NCBI Conserved Domain Search

Plant phosphoribosyltransferase C-terminal; This domain is found at the C-terminus of phosphoribosyltransferases and phosphoribosyltransferase-like proteins. It contains putative transmembrane regions. It often appears together with calcium-ion dependent C2 domains (pfam00168).

Pssm-ID: 337028 Cd Length: 156 Bit Score: 341.56 E-value: 7.10e-114

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 622 LPTIFLYLFLIGVWYYRWRPRHPPHMDTRLSHADSAHPDELDEEFDTFPTSRPADIVRMRYDRLRSIAGRIQTVVGDLAT 701
Cdd:pfam08372   1 LPTVFLYLFLIGLWNYRFRPRHPPHMDTRLSHADSVNPDELDEEFDTFPSSRPPDVVRMRYDRLRSVAGRVQTVVGDIAT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1725308502 702 QGERVQSLLSWRDPRATALFVIFCLVAAIVLYVTPFQVVALLTGFYVLRHPRFRHKLPSVPLNFFRRLPARTDCML 777
Cdd:pfam08372  81 QGERLQALLSWRDPRATALFVLFCLLAAVVLYVVPFKVLALLSGFYYLRHPRFRSRMPSVPLNFFRRLPSKSDSLL 156

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 266.07 E-value: 5.08e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 204 YLRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRISANRTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKDEVL 283
Cdd:cd04019     1 YLRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTRNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPL 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1725308502 284 GKCAIPLQYVDRRLDHRPVLTRWHNLERHvIVEGEKKKEIKFASRIHLRVCLEGGYHVLDESTHYSSDLRP 354
Cdd:cd04019    81 GRAVIPLNDIERRVDDRPVPSRWFSLERP-GGAMEQKKKRKFASRIHLRLCLDGGYHVLDESTHYSSDLRP 150

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: 224.50 E-value: 9.94e-70

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  41 YLYVRVVKAKDLPAkdvtGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFVKDDFIGR 120
Cdd:cd08378     1 YLYVRVVKARGLPA----NSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLGG 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1725308502 121 VVFDLNEIPKRVPPDSPLAPQWYRLEDRKSDKlLKGELMLAVWMGT 166
Cdd:cd08378    77 VCFDLSEVPTRVPPDSPLAPQWYRLEDKKGGR-VGGELMLAVWFGT 121

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 218.04 E-value: 2.91e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 366 VLELGILNAQGLMPMKTKDGRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDNCHLHSGdk 445
Cdd:cd08379     1 ILEVGILGAQGLDVLRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFDNSQSHWK-- 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1725308502 446 aAGGAKDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGVKKMGEIHLA 494
Cdd:cd08379    79 -EAVQPDVLIGKVRIRLSTLEDDRVYAHSYPLLSLNPSGVKKMGELECA 126

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 105.09 E-value: 8.95e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  40 QYLYVRVVKAKDLPAKDVTGSCDPYVEVKL--GNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKD-FVKDD 116
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDrFGRDD 80

                          90       100
                  ....*....|....*....|....*....
gi 1725308502 117 FIGRVVFDLNEIpkrvpPDSPLAPQWYRL 145
Cdd:pfam00168  81 FIGEVRIPLSEL-----DSGEGLDGWYPL 104

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: 97.17 E-value: 3.92e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502   41 YLYVRVVKAKDLPAKDVTGSCDPYVEVKLGNY---KGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKD-FVKDD 116
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDrFGRDD 80

                           90
                   ....*....|....*....
gi 1725308502  117 FIGRVVFDLNEIPKRVPPD 135
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHE 99

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 97.14 E-value: 5.17e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNY-KGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKD-FVKDDFIG 119
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDrFSKDDFLG 80

                          90       100
                  ....*....|....*....|....*.
gi 1725308502 120 RVVFDLNEIPKRVPPDsplaPQWYRL 145
Cdd:cd00030    81 EVEIPLSELLDSGKEG----ELWLPL 102

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 95.85 E-value: 1.37e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 365 GVLELGILNAQGLMPMktkDGRGTTDAYCVAKY--GQKWIRTRTIIDSFTPKWNEQYTWEVFDP-CTVLTIGVYDNCHLh 441
Cdd:pfam00168   1 GRLTVTVIEAKNLPPK---DGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPeNAVLEIEVYDYDRF- 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1725308502 442 sgdkaaggAKDSRIGKVRIRLSTLETDRVYTHSYPL 477
Cdd:pfam00168  77 --------GRDDFIGEVRIPLSELDSGEGLDGWYPL 104

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 95.08 E-value: 2.39e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 203 WYLRVNVIEAQDLIPNQPGRFPEAHVKASL--GNQILRTRIsANRTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKD 280
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKV-VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*....
gi 1725308502 281 EVLGKCAIPLQyvdrRLDHRPVLTRWHNL 309
Cdd:pfam00168  80 DFIGEVRIPLS----ELDSGEGLDGWYPL 104

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: 93.13 E-value: 1.97e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  41 YLYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQaSMLEVNVKDKDFVKD-DFIG 119
Cdd:cd08377     2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIH-DVLEVTVYDEDKDKKpEFLG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1725308502 120 RVVFDLNEIPKRVppdsplaPQWYRLEDRKSDKLLKGELML 160
Cdd:cd08377    81 KVAIPLLSIKNGE-------RKWYALKDKKLRTRAKGSILL 114

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: 80.16 E-value: 8.57e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDV--TGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKD-FVKDDFI 118
Cdd:cd04024     3 LRVHVVEAKDLAAKDRsgKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDrFAGKDYL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1725308502 119 GRVVFDLNEIpkRVPPDSPLAPQWYRLEDRKSDK--LLKGELML 160
Cdd:cd04024    83 GEFDIALEEV--FADGKTGQSDKWITLKSTRPGKtsVVSGEIHL 124

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: 79.61 E-value: 1.08e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL---GNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFVKDDFI 118
Cdd:cd04036     2 LTVRVLRATNITKGDLLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDHL 81

                          90
                  ....*....|.
gi 1725308502 119 GRVVFDLNEIP 129
Cdd:cd04036    82 GTVLFDVSKLK 92

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: 79.30 E-value: 1.50e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFS---KERIQASMLEVNVKDK--DFVKDD 116
Cdd:cd04022     2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNvsdPSRLSNLVLEVYVYNDrrSGRRRS 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1725308502 117 FIGRVVFDLNEipkrVPPDSPLAPQWYRLEDRKSDKLLKGELMLAVWM 164
Cdd:cd04022    82 FLGRVRISGTS----FVPPSEAVVQRYPLEKRGLFSRVRGEIGLKVYI 125

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: 78.49 E-value: 3.08e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKD------VTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFVKD 115
Cdd:cd08391     3 LRIHVIEAQDLVAKDkfvgglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPDKD 82

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1725308502 116 DFIGRVVFDLNEIPKrvppdSPLAPQWYRLEDRKSDKL 153
Cdd:cd08391    83 DFLGRLSIDLGSVEK-----KGFIDEWLPLEDVKSGRL 115

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: 75.98 E-value: 2.04e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFV-KDDFIGR 120
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVsKNDFLGK 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1725308502 121 VVFDLNEIPKRVPPDSplapqWYRLE-DRKSDKLLKGEL 158
Cdd:cd04025    82 VVFSIQTLQQAKQEEG-----WFRLLpDPRAEEESGGNL 115

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: 74.21 E-value: 8.52e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL-----GNYKGTTRHFEKKSNPEWNQVFAFS---KERIQASMLEVNVKDKD-F 112
Cdd:cd04031    18 LIVTVLQARDLPPRDDGSLRNPYVKVYLlpdrsEKSKRRTKTVKKTLNPEWNQTFEYSnvrRETLKERTLEVTVWDYDrD 97

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1725308502 113 VKDDFIGRVVFDLNeipkrvppDSPL--APQWYRLE 146
Cdd:cd04031    98 GENDFLGEVVIDLA--------DALLddEPHWYPLQ 125

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: 73.44 E-value: 1.39e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  46 VVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDF-VKDDFIGRVVFD 124
Cdd:cd08376     6 LVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTgKKDEFIGRCEID 85


                  ....*.
gi 1725308502 125 LNEIPK 130
Cdd:cd08376    86 LSALPR 91

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: 73.13 E-value: 2.48e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL---GNYKGTTRHFEKKSNPEWNQVFAF---SKERIQASMLEVNVKDKD-FVK 114
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFegfPYEKLQQRVLYLQVLDYDrFSR 97

