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: 286.61 E-value: 2.16e-96

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd08402   1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTLK 461
Cdd:cd08402  81 QKVHLIVTVLDYDRIGKNDPIGKVVLGCNATGAELRHWSDMLASPRRPIAQWHTLQ 136

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: 252.57 E-value: 2.88e-83

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 192 KLGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKsLPYADA 271
Cdd:cd08385   1 KLGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFK-VPYSEL 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDLVS 316
Cdd:cd08385  80 GNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEEWRDLES 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: 193.18 E-value: 4.21e-60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd00276   1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd00276  81 EVSLVITVVDKDSVGRNEVIGQVVLGPDSGGEELEHWNEMLASPRKPIARWHKL 134

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: 185.31 E-value: 4.97e-57

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd08405   1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTLK 461
Cdd:cd08405  81 RETTLIITVMDKDRLSRNDLIGKIYLGWKSGGLELKHWKDMLSKPRQPVAQWHRLK 136

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: 178.29 E-value: 1.80e-54

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 192 KLGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKSLPYADA 271
Cdd:cd08386   1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd08386  81 QQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTFWKDL 123

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: 164.60 E-value: 4.15e-49

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd08403   1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08403  81 NVSLIIAVVDYDRVGHNELIGVCRVGPNADGQGREHWNEMLANPRKPIAQWHQL 134

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: 149.50 E-value: 2.48e-43

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd08404   2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08404  82 DISVEFLVLDSDRVTKNEVIGRLVLGPKASGSGGHHWKEVCNPPRRQIAEWHML 135

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: 139.31 E-value: 1.10e-39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMG-GTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKsLPYADAM 272
Cdd:cd08390   1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDvAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQ-VSFKELQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24581230 273 NKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDLV 315
Cdd:cd08390  80 RRTLRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVVWRDLE 122

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: 135.94 E-value: 2.42e-38

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 192 KLGRLNFKLEYDFNSNSLAVTVIQAEELPALD-MGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKSLPYAD 270
Cdd:cd08388   1 KLGTLFFSLRYNSEKKALLVNIIECRDLPAMDeQSGTSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFTFYGIPYNQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 24581230 271 AMNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQ--TIEEWRDLVS 316
Cdd:cd08388  81 LQDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNegELLVSREIQP 128

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: 127.52 E-value: 2.65e-35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 193 LGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFkSLPYADAM 272
Cdd:cd08387   2 RGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVF-EVPPQELP 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 24581230 273 NKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd08387  81 KRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLWRKI 122

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: 127.45 E-value: 4.89e-35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGlSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd08409   1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAH-TSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQL 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIGRCILGCM--GTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08409  80 DTASLSLSVMQSGGVRKSKLLGRVVLGPFmyARGKELEHWNDMLSKPKELIKRWHAL 136

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 125.89 E-value: 5.84e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230   209 LAVTVIQAEELPALDMGGTSDPYVKVYLLpDKKKKFETKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFDRFSK 288
Cdd:pfam00168   3 LTVTVIEAKNLPPKDGNGTSDPYVKVYLL-DGKQKKKTKVVKNTLNPVWNETFTF---SVPDPENAVLEIEVYDYDRFGR 78

                          90       100
                  ....*....|....*....|....*.
gi 24581230   289 HDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:pfam00168  79 DDFIGEVRIPLSELDSGEGLDGWYPL 104

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: 126.83 E-value: 7.95e-35

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd08406   2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTLK 461
Cdd:cd08406  82 DLSLRVTVAESTEDGKTPNVGHVIIGPAASGMGLSHWNQMLASLRKPVAMWHPLR 136

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: 121.15 E-value: 9.40e-33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd08410   1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTG-TELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08410  81 NVSLVFTVYGHNVKSSNDFIGRIVIGQYSSGpSETNHWRRMLNSQRTAVEQWHSL 135

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: 111.81 E-value: 8.14e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230    208 SLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFDRFS 287
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEF---EVPPPELAELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|....
gi 24581230    288 KHDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:smart00239  78 RDDFIGQVTIPLSDLLLGGRHEKL 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: 111.78 E-value: 9.81e-30

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFDRFSK 288
Cdd:cd00030   1 LRVTVIEARNLPAKDLNGKSDPYVKVSL--GGKQKFKTKVVKNTLNPVWNETFEF---PVLDPESDTLTVEVWDKDRFSK 75

                        90       100
                ....*....|....*....|....*..
gi 24581230 289 HDQIGEVKVPLCTI-DLAQTIEEWRDL 314
Cdd:cd00030  76 DDFLGEVEIPLSELlDSGKEGELWLPL 102

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: 110.06 E-value: 7.33e-29

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 193 LGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFkSLPYAD 270
Cdd:cd04030   2 LGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKstRRKTSVKKDNLNPVFDETFEF-PVSLEE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 24581230 271 AMNKTLVFAI-FDFDRFSKH-DQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd04030  81 LKRRTLDVAVkNSKSFLSREkKLLGQVLIDLSDLDLSKGFTQWYDL 126

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: 109.29 E-value: 1.46e-28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 193 LGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLP--DKKKKFETKVHRKTLSPVFNETFTFKSLPYAD 270
Cdd:cd04035   1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPgaSKATKLRTKTVHKTRNPEFNETLTYYGITEED 80

                        90       100
                ....*....|....*....|....*....
gi 24581230 271 AMNKTLVFAIFDFDRFSkHDQIGEVKVPL 299
Cdd:cd04035  81 IQRKTLRLLVLDEDRFG-NDFLGETRIPL 108

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: 107.76 E-value: 7.65e-28

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGL--SDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQ 404
Cdd:cd08407   2 GEVLLSISYLPAANRLLVVVIKAKNLHSDQLKLLlgIDVSVKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFELPSEL 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24581230 405 IQKICLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08407  82 LAASSVELEVLNQDSPGQSLPLGRCSLGLHTSGTERQHWEEMLDNPRRQIAMWHQL 137

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: 106.57 E-value: 1.19e-27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMG-GTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFKsLPYAD 270
Cdd:cd08521   1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKqsKRKTSVKKNTTNPVFNETLKYH-ISKSQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 24581230 271 AMNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:cd08521  80 LETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEW 120

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: 106.56 E-value: 1.56e-27

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKF--ETKVHRKTLSPVFNETFTFKSLPYADA 271
Cdd:cd04031   3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSkrRTKTVKKTLNPEWNQTFEYSNVRRETL 82

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEvkvplCTIDLAQTI 308
Cdd:cd04031  83 KERTLEVTVWDYDRDGENDFLGE-----VVIDLADAL 114

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: 103.86 E-value: 1.67e-26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 192 KLGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKK----KKFETKVHRKTLSPVFNETFTFK-SL 266
Cdd:cd04009   1 PYGVLTVKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpdvPTPKTQVKKKTLFPLFDESFEFNvPP 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 24581230 267 PYADAMNKTLVFAIFDFDRFSKHDQIGEVKVPL 299
Cdd:cd04009  81 EQCSVEGALLLFTVKDYDLLGSNDFEGEAFLPL 113

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: 102.43 E-value: 5.87e-26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 329 ICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQKI 408
Cdd:cd08384   2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKK 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 24581230 409 CLVVTVVDYDRIGTSEPIGRCILGCMGTGTELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08384  82 TLEITVWDKDIGKSNDYIGGLQLGINAKGERLRHWLDCLKNPDKKIEAWHTL 133

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: 100.03 E-value: 4.64e-25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYdfNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPD--KKKKFETKVHRKTLSPVFNETFTFKSLPyADa 271
Cdd:cd04026   2 GRIYLKISV--KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDpkNETKQKTKTIKKTLNPVWNETFTFDLKP-AD- 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIdLAQTIEEWRDLVS-VEGE 320
Cdd:cd04026  78 KDRRLSIEVWDWDRTTRNDFMGSLSFGVSEL-IKMPVDGWYKLLNqEEGE 126

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: 99.04 E-value: 8.92e-25

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDM-GGTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFKsLPYAD 270
Cdd:cd08393   2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNrgKRKTSVKKKTLNPVFNETLRYK-VEREE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 24581230 271 AMNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd08393  81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 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: 95.49 E-value: 2.07e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 195 RLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPD--KKKKFETKVHRKTLSPVFNETFTFKsLPYADAM 272
Cdd:cd08384   1 KILVSLMYNTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDagKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLA 79

                        90       100
                ....*....|....*....|...
gi 24581230 273 NKTLVFAIFDFDRFSKHDQIGEV 295
Cdd:cd08384  80 KKTLEITVWDKDIGKSNDYIGGL 102

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: 95.02 E-value: 2.10e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 325 KLGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKkcTLNPYYNESFSFEVPFEQ 404
Cdd:cd08385   1 KLGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRK--TLNPVFNETFTFKVPYSE 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 24581230 405 IQKICLVVTVVDYDRIGTSEPIG--RCILGCMGTGTELRHWSDMLA 448
Cdd:cd08385  79 LGNKTLVFSVYDFDRFSKHDLIGevRVPLLTVDLGHVTEEWRDLES 124

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 92.77 E-value: 6.98e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230   340 GKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLkkkKTSIKKCTLNPYYNESFSFEVPFEQIQkiCLVVTVVDYDR 419
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKK---KTKVVKNTLNPVWNETFTFSVPDPENA--VLEIEVYDYDR 75

