NCBI Conserved Domain Search

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: 289.79 E-value: 9.31e-97

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08403   81 NVSLIIAVVDYDRVGHNELIGVCRVGPNADGQGREHWNEMLANPRKPIAQWHQL 134

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: 230.16 E-value: 1.17e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd00276   81 EVSLVITVVDKDSVGRNEVIGQVVLGPDSGGEELEHWNEMLASPRKPIARWHKL 134

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: 213.67 E-value: 2.26e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 257 CGRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPT 336
Cdd:cd08385    2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVPYSELGN 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 326676116 337 RKLHFSVYDFDRFSRHDIIGQVVVDnfLDLVDFPRETKLCRDIQY 381
Cdd:cd08385   82 KTLVFSVYDFDRFSKHDLIGEVRVP--LLTVDLGHVTEEWRDLES 124

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: 205.33 E-value: 5.13e-64

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08402    1 LGDICFSLRYVPTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08402   81 QKVHLIVTVLDYDRIGKNDPIGKVVLGCNATGAELRHWSDMLASPRRPIAQWHTL 135

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: 200.34 E-value: 4.03e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08405    1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08405   81 RETTLIITVMDKDRLSRNDLIGKIYLGWKSGGLELKHWKDMLSKPRQPVAQWHRL 135

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: 164.14 E-value: 2.59e-48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08404   82 DISVEFLVLDSDRVTKNEVIGRLVLGPKASGSGGHHWKEVCNPPRRQIAEWHML 135

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: 148.79 E-value: 1.16e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08406   82 DLSLRVTVAESTEDGKTPNVGHVIIGPAASGMGLSHWNQMLASLRKPVAMWHPL 135

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

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 147.48 E-value: 3.23e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFP-VAYADLPT 336
Cdd:cd08386    3 GRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEgFPYEKLQQ 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 326676116 337 RKLHFSVYDFDRFSRHDIIGQVVVDnfLDLVDFPRETKLCRDIQ 380
Cdd:cd08386   83 RVLYLQVLDYDRFSRNDPIGEVSLP--LNKVDLTEEQTFWKDLK 124

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: 141.77 E-value: 3.43e-40

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTR 337
Cdd:cd08387    3 GELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVPPQELPKR 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 326676116 338 KLHFSVYDFDRFSRHDIIGQVVVDnfLDLVDFPRETKLCRDIQ 380
Cdd:cd08387   83 TLEVLLYDFDQFSRDECIGVVELP--LAEVDLSEKLDLWRKIQ 123

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: 3.18e-39

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDF-SGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPT 336
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKdVAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVSFKELQR 80

                         90       100
                 ....*....|....*....|....
gi 326676116 337 RKLHFSVYDFDRFSRHDIIGQVVV 360
Cdd:cd08390   81 RTLRLSVYDVDRFSRHCIIGHVLF 104

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

Pssm-ID: 176054 [Multi-domain] Cd Length: 137 Bit Score: 130.92 E-value: 4.72e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGAsDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08409    1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHT-SVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQL 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIGVCRVGN--DAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08409   80 DTASLSLSVMQSGGVRKSKLLGRVVLGPfmYARGKELEHWNDMLSKPKELIKRWHAL 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: 126.54 E-value: 2.14e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGR-EHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08410   81 NVSLVFTVYGHNVKSSNDFIGRIVIGQYSSGPSEtNHWRRMLNSQRTAVEQWHSL 135

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 123.97 E-value: 7.67e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLLpDRKTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSR 351
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLL-DGKQKKKTKVVKNTLNPVWNETFTFSV--PDPENAVLEIEVYDYDRFGR 78

                          90
                  ....*....|
gi 326676116  352 HDIIGQVVVD 361
Cdd:pfam00168  79 DDFIGEVRIP 88

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: 124.77 E-value: 8.31e-34

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 392 LMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQI 471
Cdd:cd08384    2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKK 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 326676116 472 SLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08384   82 TLEITVWDKDIGKSNDYIGGLQLGINAKGERLRHWLDCLKNPDKKIEAWHTL 133

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: 122.84 E-value: 3.41e-33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDF-SGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVF-LFPVAYADLP 335
Cdd:cd08388    3 GTLFFSLRYNSEKKALLVNIIECRDLPAMDEqSGTSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFtFYGIPYNQLQ 82

                         90       100
                 ....*....|....*....|....
gi 326676116 336 TRKLHFSVYDFDRFSRHDIIGQVV 359
Cdd:cd08388   83 DLSLHFAVLSFDRYSRDDVIGEVV 106

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: 119.70 E-value: 6.27e-32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNL---KAMDITGaSDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPE 466
Cdd:cd08407    2 GEVLLSISYLPAANRLLVVVIKAKNLhsdQLKLLLG-IDVSVKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFELPSE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 326676116 467 NIDQISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08407   81 LLAASSVELEVLNQDSPGQSLPLGRCSLGLHTSGTERQHWEEMLDNPRRQIAMWHQL 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: 116.05 E-value: 4.75e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116   272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSR 351
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEV--PPPELAELEIEVYDKDRFGR 78

                           90
                   ....*....|
gi 326676116   352 HDIIGQVVVD 361
Cdd:smart00239  79 DDFIGQVTIP 88

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: 113.90 E-value: 5.86e-30

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDgrrlKKRKTSTK--RNTLNPVYNEAIVFDVPPE 466
Cdd:cd08385    2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPD----KKKKFETKvhRKTLNPVFNETFTFKVPYS 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 326676116 467 NIDQISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGR--EHWNEML 510
Cdd:cd08385   78 ELGNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHvtEEWRDLE 123

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 112.80 E-value: 8.68e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  403 GRLTITMIKARNLKAMDITGASDPYVKVSLMCDGrrlKKRKTSTKRNTLNPVYNEAIVFDVPPENidQISLLVAVMDYDR 482
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGK---QKKKTKVVKNTLNPVWNETFTFSVPDPE--NAVLEIEVYDYDR 75

                          90       100
                  ....*....|....*....|....*....
gi 326676116  483 VGHNEVIGVCR--VGNDAEGLGREHWNEM 509
Cdd:pfam00168  76 FGRDDFIGEVRipLSELDSGEGLDGWYPL 104

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: 113.14 E-value: 1.05e-29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRK--TKHQTKVHRKTLNPVFDEVFLFPVAYADLP 335
Cdd:cd04030    3 GRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSksTRRKTSVKKDNLNPVFDETFEFPVSLEELK 82

                         90       100
                 ....*....|....*....|....*...
gi 326676116 336 TRKLHFSV-YDFDRFSRH-DIIGQVVVD 361
Cdd:cd04030   83 RRTLDVAVkNSKSFLSREkKLLGQVLID 110

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: 110.62 E-value: 4.03e-29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLLPdrKTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSRH 352
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGG--KQKFKTKVVKNTLNPVWNETFEFPV--LDPESDTLTVEVWDKDRFSKD 76


                 ....*....
gi 326676116 353 DIIGQVVVD 361
Cdd:cd00030   77 DFLGEVEIP 85

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: 108.29 E-value: 6.21e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDL-PAKDFSGTSDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLaAADPKKQRSDPYVKTYLLPDksNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100
                 ....*....|....*....|....*..
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVVD 361
Cdd:cd08393   82 PTRVLNLSVWHRDSLGRNSFLGEVEVD 108

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: 107.45 E-value: 1.53e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 391 DLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLM-CDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENID 469
Cdd:cd08408    3 ELLLGLEYNALTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQVALFQLS 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGLGRE-HWNEMLTYPRKPIAHWHPLV 524
Cdd:cd08408   83 EVTLMFSVYNKRKMKRKEMIGWFSLGLNSSGEEEEeHWNEMKESKGQQVCRWHTLL 138

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: 103.87 E-value: 2.03e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDR--KTKHQTKVHRKTLNPVFDEVFLFPVAYA-DL 334
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRseKSKRRTKTVKKTLNPEWNQTFEYSNVRReTL 82

                         90       100
                 ....*....|....*....|....*..
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVVD 361
Cdd:cd04031   83 KERTLEVTVWDYDRDGENDFLGEVVID 109

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: 101.41 E-value: 9.27e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116   404 RLTITMIKARNLKAMDITGASDPYVKVSLmcDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDqiSLLVAVMDYDRV 483
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELA--ELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 326676116   484 GHNEVIGVCRVGNDAEGLGREHWNE 508
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

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

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 100.79 E-value: 2.50e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDL-PAKDFSGTSDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLaYADEKKKRSNPYVKVYLLPDksKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100
                 ....*....|....*....|....*.
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVV 360
Cdd:cd08521   81 ETRTLQLSVWHHDRFGRNTFLGEVEI 106

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: 100.50 E-value: 4.35e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 264 LKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTRKLHF 341
Cdd:cd08384    6 LMYNTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDagKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKKTLEI 85

                         90
                 ....*....|....*..
gi 326676116 342 SVYDFDRFSRHDIIGQV 358
Cdd:cd08384   86 TVWDKDIGKSNDYIGGL 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: 99.66 E-value: 6.31e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVF-DVPPEN 467
Cdd:cd04035    1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYyGITEED 80

                         90       100
                 ....*....|....*....|....*..
gi 326676116 468 IDQISLLVAVMDYDRVgHNEVIGVCRV 494
Cdd:cd04035   81 IQRKTLRLLVLDEDRF-GNDFLGETRI 106

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: 6.41e-25

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHfiLKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRK--TKHQTKVHRKTLNPVFDEVFLFPVAYADLP 335
Cdd:cd04026    2 GRIY--LKISVKDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKneTKQKTKTIKKTLNPVWNETFTFDLKPADKD 79