                          90
                  ....*....|....
gi 1725308502 115 DDFIGRVVFDLNEI 128
Cdd:cd08386    98 NDPIGEVSLPLNKV 111

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: 72.10 E-value: 3.26e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGN-QILRTRIsANRTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKDEVL 283
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKV-VKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79

                          90       100
                  ....*....|....*....|....*.
gi 1725308502 284 GKCAIPLQYVdrrLDHRPVLTRWHNL 309
Cdd:cd00030    80 GEVEIPLSEL---LDSGKEGELWLPL 102

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: 71.75 E-value: 3.31e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  204 YLRVNVIEAQDLIPNQPGRFPEAHVKASLGNQ---ILRTRISANrTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKD 280
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKN-TLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRD 79

                           90       100
                   ....*....|....*....|.
gi 1725308502  281 EVLGKCAIPLQYVDRRLDHRP 301
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRHEK 100

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: 71.43 E-value: 9.28e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VR--VVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTR--HFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFV-KDDFI 118
Cdd:cd04037     2 VRvyVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLgSDDLI 81


                  ....*..
gi 1725308502 119 GRVVFDL 125
Cdd:cd04037    82 GETVIDL 88

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: 71.59 E-value: 1.48e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGScDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSkerIQASM--LEVNVKDKD-FVKDDFI 118
Cdd:cd04038     4 LKVRVVRGTNLAVRDFTSS-DPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLS---VPNPMapLKLEVFDKDtFSKDDSM 79


                  ....*..
gi 1725308502 119 GRVVFDL 125
Cdd:cd04038    80 GEAEIDL 86

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: 70.03 E-value: 1.77e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKD-VTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWN-QVFAF--SKERIQASMLEVNVKDKD-FVKDD 116
Cdd:cd08688     1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNsEWFRFevDDEELQDEPLQIRVMDHDtYSAND 80

                          90
                  ....*....|
gi 1725308502 117 FIGRVVFDLN 126
Cdd:cd08688    81 AIGKVYIDLN 90

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: 68.94 E-value: 9.10e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKdVTGSCDPYVEVKLGN-YKGTTRHFE--KKSN-PEWNQVFAF---------------SKERIQASM 102
Cdd:cd08675     1 LSVRVLECRDLALK-SNGTCDPFARVTLNYsSKTDTKRTKvkKKTNnPRFDEAFYFeltigfsyekksfkvEEEDLEKSE 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1725308502 103 LEVNVKDKDFV-KDDFIGRVVFDLNEIPKRVPPDSplapqWYRLEDRKS 150
Cdd:cd08675    80 LRVELWHASMVsGDDFLGEVRIPLQGLQQAGSHQA-----WYFLQPREA 123

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: 65.94 E-value: 3.65e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 367 LELGILNAQGLMPMktkDGRGTTDAYCVAKYGQKWI-RTRTIIDSFTPKWNEQYTWEVFDP-CTVLTIGVYDNChlhsgd 444
Cdd:cd00030     1 LRVTVIEARNLPAK---DLNGKSDPYVKVSLGGKQKfKTKVVKNTLNPVWNETFEFPVLDPeSDTLTVEVWDKD------ 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1725308502 445 kaaGGAKDSRIGKVRIRLSTLETDR-VYTHSYPL 477
Cdd:cd00030    72 ---RFSKDDFLGEVEIPLSELLDSGkEGELWLPL 102

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: 66.88 E-value: 4.82e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  40 QYLYVRVVKAKDLPAKDVTGSCDPYVEVKL-------GNYKGTTRHFEKKSNPEWNQVFAFS----KERIQASMLEVNVK 108
Cdd:cd04009    16 QSLRVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQVKKKTLFPLFDESFEFNvppeQCSVEGALLLFTVK 95

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1725308502 109 DKDFV-KDDFIGRVVFDLNEIPKRVPPDSPLAPQ 141
Cdd:cd04009    96 DYDLLgSNDFEGEAFLPLNDIPGVEDTSSAQGFG 129

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: 66.13 E-value: 6.80e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  33 YDLveQMQYLYVRVVKAKDLPAKDVTGSCDPYVEVKLGN---YKGTTRHFEKKSNPEWNQVFAFS--KERIQASMLEVNV 107
Cdd:cd08385    11 YDF--QSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPdkkKKFETKVHRKTLNPVFNETFTFKvpYSELGNKTLVFSV 88

                          90       100
                  ....*....|....*....|..
gi 1725308502 108 KDKD-FVKDDFIGRVVFDLNEI 128
Cdd:cd08385    89 YDFDrFSKHDLIGEVRVPLLTV 110

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: 65.67 E-value: 8.94e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAF----SKERIQASMLEVNVKDKDFVK--- 114
Cdd:cd04027     3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFechnSSDRIKVRVWDEDDDIKSRLKqkf 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1725308502 115 ----DDFIGRVVFDLNEIpkrvppdSPLAPQWYRLEDRKSDKLLKGELMLAV 162
Cdd:cd04027    83 tresDDFLGQTIIEVRTL-------SGEMDVWYNLEKRTDKSAVSGAIRLHI 127

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: 64.05 E-value: 1.58e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  366 VLELGILNAQGLMPMktkDGRGTTDAYCVAKYGQKWI---RTRTIIDSFTPKWNEQYTWEVFDPCT-VLTIGVYDNCHLH 441
Cdd:smart00239   1 TLTVKIISARNLPPK---DKGGKSDPYVKVSLDGDPKekkKTKVVKNTLNPVWNETFEFEVPPPELaELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|....*.
gi 1725308502  442 sgdkaaggaKDSRIGKVRIRLSTLET 467
Cdd:smart00239  78 ---------RDDFIGQVTIPLSDLLL 94

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: 64.22 E-value: 3.19e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  28 KLTSTYDlvEQMQYLYVRVVKAKDLPAKDVTGSCDPYVEVKL--GNYKGTTR--HFEKKS-NPEWNQVFAF--SKERIQA 100
Cdd:cd04030     6 QLTIRYS--SQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLlpDKSKSTRRktSVKKDNlNPVFDETFEFpvSLEELKR 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1725308502 101 SMLEVNVKDKD--FVKD-DFIGRVVFDLNEIpkrvpPDSPLAPQWYRLE 146
Cdd:cd04030    84 RTLDVAVKNSKsfLSREkKLLGQVLIDLSDL-----DLSKGFTQWYDLT 127

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: 63.83 E-value: 3.45e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGN---YKGTTRHfeKKSNPEWNQVFAFSKERIQASMLeVNVKDKDFV-KDDF 117
Cdd:cd04042     2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGktvYKSKTIY--KNLNPVWDEKFTLPIEDVTQPLY-IKVFDYDRGlTDDF 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1725308502 118 IGRVVFDLNEIPKRVPPDSPLapqwyRLEDRKSDKLLkGELMLAV 162
Cdd:cd04042    79 MGSAFVDLSTLELNKPTEVKL-----KLEDPNSDEDL-GYISLVV 117

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: 64.30 E-value: 3.57e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGT-------TRHFEKKSNPEWNQVFAFSKERIQASMLeVNVKDKD-FV 113
Cdd:cd04033     2 LRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNgeidsvqTKTIKKTLNPKWNEEFFFRVNPREHRLL-FEVFDENrLT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1725308502 114 KDDFIGRVVFDLNEIPKRVP-PDSPLAPQWYRLEDRKSDKLLKGELML 160
Cdd:cd04033    81 RDDFLGQVEVPLNNLPTETPgNERRYTFKDYLLRPRSSKSRVKGHLRL 128

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: 64.36 E-value: 3.89e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLgNYKGttRHFEKKS--------NPEWNQVFAFS--KERIQASMLEVNVKDKD 111
Cdd:cd08405    17 ITVNIIKARNLKAMDINGTSDPYVKVWL-MYKD--KRVEKKKtvikkrtlNPVFNESFIFNipLERLRETTLIITVMDKD 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1725308502 112 FV-KDDFIGRVVFDLNEIPKRVP--------PDSPLApQWYRL 145
Cdd:cd08405    94 RLsRNDLIGKIYLGWKSGGLELKhwkdmlskPRQPVA-QWHRL 135

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: 64.31 E-value: 4.86e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPY------VEVKLGNYKGTTRHFEKKS-----------------------NPEWNQVFA 92
Cdd:cd08676    30 LKVTVIEAKGLLAKDVNGFSDPYcmlgivPASRERNSEKSKKRKSHRKkavlkdtvpaksikvtevkpqtlNPVWNETFR 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1725308502  93 FSKERIQASMLEVNVKDKDfvkDDFIGRVVFDLNEIPkrvppdSPLAPQWYRL 145
Cdd:cd08676   110 FEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLP------SCGLDSWFKL 153