                          90       100
                  ....*....|....*....|....*....
gi 24581230   420 IGTSEPIGRCI--LGCMGTGTELRHWSDM 446
Cdd:pfam00168  76 FGRDDFIGEVRipLSELDSGEGLDGWYPL 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: 94.70 E-value: 8.32e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 205 NSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFKSLPYADAMNKTLVFAIFD 282
Cdd:cd04020  25 STGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKksKQKTPVVKKSVNPVWNHTFVYDGVSPEDLSQACLELTVWD 104

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 24581230 283 FDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDLVSVE 318
Cdd:cd04020 105 HDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEE 140

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: 93.02 E-value: 8.65e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFDRFSK 288
Cdd:cd04040   1 LTVDVISAENLPSADRNGKSDPFVKFYL--NGEKVFKTKTIKKTLNPVWNESFEV---PVPSRVRAVLKVEVYDWDRGGK 75

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 24581230 289 HDQIGEVKVPLCTIDLAQTIEewRDLVsVEGEGGQEKLG 327
Cdd:cd04040  76 DDLLGSAYIDLSDLEPEETTE--LTLP-LDGQGGGKLGA 111

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 93.27 E-value: 9.87e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGT-SDPYVKVYLLPDK--KKKFETKVHRKTLSPVFNETFTFkSLPYAD 270
Cdd:cd04029   2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAKKrSNPYVKTYLLPDKsrQSKRKTSIKRNTTNPVYNETLKY-SISHSQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 24581230 271 AMNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:cd04029  81 LETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEEC 121

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: 88.84 E-value: 3.63e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 192 KLGRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTlSPVFNETFTFKSLPYADA 271
Cdd:cd08389   1 KCGDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLPSKKQRAKTKVQRGP-NPVFNETFTFSRVEPEEL 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd08389  80 NNMALRFRLYGVERMRKERLIGEKVVPLSQLNLEGETTVWLTL 122

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: 89.02 E-value: 4.82e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFKsLPYADA 271
Cdd:cd08404   2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRisKKKTHVKKCTLNPVFNESFVFD-IPSEEL 80

                        90       100
                ....*....|....*....|..
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIG 293
Cdd:cd08404  81 EDISVEFLVLDSDRVTKNEVIG 102

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: 86.19 E-value: 3.20e-20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYdfNSNSLAVTVIQAEELPALDmGGTSDPYVKVYLLPD--KKKKFETKVHRKTLSPVFNETFTFKSLPYADA 271
Cdd:cd08381   2 GQVKLSISY--KNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDpqKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:cd08381  79 QQRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKW 118

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: 83.96 E-value: 2.52e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 328 DICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIM-QNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQ 406
Cdd:cd08408   3 ELLLGLEYNALTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24581230 407 KICLVVTVVDYDRIGTSEPIGRCILGCMGTGT-ELRHWSDMLASPRRPIAQWHTL 460
Cdd:cd08408  83 EVTLMFSVYNKRKMKRKEMIGWFSLGLNSSGEeEEEHWNEMKESKGQQVCRWHTL 137

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: 82.54 E-value: 3.03e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230    341 KLTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQKicLVVTVVDYDRI 420
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAE--LEIEVYDKDRF 76

                           90       100       110
                   ....*....|....*....|....*....|...
gi 24581230    421 GTSEPIGRCILGcmgtgtelrhWSDMLASPRRP 453
Cdd:smart00239  77 GRDDFIGQVTIP----------LSDLLLGGRHE 99

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: 83.15 E-value: 3.65e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 325 KLGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKkcTLNPYYNESFSFE-VPFE 403
Cdd:cd08386   1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRK--NLNPHWNETFLFEgFPYE 78

                        90       100
                ....*....|....*....|....
gi 24581230 404 QIQKICLVVTVVDYDRIGTSEPIG 427
Cdd:cd08386  79 KLQQRVLYLQVLDYDRFSRNDPIG 102

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: 81.99 E-value: 2.64e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTA------------GKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNE 394
Cdd:cd04020   2 GELKVALKYVPPEsegalkskkpstGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24581230 395 SFSFE-VPFEQIQKICLVVTVVDYDRIGTSEPIGRCILGCmGTGT--------------ELRHWSDMLASP 450
Cdd:cd04020  82 TFVYDgVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGL-GTGKsygqavdwmdstgeEILLWQKMLDNP 151

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: 79.97 E-value: 5.34e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 335 YVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGK--RLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQK--ICL 410
Cdd:cd04009  11 YRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSVegALL 90

                        90       100
                ....*....|....*....|..
gi 24581230 411 VVTVVDYDRIGTSEPIGRCILG 432
Cdd:cd04009  91 LFTVKDYDLLGSNDFEGEAFLP 112

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: 78.26 E-value: 1.05e-17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRlkkkKTSIKKCTLNPYYNESFSFEVPFEQIQKicLVVTVVDYDRIG 421
Cdd:cd00030   1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF----KTKVVKNTLNPVWNETFEFPVLDPESDT--LTVEVWDKDRFS 74

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 24581230 422 TSEPIGRCILGCmgtgtelrhwsDMLASPRRPIAQWHTL 460
Cdd:cd00030  75 KDDFLGEVEIPL-----------SELLDSGKEGELWLPL 102

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: 77.71 E-value: 2.68e-17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFE-VPFEQ 404
Cdd:cd04035   1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                        90       100
                ....*....|....*....|...
gi 24581230 405 IQKICLVVTVVDYDRIGtSEPIG 427
Cdd:cd04035  81 IQRKTLRLLVLDEDRFG-NDFLG 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: 74.99 E-value: 2.67e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLK-KMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKkcTLNPYYNESFSFEVPFEQI 405
Cdd:cd08390   1 GRLWFSVQYDLEEEQLTVSLIKARNLPpRTKDVAHCDPFVKVCLLPDERRSLQSKVKRK--TQNPNFDETFVFQVSFKEL 78

                        90       100
                ....*....|....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIGRCIL 431
Cdd:cd08390  79 QRRTLRLSVYDVDRFSRHCIIGHVLF 104

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 73.46 E-value: 9.98e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTfksLPYADAmNKTLVFAIFDFDRFS 287
Cdd:cd04042   1 QLDIHLKEGRNLAARDRGGTSDPYVKFKY--GGKTVYKSKTIYKNLNPVWDEKFT---LPIEDV-TQPLYIKVFDYDRGL 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 24581230 288 KHDQIGEVKVPLCTIDLAQTIEEWRDLvsvEGEGGQEKLG--DICFSL 333
Cdd:cd04042  75 TDDFMGSAFVDLSTLELNKPTEVKLKL---EDPNSDEDLGyiSLVVTL 119

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: 73.45 E-value: 1.16e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 338 TAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQKIcLVVTVVDY 417
Cdd:cd04026  11 KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRR-LSIEVWDW 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 24581230 418 DRIGTSEPIGRCILGCmgtgTELRHWsdmlasprrPIAQWHTLKDPEE 465
Cdd:cd04026  90 DRTTRNDFMGSLSFGV----SELIKM---------PVDGWYKLLNQEE 124

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

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 72.58 E-value: 1.97e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPALDMGGTSDPYVKVYLLpdkKKKFETKVH--RKTLSPVFNETFTFK-SLPyadaMNKTLVFAIFDFDRFS 287
Cdd:cd04037   4 VYVVRARNLQPKDPNGKSDPYLKIKLG---KKKINDRDNyiPNTLNPVFGKMFELEaTLP----GNSILKISVMDYDLLG 76

                        90
                ....*....|....*..
gi 24581230 288 KHDQIGEVkvplcTIDL 304
Cdd:cd04037  77 SDDLIGET-----VIDL 88

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: 70.69 E-value: 1.27e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKK--KKFETKVHRKTLSPVFNETFTFKsLPYADA 271
Cdd:cd08410   1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKliKTKKTSCMRGTIDPFYNESFSFK-VPQEEL 79

                        90       100
                ....*....|....*....|....
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEV 295
Cdd:cd08410  80 ENVSLVFTVYGHNVKSSNDFIGRI 103

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: 69.71 E-value: 2.65e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELpALDMGGTSDPYVKV-YLLPDKKKKFETKVHRKTLSPVFNETFTF------------KSLPYADAMNKT 275
Cdd:cd08675   1 LSVRVLECRDL-ALKSNGTCDPFARVtLNYSSKTDTKRTKVKKKTNNPRFDEAFYFeltigfsyekksFKVEEEDLEKSE 79

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 24581230 276 LVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:cd08675  80 LRVELWHASMVSGDDFLGEVRIPLQGLQQAGSHQAW 115

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: 69.35 E-value: 2.94e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKkcTLNPYYNESFSFEVPFEQI 405
Cdd:cd08387   2 RGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKK--TLNPEFDESFVFEVPPQEL 79

                        90       100
                ....*....|....*....|..
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIG 427
Cdd:cd08387  80 PKRTLEVLLYDFDQFSRDECIG 101

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: 68.36 E-value: 4.74e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIKkcTLNPYYNESFSFEVPFEQIQKicLVVTVVDYDRIG 421
Cdd:cd04040   1 LTVDVISAENLPSADRNGKSDPFVKFYL--NGEKVFKTKTIKK--TLNPVWNESFEVPVPSRVRAV--LKVEVYDWDRGG 74