                         90       100
                 ....*....|....*....|.
gi 326676116 336 TRkLHFSVYDFDRFSRHDIIG 356
Cdd:cd04026   80 RR-LSIEVWDWDRTTRNDFMG 99

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: 97.69 E-value: 4.08e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRK----TKHQTKVHRKTLNPVFDEVFLFPVAYAD 333
Cdd:cd04009    3 GVLTVKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpdvPTPKTQVKKKTLFPLFDESFEFNVPPEQ 82

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 326676116 334 LPTRK--LHFSVYDFDRFSRHDIIGQVvvdnFLDLVDFP 370
Cdd:cd04009   83 CSVEGalLLFTVKDYDLLGSNDFEGEA----FLPLNDIP 117

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: 95.98 E-value: 8.71e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLMcdgrRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQISllVAVMDYDRVG 484
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLG----GKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLT--VEVWDKDRFS 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 326676116 485 HNEVIGVCRVgndaeGLgrehwnEMLTYPRKPIAHWHPL 523
Cdd:cd00030   75 KDDFLGEVEI-----PL------SELLDSGKEGELWLPL 102

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: 94.64 E-value: 4.27e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 401 TAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQiSLLVAVMDY 480
Cdd:cd04026   11 KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDR-RLSIEVWDW 89

                         90
                 ....*....|
gi 326676116 481 DRVGHNEVIG 490
Cdd:cd04026   90 DRTTRNDFMG 99

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: 93.50 E-value: 1.08e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLP--DRKTKHQTKVHRKTLNPVFDEVFLF-PVAYADL 334
Cdd:cd04035    2 GTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPgaSKATKLRTKTVHKTRNPEFNETLTYyGITEEDI 81

                         90       100
                 ....*....|....*....|....
gi 326676116 335 PTRKLHFSVYDFDRFsRHDIIGQV 358
Cdd:cd04035   82 QRKTLRLLVLDEDRF-GNDFLGET 104

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: 93.64 E-value: 1.14e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 257 CGRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLL-PDRKT-KHQTKVHRKTLNPVFDEVFLFpvayaDL 334
Cdd:cd08405    1 RGELLLSLCYNPTANRITVNIIKARNLKAMDINGTSDPYVKVWLMyKDKRVeKKKTVIKKRTLNPVFNESFIF-----NI 75

                         90       100
                 ....*....|....*....|....*....
gi 326676116 335 PTRKLH-----FSVYDFDRFSRHDIIGQV 358
Cdd:cd08405   76 PLERLRettliITVMDKDRLSRNDLIGKI 104

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: 89.99 E-value: 2.01e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 388 DLGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGR--RLKKRKTSTKRNTLNPVYNEAIVFDVPP 465
Cdd:cd04009    1 PYGVLTVKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLFPLFDESFEFNVPP 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 326676116 466 E--NIDQISLLVAVMDYDRVGHNEVIGVCRVGNDA 498
Cdd:cd04009   81 EqcSVEGALLLFTVKDYDLLGSNDFEGEAFLPLND 115

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: 90.85 E-value: 2.50e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 249 SRSSRVGSCGRLHFILKydcdleqlivkihRAQDLPAKDFSGTSDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFL 326
Cdd:cd04020   18 ALKSKKPSTGELHVWVK-------------EAKNLPALKSGGTSDSFVKCYLLPDksKKSKQKTPVVKKSVNPVWNHTFV 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 326676116 327 FP-VAYADLPTRKLHFSVYDFDRFSRHDIIGQV 358
Cdd:cd04020   85 YDgVSPEDLSQACLELTVWDHDKLSSNDFLGGV 117

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: 89.31 E-value: 3.27e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 388 DLGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDgrrlKKRK--TSTKRNTLNPVYNEAIVFD-VP 464
Cdd:cd08386    1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPD----KKHKleTKVKRKNLNPHWNETFLFEgFP 76

                         90       100
                 ....*....|....*....|....*.
gi 326676116 465 PENIDQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd08386   77 YEKLQQRVLYLQVLDYDRFSRNDPIG 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: 88.47 E-value: 5.21e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGA-SDPYVKVSLMCDGRRlkKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAhCDPFVKVCLLPDERR--SLQSKVKRKTQNPNFDETFVFQVSFKEL 78

                         90       100
                 ....*....|....*....|..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd08390   79 QRRTLRLSVYDVDRFSRHCIIG 100

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: 88.61 E-value: 5.87e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 388 DLGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDgrRLKKRKTSTKRNTLNPVYNEAIVFDVPPEN 467
Cdd:cd08387    1 TRGELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPD--RSNTKQSKIHKKTLNPEFDESFVFEVPPQE 78

                         90       100
                 ....*....|....*....|....
gi 326676116 468 IDQISLLVAVMDYDRVGHNEVIGV 491
Cdd:cd08387   79 LPKRTLEVLLYDFDQFSRDECIGV 102

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

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 85.57 E-value: 6.17e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGT-SDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDEAKKrSNPYVKTYLLPDksRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100
                 ....*....|....*....|....
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQV 358
Cdd:cd04029   82 ETRTLQLSVWHYDRFGRNTFLGEV 105

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 85.17 E-value: 1.31e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRK--TKHQTKVHRKTLNPVFDEVFLFPVAYADLP 335
Cdd:cd08404    2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKriSKKKTHVKKCTLNPVFNESFVFDIPSEELE 81

                         90       100
                 ....*....|....*....|....
gi 326676116 336 TRKLHFSVYDFDRFSRHDIIGQVV 359
Cdd:cd08404   82 DISVEFLVLDSDRVTKNEVIGRLV 105

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: 83.07 E-value: 4.47e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDIT-GASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100
                 ....*....|....*....|..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd08521   81 ETRTLQLSVWHHDRFGRNTFLG 102

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: 81.94 E-value: 1.09e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVayaDLPTRKLHFSVYDFDRFSR 351
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVKFKY--GGKTVYKSKTIYKNLNPVWDEKFTLPI---EDVTQPLYIKVFDYDRGLT 75

                         90       100
                 ....*....|....*....|....
gi 326676116 352 HDIIGQVVVDNFLDLVDFPRETKL 375
Cdd:cd04042   76 DDFMGSAFVDLSTLELNKPTEVKL 99

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: 81.33 E-value: 2.04e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMD-ITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGDeAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100
                 ....*....|....*....|..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd04029   82 ETRTLQLSVWHYDRFGRNTFLG 103

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: 79.92 E-value: 4.38e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLmcDGRRLkkRKTSTKRNTLNPVYNEAIVFDVPPEnIDQIsLLVAVMDYDRVG 484
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYL--NGEKV--FKTKTIKKTLNPVWNESFEVPVPSR-VRAV-LKVEVYDWDRGG 74

                         90
                 ....*....|
gi 326676116 485 HNEVIGVCRV 494
Cdd:cd04040   75 KDDLLGSAYI 84

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: 80.39 E-value: 5.07e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd04030    2 LGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL 81


                 ....*....
gi 326676116 469 DQISLLVAV 477
Cdd:cd04030   82 KRRTLDVAV 90

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: 79.70 E-value: 7.20e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 388 DLGDLMFSLCYLPTAGRLTITMIKARNLKAMDI-TGASDPYVKVSLMCDgrRLKKRKTSTKRNTLNPVYNEAIVF-DVPP 465
Cdd:cd08388    1 KLGTLFFSLRYNSEKKALLVNIIECRDLPAMDEqSGTSDPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFyGIPY 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 326676116 466 ENIDQISLLVAVMDYDRVGHNEVIG--VCRVgNDAEGLGREH---WNEM 509
Cdd:cd08388   79 NQLQDLSLHFAVLSFDRYSRDDVIGevVCPL-AGADLLNEGEllvSREI 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: 79.78 E-value: 7.41e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDI-TGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100
                 ....*....|....*....|..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd08393   82 PTRVLNLSVWHRDSLGRNSFLG 103

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: 79.67 E-value: 2.16e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTA------------GRLTItMIK-ARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYN 456
Cdd:cd04020    2 GELKVALKYVPPEsegalkskkpstGELHV-WVKeAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 326676116 457 EAIVFD-VPPENIDQISLLVAVMDYDRVGHNEVIGVCRVG-------------NDAEGLGREHWNEMLTYP 513
Cdd:cd04020   81 HTFVYDgVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGlgtgksygqavdwMDSTGEEILLWQKMLDNP 151

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: 77.99 E-value: 2.27e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVayadlPTR---KLHFSVYDFDRF 349
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYL--NGEKVFKTKTIKKTLNPVWNESFEVPV-----PSRvraVLKVEVYDWDRG 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 326676116 350 SRHDIIGQVVVDnfLDLVDFPRETKlcRDIQYVSSDNVDLGDLMFS 395
Cdd:cd04040   74 GKDDLLGSAYID--LSDLEPEETTE--LTLPLDGQGGGKLGAVFLP 115

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: 74.97 E-value: 3.81e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 256 SCGRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKTKHQTKVHRKTlNPVFDEVFLFP-VAYADL 334
Cdd:cd08389    1 KCGDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLPSKKQRAKTKVQRGP-NPVFNETFTFSrVEPEEL 79

                         90       100
                 ....*....|....*....|....*.
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVV 360
Cdd:cd08389   80 NNMALRFRLYGVERMRKERLIGEKVV 105

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: 73.11 E-value: 1.19e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKD-FSGTSDPYVKIYLLpdrKTKHQTKVHRKTLNPVF-DEVFLFPVAYADLPTRKLHFSVYDFDRFSRH 352
Cdd:cd08688    3 VRVVAARDLPVMDrSSDLTDAFVEVKFG---STTYKTDVVKKSLNPVWnSEWFRFEVDDEELQDEPLQIRVMDHDTYSAN 79