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: 62.99 E-value: 9.63e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEV-------KLGNYKGTTRHfeKKSNPEWNQVFAF--SKERIQASMLEVNVKDKD- 111
Cdd:cd00276    16 LTVVVLKARNLPPSDGKGLSDPYVKVsllqggkKLKKKKTSVKK--GTLNPVFNEAFSFdvPAEQLEEVSLVITVVDKDs 93

                          90
                  ....*....|....*
gi 1725308502 112 FVKDDFIGRVVFDLN 126
Cdd:cd00276    94 VGRNEVIGQVVLGPD 108

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: 61.80 E-value: 1.78e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 364 IGVLELGILNAQGLMPMKTKDgrGTTDAYCVAKYGQKWI--RTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDnchlH 441
Cdd:cd04044     1 IGVLAVTIKSARGLKGSDIIG--GTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETKYILVNSLTEPLNLTVYD----F 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1725308502 442 SGDKaaggaKDSRIGKVRIRLSTLETDRVYTH-SYPLLvlypNGVKKMGEIHLAVRF 497
Cdd:cd04044    75 NDKR-----KDKLIGTAEFDLSSLLQNPEQENlTKNLL----RNGKPVGELNYDLRF 122

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: 61.53 E-value: 2.82e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL--GNYKGT---TRHFEKKSNPEWNQVFAF---SKERIQASMLEVNVKDKDFV 113
Cdd:cd04035    17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpGASKATklrTKTVHKTRNPEFNETLTYygiTEEDIQRKTLRLLVLDEDRF 96

                          90       100
                  ....*....|....*....|
gi 1725308502 114 KDDFIGRVVFDL-NEIPKRV 132
Cdd:cd04035    97 GNDFLGETRIPLkKLKPNQT 116

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: 60.66 E-value: 3.50e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGN---YKgtTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFV-KDDF 117
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLNGekvFK--TKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGgKDDL 78

                          90
                  ....*....|.
gi 1725308502 118 IGRVVFDLNEI 128
Cdd:cd04040    79 LGSAYIDLSDL 89

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: 60.04 E-value: 9.13e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 371 ILNAQGLMPmktKDGRGTTDAYCVAKY-GQKwIRTRTIIDSFTPKWNEQYTWEVFDPCT----VLTIGVYDnchlhsgDK 445
Cdd:cd04022     6 VVDAQDLMP---KDGQGSSSAYVELDFdGQK-KRTRTKPKDLNPVWNEKLVFNVSDPSRlsnlVLEVYVYN-------DR 74

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1725308502 446 AAGGAKdSRIGKVRIRLSTL--ETDRVYTHsYPL 477
Cdd:cd04022    75 RSGRRR-SFLGRVRISGTSFvpPSEAVVQR-YPL 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: 59.97 E-value: 9.17e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL-----GNYKGTTRHFEKKSNPEWNQVFAFS-KERIQASMLEVNVKDKD-FVK 114
Cdd:cd04026    15 LTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDlKPADKDRRLSIEVWDWDrTTR 94

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1725308502 115 DDFIGRVVFDLNEIPKRvPPDSplapqWYRLEDRKSDK 152
Cdd:cd04026    95 NDFMGSLSFGVSELIKM-PVDG-----WYKLLNQEEGE 126

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: 60.25 E-value: 1.04e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  41 YLYvrvvKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAF-------SKERIQASM--LEVNVKDKD 111
Cdd:cd04017     6 YIY----QARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFdevelygSPEEIAQNPplVVVELFDQD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1725308502 112 FV-KDDFIGRVVFDlnEIPKRVP-PDSPLAPQWYRLedrKSDKLLKGELMLAV 162
Cdd:cd04017    82 SVgKDEFLGRSVAK--PLVKLDLeEDFPPKLQWFPI---YKGGQSAGELLAAF 129

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: 58.11 E-value: 3.50e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGN--YKGTTRHfEKKSNPEWNQVFAFSKERIQA---SMLEVNVKDKD-FVKD 115
Cdd:cd04049     3 LEVLLISAKGLQDTDFLGKIDPYVIIQCRTqeRKSKVAK-GDGRNPEWNEKFKFTVEYPGWggdTKLILRIMDKDnFSDD 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1725308502 116 DFIGRVVFDLNEI--PKRVPPDSPLAPQWYRLEDrkSDKLLKGEL 158
Cdd:cd04049    82 DFIGEATIHLKGLfeEGVEPGTAELVPAKYNVVL--EDDTYKGEI 124

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: 57.26 E-value: 5.85e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  41 YLYVRVVKAKDLPAKDVTGSCDPYVEVKLGnykgttrHFEKKS--------NPEWNQVFAFSKERIQASMLEVNVKDKDF 112
Cdd:cd08681     2 TLVVVVLKARNLPNKRKLDKQDPYCVLRIG-------GVTKKTktdfrggqHPEWDEELRFEITEDKKPILKVAVFDDDK 74

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1725308502 113 VKDDFIGRVVFDLNEIPKRVPPDsplapQWYRL 145
Cdd:cd08681    75 RKPDLIGDTEVDLSPALKEGEFD-----DWYEL 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: 57.65 E-value: 5.91e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  33 YDLVEQmqYLYVRVVKAKDLPAKDVT-GSCDPYVEVKL----GNYKgTTRHFEKKSNPEWNQVFAF--SKERIQASMLEV 105
Cdd:cd08390     9 YDLEEE--QLTVSLIKARNLPPRTKDvAHCDPFVKVCLlpdeRRSL-QSKVKRKTQNPNFDETFVFqvSFKELQRRTLRL 85

                          90       100
                  ....*....|....*....|...
gi 1725308502 106 NVKDKD-FVKDDFIGRVVFDLNE 127
Cdd:cd08390    86 SVYDVDrFSRHCIIGHVLFPLKD 108

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: 57.59 E-value: 8.30e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL--GNQIL---RTRISaNRTINPMWNEDLMF-VAAEPFEE-PLILSVEDRVGG 277
Cdd:cd00276    16 LTVVVLKARNLPPSDGKGLSDPYVKVSLlqGGKKLkkkKTSVK-KGTLNPVFNEAFSFdVPAEQLEEvSLVITVVDKDSV 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1725308502 278 NKDEVLGKCAIPLQYVDRRLDH---------RPVlTRWHNL 309
Cdd:cd00276    95 GRNEVIGQVVLGPDSGGEELEHwnemlasprKPI-ARWHKL 134

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: 57.27 E-value: 9.31e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  41 YLY-VRVVKAKDLPAKDVTGSCDPYVEVKLGNYK---GTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFVKD- 115
Cdd:cd04043     1 HLFtIRIVRAENLKADSSNGLSDPYVTLVDTNGKrriAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKh 80

                          90
                  ....*....|....*.
gi 1725308502 116 DFIGRVVFDLNeiPKR 131
Cdd:cd04043    81 DLCGRASLKLD--PKR 94

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: 57.39 E-value: 1.06e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKD-FVKDDFIGR 120
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDfFSPDDFLGR 96

                          90
                  ....*....|
gi 1725308502 121 VVFDLNEIPK 130
Cdd:cd08375    97 TEIRVADILK 106

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: 57.03 E-value: 1.21e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLgnYKGTTRHFEKKS-------NPEWNQVFAF--SKERIQASMLEVNVKDKDF 112
Cdd:cd08402    17 LTVVILEAKNLKKMDVGGLSDPYVKIHL--MQNGKRLKKKKTtikkrtlNPYYNESFSFevPFEQIQKVHLIVTVLDYDR 94

                          90
                  ....*....|.
gi 1725308502 113 V-KDDFIGRVV 122
Cdd:cd08402    95 IgKNDPIGKVV 105

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: 56.90 E-value: 1.24e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWN--QVFAFSKERIQASmleVNVKDKDFVKDDFIGRV 121
Cdd:cd04046     7 VHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDtqAIFYRKKPRSPIK---IQVWNSNLLCDEFLGQA 83

                          90       100
                  ....*....|....*....|
gi 1725308502 122 VFDLNEIPKRVPPDSPLAPQ 141
Cdd:cd04046    84 TLSADPNDSQTLRTLPLRKR 103

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: 55.82 E-value: 2.77e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  36 VEQMQYLYVRVVKAKDLPAKDVTGSCDPYVEVKL-----GNYKGTTRHFEKKSNPEWNQVFAF--SKERIQASMLEVNVK 108
Cdd:cd08384     9 NTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLkpdagKKSKHKTQVKKKTLNPEFNEEFFYdiKHSDLAKKTLEITVW 88

