQLGPP 228
Cdd:cd04028   94 -GKTLQVIVWgDYGRMDKKVFMGVAQILLDDLDLSNLVIGWYKLFPT 139

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 40.70 E-value: 2.07e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNPG-----LAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQL 311
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYAdekkkRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 553727180 312 QSVDLVLAVWARGLQLRTEPVGKVLLgsrasgqPLQHW 349
Cdd:cd08521   81 ETRTLQLSVWHHDRFGRNTFLGEVEI-------PLDSW 111

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

Pssm-ID: 176053 [Multi-domain] Cd Length: 138 Bit Score: 40.81 E-value: 2.33e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 111 LLLSLEYD--FG--SQEIRVGlRQAGNLKAEGTADPYAWVSVSTQSGR---RHETKVHRGTLSPMFEETCCFLVPPAELP 183
Cdd:cd08408    4 LLLGLEYNalTGrlSVEVIKG-SNFKNLAMNKAPDTYVKLTLLNSDGQeisKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 553727180 184 KATLKVQLWDFKRFSEHEPLGELQLPL---GTVDLQHVLE 220
Cdd:cd08408   83 EVTLMFSVYNKRKMKRKEMIGWFSLGLnssGEEEEEHWNE 122

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

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 40.58 E-value: 2.75e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 109 GRLLLSLEYDFGSQEIRVGLRQAGNL----KAEGTADPYAWVSV----STQSGRRheTKVHRGTLSPMFEETCCFLVPPA 180
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLaygdEKKKKCHPYVKVCLlpdkSHNSKRK--TAVKKGTVNPVFNETLKYVVEAD 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 553727180 181 ELPKATLKVQLWDFKRFSEHEPLGELQLPLGTVDLQ 216
Cdd:cd08392   80 LLSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFE 115

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

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 40.41 E-value: 3.18e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 235 QMGELCFSLRYVPSSGSLTVVVLEARGL-----NPGLAEAYVKIQLMLNQRkwKKSKTSSKKGTTTPYFNEAFVFL-VPV 308
Cdd:cd08388    1 KLGTLFFSLRYNSEKKALLVNIIECRDLpamdeQSGTSDPYVKLQLLPEKE--HKVKTRVLRKTRNPVYDETFTFYgIPY 78

                         90
                 ....*....|..
gi 553727180 309 SQLQSVDLVLAV 320
Cdd:cd08388   79 NQLQDLSLHFAV 90

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 39.47 E-value: 4.11e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKA---EGTADPYAWVSVSTQSGRRheTKVHRGTLSPMFEETCCFLVPPaeLPKATLKVQLWDFKRFSEH 200
Cdd:cd04040    1 LTVDVISAENLPSadrNGKSDPFVKFYLNGEKVFK--TKTIKKTLNPVWNESFEVPVPS--RVRAVLKVEVYDWDRGGKD 76

                         90
                 ....*....|....
gi 553727180 201 EPLGELQLPLGTVD 214
Cdd:cd04040   77 DLLGSAYIDLSDLE 90

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 39.72 E-value: 4.89e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGL-----NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFLVPVSQL 311
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLaaadpKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100
                 ....*....|....*....|....
gi 553727180 312 QSVDLVLAVWARGLQLRTEPVGKV 335
Cdd:cd08393   82 PTRVLNLSVWHRDSLGRNSFLGEV 105

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 38.97 E-value: 5.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 252 LTVVVLEARGLNP----GLAEAYVKIQLM-------------LNqrkwkksktsskkgtttPYFNEAFVFlvPVSQLQSV 314
Cdd:cd00030    1 LRVTVIEARNLPAkdlnGKSDPYVKVSLGgkqkfktkvvkntLN-----------------PVWNETFEF--PVLDPESD 61

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 553727180 315 DLVLAVWARGLQLRTEPVGKVLLgsrasgqPLQHwadmLAHARRPIAQWHHL 366
Cdd:cd00030   62 TLTVEVWDKDRFSKDDFLGEVEI-------PLSE----LLDSGKEGELWLPL 102

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 39.29 E-value: 7.44e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 120 GSQEIRVGLRQAGNLKA---EGTADPYAWVSVSTQsgrRHETKVHRGTLSPMFEETCCFLVppAELPKATLKVQLWDFKR 196
Cdd:cd08375   13 GIGRLMVVIVEGRDLKPcnsNGKSDPYCEVSMGSQ---EHKTKVVSDTLNPKWNSSMQFFV--KDLEQDVLCITVFDRDF 87

                         90
                 ....*....|....
gi 553727180 197 FSEHEPLGELQLPL 210
Cdd:cd08375   88 FSPDDFLGRTEIRV 101

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

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 39.19 E-value: 7.63e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 553727180 237 GELCFSLRYVPSSGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVF 304
Cdd:cd04035    2 GTLEFTLLYDPANSALHCTIIRAKGLKAmdanGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTY 73

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 38.71 E-value: 9.22e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKaEGTADPYAWVSVStqsGRRHETKVHRGTLSPMFEETCCF--LVPPAELPKATLKVQLWDFKRFSEHE 201
Cdd:cd04011    6 VRVRVIEARQLV-GGNIDPVVKVEVG---GQKKYTSVKKGTNCPFYNEYFFFnfHESPDELFDKIIKISVYDSRSLRSDT 81

                         90
                 ....*....|..
gi 553727180 202 PLGELQLPLGTV 213
Cdd:cd04011   82 LIGSFKLDVGTV 93

N-terminal domain of synaptotagmin-2 (Syt2) and similar proteins; Syt2, also called synaptotagmin II (SytII), exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties. It may have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It plays a role in dendrite formation by melanocytes. The model corresponds to N-terminal domain of Syt2, which is a recognition domain responsible for the binding of botulinum neurotoxin B (BoNT B).