                 ....*....
gi 326676116 353 DIIGQVVVD 361
Cdd:cd08688   80 DAIGKVYID 88

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: 73.10 E-value: 1.46e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRKtkhQTKVHRKTLNPVFDEVFLFPVAYAdlpTRKLHFSVYDFDRFSRH 352
Cdd:cd08377    3 LQVKVIRASGLAAADIGGKSDPFCVLELVNARL---QTHTIYKTLNPEWNKIFTFPIKDI---HDVLEVTVYDEDKDKKP 76


                 ....*...
gi 326676116 353 DIIGQVVV 360
Cdd:cd08377   77 EFLGKVAI 84

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: 72.28 E-value: 3.39e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVF-DVPPENI 468
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYsNVRRETL 82

                         90       100
                 ....*....|....*....|....
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIGVC 492
Cdd:cd04031   83 KERTLEVTVWDYDRDGENDFLGEV 106

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: 71.44 E-value: 4.21e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 278 HRAQDLPAKDFSGTSDPYVKIYLLPDRKTK---HQTKVHRKTLNPVFDEvFLFPV---AYADLpTRKLHFSVYDFDRFSR 351
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEISRQSEDGTWvlvYRTEVIKNTLNPVWKP-FTIPLqklCNGDY-DRPIKIEVYDYDSSGK 84


                 ....*....
gi 326676116 352 HDIIGQVVV 360
Cdd:cd04047   85 HDLIGEFET 93

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: 71.23 E-value: 7.48e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLL-PDRK---TKHQTKVHRKTLNPVFDEVFLFPVayaDLPTRKLHFSVYDFDR 348
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISLYdPDGNgeiDSVQTKTIKKTLNPKWNEEFFFRV---NPREHRLLFEVFDENR 78

                         90
                 ....*....|..
gi 326676116 349 FSRHDIIGQVVV 360
Cdd:cd04033   79 LTRDDFLGQVEV 90

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: 69.34 E-value: 4.77e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 389 LGDLMFSLCYlpTAGRLTITMIKARNLKAMDITGA-SDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPEN 467
Cdd:cd04028   17 MGDIQLGLYD--KKGQLEVEVIRARGLVQKPGSKVlPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSPTG 94

                         90       100
                 ....*....|....*....|....*...
gi 326676116 468 -IDQISLLvavMDYDRVGHNEVIGVCRV 494
Cdd:cd04028   95 kTLQVIVW---GDYGRMDKKVFMGVAQI 119

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: 67.32 E-value: 1.45e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDfsGTS-DPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVF---LFPVayADLPTRKLHFSVYDF 346
Cdd:cd08381   15 LFVMVMHAKNLPLLD--GSDpDPYVKTYLLPDpqKTTKRKTKVVRKTRNPTFNEMLvydGLPV--EDLQQRVLQVSVWSH 90

                         90       100
                 ....*....|....*....|....*..
gi 326676116 347 DRFSRHDIIGQVVVDnfLDLVDFPRET 373
Cdd:cd08381   91 DSLVENEFLGGVCIP--LKKLDLSQET 115

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: 66.84 E-value: 3.04e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYL---LPDRKTKhQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLvhgLKLIKTK-KTSCMRGTIDPFYNESFSFKVPQEEL 79

                         90       100
                 ....*....|....*....|....*....
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVVDNF 363
Cdd:cd08410   80 ENVSLVFTVYGHNVKSSNDFIGRIVIGQY 108

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: 66.16 E-value: 3.85e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITgASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFD-VPPENIDQISLLVAVMDYD 481
Cdd:cd08381   13 GTLFVMVMHAKNLPLLDGS-DPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDgLPVEDLQQRVLQVSVWSHD 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 326676116 482 RVGHNEVigvcrvgndaegLGREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08381   92 SLVENEF------------LGGVCIPLKKLDLSQETEKWYPL 121

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: 66.03 E-value: 4.93e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKVH--RKTLNPVFDEVFLFPvayADLPTRK-LHFSVYDFDRFSR 351
Cdd:cd04037    4 VYVVRARNLQPKDPNGKSDPYLKIKL---GKKKINDRDNyiPNTLNPVFGKMFELE---ATLPGNSiLKISVMDYDLLGS 77

                         90
                 ....*....|
gi 326676116 352 HDIIGQVVVD 361
Cdd:cd04037   78 DDLIGETVID 87

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: 65.74 E-value: 5.15e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLmcdGRRLKKRKTSTKrnTLNPVYNEAIVFDVPPENiDQIsLLVAVMDYDRVG 484
Cdd:cd08376    2 VTIVLVEGKNLPPMDDNGLSDPYVKFRL---GNEKYKSKVCSK--TLNPQWLEQFDLHLFDDQ-SQI-LEIEVWDKDTGK 74

                         90       100
                 ....*....|....*....|....*
gi 326676116 485 HNEVIGVCRVgnDAEGLGREHWNEM 509
Cdd:cd08376   75 KDEFIGRCEI--DLSALPREQTHSL 97

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: 64.99 E-value: 8.84e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNLKAMDITGASDPYVKVSLmcDGRRLKKRKTSTKrnTLNPVYNEaiVFDVPPENIDQiSLLVAVMDYDRV 483
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVKFKY--GGKTVYKSKTIYK--NLNPVWDE--KFTLPIEDVTQ-PLYIKVFDYDRG 73

                         90
                 ....*....|.
gi 326676116 484 GHNEVIGVCRV 494
Cdd:cd04042   74 LTDDFMGSAFV 84

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: 64.20 E-value: 1.33e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDF-SGTSDPYVKIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTR-KLHFSVYDFDRFS 350
Cdd:cd04041    3 LVVTIHRATDLPKADFgTGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEETWFVLVTPDEVKAGeRLSCRLWDSDRFT 82

                         90
                 ....*....|.
gi 326676116 351 RHDIIGQVVVD 361
Cdd:cd04041   83 ADDRLGRVEID 93

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: 64.48 E-value: 1.79e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLP--AKDFSGTSDPYVKIYLL---PDRKTKHQTK-VHRKTLNPVFDEVFLFPVAYADLPTrkLHFSVYDF 346
Cdd:cd00275    4 LTIKIISGQQLPkpKGDKGSIVDPYVEVEIHglpADDSAKFKTKvVKNNGFNPVWNETFEFDVTVPELAF--LRFVVYDE 81

                         90
                 ....*....|....
gi 326676116 347 DRFsRHDIIGQVVV 360
Cdd:cd00275   82 DSG-DDDFLGQACL 94

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: 63.43 E-value: 2.11e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPA-KDFSGTS---DPYVKIYLlpDRKTkHQTKVHRKTLNPVFDEVFLFPVaYADLPTRKLHFSVYDFDR 348
Cdd:cd04039    3 VFMEIKSITDLPPlKNMTRTGfdmDPFVIISF--GRRV-FRTSWRRHTLNPVFNERLAFEV-YPHEKNFDIQFKVLDKDK 78

                         90
                 ....*....|...
gi 326676116 349 FSRHDIIGQVVVD 361
Cdd:cd04039   79 FSFNDYVATGSLS 91

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: 62.15 E-value: 1.19e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTS-DPYVKIYLLPDR--KTKHQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKshNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81

                         90       100
                 ....*....|....*....|....*.
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVV 360
Cdd:cd08392   82 SSRQLQVSVWHSRTLKRRVFLGEVLI 107

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: 1.20e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 410 IKARNLKAMDITGASDPYVKVSLmcDGRRLKKRKTsTKRNTLNPVYNEAIVFDVP-PENidqiSLL-VAVMDYDRVGHNE 487
Cdd:cd04037    7 VRARNLQPKDPNGKSDPYLKIKL--GKKKINDRDN-YIPNTLNPVFGKMFELEATlPGN----SILkISVMDYDLLGSDD 79


                 ...
gi 326676116 488 VIG 490
Cdd:cd04037   80 LIG 82

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 65.94 E-value: 4.77e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADlpTRKLHFSVYDFDRFSRH 352
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVYKTKVVKKTLNPVWNEEFTIEVLNRV--KDVLTINVNDWDSGEKN 1117

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 326676116  353 DIIGQVVVDNFLDLVDFPRETKLCRDIQYVSSDnvdlgDLMFSLCY 398
Cdd:COG5038  1118 DLLGTAEIDLSKLEPGGTTNSNIPLDGKTFIVL-----DGTLHPGF 1158

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: 59.50 E-value: 5.35e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDR 348
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVELTV---GKTTQKSKVKERTNNPVWEEGFTFLV--RNPENQELEIEVKDDKT 72

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: 59.77 E-value: 6.84e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYlpTAGRLTITMIKARNLKAMDiTGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENiD 469
Cdd:cd08685    1 GQLKLSIEG--QNRKLTLHVLEAKGLRSTN-SGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERD-Y 76


                 ....*...
gi 326676116 470 QISLLVAV 477
Cdd:cd08685   77 QKRLLVTV 84

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: 59.88 E-value: 7.17e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDF-SGTSDPYVKIYLlPDRKTKHQTKVHRKTLNPVFDEVFLFPVayaDLPTRKLHFSVYDFDRFSR 351
Cdd:cd04044    4 LAVTIKSARGLKGSDIiGGTVDPYVTFSI-SNRRELARTKVKKDTSNPVWNETKYILV---NSLTEPLNLTVYDFNDKRK 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 326676116 352 HDIIGQVVvdnfLDLVDFpRETKLCRDIQY-VSSDNVDLGDLMFSLCYLP 400
Cdd:cd04044   80 DKLIGTAE----FDLSSL-LQNPEQENLTKnLLRNGKPVGELNYDLRFFP 124