                          90
                  ....*....|....*....
gi 1725308502 109 DKDFVK-DDFIGRVVFDLN 126
Cdd:cd08384    89 DKDIGKsNDYIGGLQLGIN 107

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 54.18 E-value: 6.64e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRiSANRTINPMWNE--DL-MFVAAepfEEPLILSVEDRVGGNKDE 281
Cdd:cd08376     2 VTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSK-VCSKTLNPQWLEqfDLhLFDDQ---SQILEIEVWDKDTGKKDE 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 1725308502 282 VLGKCAIPLQYVDRRLDHRpvltRWHNLER 311
Cdd:cd08376    78 FIGRCEIDLSALPREQTHS----LELELED 103

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 54.74 E-value: 6.83e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLgnYKGTTRHFEKKS-------NPEWNQVFAFS--KERIQASMLEVNVKDKDF 112
Cdd:cd08404    17 LTVVVLKARHLPKMDVSGLADPYVKVNL--YYGKKRISKKKThvkkctlNPVFNESFVFDipSEELEDISVEFLVLDSDR 94

                          90
                  ....*....|.
gi 1725308502 113 V-KDDFIGRVV 122
Cdd:cd08404    95 VtKNEVIGRLV 105

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: 54.22 E-value: 9.49e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 365 GVLELGILNAQGLMpmkTKD------GRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYtwEVF---DPCTVLTIGVY 435
Cdd:cd08391     1 GVLRIHVIEAQDLV---AKDkfvgglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVY--EAVvdeVPGQELEIELF 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1725308502 436 DNchlhsgDkaagGAKDSRIGKVRIRLSTLETDRVYTHSYPLlvlypNGVKKmGEIHL 493
Cdd:cd08391    76 DE------D----PDKDDFLGRLSIDLGSVEKKGFIDEWLPL-----EDVKS-GRLHL 117

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: 54.95 E-value: 9.81e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKD----------VTGS----CDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSK------ERIQas 101
Cdd:cd04018     2 FIFKIYRAEDLPQMDsgimanvkkaFLGEkkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEmfpplcERIK-- 79

                          90       100
                  ....*....|....*....|....*...
gi 1725308502 102 mleVNVKDKDFV-KDDFIGRVVFDLNEI 128
Cdd:cd04018    80 ---IQIRDWDRVgNDDVIGTHFIDLSKI 104

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: 54.09 E-value: 1.29e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 203 WYLRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRISANrTINPMWNEDLMF-----------VAAEPfeePLIlSV 271
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKE-TLSPTWDQTLIFdevelygspeeIAQNP---PLV-VV 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1725308502 272 E----DRVGgnKDEVLGKC-AIPLQYVDRRLDHRPVLtRWHNLERHVIVEGE 318
Cdd:cd04017    76 ElfdqDSVG--KDEFLGRSvAKPLVKLDLEEDFPPKL-QWFPIYKGGQSAGE 124

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: 53.43 E-value: 1.44e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 383 KDGRGTTDAYCVAKYGQKWI-RTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDNchlhsgDKaagGAKDSRIGKVRIR 461
Cdd:cd04042    15 RDRGGTSDPYVKFKYGGKTVyKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDY------DR---GLTDDFMGSAFVD 85

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1725308502 462 LSTLETDRVYTHSYPLlvLYPNGVKKMGEIHLAVRFT 498
Cdd:cd04042    86 LSTLELNKPTEVKLKL--EDPNSDEDLGYISLVVTLT 120

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 58.62 E-value: 1.49e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502   34 DLVEQMQYLYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKG-TTRHFEKKSNPEWNQVFafsKERIQA---SMLEVNVKD 109
Cdd:COG5038   1034 EMVENSGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVyKTKVVKKTLNPVWNEEF---TIEVLNrvkDVLTINVND 1110

                           90       100
                   ....*....|....*....|....*
gi 1725308502  110 KDFV-KDDFIGRVVFDLNEIPKRVP 133
Cdd:COG5038   1111 WDSGeKNDLLGTAEIDLSKLEPGGT 1135

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: 53.41 E-value: 1.60e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 201 KLWY------LRVNVIEAQDLIPNQPGRFPEAHVK------ASLGNQiLRTRISAnRTINPMWNEDLMF--VAAEPFEEP 266
Cdd:cd04031     8 QLWYdkvtsqLIVTVLQARDLPPRDDGSLRNPYVKvyllpdRSEKSK-RRTKTVK-KTLNPEWNQTFEYsnVRRETLKER 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1725308502 267 LI-LSVEDRVGGNKDEVLGKCAIPLQyvDRRLDHRPvltRWHNLE 310
Cdd:cd04031    86 TLeVTVWDYDRDGENDFLGEVVIDLA--DALLDDEP---HWYPLQ 125

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: 53.56 E-value: 1.65e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  32 TYDlvEQMQYLYVRVVKAKDLPAKDVTGSCDPYVEVKL----GNYKGTTRHfEKKSNPEWNQVFAF--SKERIQASMLEV 105
Cdd:cd08387    10 EYD--KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLlpdrSNTKQSKIH-KKTLNPEFDESFVFevPPQELPKRTLEV 86

                          90       100
                  ....*....|....*....|....
gi 1725308502 106 NVKDKD-FVKDDFIGRVVFDLNEI 128
Cdd:cd08387    87 LLYDFDqFSRDECIGVVELPLAEV 110

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: 53.87 E-value: 2.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRfPEAHVKASLGNQILRTRIsANRTINPMWNEDLMFVAAEPfEEPLILSVEDRVGGNKDEVLG 284
Cdd:cd04038     4 LKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRV-IKKNLNPVWNEELTLSVPNP-MAPLKLEVFDKDTFSKDDSMG 80


                  ....*..
gi 1725308502 285 KCAIPLQ 291
Cdd:cd04038    81 EAEIDLE 87

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: 52.74 E-value: 3.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDV-TGSCDPYVEVKL---GNYKGTTRHFEKKSNPEWNQVFAF---SKERIQASMLEVNVKDKD-FV 113
Cdd:cd08388    18 LLVNIIECRDLPAMDEqSGTSDPYVKLQLlpeKEHKVKTRVLRKTRNPVYDETFTFygiPYNQLQDLSLHFAVLSFDrYS 97

                          90
                  ....*....|....*.
gi 1725308502 114 KDDFIGRVVFDLNEIP 129
Cdd:cd08388    98 RDDVIGEVVCPLAGAD 113

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: 52.78 E-value: 4.38e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDvtGSCDPYVEVKL--GNYKGTTRHFE---KKSNPEWNQVFAF------SKERIQ-------ASML 103
Cdd:cd04010     2 LSVRVIECSDLALKN--GTCDPYASVTLiySNKKQDTKRTKvkkKTNNPQFDEAFYFdvtidsSPEKKQfempeedAEKL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1725308502 104 EVNVK---DKDFVKDDFIGRVvfdlnEIPKRVPPDSPLAPQ-WYRLEDR 148
Cdd:cd04010    80 ELRVDlwhASMGGGDVFLGEV-----RIPLRGLDLQAGSHQaWYFLQPR 123

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: 52.04 E-value: 6.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 365 GVLELGILNAQGLMPmKTKDGRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDP-CTVLTIGVYDNchlhsg 443
Cdd:cd04024     1 GVLRVHVVEAKDLAA-KDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAqNQLLKLILWDK------ 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1725308502 444 DKaagGAKDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGVKKM----GEIHLavRFT 498
Cdd:cd04024    74 DR---FAGKDYLGEFDIALEEVFADGKTGQSDKWITLKSTRPGKTsvvsGEIHL--QFS 127

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: 51.46 E-value: 8.89e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VRVVKAKDLpaKDVTGSC--DPYVEVKL-GNYKGTTR-HFEKKSNPEWNQVFAFS-KERI---QASMLEVNVKDKD-FVK 114
Cdd:cd04051     4 ITIISAEDL--KNVNLFGkmKVYAVVWIdPSHKQSTPvDRDGGTNPTWNETLRFPlDERLlqqGRLALTIEVYCERpSLG 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1725308502 115 DDFIGRVVFDLNEIPKRVPPDSPLAPQWYRLED 147
Cdd:cd04051    82 DKLIGEVRVPLKDLLDGASPAGELRFLSYQLRR 114