                        90
                ....*....|
gi 24581230 422 TSEPIGRCIL 431
Cdd:cd04040  75 KDDLLGSAYI 84

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

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 67.28 E-value: 8.78e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPAL--------DMggtsDPYVKVYLlpdKKKKFETKVHRKTLSPVFNETFTFKSLPYadAMNKTLVFAIFD 282
Cdd:cd04039   5 MEIKSITDLPPLknmtrtgfDM----DPFVIISF---GRRVFRTSWRRHTLNPVFNERLAFEVYPH--EKNFDIQFKVLD 75

                        90       100       110
                ....*....|....*....|....*....|...
gi 24581230 283 FDRFSKHDQIGEVKVPLCT-IDLAQTIEEWRDL 314
Cdd:cd04039  76 KDKFSFNDYVATGSLSVQElLNAAPQPDPETGL 108

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 72.10 E-value: 3.78e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  205 NSNSLAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTfksLPYADAMNKTLVFAIFDFD 284
Cdd:COG5038 1038 NSGYLTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVYKTKVVKKTLNPVWNEEFT---IEVLNRVKDVLTINVNDWD 1112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 24581230  285 RFSKHDQIGEVKVPLCTIDLAQTiEEWRdlVSVEGEGGQEKlgDICFSLRYV 336
Cdd:COG5038 1113 SGEKNDLLGTAEIDLSKLEPGGT-TNSN--IPLDGKTFIVL--DGTLHPGFN 1159

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: 64.24 E-value: 1.33e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMG------GTSDPYVKVYLLPdkkKKFETKVHRKTLSPVFNEtfTFKSLPYaDAMNKTLVFAIFD 282
Cdd:cd08391   3 LRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGA---QTFKSKVIKENLNPKWNE--VYEAVVD-EVPGQELEIELFD 76

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 24581230 283 FDRfSKHDQIGEVKVPLCTIDLAQTIEEWRDLVSVE 318
Cdd:cd08391  77 EDP-DKDDFLGRLSIDLGSVEKKGFIDEWLPLEDVK 111

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: 63.91 E-value: 2.34e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 325 KLGDICFSLRYVPTAGKLTVVILEAKNLKKMDV-GGLSDPYVKIAIMQNGK-----RLKKKktsikkcTLNPYYNESFSF 398
Cdd:cd08388   1 KLGTLFFSLRYNSEKKALLVNIIECRDLPAMDEqSGTSDPYVKLQLLPEKEhkvktRVLRK-------TRNPVYDETFTF 73

                        90       100       110
                ....*....|....*....|....*....|...
gi 24581230 399 -EVPFEQIQKICLVVTVVDYDRIGTSEPIGRCI 430
Cdd:cd08388  74 yGIPYNQLQDLSLHFAVLSFDRYSRDDVIGEVV 106

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: 63.83 E-value: 2.43e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd04030   2 LGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL 81


                ....*....
gi 24581230 406 QKICLVVTV 414
Cdd:cd04030  82 KRRTLDVAV 90

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 63.47 E-value: 2.50e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDkkkKFETKVHRKTLSPVFNETFTFkslPYADaMNKTLVFAIFDFDRFSK 288
Cdd:cd08377   3 LQVKVIRASGLAAADIGGKSDPFCVLELVNA---RLQTHTIYKTLNPEWNKIFTF---PIKD-IHDVLEVTVYDEDKDKK 75

                        90
                ....*....|....
gi 24581230 289 HDQIGEVKVPLCTI 302
Cdd:cd08377  76 PEFLGKVAIPLLSI 89

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 63.14 E-value: 5.33e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLL-PDKKK---KFETKVHRKTLSPVFNETFTFKSLPyadaMNKTLVFAIFDFD 284
Cdd:cd04033   2 LRVKVLAGIDLAKKDIFGASDPYVKISLYdPDGNGeidSVQTKTIKKTLNPKWNEEFFFRVNP----REHRLLFEVFDEN 77

                        90
                ....*....|....*
gi 24581230 285 RFSKHDQIGEVKVPL 299
Cdd:cd04033  78 RLTRDDFLGQVEVPL 92

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: 62.50 E-value: 5.93e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLlpdKKKKFETKVHRKTLSPVFNETFTFKSLPYADAMnktLVFAIFDFDRFSK 288
Cdd:cd04025   2 LRCHVLEARDLAPKDRNGTSDPFVRVFY---NGQTLETSVVKKSCYPRWNEVFEFELMEGADSP---LSVEVWDWDLVSK 75

                        90       100
                ....*....|....*....|...
gi 24581230 289 HDQIGEVKVPLCTIDLAQTIEEW 311
Cdd:cd04025  76 NDFLGKVVFSIQTLQQAKQEEGW 98

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: 62.73 E-value: 9.56e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGgTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTFkSLPyadAMNKTLVFAIFDFDRFSK 288
Cdd:cd04038   4 LKVRVVRGTNLAVRDFT-SSDPYVVLTLGNQKVK---TRVIKKNLNPVWNEELTL-SVP---NPMAPLKLEVFDKDTFSK 75

                        90
                ....*....|.
gi 24581230 289 HDQIGEVKVPL 299
Cdd:cd04038  76 DDSMGEAEIDL 86

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

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 61.80 E-value: 1.14e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 344 VVILEAKNLKKMDVGGLSDPYVKIaimQNGKRLKKKKTSIKKCTLNPYYNESFSFE--VPFEQIqkicLVVTVVDYDRIG 421
Cdd:cd04037   4 VYVVRARNLQPKDPNGKSDPYLKI---KLGKKKINDRDNYIPNTLNPVFGKMFELEatLPGNSI----LKISVMDYDLLG 76


                ....*..
gi 24581230 422 TSEPIGR 428
Cdd:cd04037  77 SDDLIGE 83

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: 61.49 E-value: 1.59e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSF-EVPFEQI 405
Cdd:cd04031   3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYsNVRRETL 82

                        90       100
                ....*....|....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIGTSEPIGRCIL 431
Cdd:cd04031  83 KERTLEVTVWDYDRDGENDFLGEVVI 108

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: 61.29 E-value: 1.87e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMG--GTSDPYVKVYLlpdKKKKFETKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFDRF 286
Cdd:cd04024   3 LRVHVVEAKDLAAKDRSgkGKSDPYAILSV---GAQRFKTQTIPNTLNPKWNYWCEF---PIFSAQNQLLKLILWDKDRF 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 24581230 287 SKHDQIGEVKVPLCTIDLAQTIEE---WRDLVSVEGEGGQEKLGDI 329
Cdd:cd04024  77 AGKDYLGEFDIALEEVFADGKTGQsdkWITLKSTRPGKTSVVSGEI 122

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: 60.36 E-value: 2.77e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPAldmGGTSDPYVKVYLlpDKKKKFETKVhRKTLSPVFNETFTFKSLPyADAMNKTLVFAIFDFDrfS 287
Cdd:cd08383   1 SLRLRILEAKNLPS---KGTRDPYCTVSL--DQVEVARTKT-VEKLNPFWGEEFVFDDPP-PDVTFFTLSFYNKDKR--S 71

                        90       100       110
                ....*....|....*....|....*....|
gi 24581230 288 KHDQIGEVKVPLCTIDLAQTIEEWRDLVSV 317
Cdd:cd08383  72 KDRDIVIGKVALSKLDLGQGKDEWFPLTPV 101

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: 59.13 E-value: 6.20e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPaldmGGTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTFK-SLPYADAMNKTLVFAIFDFDRFSKH 289
Cdd:cd04011   8 VRVIEARQLV----GGNIDPVVKVEVGGQKKY---TSVKKGTNCPFYNEYFFFNfHESPDELFDKIIKISVYDSRSLRSD 80

                        90
                ....*....|...
gi 24581230 290 DQIGEVKVPLCTI 302
Cdd:cd04011  81 TLIGSFKLDVGTV 93

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: 58.81 E-value: 8.79e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMG-GTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKSLPYADAMNKTLVFAIFDFDRFS 287
Cdd:cd04041   3 LVVTIHRATDLPKADFGtGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEETWFVLVTPDEVKAGERLSCRLWDSDRFT 82

                        90
                ....*....|..
gi 24581230 288 KHDQIGEVKVPL 299
Cdd:cd04041  83 ADDRLGRVEIDL 94

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: 58.26 E-value: 2.34e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFkSLPYADA 271
Cdd:cd08406   2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKisKKKTSVKRDDTNPIFNEAMIF-SVPAIVL 80

                        90       100
                ....*....|....*....|....
gi 24581230 272 MNKTLVFAIFDFDRFSKHDQIGEV 295
Cdd:cd08406  81 QDLSLRVTVAESTEDGKTPNVGHV 104

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 57.29 E-value: 3.62e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIKkcTLNPYYNESFSfeVPFEQIQKIcLVVTVVDYDRI 420
Cdd:cd04042   1 QLDIHLKEGRNLAARDRGGTSDPYVKFKY--GGKTVYKSKTIYK--NLNPVWDEKFT--LPIEDVTQP-LYIKVFDYDRG 73