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: 59.52 E-value: 8.42e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGASDPYVKVSLmcdgRRLKKRKTSTKRNTLNPVYNEaiVFDVPPENIDQIsLLVAVMDYDR 482
Cdd:cd04045    1 GVLRLHIRKANDLKNLEGVGKIDPYVRVLV----NGIVKGRTVTISNTLNPVWDE--VLYVPVTSPNQK-ITLEVMDYEK 73

                         90
                 ....*....|..
gi 326676116 483 VGHNEVIGVCRV 494
Cdd:cd04045   74 VGKDRSLGSVEI 85

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 64.78 E-value: 1.04e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  402 AGRLTITMIKARNLKAMDITGASDPYVKVSLmcdgRRLKKRKTSTKRNTLNPVYNEAivFDVPPENIDQISLLVAVMDYD 481
Cdd:COG5038  1039 SGYLTIMLRSGENLPSSDENGYSDPFVKLFL----NEKSVYKTKVVKKTLNPVWNEE--FTIEVLNRVKDVLTINVNDWD 1112

                          90
                  ....*....|.
gi 326676116  482 RVGHNEVIGVC 492
Cdd:COG5038  1113 SGEKNDLLGTA 1123

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: 59.09 E-value: 1.18e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNL--KAMDITGASDPYVKVSL-MCDGRRLKKRKTST-KRNTLNPVYNEAIVFDVppENIDQISLLVAVMD 479
Cdd:cd00275    3 TLTIKIISGQQLpkPKGDKGSIVDPYVEVEIhGLPADDSAKFKTKVvKNNGFNPVWNETFEFDV--TVPELAFLRFVVYD 80

                         90
                 ....*....|...
gi 326676116 480 YDRvGHNEVIGVC 492
Cdd:cd00275   81 EDS-GDDDFLGQA 92

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: 58.74 E-value: 1.22e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 407 ITMIKARNLKAMDItgasDPYVKVSLMCdgrrlKKRKTSTKRNTLNPVYNEAIVFDV--PPENIDQISLLVAVMDYDRVG 484
Cdd:cd04011    8 VRVIEARQLVGGNI----DPVVKVEVGG-----QKKYTSVKKGTNCPFYNEYFFFNFheSPDELFDKIIKISVYDSRSLR 78


                 ....*.
gi 326676116 485 HNEVIG 490
Cdd:cd04011   79 SDTLIG 84

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: 59.65 E-value: 1.35e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFsGTSDPYVkIYLLPDRKTKhqTKVHRKTLNPVFDEVFLFPVAYadlPTRKLHFSVYDFDRFSRH 352
Cdd:cd04038    4 LKVRVVRGTNLAVRDF-TSSDPYV-VLTLGNQKVK--TRVIKKNLNPVWNEELTLSVPN---PMAPLKLEVFDKDTFSKD 76

                         90
                 ....*....|....*..
gi 326676116 353 DIIGqvvvDNFLDLVDF 369
Cdd:cd04038   77 DSMG----EAEIDLEPL 89

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: 58.92 E-value: 1.92e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDfSGTSDPYVKIYLLPDRKTKHQ-TKVHRKTLNPVFDEVFLFPV-------------AYADLPTRK 338
Cdd:cd08675    1 LSVRVLECRDLALKS-NGTCDPFARVTLNYSSKTDTKrTKVKKKTNNPRFDEAFYFELtigfsyekksfkvEEEDLEKSE 79

                         90       100
                 ....*....|....*....|..
gi 326676116 339 LHFSVYDFDRFSRHDIIGQVVV 360
Cdd:cd08675   80 LRVELWHASMVSGDDFLGEVRI 101

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: 58.07 E-value: 2.50e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 274 IVKIH--RAQDLPAKD------FSGTSDPYVKIYLLPdrkTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYD 345
Cdd:cd08391    2 VLRIHviEAQDLVAKDkfvgglVKGKSDPYVIVRVGA---QTFKSKVIKENLNPKWNEVYEAVV--DEVPGQELEIELFD 76

                         90
                 ....*....|....*.
gi 326676116 346 FDRfSRHDIIGQVVVD 361
Cdd:cd08391   77 EDP-DKDDFLGRLSID 91

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: 57.30 E-value: 4.47e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDI------TGASDPYVKVSLmcdGRRlkKRKTSTKRNTLNPVYNEaiVFDVPPENIDQISLLVA 476
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKfvgglvKGKSDPYVIVRV---GAQ--TFKSKVIKENLNPKWNE--VYEAVVDEVPGQELEIE 73

                         90
                 ....*....|....*...
gi 326676116 477 VMDYDrVGHNEVIGVCRV 494
Cdd:cd08391   74 LFDED-PDKDDFLGRLSI 90

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: 56.93 E-value: 4.49e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMD-ITGASDPYVKVSLMCdgrrlKKRKTSTKRNTLNPVYN-EAIVFDVPPENIDQISLLVAVMDYDR 482
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGS-----TTYKTDVVKKSLNPVWNsEWFRFEVDDEELQDEPLQIRVMDHDT 75


                 ....*...
gi 326676116 483 VGHNEVIG 490
Cdd:cd08688   76 YSANDAIG 83

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: 57.11 E-value: 5.43e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNLKAMDITGASDPYVKVSlmCDGrrlKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQISllVAVMDYDRV 483
Cdd:cd04025    1 RLRCHVLEARDLAPKDRNGTSDPFVRVF--YNG---QTLETSVVKKSCYPRWNEVFEFELMEGADSPLS--VEVWDWDLV 73

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 326676116 484 GHNEVIGvcRVGNDAEGLGR----EHWNEMLTYPRK 515
Cdd:cd04025   74 SKNDFLG--KVVFSIQTLQQakqeEGWFRLLPDPRA 107

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: 56.42 E-value: 8.05e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 407 ITM-IKARNLKAMDITGASDPYVKVSLMC-DGRRLKKRKTSTKRNTLNPVYNEaivFDVPPE-----NIDQiSLLVAVMD 479
Cdd:cd04047    3 VELqFSGKKLDKKDFFGKSDPFLEISRQSeDGTWVLVYRTEVIKNTLNPVWKP---FTIPLQklcngDYDR-PIKIEVYD 78

                         90
                 ....*....|....*
gi 326676116 480 YDRVGHNEVIGVCRV 494
Cdd:cd04047   79 YDSSGKHDLIGEFET 93

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: 56.66 E-value: 8.44e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFS--GTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTrkLHFSVYDFDRFS 350
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSgkGKSDPYAILSV---GAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQL--LKLILWDKDRFA 77

                         90
                 ....*....|.
gi 326676116 351 RHDIIGQVVVD 361
Cdd:cd04024   78 GKDYLGEFDIA 88

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: 56.59 E-value: 9.65e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLM--CDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENidqISLLVAVMDYDR 482
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISLYdpDGNGEIDSVQTKTIKKTLNPKWNEEFFFRVNPRE---HRLLFEVFDENR 78


                 ....*....
gi 326676116 483 VGHNEVIGV 491
Cdd:cd04033   79 LTRDDFLGQ 87

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: 57.02 E-value: 1.13e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 326676116 272 QLIVKIHRAQDLPAKdfSGTSDPYVKIYLL--PDRKTKHQTKVHRKTLNPVFDEVFLFPVaYADLPTRKLHFSVYDFD 347
Cdd:cd04010    1 KLSVRVIECSDLALK--NGTCDPYASVTLIysNKKQDTKRTKVKKKTNNPQFDEAFYFDV-TIDSSPEKKQFEMPEED 75

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: 56.15 E-value: 1.15e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGASDPYVKVSLMcdGRRLkkrKTSTKRNTLNPVYNEAIVFDVppENIDQIsLLVAVMDYDR 482
Cdd:cd08377    1 GFLQVKVIRASGLAAADIGGKSDPFCVLELV--NARL---QTHTIYKTLNPEWNKIFTFPI--KDIHDV-LEVTVYDEDK 72


                 ....*...
gi 326676116 483 VGHNEVIG 490
Cdd:cd08377   73 DKKPEFLG 80

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

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 55.73 E-value: 1.22e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDI-TGASDPYVKVSLMCDGRRLkkRKTSTKRNTLNPVYNE-AIVFDVPPENIDQISLLVAVMDY 480
Cdd:cd04041    1 GVLVVTIHRATDLPKADFgTGSSDPYVTASFAKFGKPL--YSTRIIRKDLNPVWEEtWFVLVTPDEVKAGERLSCRLWDS 78

                         90
                 ....*....|
gi 326676116 481 DRVGHNEVIG 490
Cdd:cd04041   79 DRFTADDRLG 88

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: 55.66 E-value: 1.29e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPakdfSGTSDPYVKIYLLPDrktKHQTKVHRKTLNPVFDEVFLFPV--AYADLPTRKLHFSVYDFDRF 349
Cdd:cd04011    5 QVRVRVIEARQLV----GGNIDPVVKVEVGGQ---KKYTSVKKGTNCPFYNEYFFFNFheSPDELFDKIIKISVYDSRSL 77


                 ....*..
gi 326676116 350 SRHDIIG 356
Cdd:cd04011   78 RSDTLIG 84

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: 56.40 E-value: 1.44e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 412 ARNLKAMDITGASDPYVKVSLMCdgrrlKKRKTSTKRNTLNPVYNEAIVFD--VPPENIDQI-----SLLVAVMDYDRVG 484
Cdd:cd04017   10 ARDLLAADKSGLSDPFARVSFLN-----QSQETEVIKETLSPTWDQTLIFDevELYGSPEEIaqnppLVVVELFDQDSVG 84