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: 51.36 E-value: 9.71e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYK-GTTRHFEKKSNPEWNQVFAFSKERIQASmLEVNVKDKDFV-KDDFIG 119
Cdd:cd04054     2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNEViIRTATVWKTLNPFWGEEYTVHLPPGFHT-VSFYVLDEDTLsRDDVIG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1725308502 120 RVVFDLNEI---PKRVppDSplapqWYRLEDRKSDKLLKGELMLAVWM 164
Cdd:cd04054    81 KVSLTREVIsahPRGI--DG-----WMNLTEVDPDEEVQGEIHLELSV 121

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: 50.14 E-value: 2.71e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 206 RVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRIsANRTINPMWNEDLMF-----VAAEPFEEPLILSVEDRVGGNKD 280
Cdd:cd08682     2 QVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSV-KEKTTSPVWKEECSFelpglLSGNGNRATLQLTVMHRNLLGLD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1725308502 281 EVLGKCAIPLQYVDRRLDHRpvLTRWHNLERHvivEGEKKKE 322
Cdd:cd08682    81 KFLGQVSIPLNDLDEDKGRR--RTRWFKLESK---PGKDDKE 117

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: 48.83 E-value: 5.33e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1725308502 365 GVLELGILNAQGLMpmkTKDGRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYD 436
Cdd:cd08377     1 GFLQVKVIRASGLA---AADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYD 69

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: 48.97 E-value: 6.16e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 366 VLELGILNAQGLMPmkTKDGRGTTDAYCVAKYGQKWI-RTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDNchlhsgD 444
Cdd:cd08401     1 SLKIKIGEAKNLPP--RSGPNKMRDCYCTVNLDQEEVfRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDR------D 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1725308502 445 KAAggaKDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGvKKMGEIHLAVRF 497
Cdd:cd08401    73 VLR---RDSVIGKVAIKKEDLHKYYGKDTWFPLQPVDADS-EVQGKVHLELRL 121

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: 48.99 E-value: 6.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAF-----SKERIQASMLEVNVKDKDFV-KDDF 117
Cdd:cd08682     3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFelpglLSGNGNRATLQLTVMHRNLLgLDKF 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1725308502 118 IGRVVFDLNEI------PKRvppdsplapQWYRLEDRKSDK 152
Cdd:cd08682    83 LGQVSIPLNDLdedkgrRRT---------RWFKLESKPGKD 114

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 48.02 E-value: 1.06e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 374 AQGLMPMktkDGRGTTDAYCVAKYG-QKWiRTRTIIDSFTPKWNEQYTWEVF-DPCTVLTIGVYDNchlhsgdkaAGGAK 451
Cdd:cd08376     9 GKNLPPM---DDNGLSDPYVKFRLGnEKY-KSKVCSKTLNPQWLEQFDLHLFdDQSQILEIEVWDK---------DTGKK 75

                          90       100
                  ....*....|....*....|....*.
gi 1725308502 452 DSRIGKVRIRLSTLETDRVYTHSYPL 477
Cdd:cd08376    76 DEFIGRCEIDLSALPREQTHSLELEL 101

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: 48.86 E-value: 1.19e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1725308502 387 GTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYD 436
Cdd:cd04038    20 TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFD 69

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 51.68 E-value: 1.87e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502   42 LYVRVVKAKDLPAKD--VTGSCDPYVEVKL-GNYKGTTRHFEKKSNPEWNQ-----VFAFSkERIQASMLEVNvkdkDFV 113
Cdd:COG5038    438 VEVKIKSAEGLKKSDstINGTVDPYITVTFsDRVIGKTRVKKNTLNPVWNEtfyilLNSFT-DPLNLSLYDFN----SFK 512

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  114 KDDFIGRVVFDLNEIPKrvppDSPLAPQWYRLedrKSDKLLKGELmlavwmgtqadeAFPEAWHSDAATVSGTDGlanir 193
Cdd:COG5038    513 SDKVVGSTQLDLALLHQ----NPVKKNELYEF---LRNTKNVGRL------------TYDLRFFPVIEDKKELKG----- 568

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  194 SKVYL-SPKLWYLRVNVIEAQDLiPNQPGRFPEAHVKASLGNQILRTRISANRTINPMWNEDLMFVAAEPFEEPLILSVE 272
Cdd:COG5038    569 SVEPLeDSNTGILKVTLREVKAL-DELSSKKDNKSAELYTNAKEVYSTGKLKFTNHPSWNLQYNVLVTDRKNSSIKVVTF 647

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  273 DrvgGNKDEVLGKCAIPLQ-YVDRRLDhrpvltrwhnlERHVIVEGEKKKEIkFASRIHLRVCLEGGyhvLDESTHYSSD 351
Cdd:COG5038    648 D---VQSGKVIATEGSTLPdLIDRTLD-----------TFLVFPLRNPKGRI-FITNYWKPIYNAGG---SSSKTVYDTP 709

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  352 lrptakqlwkshIGVLELGILNAQGLmpmKTKDGRGTTDAYC-VAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVL 430
Cdd:COG5038    710 ------------IGAIRVSVRKANDL---RNEIPGGKSDPYAtVLVNNLVKYRTIYGSSTLNPIWNEILYVPVTSKNQRL 774


                   ....*.
gi 1725308502  431 TIGVYD 436
Cdd:COG5038    775 TLECMD 780

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: 48.09 E-value: 2.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL-----GNYKGTTRHFEKKSNPEWNQVF---AFSKERIQASMLEVNVKDKD-F 112
Cdd:cd04020    29 LHVWVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFvydGVSPEDLSQACLELTVWDHDkL 108


                  ....*..
gi 1725308502 113 VKDDFIG 119
Cdd:cd04020   109 SSNDFLG 115

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 46.79 E-value: 2.62e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASMLEVNVKDKDFVKDdfIGRV 121
Cdd:cd04050     2 LFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKS--LGSL 79


                  ....*..
gi 1725308502 122 VFDLNEI 128
Cdd:cd04050    80 TLPLSEL 86

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

Pssm-ID: 176013 [Multi-domain] Cd Length: 120 Bit Score: 46.79 E-value: 3.25e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  47 VKAKDLPAKDVTGSCDPYVEVKL--GNYKGTTRHF-----EKKSNPEWNQVFAF-----SKERIQASMLEVNVKDKDFVK 114
Cdd:cd04048     7 ISCRNLLDKDVLSKSDPFVVVYVktGGSGQWVEIGrteviKNNLNPDFVTTFTVdyyfeEVQKLRFEVYDVDSKSKDLSD 86

                          90
                  ....*....|....
gi 1725308502 115 DDFIGRVVFDLNEI 128
Cdd:cd04048    87 HDFLGEAECTLGEI 100

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 46.52 E-value: 4.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 204 YLRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRiSANRTINPMWNEDLMFvAAEPFEEPLILSVEDRVGGNKDEVL 283
Cdd:cd08377     2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTH-TIYKTLNPEWNKIFTF-PIKDIHDVLEVTVYDEDKDKKPEFL 79

                          90       100
                  ....*....|....*....|....*.
gi 1725308502 284 GKCAIPLqyvdrrLDHRPVLTRWHNL 309
Cdd:cd08377    80 GKVAIPL------LSIKNGERKWYAL 99

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 176025 [Multi-domain] Cd Length: 126 Bit Score: 46.25 E-value: 5.44e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1725308502  52 LPAKDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFS----KERIQASMLEVNV--KDKDFVKDDFIGRV 121
Cdd:cd08379    15 LRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPvydpCTVLTVGVFDNSQshWKEAVQPDVLIGKV 90

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: 46.38 E-value: 5.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLP--AKDVTGSCDPYVEVKL------GNYKGTTRHFEKKS-NPEWNQVFAFSKERIQASMLEVNVKDKDF 112
Cdd:cd00275     4 LTIKIISGQQLPkpKGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKNNGfNPVWNETFEFDVTVPELAFLRFVVYDEDS 83

                          90
                  ....*....|....*.
gi 1725308502 113 VKDDFIGRVVFDLNEI 128
Cdd:cd00275    84 GDDDFLGQACLPLDSL 99

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176040 [Multi-domain] Cd Length: 127 Bit Score: 46.29 E-value: 6.00e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  39 MQYLYVRVVKAKdlpAKDVTGSCDPYVEVKLGNYKGTTRHFeKKSNPEWNQVFAFSKERIQASMLeVNVKDKDFVKDDFI 118
Cdd:cd08394     1 MSLLCVLVKKAK---LDGAPDKFNTYVTLKVQNVKSTTIAV-RGSQPCWEQDFMFEINRLDLGLV-IELWNKGLIWDTLV 75