                        90
                ....*....|.
gi 24581230 421 GTSEPIGRCIL 431
Cdd:cd04042  74 LTDDFMGSAFV 84

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: 56.29 E-value: 1.15e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDV-GGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd08393   2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                        90
                ....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIG 421
Cdd:cd08393  82 PTRVLNLSVWHRDSLG 97

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

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 55.39 E-value: 1.30e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALD-MGGTSDPYVKVYLLpdkKKKFETKVHRKTLSPVFN-ETFTFKsLPYADAMNKTLVFAIFDFDRF 286
Cdd:cd08688   1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFG---STTYKTDVVKKSLNPVWNsEWFRFE-VDDEELQDEPLQIRVMDHDTY 76

                        90       100
                ....*....|....*....|....*...
gi 24581230 287 SKHDQIGEVKV---PLCTIDLAQTIEEW 311
Cdd:cd08688  77 SANDAIGKVYIdlnPLLLKDSVSQISGW 104

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: 55.61 E-value: 1.76e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 194 GRLNFKLEYDFNSNSLAVTVIQAEELPALDMGGTS-DPYVKVYLLPDKKK--KFETKVHRKTLSPVFNETFTFKsLPYAD 270
Cdd:cd08392   2 GEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKSHnsKRKTAVKKGTVNPVFNETLKYV-VEADL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 24581230 271 AMNKTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQT 307
Cdd:cd08392  81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDT 117

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: 55.52 E-value: 1.79e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNLKKMDVG-GLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQI 405
Cdd:cd04029   2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAkKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                        90
                ....*....|....*.
gi 24581230 406 QKICLVVTVVDYDRIG 421
Cdd:cd04029  82 ETRTLQLSVWHYDRFG 97

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: 55.87 E-value: 2.00e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPAldMGGTSDPYVKVYLL-PDKK---KKfeTKVHRKTLSPVFNETFTF------------KSLPYADAM 272
Cdd:cd04010   2 LSVRVIECSDLAL--KNGTCDPYASVTLIySNKKqdtKR--TKVKKKTNNPQFDEAFYFdvtidsspekkqFEMPEEDAE 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24581230 273 NKTLVFA------IFDfDRFskhdqIGEVKVPLCTIDLAQTIEE-W-----RDLVSVEGEGGQEKLGDICfSLR 334
Cdd:cd04010  78 KLELRVDlwhasmGGG-DVF-----LGEVRIPLRGLDLQAGSHQaWyflqpREEKSTPPGTRSSKDNSLG-SLR 144

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: 55.25 E-value: 2.05e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALD-MGGTSDPYVKVYLlpDKKKKFE-TKVHRKTLSPVFNETFTF--KSLpyadamNKTLVFAIFDFD 284
Cdd:cd04044   4 LAVTIKSARGLKGSDiIGGTVDPYVTFSI--SNRRELArTKVKKDTSNPVWNETKYIlvNSL------TEPLNLTVYDFN 75

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 24581230 285 RFSKHDQIGEVKVPLCtiDLAQTiEEWRDLVSVEGEGGQEKlGDICFSLRYVP 337
Cdd:cd04044  76 DKRKDKLIGTAEFDLS--SLLQN-PEQENLTKNLLRNGKPV-GELNYDLRFFP 124

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: 55.86 E-value: 2.61e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 193 LGRLNFKLEYdfNSNSLAVTVIQAEEL-PALDMGGTSDPYVKVYLLPDKK--KKFETKVHRKTLSPVFNETFTFKSLPYa 269
Cdd:cd04028  17 MGDIQLGLYD--KKGQLEVEVIRARGLvQKPGSKVLPAPYVKVYLLEGKKciAKKKTKIARKTLDPLYQQQLVFDVSPT- 93

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 24581230 270 damNKTLVFAIF-DFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd04028  94 ---GKTLQVIVWgDYGRMDKKVFMGVAQILLDDLDLSNLVIGWYKL 136

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 54.18 E-value: 4.19e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIaimqngkRLKKKKTSIKKC--TLNPYYNESFSFEVpFEQIQKIcLVVTVVDYDR 419
Cdd:cd08376   2 VTIVLVEGKNLPPMDDNGLSDPYVKF-------RLGNEKYKSKVCskTLNPQWLEQFDLHL-FDDQSQI-LEIEVWDKDT 72

                        90
                ....*....|
gi 24581230 420 IGTSEPIGRC 429
Cdd:cd08376  73 GKKDEFIGRC 82

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: 53.72 E-value: 5.54e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 214 IQAEELPALDMGGTSDPYVKVY-LLPDKKKK--FETKVHRKTLSPVFNE-TFTFKSLPYADaMNKTLVFAIFDFDRFSKH 289
Cdd:cd04047   7 FSGKKLDKKDFFGKSDPFLEISrQSEDGTWVlvYRTEVIKNTLNPVWKPfTIPLQKLCNGD-YDRPIKIEVYDYDSSGKH 85

                        90       100
                ....*....|....*....|..
gi 24581230 290 DQIGEVKVPLCTIdLAQTIEEW 311
Cdd:cd04047  86 DLIGEFETTLDEL-LKSSPLEF 106

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 53.70 E-value: 9.76e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELP--ALDMGGTSDPYVKVYLL---PDKKKKFETK-VHRKTLSPVFNETFTF-KSLPyaD-AMnktLVFA 279
Cdd:cd00275   3 TLTIKIISGQQLPkpKGDKGSIVDPYVEVEIHglpADDSAKFKTKvVKNNGFNPVWNETFEFdVTVP--ElAF---LRFV 77

                        90       100
                ....*....|....*....|
gi 24581230 280 IFDFDRFsKHDQIGEVKVPL 299
Cdd:cd00275  78 VYDEDSG-DDDFLGQACLPL 96

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: 53.23 E-value: 1.08e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPALDMGGTSDPYVKVYLlpdKKKKFETKVHRKTLSPVFNE--TFTFKSLPYADAMNKTLVFAIFDFDRFSK 288
Cdd:cd08682   3 VTVLQARGLLCKGKSGTNDAYVIIQL---GKEKYSTSVKEKTTSPVWKEecSFELPGLLSGNGNRATLQLTVMHRNLLGL 79

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 24581230 289 HDQIGEVKVPLCTIDLAQTIE--EWRDLVSVEGEGGQEK 325
Cdd:cd08682  80 DKFLGQVSIPLNDLDEDKGRRrtRWFKLESKPGKDDKER 118

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

Pssm-ID: 176062 Cd Length: 124 Bit Score: 52.62 E-value: 1.59e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 199 KLEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLP---DKKKKFETKVHRKTLSPVFNETFTFkSLPYADAMNKT 275
Cdd:cd08680   6 GLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPcssSTSCLFRTKALEDQDKPVFNEVFRV-PISSTKLYQKT 84


                .
gi 24581230 276 L 276
Cdd:cd08680  85 L 85

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 52.26 E-value: 2.20e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPALDMGGTSDPYVKVYLlpdKKKKFETKVHRKTLSPVFNETFTFKslpYADAMNKTLVFAIFDFDRFSKHD 290
Cdd:cd08376   4 IVLVEGKNLPPMDDNGLSDPYVKFRL---GNEKYKSKVCSKTLNPQWLEQFDLH---LFDDQSQILEIEVWDKDTGKKDE 77

                        90       100       110
                ....*....|....*....|....*....|
gi 24581230 291 QIGEVKVPLCTIDLAQTIEEWRDLVSVEGE 320
Cdd:cd08376  78 FIGRCEIDLSALPREQTHSLELELEDGEGS 107

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 52.13 E-value: 2.34e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALDMGGTSDPY--VKVyllpDKKKKFETKVHRKTLSPVFNETFTFKSLPYAdamnKTLVFAIFDFDR 285
Cdd:cd04054   1 SLYIRIVEGKNLPAKDITGSSDPYciVKV----DNEVIIRTATVWKTLNPFWGEEYTVHLPPGF----HTVSFYVLDEDT 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 24581230 286 FSKHDQIGEVKVPLCTIDL-AQTIEEWRDLVSVEGEggQEKLGDICFSLR 334
Cdd:cd04054  73 LSRDDVIGKVSLTREVISAhPRGIDGWMNLTEVDPD--EEVQGEIHLELS 120

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 56.31 E-value: 3.12e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  162 SAYKEKVQPDMEE---LTENAEEGDEEDKQSEQKLGRLNFKLeyDFNSNSLAVTVIQAEEL-PALDMG-GTSDPYVKVYL 236
Cdd:COG5038  869 SALDEKTISLVDKedsVEESIEVEELTDMYSLKPKLDLNEAL--QYKSGVLGIQILSGELPdPGQYLQiFFDDASHPQIV 946

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  237 LPDKKKKFETkvhrktlSPVFNETFTfKSLPYADamnktLVFAIFDFDRFSKhDQIGEVKVPlcTIDLAQTIEEWRDLVS 316
Cdd:COG5038  947 SSKAPTRGER-------NGESGDTFI-RELEYSE-----TTFRVTKNAKKSD-KVVCEVTLP--TLDLVSNAYEKPSSLN 1010

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  317 VEGEGGQEklgdicFSLRYVPT------------AGKLTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIK 384
Cdd:COG5038 1011 FPGSAKVL------VQVSYTPVpvklppvemvenSGYLTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVYKTKVVKK 1082