                 ....*.
gi 326676116 485 HNEVIG 490
Cdd:cd04017   85 KDEFLG 90

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: 55.81 E-value: 1.94e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLLpdrKTKHQTKVHRKTLNPVFDEVFLFPVA-YADLPTRKLHFSVYDFDRFSR 351
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFD---GQKKRTRTKPKDLNPVWNEKLVFNVSdPSRLSNLVLEVYVYNDRRSGR 78

                         90
                 ....*....|
gi 326676116 352 -HDIIGQVVV 360
Cdd:cd04022   79 rRSFLGRVRI 88

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: 54.52 E-value: 4.03e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 277 IHRAQDLPAKDFSGTSDPYVKIylLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYadlPTRKLHFSVYDF-----DRFsr 351
Cdd:cd04045    7 IRKANDLKNLEGVGKIDPYVRV--LVNGIVKGRTVTISNTLNPVWDEVLYVPVTS---PNQKITLEVMDYekvgkDRS-- 79


                 ....*..
gi 326676116 352 hdiIGQV 358
Cdd:cd04045   80 ---LGSV 83

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 59.00 E-value: 6.49e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  266 YDCDLEQLI------------VKIHRAQDLPAKDFS--GTSDPYVkIYLLPDRkTKHQTKVHRKTLNPVFDEVFLFPVAY 331
Cdd:COG5038   419 LTIDISQIMagdsgtaigvveVKIKSAEGLKKSDSTinGTVDPYI-TVTFSDR-VIGKTRVKKNTLNPVWNETFYILLNS 496

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  332 AdlpTRKLHFSVYDFDRFSRHDIIGQVvvdnFLDLVDFPRETKLCRDIQYVSSDNVDLGDLMFSLCYLPTA--------- 402
Cdd:COG5038   497 F---TDPLNLSLYDFNSFKSDKVVGST----QLDLALLHQNPVKKNELYEFLRNTKNVGRLTYDLRFFPVIedkkelkgs 569

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  403 ---------GRLTITMIKarnLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNtlNPVYNEAivFDVPPENIDQISL 473
Cdd:COG5038   570 vepledsntGILKVTLRE---VKALDELSSKKDNKSAELYTNAKEVYSTGKLKFTN--HPSWNLQ--YNVLVTDRKNSSI 642

                         250
                  ....*....|..
gi 326676116  474 LVAVMDyDRVGH 485
Cdd:COG5038   643 KVVTFD-VQSGK 653

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: 53.64 E-value: 9.20e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 280 AQDLPAKDFSGTSDPYVKIYLlpDRKTKhQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSRHDIIGQVV 359
Cdd:cd04025    9 ARDLAPKDRNGTSDPFVRVFY--NGQTL-ETSVVKKSCYPRWNEVFEFEL--MEGADSPLSVEVWDWDLVSKNDFLGKVV 83


                 ..
gi 326676116 360 VD 361
Cdd:cd04025   84 FS 85

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: 54.18 E-value: 1.08e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 425 DPYVKVSLMcdGrrlKKRKTSTKRNTLNPVYNEAIVFDV--PP--ENIDqisllVAVMDYDRVGHNEVIG 490
Cdd:cd04018   36 DPYVEVSFA--G---QKVKTSVKKNSYNPEWNEQIVFPEmfPPlcERIK-----IQIRDWDRVGNDDVIG 95

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: 53.03 E-value: 1.13e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 280 AQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDEVFLFpvAYADLPTRKLHFSVYDFDRFSRHDIIGQVV 359
Cdd:cd08376    9 GKNLPPMDDNGLSDPYVKFRL---GNEKYKSKVCSKTLNPQWLEQFDL--HLFDDQSQILEIEVWDKDTGKKDEFIGRCE 83


                 ..
gi 326676116 360 VD 361
Cdd:cd08376   84 ID 85

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: 53.04 E-value: 1.31e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNLKAMDITGASDPYVKVSL--MCDGRrlkKRkTSTKRNTLNPVYNEAIVFDVPP--ENIdqisLLVAVMD 479
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLptASDEK---KR-TKTIKNSINPVWNETFEFRIQSqvKNV----LELTVMD 72


                 ....*
gi 326676116 480 YDRVG 484
Cdd:cd04036   73 EDYVM 77

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: 53.44 E-value: 1.37e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDFSGTSDPYVKIYllpDRKTKHQTKVHRKTLNPVFDEVFLFpvaYADLPTRKLHFSVYDFDRFSRhDI 354
Cdd:cd04046    7 VHVHSAEGLSKQDSGGGADPYVIIK---CEGESVRSPVQKDTLSPEFDTQAIF---YRKKPRSPIKIQVWNSNLLCD-EF 79


                 ....*.
gi 326676116 355 IGQVVV 360
Cdd:cd04046   80 LGQATL 85

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: 52.94 E-value: 1.57e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMD-ITGASDPYVKVSLmcDGRRLKKRkTSTKRNTLNPVYNEAIVFDVppeNIDQISLLVAVMDYD 481
Cdd:cd04044    2 GVLAVTIKSARGLKGSDiIGGTVDPYVTFSI--SNRRELAR-TKVKKDTSNPVWNETKYILV---NSLTEPLNLTVYDFN 75


                 ....*....
gi 326676116 482 RVGHNEVIG 490
Cdd:cd04044   76 DKRKDKLIG 84

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: 53.53 E-value: 1.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLLPD------RKTK--------------------HQTKVHRKTLNPVFDEVFL 326
Cdd:cd08676   30 LKVTVIEAKGLLAKDVNGFSDPYCMLGIVPAsrernsEKSKkrkshrkkavlkdtvpaksiKVTEVKPQTLNPVWNETFR 109

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 326676116 327 FPVayADLPTRKLHFSVYDfdrfsrHDiigqvvvDNFLDLVDFP 370
Cdd:cd08676  110 FEV--EDVSNDQLHLDIWD------HD-------DDFLGCVNIP 138

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: 52.22 E-value: 2.44e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 259 RLHFILKYDCDLEQLIVKIHRAQDLpakDFSGTSDPYVKIYLLPDRKTKH-QTKVHRKTLNPVFDEVFLFPVAYADLPTR 337
Cdd:cd08677    2 KLHYSLSYDKQKAELHVNILEAENI---SVDAGCECYISGCVSVSEGQKEaQTALKKLALHTQWEEELVFPLPEEESLDG 78

                         90       100
                 ....*....|....*....|.
gi 326676116 338 KLHFSVYDFDRFSRHDIIGQV 358
Cdd:cd08677   79 TLTLTLRCCDRFSRHSTLGEL 99

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: 52.57 E-value: 2.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDEVFLFPVAYAdlpTRKLHFSVYDFD---- 347
Cdd:cd04027    2 KISITVVCAQGLIAKDKTGTSDPYVTVQV---GKTKKRTKTIPQNLNPVWNEKFHFECHNS---SDRIKVRVWDEDddik 75

                         90       100
                 ....*....|....*....|.
gi 326676116 348 -----RFSRH--DIIGQVVVD 361
Cdd:cd04027   76 srlkqKFTREsdDFLGQTIIE 96

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: 52.23 E-value: 2.96e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLmcDGrrlkKRKTSTKRNTL---NPVYNEAIVFDVPPENIDQ--ISLLVAVMD 479
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWI--DP----SHKQSTPVDRDggtNPTWNETLRFPLDERLLQQgrLALTIEVYC 75

                         90
                 ....*....|....*
gi 326676116 480 YDRVGHNEVIGVCRV 494
Cdd:cd04051   76 ERPSLGDKLIGEVRV 90

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: 52.19 E-value: 3.12e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 326676116 404 RLTITMIKARNLKAMDITGASDPYVKVSLmcdGRrlKKRKTSTKRNTLNPVYNEAIVFDVpPENIDQISLLVAVMDYD 481
Cdd:cd04027    2 KISITVVCAQGLIAKDKTGTSDPYVTVQV---GK--TKKRTKTIPQNLNPVWNEKFHFEC-HNSSDRIKVRVWDEDDD 73

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: 51.49 E-value: 3.52e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 425 DPYVKVSLmcdGRRLkkRKTSTKRNTLNPVYNEAIVFDVPPENIDqISLLVAVMDYDRVGHNEVIGVCRV 494
Cdd:cd04039   27 DPFVIISF---GRRV--FRTSWRRHTLNPVFNERLAFEVYPHEKN-FDIQFKVLDKDKFSFNDYVATGSL 90

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: 51.87 E-value: 4.45e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPakdfsGTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTRKLHFSVYDFDRFSRH 352
Cdd:cd08373    1 LVVSLKNLPGLK-----GKGDRIAKVTF---RGVKKKTRVLENELNPVWNETFEWPLAGSPDPDESLEIVVKDYEKVGRN 72


                 ....*....
gi 326676116 353 DIIGQVVVD 361
Cdd:cd08373   73 RLIGSATVS 81

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: 51.99 E-value: 5.20e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 326676116 293 DPYVKIYLL-PDRK--TKHQTKVHRKTLNPVFDEVFLFPVAYADLPTRKLHFSVYDFDRFSRHDIIGQV 358
Cdd:cd08408   37 DTYVKLTLLnSDGQeiSKSKTSIRRGQPDPEFKETFVFQVALFQLSEVTLMFSVYNKRKMKRKEMIGWF 105