                          90
                  ....*....|.
gi 1725308502 119 GRVVFDLNEIP 129
Cdd:cd08394    76 GTVWIPLSTIR 86

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: 45.62 E-value: 8.87e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDL-----IPNQPGrfPEAHVKASLGNQILRTRISANrTINPMWNEDLMFVAAEpFEEPLILSVEDRVGGNK 279
Cdd:cd04044     4 LAVTIKSARGLkgsdiIGGTVD--PYVTFSISNRRELARTKVKKD-TSNPVWNETKYILVNS-LTEPLNLTVYDFNDKRK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1725308502 280 DEVLGKCAIPLqyvdRRLDHRPVLTrwhNLERHVIVEGEKKKEIKF 325
Cdd:cd04044    80 DKLIGTAEFDL----SSLLQNPEQE---NLTKNLLRNGKPVGELNY 118

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: 45.62 E-value: 9.96e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKD-VTGSCDPYVEVKLGNYK--GTTRHFEKKSNPEWNQvfafSKERIQAS---MLEVNVKDK-DFVK 114
Cdd:cd04044     4 LAVTIKSARGLKGSDiIGGTVDPYVTFSISNRRelARTKVKKDTSNPVWNE----TKYILVNSltePLNLTVYDFnDKRK 79

                          90
                  ....*....|....
gi 1725308502 115 DDFIGRVVFDLNEI 128
Cdd:cd04044    80 DKLIGTAEFDLSSL 93

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: 45.25 E-value: 1.21e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 367 LELGILNAQGLMpmkTKDGRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYD 436
Cdd:cd04027     3 ISITVVCAQGLI---AKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWD 69

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: 44.98 E-value: 1.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPN--------QPGRFPeaHVKASLGNQILRTRISANrTINPMWNEdlMFVAAEPFEEPLILSVE--DR 274
Cdd:cd08391     3 LRIHVIEAQDLVAKdkfvgglvKGKSDP--YVIVRVGAQTFKSKVIKE-NLNPKWNE--VYEAVVDEVPGQELEIElfDE 77

                          90
                  ....*....|....*....
gi 1725308502 275 VGGnKDEVLGKCAIPLQYV 293
Cdd:cd08391    78 DPD-KDDFLGRLSIDLGSV 95

Integral peroxisomal membrane peroxin; Peroxisomes play diverse roles in the cell, compartmentalising many activities related to lipid metabolism and functioning in the decomposition of toxic hydrogen peroxide. Sequence similarity was identified between two hypothetical proteins and the peroxin integral membrane protein Pex24p.

Pssm-ID: 399414 [Multi-domain] Cd Length: 369 Bit Score: 48.19 E-value: 1.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 595 ICNWKNP-IT-TVLIHILFIILVLYPELILPTIFLYLFLIGVWYYRWRPRHPPHMDTRLSHADSAHPDELDEEFdtfpts 672
Cdd:pfam06398  35 ILTWTNPdYTlSFLLVYTFICLVPYLVLLSLPLGYLLFVVMVPGYLYRHSPLPRSSLEDANPSPAEGPTLDEAL------ 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 673 rPADIVRMrydrLRSIAGRIQTVVGDLATQGERVQSLLSWRDPRATALFVIFCLVAAI----VLYVTPFQVVALLTGFYV 748
Cdd:pfam06398 109 -SMEIVLN----LRDLQNKMTLLLSPIDALEKFLYPFAGFKDEDLSTLLFLTLLLTPIyiflTLPLIPWRLILLVLGAFL 183


                  ....*...
gi 1725308502 749 LR-HPRFR 755
Cdd:pfam06398 184 LTyHPSWR 191

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: 44.56 E-value: 1.51e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKD-VTGSCDPYVEV---KLGNYKGTTRHFEKKSNPEWNQ--VFAFSKERIQASM-LEVNVKDKD-FV 113
Cdd:cd04041     3 LVVTIHRATDLPKADfGTGSSDPYVTAsfaKFGKPLYSTRIIRKDLNPVWEEtwFVLVTPDEVKAGErLSCRLWDSDrFT 82

                          90
                  ....*....|....*
gi 1725308502 114 KDDFIGRVVFDLNEI 128
Cdd:cd04041    83 ADDRLGRVEIDLKEL 97

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: 45.07 E-value: 1.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRISANrTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKDEVLG 284
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSD-TLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPDDFLG 95


                  ....*.
gi 1725308502 285 KCAIPL 290
Cdd:cd08375    96 RTEIRV 101

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: 45.19 E-value: 1.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 194 SKVYLsPKLWYLRVNVIEAQDLIPNQPGRFPEAHVKASL---GNQILRTRISANR-TINPMWNEDLMF-VAAEPFEE-PL 267
Cdd:cd08403     6 SLCYL-PTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKnTLNPTYNEALVFdVPPENVDNvSL 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1725308502 268 ILSV--EDRVGGNkdEVLGKCAIPLQYVDRRLDH--------RPVLTRWHNL 309
Cdd:cd08403    85 IIAVvdYDRVGHN--ELIGVCRVGPNADGQGREHwnemlanpRKPIAQWHQL 134

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: 44.55 E-value: 2.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  46 VVKAKDLPAKdvTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERI--QASMLEVNVKDKD-FVKDDFIGRVV 122
Cdd:cd08373     2 VVSLKNLPGL--KGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSpdPDESLEIVVKDYEkVGRNRLIGSAT 79


                  ....*.
gi 1725308502 123 FDLNEI 128
Cdd:cd08373    80 VSLQDL 85

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: 44.56 E-value: 2.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAkDVTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAF-SKERIQASMLEVNVKDKD-FVKDDFIG 119
Cdd:cd04032    30 LTVTVLRATGLWG-DYFTSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDnGWDDDLLG 108


                  ....
gi 1725308502 120 RVVF 123
Cdd:cd04032   109 TCSV 112

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176045 [Multi-domain] Cd Length: 126 Bit Score: 43.90 E-value: 3.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 367 LELGILNAQGLmPMKTkdgrgTTDAYCVAKYGQ-KWIRTRTIIDSfTPKWNEQYtweVFD--PCTV--LTIGVYDnchlh 441
Cdd:cd08400     6 LQLNVLEAHKL-PVKH-----VPHPYCVISLNEvKVARTKVREGP-NPVWSEEF---VFDdlPPDVnsFTISLSN----- 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1725308502 442 sgdkAAGGAKDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGVKKMGEIHLAVRFT 498
Cdd:cd08400    71 ----KAKRSKDSEIAEVTVQLSKLQNGQETDEWYPLSSASPLKGGEWGSLRIRARYS 123

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: 44.60 E-value: 3.63e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1725308502  62 DPYVEVKLGNYK-GTTRHFEKKSNPEWNQVFafskeRI----QASMLEVNVKDKDFVKDDFIGRVV 122
Cdd:cd04015    59 DPYATVDLAGARvARTRVIENSENPVWNESF-----HIycahYASHVEFTVKDNDVVGAQLIGRAY 119

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

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 43.41 E-value: 4.58e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKdvtGSCDPYVEVKLGNYK-GTTRHFEKKsNPEWNQVFAFSKERIQAS--MLEVNVKDKD-FVKDDF 117
Cdd:cd08383     2 LRLRILEAKNLPSK---GTRDPYCTVSLDQVEvARTKTVEKL-NPFWGEEFVFDDPPPDVTffTLSFYNKDKRsKDRDIV 77


                  ....
gi 1725308502 118 IGRV 121
Cdd:cd08383    78 IGKV 81

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: 43.35 E-value: 5.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VRVVKAKDLPAKDVTGSCDPYVEVKLGNY-KGTTRHFEKKSNPEWNQVFAFS----KERIqasMLEVNVKDKDfVKDDFI 118
Cdd:cd04045     5 LHIRKANDLKNLEGVGKIDPYVRVLVNGIvKGRTVTISNTLNPVWDEVLYVPvtspNQKI---TLEVMDYEKV-GKDRSL 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1725308502 119 GRVVFDLNEIPKRVPPDS-----PLAPQWYRLEDRKSDK 152
Cdd:cd04045    81 GSVEINVSDLIKKNEDGKyveydDEEERLKRLLSLKGVK 119

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: 43.04 E-value: 6.89e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 371 ILNAQGLmpmKTKDGRGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDNCHLhsgdkaagga 450
Cdd:cd04046     9 VHSAEGL---SKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSNLL---------- 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1725308502 451 KDSRIGKVriRLSTLETDRVYTHSYPllvLYPNGVKKMGEI--HLAVRFTCS 500
Cdd:cd04046    76 CDEFLGQA--TLSADPNDSQTLRTLP---LRKRGRDAAGEVpgTISVKVTSS 122