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*....
gi 24581230  385 kcTLNPYYNESFSFEVPFEqiQKICLVVTVVDYDRIGTSEPIGRCILGC 433
Cdd:COG5038 1083 --TLNPVWNEEFTIEVLNR--VKDVLTINVNDWDSGEKNDLLGTAEIDL 1127

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: 51.69 E-value: 3.64e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 322 GQEKLgDICFslryvpTAGKLTVVILEAKNLKKMDVGGlSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVP 401
Cdd:cd08685   1 GQLKL-SIEG------QNRKLTLHVLEAKGLRSTNSGT-CNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVN 72

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 24581230 402 FEQIQKIcLVVTVvdYDRIGTSEPIGrcILGCMGTG 437
Cdd:cd08685  73 ERDYQKR-LLVTV--WNKLSKSRDSG--LLGCMSFG 103

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 51.18 E-value: 6.91e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVyllpdkkkKFETKVHRKTLS------PVFNETFTFKsLPYADAMNKT-LVFAIF 281
Cdd:cd04049   3 LEVLLISAKGLQDTDFLGKIDPYVII--------QCRTQERKSKVAkgdgrnPEWNEKFKFT-VEYPGWGGDTkLILRIM 73

                        90
                ....*....|....*...
gi 24581230 282 DFDRFSKHDQIGEVKVPL 299
Cdd:cd04049  74 DKDNFSDDDFIGEATIHL 91

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

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 50.72 E-value: 7.96e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSPVFNETFTFKSLPyadAMNKTLVFAIFDFDRFsK 288
Cdd:cd04036   2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQS---QVKNVLELTVMDEDYV-M 77

                        90       100
                ....*....|....*....|..
gi 24581230 289 HDQIGEVKVPLCTIDLAQTIEE 310
Cdd:cd04036  78 DDHLGTVLFDVSKLKLGEKVRV 99

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: 50.72 E-value: 8.66e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 327 GDICFSLRYVPTAGKLTVVILEAKNL-----KKMdvggLSDPYVKIAIM----QNGKRlkkkKTSIKKCTLNPYYNESFS 397
Cdd:cd08521   1 GEIEFSLSYNYKTGSLEVHIKECRNLayadeKKK----RSNPYVKVYLLpdksKQSKR----KTSVKKNTTNPVFNETLK 72

                        90       100
                ....*....|....*....|....
gi 24581230 398 FEVPFEQIQKICLVVTVVDYDRIG 421
Cdd:cd08521  73 YHISKSQLETRTLQLSVWHHDRFG 96

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 50.72 E-value: 9.19e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 211 VTVIQAEELPALDMGGTSDPYVkvyLLPDKKKKFE---TKVHRKTLSPVFNETFTFKSLPYADAMnktLVFAIFDFDRFS 287
Cdd:cd04043   5 IRIVRAENLKADSSNGLSDPYV---TLVDTNGKRRiakTRTIYDTLNPRWDEEFELEVPAGEPLW---ISATVWDRSFVG 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 24581230 288 KHDQIGEVKV---PLCTIDLAQTIEEWRDL---------VSVEGE 320
Cdd:cd04043  79 KHDLCGRASLkldPKRFGDDGLPREIWLDLdtqgrlllrVSMEGE 123

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 50.43 E-value: 1.25e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIAIM--QNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIQkicLVVTVVDYDR 419
Cdd:cd04033   2 LRVKVLAGIDLAKKDIFGASDPYVKISLYdpDGNGEIDSVQTKTIKKTLNPKWNEEFFFRVNPREHR---LLFEVFDENR 78


                ..
gi 24581230 420 IG 421
Cdd:cd04033  79 LT 80

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

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 49.88 E-value: 1.48e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 214 IQAEELPALDMGGTSDPYVKVYLLPDKKKKFE----TKVHRKTLSPVFNETFTFkslPYADAMNKTLVFAIFDFD----R 285
Cdd:cd04048   7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVeigrTEVIKNNLNPDFVTTFTV---DYYFEEVQKLRFEVYDVDskskD 83

                        90
                ....*....|....*..
gi 24581230 286 FSKHDQIGEVKVPLCTI 302
Cdd:cd04048  84 LSDHDFLGEAECTLGEI 100

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

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 50.23 E-value: 1.83e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 215 QAEELPALDMGGTSDPYVKVYLLPDKKkkfETKVHRKTLSPVFNETFTFKSLPY---ADAMNK---TLVFAIFDFDRFSK 288
Cdd:cd04017   9 QARDLLAADKSGLSDPFARVSFLNQSQ---ETEVIKETLSPTWDQTLIFDEVELygsPEEIAQnppLVVVELFDQDSVGK 85


                ....*
gi 24581230 289 HDQIG 293
Cdd:cd04017  86 DEFLG 90

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: 49.20 E-value: 2.82e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 24581230 211 VTVIQAEELPALDMGGTSDPYVKVYllpDKKKKFETKVHRKTLSPVFNETFTF 263
Cdd:cd04046   7 VHVHSAEGLSKQDSGGGADPYVIIK---CEGESVRSPVQKDTLSPEFDTQAIF 56

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: 48.33 E-value: 3.35e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVyLLPDKKKKfeTKVHRKTLSPVFNETFTFKslpYADAMNKTLVFAIFDFDRFSk 288
Cdd:cd04050   2 LFVYLDSAKNLPLAKSTKEPSPYVEL-TVGKTTQK--SKVKERTNNPVWEEGFTFL---VRNPENQELEIEVKDDKTGK- 74

                        90       100
                ....*....|....*....|....*...
gi 24581230 289 hdQIGEVKVPLCTIDLAQ--TIEEWRDL 314
Cdd:cd04050  75 --SLGSLTLPLSELLKEPdlTLDQPFPL 100

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 48.87 E-value: 3.52e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTFKSLPYADAMNKTLVFAIFDFDRFS- 287
Cdd:cd04022   2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKR---TRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYNDRRSGr 78

                        90
                ....*....|....*
gi 24581230 288 KHDQIGEVKVPLCTI 302
Cdd:cd04022  79 RRSFLGRVRISGTSF 93

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

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 48.46 E-value: 4.22e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMD-VGGLSDPYVKIaimqngkRLKKKKTSIKKC--TLNPYYN-ESFSFEVPFEQIQKICLVVTVVDY 417
Cdd:cd08688   1 LKVRVVAARDLPVMDrSSDLTDAFVEV-------KFGSTTYKTDVVkkSLNPVWNsEWFRFEVDDEELQDEPLQIRVMDH 73

                        90
                ....*....|....*.
gi 24581230 418 DRIGTSEPIGRCILGC 433
Cdd:cd08688  74 DTYSANDAIGKVYIDL 89

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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: 176045 [Multi-domain] Cd Length: 126 Bit Score: 48.13 E-value: 7.82e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPaldMGGTSDPYVKVYLlpDKKKKFETKVhRKTLSPVFNETFTFKSLPyADAMNKTLvfAIFDFDRFS 287
Cdd:cd08400   5 SLQLNVLEAHKLP---VKHVPHPYCVISL--NEVKVARTKV-REGPNPVWSEEFVFDDLP-PDVNSFTI--SLSNKAKRS 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 24581230 288 KHDQIGEVKVPLCTIDLAQTIEEWRDLVSVEGEGGQEkLGDICFSLRYV 336
Cdd:cd08400  76 KDSEIAEVTVQLSKLQNGQETDEWYPLSSASPLKGGE-WGSLRIRARYS 123

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: 47.83 E-value: 8.92e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24581230 199 KLEYDFNSNSLAVTVIQAEELPALDmGGTSDPYVKVYLLPDKKKKFE--TKVHRKTLSPVFNETFTF 263
Cdd:cd08685   4 KLSIEGQNRKLTLHVLEAKGLRSTN-SGTCNSYVKISLSPDKEVRFRqkTSTVPDSANPLFHETFSF 69

C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 48.14 E-value: 1.27e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPD--------KKKKFE------------------TKVHRKTLSPVFNETFT 262
Cdd:cd08676  30 LKVTVIEAKGLLAKDVNGFSDPYCMLGIVPAsrernsekSKKRKShrkkavlkdtvpaksikvTEVKPQTLNPVWNETFR 109

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 24581230 263 FKslpYADAMNKTLVFAIFDFDrfskHDQIGEVKVPLCTIDlAQTIEEWRDL 314
Cdd:cd08676 110 FE---VEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLP-SCGLDSWFKL 153

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: 47.29 E-value: 1.43e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 321 GGQEKLgdicfSLRYvpTAGKLTVVILEAKNLKKMDvGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFE- 399
Cdd:cd08381   1 GGQVKL-----SISY--KNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDg 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 24581230 400 VPFEQIQKICLVVTVVDYDRIGTSEPIGR-CI-LGCMGTGTELRHW 443
Cdd:cd08381  73 LPVEDLQQRVLQVSVWSHDSLVENEFLGGvCIpLKKLDLSQETEKW 118

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: 46.79 E-value: 1.46e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 347 LEAKNLKKMDVGGLSDPYVKIAIM-QNGKRLKKKKTSIKKCTLNPYYNEsfsFEVPfeqIQKIC-------LVVTVVDYD 418
Cdd:cd04047   7 FSGKKLDKKDFFGKSDPFLEISRQsEDGTWVLVYRTEVIKNTLNPVWKP---FTIP---LQKLCngdydrpIKIEVYDYD 80