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: 51.95 E-value: 5.52e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 258 GRLHFILKYDCDLEQLIVKIHRAQDLPAKDFSGTsDPYVKIYLLPDR---KTKhQTKVHRKTLNPVFDEVFLFPVAYADL 334
Cdd:cd08409    2 GDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHT-SVYVKVSLMIHNkvvKTK-KTEVVDGAASPSFNESFSFKVTSRQL 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 326676116 335 PTRKLHFSVYDFDRFSRHDIIGQVVVDNFL-----------DLVDFPRET 373
Cdd:cd08409   80 DTASLSLSVMQSGGVRKSKLLGRVVLGPFMyargkelehwnDMLSKPKEL 129

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: 52.00 E-value: 6.65e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAK-DFSGTSDPYVKIYLLPDRK--TKHQTKVHRKTLNPVFDEVFLFPVAYADlptRKLHFSVY-DFD 347
Cdd:cd04028   30 QLEVEVIRARGLVQKpGSKVLPAPYVKVYLLEGKKciAKKKTKIARKTLDPLYQQQLVFDVSPTG---KTLQVIVWgDYG 106

                         90       100
                 ....*....|....*....|.
gi 326676116 348 RFSRHDIIG--QVVVDNfLDL 366
Cdd:cd04028  107 RMDKKVFMGvaQILLDD-LDL 126

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: 51.17 E-value: 9.43e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGaSDPYVKVSLmcdGRrlKKRKTSTKRNTLNPVYNEAIVFDVpPENIDQISLLvaVMDYDR 482
Cdd:cd04038    2 GLLKVRVVRGTNLAVRDFTS-SDPYVVLTL---GN--QKVKTRVIKKNLNPVWNEELTLSV-PNPMAPLKLE--VFDKDT 72

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: 50.53 E-value: 1.05e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 326676116 273 LIVKIHRAQDLPAKDfSGTSDPYVKIYLLPD--RKTKHQTKVHRKTLNPVFDEVFLFPVAYADLpTRKLHFSVY 344
Cdd:cd08685   14 LTLHVLEAKGLRSTN-SGTCNSYVKISLSPDkeVRFRQKTSTVPDSANPLFHETFSFDVNERDY-QKRLLVTVW 85

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: 50.33 E-value: 1.28e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 326676116 421 TGASDPYVKVSLmcdgrRLKKRKTSTKRNTLNPVYNEAIVFDV--PPENIDqiSLLVAVMDYDRVGHNEVIGVCRV 494
Cdd:cd08373   12 KGKGDRIAKVTF-----RGVKKKTRVLENELNPVWNETFEWPLagSPDPDE--SLEIVVKDYEKVGRNRLIGSATV 80

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: 50.34 E-value: 1.39e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDFSGTSDPYVkiyLLPDRKTKHQ---TKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSR 351
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYV---TLVDTNGKRRiakTRTIYDTLNPRWDEEFELEV--PAGEPLWISATVWDRSFVGK 79


                 ....*
gi 326676116 352 HDIIG 356
Cdd:cd04043   80 HDLCG 84

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: 49.82 E-value: 1.72e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPY--VKIyllpDRKTKHQTKVHRKTLNPVFDEVFLFpvayaDLPT--RKLHFSVYDFDR 348
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYciVKV----DNEVIIRTATVWKTLNPFWGEEYTV-----HLPPgfHTVSFYVLDEDT 72

                         90
                 ....*....|
gi 326676116 349 FSRHDIIGQV 358
Cdd:cd04054   73 LSRDDVIGKV 82

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: 50.71 E-value: 1.76e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKD-------FSGTS-------DPYVKIYLLpDRKTKhqTKVHRKTLNPVFDEVFLFPVAYADLpTRK 338
Cdd:cd04018    2 FIFKIYRAEDLPQMDsgimanvKKAFLgekkelvDPYVEVSFA-GQKVK--TSVKKNSYNPEWNEQIVFPEMFPPL-CER 77

                         90       100
                 ....*....|....*....|....*...
gi 326676116 339 LHFSVYDFDRFSRHDIIGQvvvdNFLDL 366
Cdd:cd04018   78 IKIQIRDWDRVGNDDVIGT----HFIDL 101

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: 50.06 E-value: 2.03e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLkAMDITGASDPYVKVSlMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPP-------------ENIDQI 471
Cdd:cd08675    1 LSVRVLECRDL-ALKSNGTCDPFARVT-LNYSSKTDTKRTKVKKKTNNPRFDEAFYFELTIgfsyekksfkveeEDLEKS 78

                         90       100
                 ....*....|....*....|...
gi 326676116 472 SLLVAVMDYDRVGHNEVIGVCRV 494
Cdd:cd08675   79 ELRVELWHASMVSGDDFLGEVRI 101

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: 49.92 E-value: 2.09e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 264 LKYDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLLP---DRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTRKLH 340
Cdd:cd08680    7 LRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPcssSTSCLFRTKALEDQDKPVFNEVFRVPISSTKLYQKTLQ 86

                         90
                 ....*....|....*.
gi 326676116 341 FSVYDFDRFSRHDIIG 356
Cdd:cd08680   87 VDVCSVGPDQQEECLG 102

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: 49.44 E-value: 2.48e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLmcDGRRLKkrKTSTKRNTLNPVYNEAIVFDVPPENidqISLLVAVMDYDRVG 484
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKV--DNEVII--RTATVWKTLNPFWGEEYTVHLPPGF---HTVSFYVLDEDTLS 74


                 ....*.
gi 326676116 485 HNEVIG 490
Cdd:cd04054   75 RDDVIG 80

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: 49.57 E-value: 2.59e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 406 TITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKkrKTSTKRNTLNPVYNEaiVFDVPPENIDQISLLVAVMDYDRVGH 485
Cdd:cd04043    4 TIRIVRAENLKADSSNGLSDPYVTLVDTNGKRRIA--KTRTIYDTLNPRWDE--EFELEVPAGEPLWISATVWDRSFVGK 79


                 ....*
gi 326676116 486 NEVIG 490
Cdd:cd04043   80 HDLCG 84

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: 49.68 E-value: 3.96e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRK------------------------TSTKRNTLNPVYNEAIV 460
Cdd:cd08676   30 LKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRERNSEKskkrkshrkkavlkdtvpaksikvTEVKPQTLNPVWNETFR 109

                         90       100
                 ....*....|....*....|.
gi 326676116 461 FDVPPENIDQisLLVAVMDYD 481
Cdd:cd08676  110 FEVEDVSNDQ--LHLDIWDHD 128

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: 49.08 E-value: 4.85e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLLpdrktkHQ---TKVHRKTLNPVFDEVFLFP--VAYADLPTRKLH-----F 341
Cdd:cd04017    2 QLRAYIYQARDLLAADKSGLSDPFARVSFL------NQsqeTEVIKETLSPTWDQTLIFDevELYGSPEEIAQNpplvvV 75

                         90
                 ....*....|....*...
gi 326676116 342 SVYDFDRFSRHDIIGQVV 359
Cdd:cd04017   76 ELFDQDSVGKDEFLGRSV 93

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: 48.52 E-value: 5.58e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKdfSGTSDPYVkIYLLPDRKTKHQTKVHRKTLNPVFDEVFLFpvayaDLP--TRKLHFSVYDFDRFS 350
Cdd:cd08678    1 LLVKNIKANGLSEA--AGSSNPYC-VLEMDEPPQKYQSSTQKNTSNPFWDEHFLF-----ELSpnSKELLFEVYDNGKKS 72

                         90
                 ....*....|
gi 326676116 351 RHDIIGQVVV 360
Cdd:cd08678   73 DSKFLGLAIV 82

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: 48.33 E-value: 7.16e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 280 AQDLPAKDFSGTSDPYVKIYLLPDRKTK----HQTKVHRKTLNPVFDEVFLFPVAYADLPtrKLHFSVYDFD----RFSR 351
Cdd:cd04048    9 CRNLLDKDVLSKSDPFVVVYVKTGGSGQwveiGRTEVIKNNLNPDFVTTFTVDYYFEEVQ--KLRFEVYDVDskskDLSD 86

                         90
                 ....*....|
gi 326676116 352 HDIIGQVVVD 361
Cdd:cd04048   87 HDFLGEAECT 96

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: 48.01 E-value: 7.58e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKV-HRKTLNPVFDEVFLFPVAYADLPTRKLhfSVYDfDRFSR 351
Cdd:cd08681    3 LVVVVLKARNLPNKRKLDKQDPYCVLRI---GGVTKKTKTdFRGGQHPEWDEELRFEITEDKKPILKV--AVFD-DDKRK 76

                         90
                 ....*....|
gi 326676116 352 HDIIGQVVVD 361
Cdd:cd08681   77 PDLIGDTEVD 86

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: 47.64 E-value: 9.87e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYL--LPDRktKHQTKVHRKTLNPVFDEVFLFPVAyadlPTRK--LHFSVYDFD 347
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLptASDE--KKRTKTIKNSINPVWNETFEFRIQ----SQVKnvLELTVMDED 74

                         90       100
                 ....*....|....*....|...
gi 326676116 348 rfsrhdiigqVVVDNFLDLVDFP 370
Cdd:cd04036   75 ----------YVMDDHLGTVLFD 87

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: 47.78 E-value: 1.02e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNLKaMDITGASDPYVKVSLMcdGRRL--KKRKTST--KRNTLNPVYNEAIVF----DVPPENIDqisLLV 475
Cdd:cd08395    1 KVTVKVVAANDLK-WQTTGMFRPFVEVNLI--GPHLsdKKRKFATksKNNNWSPKYNETFQFilgnEDDPESYE---LHI 74

                         90
                 ....*....|....*..
gi 326676116 476 AVMDYDRVGHNEVIGVC 492
Cdd:cd08395   75 CVKDYCFARDDRLVGVT 91

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: 47.52 E-value: 1.43e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGAS-DPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENI 468
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81