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: 43.27 E-value: 8.09e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKL---GNYKGTTRHFEKKS--NPEWNQ--VFAFSKERIQASMLEVNVKDKDFV 113
Cdd:cd08403    16 LTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKNtlNPTYNEalVFDVPPENVDNVSLIIAVVDYDRV 94

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: 42.18 E-value: 1.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  44 VRVVKAKDLPakdvTGSCDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAF----SKERIQASMLEVNVKDKD-FVKDDFI 118
Cdd:cd04011     8 VRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFnfheSPDELFDKIIKISVYDSRsLRSDTLI 83


                  ....*..
gi 1725308502 119 GRVVFDL 125
Cdd:cd04011    84 GSFKLDV 90

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 42.17 E-value: 1.32e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 367 LELGILNAQGLMPMktkDGRGTTDAYCVAKY-GQKWIRTRTIIDSFTPKWNEQYTWEVfdPC---TVLTIGVYDnchlhs 442
Cdd:cd04040     1 LTVDVISAENLPSA---DRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPV--PSrvrAVLKVEVYD------ 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1725308502 443 GDkaAGGAKDSrIGKVRIRLSTLETDRVYTHSYPllvLYPNGVKKMGEIHL 493
Cdd:cd04040    70 WD--RGGKDDL-LGSAYIDLSDLEPEETTELTLP---LDGQGGGKLGAVFL 114

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 41.82 E-value: 1.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  50 KDL-PAKDVTGSCDPYVEVKLGNYK-GTTRHFEKKSNPEWNQ---VFAFSKERiqaSMLEVNVKDKDFVKDDFIGRVVFD 124
Cdd:cd04052     1 KGLdTSESKTGLLSPYAELYLNGKLvYTTRVKKKTNNPSWNAsteFLVTDRRK---SRVTVVVKDDRDRHDPVLGSVSIS 77


                  ....
gi 1725308502 125 LNEI 128
Cdd:cd04052    78 LNDL 81

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: 41.40 E-value: 1.53e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1725308502 212 AQDLIPNQPGRFPEAHVKASLGNQILRTRIsANRTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNkdeVLGKCAIPL 290
Cdd:cd04050     9 AKNLPLAKSTKEPSPYVELTVGKTTQKSKV-KERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGK---SLGSLTLPL 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: 1.89e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  364 IGVLELGILNAQGLmpmktKDGR----GTTDAYCVAKYGQKWI-RTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDnc 438
Cdd:COG5038    435 IGVVEVKIKSAEGL-----KKSDstinGTVDPYITVTFSDRVIgKTRVKKNTLNPVWNETFYILLNSFTDPLNLSLYD-- 507

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1725308502  439 hlhsgdkAAGGAKDSRIGKVRIRLSTLETDRVYTHsypLLVLYPNGVKKMGEIHLAVRF 497
Cdd:COG5038    508 -------FNSFKSDKVVGSTQLDLALLHQNPVKKN---ELYEFLRNTKNVGRLTYDLRF 556

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

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 41.48 E-value: 2.63e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 207 VNVIEAQDLIPNQPGRFPEAHVkaSLGNQILRTRISANRTI----NPMWNEDlmFVAAEPFEEPLILS--VEDRVGGNKD 280
Cdd:cd04043     5 IRIVRAENLKADSSNGLSDPYV--TLVDTNGKRRIAKTRTIydtlNPRWDEE--FELEVPAGEPLWISatVWDRSFVGKH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1725308502 281 EVLGKCAI---PLQYVDrrldhrPVLTR--WHNLER------HVIVEGEKK 320
Cdd:cd04043    81 DLCGRASLkldPKRFGD------DGLPReiWLDLDTqgrlllRVSMEGERD 125

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: 41.32 E-value: 2.76e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRIsANRTINPMWNEDLMFVAAEPFEEPliLSVE----DRVGgnKD 280
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSV-VKKSCYPRWNEVFEFELMEGADSP--LSVEvwdwDLVS--KN 76

                          90       100
                  ....*....|....*....|....*....
gi 1725308502 281 EVLGKCAIPLQyvdrRLDHRPVLTRWHNL 309
Cdd:cd04025    77 DFLGKVVFSIQ----TLQQAKQEEGWFRL 101

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: 41.55 E-value: 2.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRISAnRTINPMWNEDLMFVAAEP---FEEPLILSV-EDRVGGNKD 280
Cdd:cd04022     2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKP-KDLNPVWNEKLVFNVSDPsrlSNLVLEVYVyNDRRSGRRR 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1725308502 281 EVLGKCAIPLQYVDRRLDHRPvltRWHNLER 311
Cdd:cd04022    81 SFLGRVRISGTSFVPPSEAVV---QRYPLEK 108

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: 41.01 E-value: 3.26e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL-GNQILRTRIsANRTINPMWNEDlmfvaaepFEEPLI------LSVE----D 273
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKT-IKKTLNPVWNES--------FEVPVPsrvravLKVEvydwD 71

                          90       100
                  ....*....|....*....|.
gi 1725308502 274 RvgGNKDEVLGKCAIPLQYVD 294
Cdd:cd04040    72 R--GGKDDLLGSAYIDLSDLE 90

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: 41.26 E-value: 3.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRF--PEAHVKASLGNQILRTRIsANRTINPMWNEDLMFVAAEPFEEPLILSVEDRVGGNKDEV 282
Cdd:cd04024     3 LRVHVVEAKDLAAKDRSGKgkSDPYAILSVGAQRFKTQT-IPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81


                  ....*....
gi 1725308502 283 LGKCAIPLQ 291
Cdd:cd04024    82 LGEFDIALE 90

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. 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: 176068 Cd Length: 118 Bit Score: 40.57 E-value: 4.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 367 LELGILNAQGLmpmktkdgRGTTDAYC---VAKYGQ--KWIRTRTIIDSFTPKWNEQYTWEVfDPCTVLTIGVYDNChlH 441
Cdd:cd08686     1 LNVIVHSAQGF--------KQSANLYCtleVDSFGYfvKKAKTRVCRDTTEPNWNEEFEIEL-EGSQTLRILCYEKC--Y 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1725308502 442 SGDKAAGGAKDSRIGKVRIRlstLETDRVYTHSYPLLVLYPNGVkkmgEIHLAVRF 497
Cdd:cd08686    70 SKVKLDGEGTDAIMGKGQIQ---LDPQSLQTKKWQEKVISMNGI----TVNLSIKF 118

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: 40.79 E-value: 5.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL---GNQILRTRISAN-RTINPMWNEDLMFVAAEP--FEEPLILSVEDRVGGN 278
Cdd:cd08384    15 LIVGIIRCVNLAAMDANGYSDPFVKLYLkpdAGKKSKHKTQVKkKTLNPEFNEEFFYDIKHSdlAKKTLEITVWDKDIGK 94

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1725308502 279 KDEVLGKCAIPLQYVDRRLDH-----RP---VLTRWHNL 309
Cdd:cd08384    95 SNDYIGGLQLGINAKGERLRHwldclKNpdkKIEAWHTL 133

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

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 40.32 E-value: 7.01e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVT-GSCDPYVEV-----KLGNYKGTTRHFEKKSNPEWNQVFAF--SKERIQASMLEVNVKDKD-F 112
Cdd:cd08521    16 LEVHIKECRNLAYADEKkKRSNPYVKVyllpdKSKQSKRKTSVKKNTTNPVFNETLKYhiSKSQLETRTLQLSVWHHDrF 95

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1725308502 113 VKDDFIGRVVFDLNEIPKrvppDSPlAPQWYRL 145
Cdd:cd08521    96 GRNTFLGEVEIPLDSWDL----DSQ-QSEWYPL 123

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: 40.46 E-value: 7.30e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL--GNQILRTRISA--NRTINPMWNEDLMFVAaePFEE----PLILSV--EDR 274
Cdd:cd08402    17 LTVVILEAKNLKKMDVGGLSDPYVKIHLmqNGKRLKKKKTTikKRTLNPYYNESFSFEV--PFEQiqkvHLIVTVldYDR 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1725308502 275 VGgnKDEVLGKCAIPLQYVDRRLDH---------RPVlTRWHNLE 310
Cdd:cd08402    95 IG--KNDPIGKVVLGCNATGAELRHwsdmlasprRPI-AQWHTLQ 136