                        90
                ....*....|.
gi 24581230 419 RIGTSEPIGRC 429
Cdd:cd04047  81 SSGKHDLIGEF 91

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

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 46.79 E-value: 1.80e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 345 VILEAKNLKKMDVGGLSDPYVKIAIMQNGKRlkkkktSIKKC--------TLNPYYNESFSFEVPFEQIQKICLVVTVVD 416
Cdd:cd04048   5 LSISCRNLLDKDVLSKSDPFVVVYVKTGGSG------QWVEIgrteviknNLNPDFVTTFTVDYYFEEVQKLRFEVYDVD 78

                        90
                ....*....|....*.
gi 24581230 417 --YDRIGTSEPIGRCI 430
Cdd:cd04048  79 skSKDLSDHDFLGEAE 94

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: 46.71 E-value: 2.02e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKMDVGGLSDPYVKiaIMQNGKRLKKKKTSIkkcTLNPYYNESFSFEVPFEQIQKIClvVTVVDYDRI 420
Cdd:cd04025   1 RLRCHVLEARDLAPKDRNGTSDPFVR--VFYNGQTLETSVVKK---SCYPRWNEVFEFELMEGADSPLS--VEVWDWDLV 73


                ....*...
gi 24581230 421 GTSEPIGR 428
Cdd:cd04025  74 SKNDFLGK 81

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: 46.42 E-value: 2.30e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 344 VVILEAKNLkkmdVGGLSDPYVKIAIMQNGKRlkkkkTSIKKCTLNPYYNESFSFEV--PFEQIQKICLVVTVVDYDRIG 421
Cdd:cd04011   8 VRVIEARQL----VGGNIDPVVKVEVGGQKKY-----TSVKKGTNCPFYNEYFFFNFheSPDELFDKIIKISVYDSRSLR 78


                ....*.
gi 24581230 422 TSEPIG 427
Cdd:cd04011  79 SDTLIG 84

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

Pssm-ID: 176041 [Multi-domain] Cd Length: 120 Bit Score: 46.24 E-value: 3.12e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24581230 211 VTVIQAEELpALDMGGTSDPYVKVYL----LPDKKKKFETKVHRKTLSPVFNETFTF 263
Cdd:cd08395   4 VKVVAANDL-KWQTTGMFRPFVEVNLigphLSDKKRKFATKSKNNNWSPKYNETFQF 59

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 46.14 E-value: 3.27e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 340 GKLTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIkkcTLNPYYNESFSFevPFEQIQKIcLVVTVVDYDR 419
Cdd:cd08377   1 GFLQVKVIRASGLAAADIGGKSDPFCVLEL--VNARLQTHTIYK---TLNPEWNKIFTF--PIKDIHDV-LEVTVYDEDK 72

                        90
                ....*....|.
gi 24581230 420 IGTSEPIGRCI 430
Cdd:cd08377  73 DKKPEFLGKVA 83

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 46.02 E-value: 4.23e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTFK 264
Cdd:cd04027   3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKR---TKTIPQNLNPVWNEKFHFE 55

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: 45.66 E-value: 4.24e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 213 VIQAEELPALDMGGTSDPYVKVylLPDKKKKFETKVHRKTLSPVFNETFtfkslpYA--DAMNKTLVFAIFDF-----DR 285
Cdd:cd04045   7 IRKANDLKNLEGVGKIDPYVRV--LVNGIVKGRTVTISNTLNPVWDEVL------YVpvTSPNQKITLEVMDYekvgkDR 78

                        90
                ....*....|....
gi 24581230 286 FskhdqIGEVKVPL 299
Cdd:cd04045  79 S-----LGSVEINV 87

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176016 [Multi-domain] Cd Length: 125 Bit Score: 44.91 E-value: 1.01e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEEL----PALDMggtsDPYVKVYLLPDKKKKfeTKVHRK--TlSPVFNETFTFkSLP--YADAMNKTLVFA 279
Cdd:cd04051   1 TLEITIISAEDLknvnLFGKM----KVYAVVWIDPSHKQS--TPVDRDggT-NPTWNETLRF-PLDerLLQQGRLALTIE 72

                        90       100
                ....*....|....*....|.
gi 24581230 280 IFDfDRFSKHDQ-IGEVKVPL 299
Cdd:cd04051  73 VYC-ERPSLGDKlIGEVRVPL 92

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: 45.46 E-value: 1.03e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 326 LGDICFSLRYvpTAGKLTVVILEAKNL-KKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFevpFEQ 404
Cdd:cd04028  17 MGDIQLGLYD--KKGQLEVEVIRARGLvQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVF---DVS 91

                        90
                ....*....|....*..
gi 24581230 405 IQKICLVVTVV-DYDRI 420
Cdd:cd04028  92 PTGKTLQVIVWgDYGRM 108

N-terminal domain of synaptotagmin-1 (Syt1) and similar proteins; Syt1, also called synaptotagmin I (SytI), or p65, is a calcium sensor that participates in triggering neurotransmitter release at the synapse. It may have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. Syt1 binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Syt1 also plays a role in dendrite formation by melanocytes. The model corresponds to N-terminal domain of Syt1, which is a recognition domain responsible for the binding of botulinum neurotoxin B (BoNT B).

Pssm-ID: 409248 Cd Length: 108 Bit Score: 44.10 E-value: 1.42e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  62 SQRIAQVESTTRSATTEAQESTTTAVPVIKKIEHVGEVVTEVIAE--RTGLPTWGVVAIIILVFLVVFGIIF-FCVRRFL 138
Cdd:cd21963   1 HHEALAAPPVTTVAAVLPGNATEAAGPGGGKEDAFSKLKDKFMNElhKIPLPPWALIAIAIVAVLLILTCCFcICKKCLF 80

                        90       100
                ....*....|....*....|....*.
gi 24581230 139 KKRRTKDGK---GKKGVDMKSVQLLG 161
Cdd:cd21963  81 KKKNKKKGKekgGKNAINMKDVKDLG 106

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: 44.28 E-value: 1.71e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 200 LEYDFNSNSLAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKK---KFETKVHRKTLSPVFNETFTFKsLPYADAMNKTL 276
Cdd:cd08408   8 LEYNALTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLNSDGQeisKSKTSIRRGQPDPEFKETFVFQ-VALFQLSEVTL 86

                        90
                ....*....|....*..
gi 24581230 277 VFAIFDFDRFSKHDQIG 293
Cdd:cd08408  87 MFSVYNKRKMKRKEMIG 103

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: 44.30 E-value: 2.00e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 340 GKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTsikkcTLNPYYNESFSFEVpfEQIQKICLVVTVVDYDR 419
Cdd:cd08375  15 GRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSD-----TLNPKWNSSMQFFV--KDLEQDVLCITVFDRDF 87

                        90       100
                ....*....|....*....|....*
gi 24581230 420 IGTSEPIGRcilgcmgtgTELRHWS 444
Cdd:cd08375  88 FSPDDFLGR---------TEIRVAD 103

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 47.06 E-value: 2.16e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  209 LAVTVIQAEELPALD--MGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFtfkslpYA--DAMNKTLVFAIFDFD 284
Cdd:COG5038  438 VEVKIKSAEGLKKSDstINGTVDPYITVTF--SDRVIGKTRVKKNTLNPVWNETF------YIllNSFTDPLNLSLYDFN 509

                         90
                 ....*....|....*
gi 24581230  285 RFSKHDQIGEVKVPL 299
Cdd:COG5038  510 SFKSDKVVGSTQLDL 524

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: 43.91 E-value: 2.26e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTFKslpYADAMNKTLVFAIFDFDRFSK 288
Cdd:cd08375  17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHK---TKVVSDTLNPKWNSSMQFF---VKDLEQDVLCITVFDRDFFSP 90

                        90
                ....*....|....
gi 24581230 289 HDQIGEVKVPLCTI 302
Cdd:cd08375  91 DDFLGRTEIRVADI 104

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 43.39 E-value: 4.37e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALD---MGGT-----------SDPYVKVYLLpdkKKKFETKVHRKTLSPVFNETFTFKSL-PyadAM 272
Cdd:cd04018   1 RFIFKIYRAEDLPQMDsgiMANVkkaflgekkelVDPYVEVSFA---GQKVKTSVKKNSYNPEWNEQIVFPEMfP---PL 74

                        90       100
                ....*....|....*....|.
gi 24581230 273 NKTLVFAIFDFDRFSKHDQIG 293
Cdd:cd04018  75 CERIKIQIRDWDRVGNDDVIG 95

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: 42.59 E-value: 4.92e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 195 RLNFKLEYDFNSNSLAVTVIQAEELpalDMGGTSDPYVKVYLL-PDKKKKFETKVHRKTLSPVFNETFTFkSLPYADAMN 273
Cdd:cd08677   2 KLHYSLSYDKQKAELHVNILEAENI---SVDAGCECYISGCVSvSEGQKEAQTALKKLALHTQWEEELVF-PLPEEESLD 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 24581230 274 KTLVFAIFDFDRFSKHDQIGEVKVPLCTIDLAQTIEEWRDL 314
Cdd:cd08677  78 GTLTLTLRCCDRFSRHSTLGELRLKLADVSMMLGAAQWVDL 118