                 ....*....
gi 326676116 469 DQISLLVAV 477
Cdd:cd08392   82 SSRQLQVSV 90

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: 47.33 E-value: 1.57e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 404 RLTITMIKARNLKAMDITGASDPYVKVSLmcDGRRlkkRKTSTKRNTLNPVYNEAIVFDV 463
Cdd:cd04022    1 KLVVEVVDAQDLMPKDGQGSSSAYVELDF--DGQK---KRTRTKPKDLNPVWNEKLVFNV 55

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: 47.38 E-value: 1.96e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGASDPYVKVSLMCdgrrlKKRKTSTKRNTLNPVYNEAIVFDVppENIDQISLLVAVMDYDR 482
Cdd:cd08375   15 GRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGS-----QEHKTKVVSDTLNPKWNSSMQFFV--KDLEQDVLCITVFDRDF 87


                 ....*...
gi 326676116 483 VGHNEVIG 490
Cdd:cd08375   88 FSPDDFLG 95

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: 46.87 E-value: 2.17e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAmdiTGASDPYVKVSLmcDGRRLKKRKTSTKrntLNPVYNEAIVFDVPPENIDQISLLVAVMDYDRVG 484
Cdd:cd08383    2 LRLRILEAKNLPS---KGTRDPYCTVSL--DQVEVARTKTVEK---LNPFWGEEFVFDDPPPDVTFFTLSFYNKDKRSKD 73

                         90       100
                 ....*....|....*....|..
gi 326676116 485 HNEVIGVCRVGNDAEGLGREHW 506
Cdd:cd08383   74 RDIVIGKVALSKLDLGQGKDEW 95

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: 46.49 E-value: 2.66e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKdfsGTSDPYVKIYLlpdrktkHQTKVHR-KT---LNPVFDEVFLFPVAYADLPTRKLHFSVYDFD 347
Cdd:cd08383    1 SLRLRILEAKNLPSK---GTRDPYCTVSL-------DQVEVARtKTvekLNPFWGEEFVFDDPPPDVTFFTLSFYNKDKR 70

                         90
                 ....*....|.
gi 326676116 348 RFSRHDIIGQV 358
Cdd:cd08383   71 SKDRDIVIGKV 81

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: 46.17 E-value: 3.83e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 270 LEQLIVKIHRAQDlpaKDFSGTSDPYVKI-YLLPDRKTKHQTKVHRktlNPVFDEVFLFPVAYADL-PTRKLHFSVYDFD 347
Cdd:cd04049    3 LEVLLISAKGLQD---TDFLGKIDPYVIIqCRTQERKSKVAKGDGR---NPEWNEKFKFTVEYPGWgGDTKLILRIMDKD 76

                         90
                 ....*....|....
gi 326676116 348 RFSRHDIIGQVVVD 361
Cdd:cd04049   77 NFSDDDFIGEATIH 90

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: 46.29 E-value: 4.04e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 407 ITMIKARNLKAMDITGASDPYVKVSLmcdGRrlKKRKTSTKRNTLNPVYNEAIVFDVP---PENIDQISLLVAVMDYDRV 483
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQL---GK--EKYSTSVKEKTTSPVWKEECSFELPgllSGNGNRATLQLTVMHRNLL 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 326676116 484 GHNEVIGVCRVgndaeglgreHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08682   78 GLDKFLGQVSI----------PLNDLDEDKGRRRTRWFKL 107

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: 45.89 E-value: 4.18e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPA-KDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFpvayaDLPT--RKLHFSVYDFDR 348
Cdd:cd08401    1 SLKIKIGEAKNLPPrSGPNKMRDCYCTVNL--DQEEVFRTKTVEKSLCPFFGEDFYF-----EIPRtfRHLSFYIYDRDV 73

                         90
                 ....*....|..
gi 326676116 349 FSRHDIIGQVVV 360
Cdd:cd08401   74 LRRDSVIGKVAI 85

C2 domain second repeat found in Tac2-N (Tandem C2 protein in Nucleus); Tac2-N contains two C2 domains and a short C-terminus including a WHXL motif, which are key in stabilizing transport vesicles to the plasma membrane by binding to a plasma membrane. However unlike the usual carboxyl-terminal-type (C-type) tandem C2 proteins, it lacks a transmembrane domain, a Slp-homology domain, and a Munc13-1-interacting domain. Homology search analysis indicate that no known protein motifs are located in its N-terminus, making Tac2-N a novel class of Ca2+-independent, C-type tandem C2 proteins. 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: 176074 Cd Length: 135 Bit Score: 46.07 E-value: 6.08e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 391 DLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPV-YNEAIVFDVPPENiD 469
Cdd:cd08692    2 ELQLGTCFQAVNSRIQLQILEAQNLPSSSTPLTLSFFVKVGMFSTGGLLYKKKTRLVKSSNGQVkWGETMIFPVTQQE-H 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 326676116 470 QISLLVAVMDYDRVGHNEVIGVCRVGNDAEGL-GREHWNEMLTYPRKPIAHWHPL 523
Cdd:cd08692   81 GIQFLIKLYSRSSVRRKHFLGQVWISSDSSSSeAVEQWKDTIANPEKVVTKWHSL 135

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: 45.69 E-value: 6.42e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 390 GDLMFSLCYLPTAGRLTITMIKARNLKAMDITGASDPYVKVSLMcDGRRlKKRKTSTKRNTlNPVYNEAIVFD-VPPENI 468
Cdd:cd08389    3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWQVHLVLL-PSKK-QRAKTKVQRGP-NPVFNETFTFSrVEPEEL 79

                         90       100
                 ....*....|....*....|..
gi 326676116 469 DQISLLVAVMDYDRVGHNEVIG 490
Cdd:cd08389   80 NNMALRFRLYGVERMRKERLIG 101

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: 45.35 E-value: 9.14e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 326676116 406 TITMIKARNLKAMDITGASDPYVKVslMCDGrrlKKRKTSTKRNTLNPVYNEAIVF 461
Cdd:cd04046    6 QVHVHSAEGLSKQDSGGGADPYVII--KCEG---ESVRSPVQKDTLSPEFDTQAIF 56

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 48.22 E-value: 1.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  403 GRLTITMIKARNLKAMD--ITGASDPYVKVSLmcDGRrlKKRKTSTKRNTLNPVYNEAIVfdVPPENIDQiSLLVAVMDY 480
Cdd:COG5038   436 GVVEVKIKSAEGLKKSDstINGTVDPYITVTF--SDR--VIGKTRVKKNTLNPVWNETFY--ILLNSFTD-PLNLSLYDF 508

                          90
                  ....*....|
gi 326676116  481 DRVGHNEVIG 490
Cdd:COG5038   509 NSFKSDKVVG 518

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: 44.48 E-value: 1.33e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 326676116 410 IKARNLKAMDITGASDPYVKVsLMCDGRRLKKRK---TSTKRNTLNPVYNEAIVFDVPPENIDQisLLVAVMDYD 481
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVV-YVKTGGSGQWVEigrTEVIKNNLNPDFVTTFTVDYYFEEVQK--LRFEVYDVD 78

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: 44.70 E-value: 1.98e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 326676116 404 RLTITMIKARNLKAmdITGASDPYVKVSLMCDGRRLKKRKTSTKRNTLNPVYNEAIVFDVP 464
Cdd:cd04010    1 KLSVRVIECSDLAL--KNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVT 59

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: 43.15 E-value: 3.81e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDfSGTSDPYVKIYL----LPDRKTKHQTKVHRKTLNPVFDEVFLFPVAYADLPTR-KLHFSVYDFdRF 349
Cdd:cd08395    4 VKVVAANDLKWQT-TGMFRPFVEVNLigphLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESyELHICVKDY-CF 81

                         90
                 ....*....|..
gi 326676116 350 SRHD-IIGQVVV 360
Cdd:cd08395   82 ARDDrLVGVTVL 93

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: 43.21 E-value: 3.98e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDFSGTSDPYVKIYLlpdRKTKHQTKVHRKTLNPVFDE--VFLFPVAYADLPTR------KLHFSVYDF 346
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQL---GKEKYSTSVKEKTTSPVWKEecSFELPGLLSGNGNRatlqltVMHRNLLGL 79

                         90       100
                 ....*....|....*....|....*....
gi 326676116 347 DRFsrhdiIGQVVVD-NFLDLVDFPRETK 374
Cdd:cd08682   80 DKF-----LGQVSIPlNDLDEDKGRRRTR 103

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: 43.57 E-value: 4.02e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDI--TGASDPYVKVSLmcdGRrlKKRKTSTKRNTLNPVYNEAIVFdvpPENIDQISLL-VAVMD 479
Cdd:cd04024    1 GVLRVHVVEAKDLAAKDRsgKGKSDPYAILSV---GA--QRFKTQTIPNTLNPKWNYWCEF---PIFSAQNQLLkLILWD 72

                         90
                 ....*....|.
gi 326676116 480 YDRVGHNEVIG 490
Cdd:cd04024   73 KDRFAGKDYLG 83

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 45.14 E-value: 1.32e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  403 GRLTITMIKARNLKAMDITGASDPYVKVSLmcdgRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENidQIsLLVAVMDYDR 482
Cdd:COG5038   711 GAIRVSVRKANDLRNEIPGGKSDPYATVLV----NNLVKYRTIYGSSTLNPIWNEILYVPVTSKN--QR-LTLECMDYEE 783