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: 39.94 E-value: 8.37e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 226 AHVKASLGNQILRTRISANRTiNPMWNE--DLMFVAAEPFEePLILSVEDRVGGNKDEVLGKCAIPLQ----YVDRRLDH 299
Cdd:cd04032    50 GYVKVFFGGQEKRTEVIWNNN-NPRWNAtfDFGSVELSPGG-KLRFEVWDRDNGWDDDLLGTCSVVPEagvhEDSCQLNH 127

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: 39.16 E-value: 1.00e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPA-KDVTGS---CDPYVEVKLGNYKGTTRHFEKKSNPEWNQVFAFSKERIQASM-LEVNVKDKD-FVKD 115
Cdd:cd04039     3 VFMEIKSITDLPPlKNMTRTgfdMDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVYPHEKNFdIQFKVLDKDkFSFN 82

                          90       100
                  ....*....|....*....|..
gi 1725308502 116 DFIGRVVFDLNEIPKRVPPDSP 137
Cdd:cd04039    83 DYVATGSLSVQELLNAAPQPDP 104

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: 39.06 E-value: 2.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLiPNQPGRFPEA---HVKASL------GNQILRTRISANRTINPMWNEDLMFvaaePFEEP----LILSV 271
Cdd:cd00275     4 LTIKIISGQQL-PKPKGDKGSIvdpYVEVEIhglpadDSAKFKTKVVKNNGFNPVWNETFEF----DVTVPelafLRFVV 78

                          90
                  ....*....|....*....
gi 1725308502 272 EDRvGGNKDEVLGKCAIPL 290
Cdd:cd00275    79 YDE-DSGDDDFLGQACLPL 96

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

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 38.34 E-value: 2.75e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 365 GVLELGILNAQGLmpmKTKDGRGTTDAYC-VAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDncHLHSG 443
Cdd:cd04045     1 GVLRLHIRKANDL---KNLEGVGKIDPYVrVLVNGIVKGRTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMD--YEKVG 75

                          90       100
                  ....*....|....*....|
gi 1725308502 444 dkaaggaKDSRIGKVRIRLS 463
Cdd:cd04045    76 -------KDRSLGSVEINVS 88

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: 38.42 E-value: 2.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL--GNQI---LRTRISANrTINPMWNEDLMFVAAEPFE---EPLILSV--EDR 274
Cdd:cd04035    17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpGASKatkLRTKTVHK-TRNPEFNETLTYYGITEEDiqrKTLRLLVldEDR 95

                          90
                  ....*....|....*.
gi 1725308502 275 VGgnkDEVLGKCAIPL 290
Cdd:cd04035    96 FG---NDFLGETRIPL 108

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: 38.27 E-value: 2.93e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 383 KDGRGTTDAYCVAKY-GQKWIRTRTIIDSFTPKWNEQYTWEVFDPCTVLTIGVYDNCHLhsgdkaaggAKDSRIGKVRIR 461
Cdd:cd04054    15 KDITGSSDPYCIVKVdNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTL---------SRDDVIGKVSLT 85

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1725308502 462 LSTLETDRVYTHSYPLLVLYPNGVKKMGEIHLAVR 496
Cdd:cd04054    86 REVISAHPRGIDGWMNLTEVDPDEEVQGEIHLELS 120

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: 38.52 E-value: 2.96e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 355 TAKQLWKSHIGVLELGILNAQGLMPMKTKdgrGTTDAYCVAKYGQKWIRTRTIIDSFTPKWNEQYTWEVFD-PCTVLTIG 433
Cdd:cd08375     5 LARSQRASGIGRLMVVIVEGRDLKPCNSN---GKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDlEQDVLCIT 81

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1725308502 434 VYDNCHLhsgdkaaggAKDSRIGKVRIRLSTLETDR 469
Cdd:cd08375    82 VFDRDFF---------SPDDFLGRTEIRVADILKET 108

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: 37.94 E-value: 3.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 200 PKLWYLRVNVIEAQDLipnqPGRFPEAHVKASLGNQILRTRISaNRTINPMWNEDLMF----VAAEPFEEPLILSVEDRV 275
Cdd:cd04011     1 PQDFQVRVRVIEARQL----VGGNIDPVVKVEVGGQKKYTSVK-KGTNCPFYNEYFFFnfheSPDELFDKIIKISVYDSR 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1725308502 276 GGNKDEVLGKCAIPLQYVDRRLDHRpVLTRW 306
Cdd:cd04011    76 SLRSDTLIGSFKLDVGTVYDQPDHA-FLRKW 105

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: 37.95 E-value: 3.53e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQIL-RTRISANrTINPMWNEdLMFVAAEPFEEPLILSVEDRVGGNKDEVL 283
Cdd:cd04045     3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKgRTVTISN-TLNPVWDE-VLYVPVTSPNQKITLEVMDYEKVGKDRSL 80


                  ....*...
gi 1725308502 284 GKCAIPLQ 291
Cdd:cd04045    81 GSVEINVS 88

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 37.95 E-value: 5.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  42 LYVRVVKAKDLPAKDVTGSCDPYVEVKLgnYKGTTRHFEKKS-------NPEWNQVFAF--SKERIQASMLEVNVKDKDF 112
Cdd:cd08410    16 LNVDIIRAKQLLQTDMSQGSDPFVKIQL--VHGLKLIKTKKTscmrgtiDPFYNESFSFkvPQEELENVSLVFTVYGHNV 93

                          90
                  ....*....|.
gi 1725308502 113 -VKDDFIGRVV 122
Cdd:cd08410    94 kSSNDFIGRIV 104

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: 38.04 E-value: 5.37e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRF--PEAHVKASLGNQILRTRISANR----TINPMWNEDLMF------VAAEPFEepliLSVE 272
Cdd:cd08407    17 LLVVVIKAKNLHSDQLKLLlgIDVSVKVTLKHQNAKLKKKQTKrakhKINPVWNEMIMFelpselLAASSVE----LEVL 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1725308502 273 DRVGGNKDEVLGKCAIPLQYVDRRLDH--------RPVLTRWHNL 309
Cdd:cd08407    93 NQDSPGQSLPLGRCSLGLHTSGTERQHweemldnpRRQIAMWHQL 137

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: 37.60 E-value: 6.03e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASL-GNQILRTRISANRTINPMWNEDLMFV--AAEPFEEPLILSVE--DRVGGNK 279
Cdd:cd04051     2 LEITIISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRDGGTNPTWNETLRFPldERLLQQGRLALTIEvyCERPSLG 81

                          90
                  ....*....|....
gi 1725308502 280 DEVLGKCAIPLQYV 293
Cdd:cd04051    82 DKLIGEVRVPLKDL 95

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: 37.26 E-value: 6.16e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQPGRFPEAHVKASLGNQILRTRISANRTINPMWNEDLMfVAAEPFEEPLILSVEDRVGGNKDEVLG 284
Cdd:cd04042     2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTVYKSKTIYKNLNPVWDEKFT-LPIEDVTQPLYIKVFDYDRGLTDDFMG 80


                  ....*.
gi 1725308502 285 KCAIPL 290
Cdd:cd04042    81 SAFVDL 86

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: 36.86 E-value: 7.62e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502 205 LRVNVIEAQDLIPNQpgrFPEAHVKASLGN-QILRTRisANRTINPMWNEDLMF----VAAEPFEepLILSVEDRVGGNK 279
Cdd:cd08383     2 LRLRILEAKNLPSKG---TRDPYCTVSLDQvEVARTK--TVEKLNPFWGEEFVFddppPDVTFFT--LSFYNKDKRSKDR 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1725308502 280 DEVLGKCAIplqyvdRRLDHRPVLTRWHNLERHV---IVEGEKKKEIKF 325
Cdd:cd08383    75 DIVIGKVAL------SKLDLGQGKDEWFPLTPVDpdsEVQGSVRLRARY 117

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: 36.77 E-value: 7.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1725308502  47 VKAKDLPAKDVTGSCDPYVEVKLGNYKGT------TRHFEKKSNPEWN----QVFAFSKERIQASmLEVNVKDKDFV-KD 115
Cdd:cd04047     7 FSGKKLDKKDFFGKSDPFLEISRQSEDGTwvlvyrTEVIKNTLNPVWKpftiPLQKLCNGDYDRP-IKIEVYDYDSSgKH 85

                          90       100
                  ....*....|....*....|...
gi 1725308502 116 DFIGRVVFDLNEIPKRVPPDSPL 138
Cdd:cd04047    86 DLIGEFETTLDELLKSSPLEFEL 108