Pssm-ID: 409249 Cd Length: 111 Bit Score: 38.23 E-value: 1.07e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 553727180  29 ITRIPWPRWTLfIAI-LAAGVLLVSCLLCVI--CCyCHRHRHRKQPKDK 74
Cdd:cd21964   53 INKIPLPPWAL-IAIaVVAGLLILTCCFCICkkCC-CKKKKNKKEKGKG 99

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 37.97 E-value: 1.28e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 135 KAEGTADPYAWVSVSTQSgrRHETKVHRGTLSPMFEETCCFLVPpaELPKATLKVQLWDFKRFSEhEPLGELQLPLGTV- 213
Cdd:cd04052    8 SKTGLLSPYAELYLNGKL--VYTTRVKKKTNNPSWNASTEFLVT--DRRKSRVTVVVKDDRDRHD-PVLGSVSISLNDLi 82

                         90
                 ....*....|..
gi 553727180 214 DLQHVLESWYQL 225
Cdd:cd04052   83 DATSVGQQWFPL 94

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

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 38.85 E-value: 1.33e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 138 GTADPYAWVSVSTQSGRrheTKVHRGTLSPMFEETCCFLVPPAELPkatLKVQLWDFKRFSEHEPLGElqlplGTVDLQH 217
Cdd:cd04038   20 TSSDPYVVLTLGNQKVK---TRVIKKNLNPVWNEELTLSVPNPMAP---LKLEVFDKDTFSKDDSMGE-----AEIDLEP 88


                 ...
gi 553727180 218 VLE 220
Cdd:cd04038   89 LVE 91

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 38.34 E-value: 1.39e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQA---GNLKAEGTADPYAWVSVSTQSgrRHETKVHRGTLSPMFEEtcCFLVPPAElPKATLKVQLWDFKRFSEH 200
Cdd:cd04045    3 LRLHIRKAndlKNLEGVGKIDPYVRVLVNGIV--KGRTVTISNTLNPVWDE--VLYVPVTS-PNQKITLEVMDYEKVGKD 77

                         90
                 ....*....|
gi 553727180 201 EPLGELQLPL 210
Cdd:cd04045   78 RSLGSVEINV 87

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

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 37.55 E-value: 1.76e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 138 GTADPYAWVSVSTQSGRR---HETKVHRGTLSPMFEEtccFLVPPAEL----PKATLKVQLWDFKRFSEHEPLGELQLPL 210
Cdd:cd04047   19 GKSDPFLEISRQSEDGTWvlvYRTEVIKNTLNPVWKP---FTIPLQKLcngdYDRPIKIEVYDYDSSGKHDLIGEFETTL 95

                         90
                 ....*....|
gi 553727180 211 GTVDLQHVLE 220
Cdd:cd04047   96 DELLKSSPLE 105

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

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 37.63 E-value: 2.41e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 249 SGSLTVVVLEARGLNP----GLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFlvpvsQLQSVD----LVLAV 320
Cdd:cd04026   12 DNKLTVEVREAKNLIPmdpnGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTF-----DLKPADkdrrLSIEV 86


                 .
gi 553727180 321 W 321
Cdd:cd04026   87 W 87

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

Pssm-ID: 176067 [Multi-domain] Cd Length: 119 Bit Score: 37.05 E-value: 3.45e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 237 GELCFSLRYvpSSGSLTVVVLEARGL---NPGLAEAYVKIQLMLNQRKWKKSKTSSKKGTTTPYFNEAFVFlvPVSQLQS 313
Cdd:cd08685    1 GQLKLSIEG--QNRKLTLHVLEAKGLrstNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSF--DVNERDY 76

                         90
                 ....*....|.
gi 553727180 314 VD-LVLAVWAR 323
Cdd:cd08685   77 QKrLLVTVWNK 87

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 37.05 E-value: 3.81e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 553727180 124 IRVGLRQAGNLKAEG---TADPYAWVSVSTQsgrRHETKVHRGTLSPMFEETCCFLVP---PAELPKATLKVQLWDFKRF 197
Cdd:cd08682    1 VQVTVLQARGLLCKGksgTNDAYVIIQLGKE---KYSTSVKEKTTSPVWKEECSFELPgllSGNGNRATLQLTVMHRNLL 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 553727180 198 SEHEPLGELQLPLGTVDLQHVLE--SWYQL-GPPGTTEPEQmGEL 239
Cdd:cd08682   78 GLDKFLGQVSIPLNDLDEDKGRRrtRWFKLeSKPGKDDKER-GEI 121

N-terminal domain of synaptotagmin-1 and -2; The synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Calcium binding to synaptotagmin-1 participates in triggering neurotransmitter release at the synapse. In general, synaptotagmins contain 2 calcium binding C2 domains. Synaptotagmin-1 and -2 have an additional N-terminal domain that has been shown to bind to Botulinum neurotoxin B.

Pssm-ID: 409247 Cd Length: 93 Bit Score: 35.48 E-value: 7.61e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 553727180  29 ITRIPWPRWTLFIAILAAGVLLVSCLLCvICCYCHRHRHRKQPKDK 74
Cdd:cd21342   36 LHKIPLPPWALAAIAIVAGLLLLSCCFC-ICKKCCFKKKKKKEGKK 80

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176011 [Multi-domain] Cd Length: 126 Bit Score: 36.10 E-value: 9.18e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 553727180 131 AGNLKAE---GTADPYAWVSVSTQSGRrheTKVHRGTLSPMFEETCCFLVppaELPKATLKVQLWD 193
Cdd:cd04046   12 AEGLSKQdsgGGADPYVIIKCEGESVR---SPVQKDTLSPEFDTQAIFYR---KKPRSPIKIQVWN 71