                  ....*...
gi 326676116  483 VGHNEVIG 490
Cdd:COG5038   784 SGDDRNLG 791

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: 41.43 E-value: 1.66e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 392 LMFSLCYLPTAGRLTITMIKARNLKamdITGASDPYVKVSLMcDGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQI 471
Cdd:cd08677    3 LHYSLSYDKQKAELHVNILEAENIS---VDAGCECYISGCVS-VSEGQKEAQTALKKLALHTQWEEELVFPLPEEESLDG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 326676116 472 SLLVAVMDYDRVGHNEVIGVCRVG--NDAEGLGREHWNEM 509
Cdd:cd08677   79 TLTLTLRCCDRFSRHSTLGELRLKlaDVSMMLGAAQWVDL 118

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: 41.14 E-value: 2.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 275 VKIHRAQDLPAKDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVAyadlPTRKLHFSVYDFDRFSRHDI 354
Cdd:cd08382    4 LTVLCADGLAKRDLFRLPDPFAVITV--DGGQTHSTDVAKKTLDPKWNEHFDLTVG----PSSIITIQVFDQKKFKKKDQ 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 326676116 355 ----IGQVVVDNFLDLVDFPRETKLCRDIQYVSSDNVdLGDLMFSLC 397
Cdd:cd08382   78 gflgCVRIRANAVLPLKDTGYQRLDLRKLKKSDNLSV-RGKIVVSLS 123

C2 domain sixth 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 sixth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176020 Cd Length: 133 Bit Score: 41.49 E-value: 2.19e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 292 SDPYVKIYLLPDRKTKHQTKVHRKTLN--PVFDEVFLFPVAYadLPT-------RKLHFS----------------VYDF 346
Cdd:cd08374   25 SDIYVKGWLDGLEEDKQKTDVHYRSLDgeGNFNWRFVFPFDY--LPAekkivviKKEHFWsldeteykippkltlqVWDN 102

                         90       100       110
                 ....*....|....*....|....*....|...
gi 326676116 347 DRFSRHDIIGQVVvdnfLDLVDFPR---ETKLC 376
Cdd:cd08374  103 DKFSPDDFLGSLE----LDLSILPRpakTSKKC 131

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: 41.16 E-value: 2.50e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGASDPYVKvsLMCdgrRLKKRKTSTKRNT-LNPVYNEAIVFDVP-PENIDQISLLVAVMDY 480
Cdd:cd04049    1 GTLEVLLISAKGLQDTDFLGKIDPYVI--IQC---RTQERKSKVAKGDgRNPEWNEKFKFTVEyPGWGGDTKLILRIMDK 75

                         90
                 ....*....|
gi 326676116 481 DRVGHNEVIG 490
Cdd:cd04049   76 DNFSDDDFIG 85

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: 40.47 E-value: 4.77e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 326676116 405 LTITMIKARNLKAmDITGASDPYVKVSLMC---DGRRLKK-----RKTSTKRNTLNPVY-NEAIVFDVPPENIDQI 471
Cdd:cd08691    3 FSLSGLQARNLKK-GMFFNPDPYVKISIQPgkrHIFPALPhhgqeCRTSIVENTINPVWhREQFVFVGLPTDVLEI 77

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: 39.57 E-value: 8.41e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQdLPAKDFSGTSDPYVKIylLPDRKTKHQTKVHRKTLNPVFDEVFLFPVAyadlPTRKLHFSVYDFDRFSR 351
Cdd:cd04021    3 QLQITVESAK-LKSNSKSFKPDPYVEV--TVDGQPPKKTEVSKKTSNPKWNEHFTVLVT----PQSTLEFKVWSHHTLKA 75

                         90
                 ....*....|
gi 326676116 352 HDIIGQVVVD 361
Cdd:cd04021   76 DVLLGEASLD 85

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

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 39.68 E-value: 1.03e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 272 QLIVKIHRAQDLPAKDFSGTSDPYVKIYLLPDRktkHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDFDRFSR 351
Cdd:cd08375   16 RLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQE---HKTKVVSDTLNPKWNSSMQFFV--KDLEQDVLCITVFDRDFFSP 90


                 ....*
gi 326676116 352 HDIIG 356
Cdd:cd08375   91 DDFLG 95

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

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 39.22 E-value: 1.04e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 273 LIVKIHRAQDLPAkdfsGTSDPYVKIyLLPDRKTKhqTKVHRKTLNPVFDEVFLFpvAYADLPTRKLHFSVYDFDrFSRH 352
Cdd:cd08378    2 LYVRVVKARGLPA----NSNDPVVEV-KLGNYKGS--TKAIERTSNPEWNQVFAF--SKDRLQGSTLEVSVWDKD-KAKD 71

                         90
                 ....*....|....*....
gi 326676116 353 DIIGQVvvdNFlDLVDFPR 371
Cdd:cd08378   72 DFLGGV---CF-DLSEVPT 86

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: 38.12 E-value: 2.58e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKARNLKAMdiTGASDPYVKVSLmcdGRRLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDqisLLVAVMDYDRVG 484
Cdd:cd08678    1 LLVKNIKANGLSEA--AGSSNPYCVLEM---DEPPQKYQSSTQKNTSNPFWDEHFLFELSPNSKE---LLFEVYDNGKKS 72

                         90
                 ....*....|...
gi 326676116 485 HNEVIGVCRVGND 497
Cdd:cd08678   73 DSKFLGLAIVPFD 85

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: 38.03 E-value: 2.80e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 405 LTITMIKArNLKAMDITGASDPYVKVSLmcDGrrLKKRKTSTKRNTLNPVYNEAIVFDVPPENIDQISllvaVMDYDRVG 484
Cdd:cd04021    4 LQITVESA-KLKSNSKSFKPDPYVEVTV--DG--QPPKKTEVSKKTSNPKWNEHFTVLVTPQSTLEFK----VWSHHTLK 74

                         90
                 ....*....|
gi 326676116 485 HNEVIGVCRV 494
Cdd:cd04021   75 ADVLLGEASL 84

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: 37.61 E-value: 3.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 403 GRLTITMIKARNLKAMDITGASDPYVKVSLmcdgRRLKKRKTSTKRNTLNPVYNEAIVFDVPPEniDQISLLVAVMDYDR 482
Cdd:cd08681    1 GTLVVVVLKARNLPNKRKLDKQDPYCVLRI----GGVTKKTKTDFRGGQHPEWDEELRFEITED--KKPILKVAVFDDDK 74

                         90
                 ....*....|.
gi 326676116 483 -----VGHNEV 488
Cdd:cd08681   75 rkpdlIGDTEV 85

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 40.51 E-value: 3.42e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116  266 YDCDLEQLIVKIHRAQDLPAKDFSGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVAyadLPTRKLHFSVYD 345
Cdd:COG5038   706 YDTPIGAIRVSVRKANDLRNEIPGGKSDPYATVLV--NNLVKYRTIYGSSTLNPIWNEILYVPVT---SKNQRLTLECMD 780

                          90
                  ....*....|...
gi 326676116  346 FDRFSRHDIIGQV 358
Cdd:COG5038   781 YEESGDDRNLGEV 793

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain] Cd Length: 158 Bit Score: 38.44 E-value: 3.45e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 232 GQLKPELYKQRSLDGEDSRSSRVGSCGRLHFILKYDCDLEQLIVKIHRaqdlpakdfSGTSDPYVKIYLlpDRKTKHQTK 311
Cdd:cd04015    7 GTLDVTIYEADNLPNMDMFSEKLRRFFSKLVGCSEPTLKRPSSHRHVG---------KITSDPYATVDL--AGARVARTR 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 326676116 312 VHRKTLNPVFDEVFLFPVAYadlPTRKLHFSVYDFDRFSRhDIIGQVVV 360
Cdd:cd04015   76 VIENSENPVWNESFHIYCAH---YASHVEFTVKDNDVVGA-QLIGRAYI 120

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. 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-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 37.64 E-value: 4.02e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 425 DPYVKVSlmCDGRRLKKrkTSTKRNTLNPVYNEAIVFDVppENIDQISLLV---AVMDYD 481
Cdd:cd04014   36 DPYVSID--VDDTHIGK--TSTKPKTNSPVWNEEFTTEV--HNGRNLELTVfhdAAIGPD 89

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: 36.77 E-value: 4.32e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 326676116 405 LTITMIKARNLKAMDITGASDPYVKVSLmcdgrRLKKRKTSTKRNTLNPVYNEAIVFDVP-PEN 467
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVELTV-----GKTTQKSKVKERTNNPVWEEGFTFLVRnPEN 60

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: 36.81 E-value: 5.70e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 289 SGTSDPYVKIYLlpDRKTKHQTKVHRKTLNPVFDEVFLFPVayADLPTRKLHFSVYDfDRFSRHDIIGQVVVdNFLDLVD 368
Cdd:cd04052   10 TGLLSPYAELYL--NGKLVYTTRVKKKTNNPSWNASTEFLV--TDRRKSRVTVVVKD-DRDRHDPVLGSVSI-SLNDLID 83

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. 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: 175998 [Multi-domain] Cd Length: 127 Bit Score: 36.47 E-value: 9.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 326676116 270 LEQLIVKIHRAQDLPAKDFSGTsDPYVKIYLlpDRKTKhQTKVHRKTLNPVFDEVFLF-PVayaDLPTR-KLHFSVYDFD 347
Cdd:cd04032   27 LATLTVTVLRATGLWGDYFTST-DGYVKVFF--GGQEK-RTEVIWNNNNPRWNATFDFgSV---ELSPGgKLRFEVWDRD 99

                         90
                 ....*....|...
gi 326676116 348 RFSRHDIIGQVVV 360
Cdd:cd04032  100 NGWDDDLLGTCSV 112