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: 42.03 E-value: 5.10e-05

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24581230 110 LPTWGVVAIIILVFLVVFGIIFFCVRRFL---KKRRTKDGKGKKGVDMKSVQ 158
Cdd:cd21342  41 LPPWALAAIAIVAGLLLLSCCFCICKKCCfkkKKKKEGKKKGKAQINMKSVK 92

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 42.29 E-value: 7.70e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTFKSLPyadamNKTLVFAIFDFDRFS 287
Cdd:cd08382   1 KVRLTVLCADGLAKRDLFRLPDPFAVITV--DGGQTHSTDVAKKTLDPKWNEHFDLTVGP-----SSIITIQVFDQKKFK 73

                        90
                ....*....|...
gi 24581230 288 KHDQ--IGEVKVP 298
Cdd:cd08382  74 KKDQgfLGCVRIR 86

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 42.14 E-value: 8.70e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKM--DVGGLSDPYVKIAI--MQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPFEQIqkICLVVTVVD 416
Cdd:cd00275   3 TLTIKIISGQQLPKPkgDKGSIVDPYVEVEIhgLPADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPEL--AFLRFVVYD 80

                        90       100
                ....*....|....*....|....*...
gi 24581230 417 YDRIGtSEPIG-RCI-LGCMGTGteLRH 442
Cdd:cd00275  81 EDSGD-DDFLGqACLpLDSLRQG--YRH 105

Podoplanin; This family consists of several mammalian podoplanin like proteins which are thought to control specifically the unique shape of podocytes.

Pssm-ID: 461746 Cd Length: 135 Bit Score: 42.11 E-value: 9.32e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24581230    69 ESTTRsATTEAQESTTTAVPVIKKIEHVGEVvTEVIAERTGLPTWGVVAIIILVFL---VVFGIIFFCVRR 136
Cdd:pfam05808  61 ESTVH-AHEESQSTTTPNVATSHSREKVGEE-TQTTVEKDGLATVTLVGIIVGVLLaigFIGGIIIVVVRK 129

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 42.27 E-value: 1.15e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKMDVGGLSDPYVKIAI---MQNGKRlkkkktsIKKCTLNPYYNESFSFEV--PFEQiqkiCLVVTVV 415
Cdd:cd04019   1 YLRVTVIEAQDLVPSDKNRVPEVFVKAQLgnqVLRTRP-------SQTRNGNPSWNEELMFVAaePFED----HLILSVE 69

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24581230 416 DYDRIGTSEPIGRCILGcMGTgTELRHwsdmlaSPRRPIAQWHTLKDPEETDEILK 471
Cdd:cd04019  70 DRVGPNKDEPLGRAVIP-LND-IERRV------DDRPVPSRWFSLERPGGAMEQKK 117

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: 41.51 E-value: 1.25e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 340 GKLTVVILEAKNLKKMD------VGGLSDPYVKIAI-MQNGKrlkkkkTSIKKCTLNPYYNESFSFEVPFEQIQKicLVV 412
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDkfvgglVKGKSDPYVIVRVgAQTFK------SKVIKENLNPKWNEVYEAVVDEVPGQE--LEI 72

                        90
                ....*....|....*..
gi 24581230 413 TVVDYDrIGTSEPIGRC 429
Cdd:cd08391  73 ELFDED-PDKDDFLGRL 88

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: 41.05 E-value: 1.40e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 223 DMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTF----KSlpyadamNKTLVFAIFDfDRFSKHDQIGEVKVP 298
Cdd:cd04052   8 SKTGLLSPYAELYL--NGKLVYTTRVKKKTNNPSWNASTEFlvtdRR-------KSRVTVVVKD-DRDRHDPVLGSVSIS 77

                        90
                ....*....|....
gi 24581230 299 LCT-IDLAQTIEEW 311
Cdd:cd04052  78 LNDlIDATSVGQQW 91

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 41.89 E-value: 1.50e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPdkkKKFETKV-HRKTLSPVFNETFTF-KSLPYADamnkTLVFAIFDFDRF 286
Cdd:cd04019   2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGN---QVLRTRPsQTRNGNPSWNEELMFvAAEPFED----HLILSVEDRVGP 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 24581230 287 SKHDQIGEVKVPLCTI---DLAQTIE-EWRDLVSVEGEGGQEK 325
Cdd:cd04019  75 NKDEPLGRAVIPLNDIerrVDDRPVPsRWFSLERPGGAMEQKK 117

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 41.48 E-value: 1.53e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 343 TVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKkcTLNPYYNESFSFEVPFEQIQKIclVVTVVDYDRIGT 422
Cdd:cd04043   4 TIRIVRAENLKADSSNGLSDPYVTLVDTNGKRRIAKTRTIYD--TLNPRWDEEFELEVPAGEPLWI--SATVWDRSFVGK 79


                ....*....
gi 24581230 423 SEPIGRCIL 431
Cdd:cd04043  80 HDLCGRASL 88

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

Pssm-ID: 176004 [Multi-domain] Cd Length: 108 Bit Score: 40.70 E-value: 1.98e-04

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24581230 387 TLNPYYNESFSFEV-PFEqiQKICLVVTVVDYDRIGTSEPIGRCILgcmgtgtelrHWSDMLASPRRPIAQW 457
Cdd:cd04039  47 TLNPVFNERLAFEVyPHE--KNFDIQFKVLDKDKFSFNDYVATGSL----------SVQELLNAAPQPDPET 106

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

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 40.99 E-value: 2.23e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 346 ILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTsikkcTLNPYYNESFSFEV-----PFEQIQKIC--LVVTVVDYD 418
Cdd:cd04017   7 IYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKE-----TLSPTWDQTLIFDEvelygSPEEIAQNPplVVVELFDQD 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24581230 419 RIGTSEPIGRCIlgcmgtgtelrhWSDMLA----SPRRPIAQWHTL-KDPEETDEIL 470
Cdd:cd04017  82 SVGKDEFLGRSV------------AKPLVKldleEDFPPKLQWFPIyKGGQSAGELL 126

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 40.70 E-value: 2.64e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 212 TVIQAEELPALdmGGTSDPYVKVYLLPDKKKkfeTKVHRKTLSPVFNETFTF--KSLPYADAMnktLVFAIFDFDRFSKH 289
Cdd:cd08373   1 LVVSLKNLPGL--KGKGDRIAKVTFRGVKKK---TRVLENELNPVWNETFEWplAGSPDPDES---LEIVVKDYEKVGRN 72

                        90
                ....*....|
gi 24581230 290 DQIGEVKVPL 299
Cdd:cd08373  73 RLIGSATVSL 82

C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 41.20 E-value: 3.08e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 337 PTAGKLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSIKKC------------------------TLNPYY 392
Cdd:cd08676  25 PPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRERNSEKSKKRKShrkkavlkdtvpaksikvtevkpqTLNPVW 104

                        90       100
                ....*....|....*....|....*.
gi 24581230 393 NESFSFEVpfEQIQKICLVVTVVDYD 418
Cdd:cd08676 105 NETFRFEV--EDVSNDQLHLDIWDHD 128

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 39.86 E-value: 4.94e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24581230 341 KLTVVILEAKNLKKMDVGGLSDPYVKIAIMQNGKRLKKKKTSikkctLNPYYNESFSFE 399
Cdd:cd04027   2 KISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQN-----LNPVWNEKFHFE 55

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 39.73 E-value: 5.10e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALD-MGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFTFKsLPYADAMnktLVFAIFDFDRF 286
Cdd:cd08401   1 SLKIKIGEAKNLPPRSgPNKMRDCYCTVNL--DQEEVFRTKTVEKSLCPFFGEDFYFE-IPRTFRH---LSFYIYDRDVL 74

                        90
                ....*....|.
gi 24581230 287 SKHDQIGEVKV 297
Cdd:cd08401  75 RRDSVIGKVAI 85

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

Pssm-ID: 176063 [Multi-domain] Cd Length: 118 Bit Score: 39.54 E-value: 5.33e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELPALDMGGTSDPYVKVYLLPDKKKkfeTKV-HRKTLSPVFNETFTFKSLPyadAMNKTLVFAIFDfDRFS 287
Cdd:cd08681   3 LVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKK---TKTdFRGGQHPEWDEELRFEITE---DKKPILKVAVFD-DDKR 75

                        90       100       110
                ....*....|....*....|....*....|..
gi 24581230 288 KHDQIGEvkvplCTIDLAQTIEE-----WRDL 314
Cdd:cd08681  76 KPDLIGD-----TEVDLSPALKEgefddWYEL 102

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: 39.69 E-value: 9.58e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKmdVGGLSDPYVKIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEV-------------PFEQIQK 407
Cdd:cd04010   1 KLSVRVIECSDLAL--KNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfemPEEDAEK 78


                ....*..
gi 24581230 408 ICLVVTV 414
Cdd:cd04010  79 LELRVDL 85

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

Pssm-ID: 176060 [Multi-domain] Cd Length: 126 Bit Score: 39.27 E-value: 9.75e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 209 LAVTVIQAEELpaLDMGGTSDPYVkVYLLPDKKKKFETKVHRKTLSPVFNETFTFKslpyADAMNKTLVFAIFDFDRFSK 288
Cdd:cd08678   1 LLVKNIKANGL--SEAAGSSNPYC-VLEMDEPPQKYQSSTQKNTSNPFWDEHFLFE----LSPNSKELLFEVYDNGKKSD 73

                        90
                ....*....|.
gi 24581230 289 HDQIGEVKVPL 299
Cdd:cd08678  74 SKFLGLAIVPF 84

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

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 38.78 E-value: 1.07e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIAI------------MQNGKrlkkkktsikkctlNPYYNESFSFEVPFEqiQKIC 409
Cdd:cd04036   2 LTVRVLRATNITKGDLLSTPDCYVELWLptasdekkrtktIKNSI--------------NPVWNETFEFRIQSQ--VKNV 65

                        90
                ....*....|..
gi 24581230 410 LVVTVVDYDRIG 421
Cdd:cd04036  66 LELTVMDEDYVM 77

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: 38.72 E-value: 1.08e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 340 GKLTVVILEAKNLKKMDVGGLSDPYVKiaIMQNGKRLKKKKTSIKkcTLNPYYNESFSFEVpFEQIQKIclVVTVVDYDR 419
Cdd:cd04045   1 GVLRLHIRKANDLKNLEGVGKIDPYVR--VLVNGIVKGRTVTISN--TLNPVWDEVLYVPV-TSPNQKI--TLEVMDYEK 73

                        90
                ....*....|
gi 24581230 420 IGTSEPIGRC 429
Cdd:cd04045  74 VGKDRSLGSV 83

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 41.28 E-value: 1.54e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  209 LAVTVIQAEELPALDMGGTSDPYVKVYLlpDKKKKFETKVHRKTLSPVFNETFtfkslpYADAMNKTLVFAI--FDFDRF 286
Cdd:COG5038  713 IRVSVRKANDLRNEIPGGKSDPYATVLV--NNLVKYRTIYGSSTLNPIWNEIL------YVPVTSKNQRLTLecMDYEES 784

                         90
                 ....*....|..
gi 24581230  287 SKHDQIGEVKVP 298
Cdd:COG5038  785 GDDRNLGEVNIN 796

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: 38.01 E-value: 2.16e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKkmdVGGLSDPYVKIAIMQngkrlKKKKTSIKKCTLNPYYNESFSFEVPFEQIQKICLVVTVVDYDRIG 421
Cdd:cd08383   2 LRLRILEAKNLP---SKGTRDPYCTVSLDQ-----VEVARTKTVEKLNPFWGEEFVFDDPPPDVTFFTLSFYNKDKRSKD 73

                        90       100
                ....*....|....*....|..
gi 24581230 422 TSEPIGRCILGCMGTGTELRHW 443
Cdd:cd08383  74 RDIVIGKVALSKLDLGQGKDEW 95

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: 37.79 E-value: 3.26e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 340 GKLTVVILEAKNLKKMDVGGL--SDPYVkiaIMQNGKrlKKKKTSIKKCTLNPYYNESFSFEVPFEQIQKICLVVTvvDY 417
Cdd:cd04024   1 GVLRVHVVEAKDLAAKDRSGKgkSDPYA---ILSVGA--QRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILW--DK 73

                        90
                ....*....|.
gi 24581230 418 DRIGTSEPIGR 428
Cdd:cd04024  74 DRFAGKDYLGE 84

FeoB-associated Cys-rich membrane protein; Members of this family typically are small proteins encoded next to FeoB, part of a ferrous iron uptake system. They consist of a highly hydrophobic predicted membrane segment, followed by a short, Cys-rich region, for an average length of less than sixty amino acids. In some cases, member proteins are fusion proteins, with the region described by this family occurring as a C-terminal extension to FeoB.

Pssm-ID: 463663 Cd Length: 45 Bit Score: 35.34 E-value: 3.26e-03

                          10        20
                  ....*....|....*....|....*....
gi 24581230   120 ILVFLVVFGIIFFCVRRFLKKRrtKDGKG 148
Cdd:pfam12669   3 IIVGAILLAIVALIIRRMVKDK--KKGKS 29

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 39.36 E-value: 5.40e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  194 GRLNFKLEY------------------DFNSNSLAVTVIqaeELPALDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLSP 255
Cdd:COG5038  548 GRLTYDLRFfpviedkkelkgsvepleDSNTGILKVTLR---EVKALDELSSKKDNKSAELYTNAKEVYSTGKLKFTNHP 624

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  256 VFNETFTfksLPYADAMNKTLVFAIFDFDrfsKHDQIGEVKVPL-----CTIDLAQTIE------------EWRdlvSVE 318
Cdd:COG5038  625 SWNLQYN---VLVTDRKNSSIKVVTFDVQ---SGKVIATEGSTLpdlidRTLDTFLVFPlrnpkgrifitnYWK---PIY 695

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230  319 GEGGQEKLGDICfslryvPTAGKLTVVILEAKNLKKMDVGGLSDPYVKiaIMQNGKRLKKKKTSIKkcTLNPYYNESFSF 398
Cdd:COG5038  696 NAGGSSSKTVYD------TPIGAIRVSVRKANDLRNEIPGGKSDPYAT--VLVNNLVKYRTIYGSS--TLNPIWNEILYV 765

                        250       260
                 ....*....|....*....|....*....
gi 24581230  399 EVpFEQIQKICLvvTVVDYDRIGTSEPIG 427
Cdd:COG5038  766 PV-TSKNQRLTL--ECMDYEESGDDRNLG 791

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 36.73 E-value: 5.47e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMDVGGLSDPYVKIAIMQNgkrlKKKKTSIKKCTLNPYYNESFSFEVP--FEQiqkicLVVTVVDYDR 419
Cdd:cd04054   2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNE----VIIRTATVWKTLNPFWGEEYTVHLPpgFHT-----VSFYVLDEDT 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 24581230 420 IGTSEPIGRCILGcmgtgtelrhwSDMLASPRRPIAQWHTLK--DPEE 465
Cdd:cd04054  73 LSRDDVIGKVSLT-----------REVISAHPRGIDGWMNLTevDPDE 109

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 36.90 E-value: 5.56e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 341 KLTVVILEAKNLKKMDVGGLSDPYVKIAImqNGKRLKKKKTSIKkcTLNPYYNESFSFEVpfeqIQKICLVVTVVDYDRI 420
Cdd:cd08382   1 KVRLTVLCADGLAKRDLFRLPDPFAVITV--DGGQTHSTDVAKK--TLDPKWNEHFDLTV----GPSSIITIQVFDQKKF 72

Heme/copper-type cytochrome/quinol oxidase, subunit 2 [Energy production and conversion];

Pssm-ID: 441229 [Multi-domain] Cd Length: 229 Bit Score: 38.27 E-value: 6.63e-03

                        10        20        30
                ....*....|....*....|....*....|....*
gi 24581230 113 WGVVAIIILVFLVVFGIIFFCVRRFLKKRRTKDGK 147
Cdd:COG1622  37 WVSLIIMLVIFVLVFGLLLYFAIRYRRRKGDADPA 71

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: 36.97 E-value: 7.53e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 342 LTVVILEAKNLKKMdVGGLSDPYVkIAIMQNGKRLKKKKTSIKKCTLNPYYNESFSFEVPF-------------EQIQKI 408
Cdd:cd08675   1 LSVRVLECRDLALK-SNGTCDPFA-RVTLNYSSKTDTKRTKVKKKTNNPRFDEAFYFELTIgfsyekksfkveeEDLEKS 78

                        90
                ....*....|...
gi 24581230 409 CLVVTVVDYDRIG 421
Cdd:cd08675  79 ELRVELWHASMVS 91

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

Pssm-ID: 176073 [Multi-domain] Cd Length: 137 Bit Score: 36.61 E-value: 7.58e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPAlDMGGTSDPYVKVYLLPDKKKKFETKVHRK----------TLSPVF-NETFTFKSLPyadamnkTL 276
Cdd:cd08691   2 SFSLSGLQARNLKK-GMFFNPDPYVKISIQPGKRHIFPALPHHGqecrtsivenTINPVWhREQFVFVGLP-------TD 73

                        90       100       110
                ....*....|....*....|....*....|.
gi 24581230 277 VFAIFDFDRFSKHDQI-----GEVKVPLCTI 302
Cdd:cd08691  74 VLEIEVKDKFAKSRPIirrflGKLSIPVQRL 104

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

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 36.10 E-value: 9.22e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24581230 208 SLAVTVIQAEELPALDMGGTsDPYVKVylLPDKKKKFETKVHRKTLSPVFNETFTFKSLPYAdamnkTLVFAIFDFDRFS 287
Cdd:cd04021   3 QLQITVESAKLKSNSKSFKP-DPYVEV--TVDGQPPKKTEVSKKTSNPKWNEHFTVLVTPQS-----TLEFKVWSHHTLK 74

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24581230 288 KHDQIGEVKvplctIDLAQTIEEWR----------DLvSVEGEGGQEKLGD--ICFS 332
Cdd:cd04021  75 ADVLLGEAS-----LDLSDILKNHNgklenvkltlNL-SSENKGSSVKVGEltVILD 125