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: 341.18 E-value: 7.45e-114

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  608 LPTVFLYLFLIGVWYYRWRPRHPPHMDTRLSHADSAHPDELDEEFDTFPTSRPSDIVRMRYDRLRSIAGRIQTVVGDLAT 687
Cdd:pfam08372   1 LPTVFLYLFLIGLWNYRFRPRHPPHMDTRLSHADSVNPDELDEEFDTFPSSRPPDVVRMRYDRLRSVAGRVQTVVGDIAT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 641838788  688 QGERLQSLLSWRDPRATALFVIFCLIAAIVLYVTPFQVVALLTGFYVLRHPRFRHKLPSVPLNFFRRLPARTDCML 763
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: 283.02 E-value: 1.24e-91

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 201 YLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:cd04019    1 YLRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPSQTRNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPL 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 641838788 281 GKCMIPLQYVDKRLDHKPVNTRWYNLEKHIVVEGEKKKDtKFASRIHMRICLEGGYHVLDESTHYSSDLRP 351
Cdd:cd04019   81 GRAVIPLNDIERRVDDRPVPSRWFSLERPGGAMEQKKKR-KFASRIHLRLCLDGGYHVLDESTHYSSDLRP 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: 232.20 E-value: 9.55e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  39 YLYVRVVKAKDLPpkdvTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDFVKDDFMGR 118
Cdd:cd08378    1 YLYVRVVKARGLP----ANSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLGG 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 641838788 119 VLFDLNEIPKRVPPDSPLAPQWYRLEDRKGDKVRGELMLAVWMGT 163
Cdd:cd08378   77 VCFDLSEVPTRVPPDSPLAPQWYRLEDKKGGRVGGELMLAVWFGT 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: 218.43 E-value: 1.61e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 363 VLELGILNAQGLMPMKTKDGRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNCHLHggDK 442
Cdd:cd08379    1 ILEVGILGAQGLDVLRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFDNSQSH--WK 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 641838788 443 AGGARDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGVKKMGEIHLA 490
Cdd:cd08379   79 EAVQPDVLIGKVRIRLSTLEDDRVYAHSYPLLSLNPSGVKKMGELECA 126

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 106.63 E-value: 2.41e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788   38 QYLYVRVVKAKDLPPKDVTGSCDPYVEVKM--GNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKD-FVKDD 114
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDrFGRDD 80

                          90       100
                  ....*....|....*....|....*....
gi 641838788  115 FMGRVLFDLNEIpkrvpPDSPLAPQWYRL 143
Cdd:pfam00168  81 FIGEVRIPLSEL-----DSGEGLDGWYPL 104

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 99.32 E-value: 8.61e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  200 WYLRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKD 277
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKV-VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*....
gi 641838788  278 EVLGKCMIPLQyvdkRLDHKPVNTRWYNL 306
Cdd:pfam00168  80 DFIGEVRIPLS----ELDSGEGLDGWYPL 104

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: 4.74e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNY-KGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKD-FVKDDFMG 117
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDrFSKDDFLG 80

                         90       100
                 ....*....|....*....|....*.
gi 641838788 118 RVLFDLNEIPKRVPPDsplaPQWYRL 143
Cdd:cd00030   81 EVEIPLSELLDSGKEG----ELWLPL 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: 96.79 E-value: 5.45e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788    39 YLYVRVVKAKDLPPKDVTGSCDPYVEVKMGNY---KGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKD-FVKDD 114
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDrFGRDD 80

                           90
                   ....*....|....*....
gi 641838788   115 FMGRVLFDLNEIPKRVPPD 133
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHE 99

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 94.69 E-value: 3.04e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  362 GVLELGILNAQGLMPMktkDGRGTTDAYCVAKY--GQKWVRTRTIIDSPTPKWNEQYTWEVFDP-CTVITIGVFDNCHLh 438
Cdd:pfam00168   1 GRLTVTVIEAKNLPPK---DGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPeNAVLEIEVYDYDRF- 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 641838788  439 ggdkaggARDSRIGKVRIRLSTLETDRVYTHSYPL 473
Cdd:pfam00168  77 -------GRDDFIGEVRIPLSELDSGEGLDGWYPL 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: 86.97 E-value: 2.91e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  39 YLYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQsSVLEVTVKDKDFVKD-DFMG 117
Cdd:cd08377    2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIH-DVLEVTVYDEDKDKKpEFLG 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 641838788 118 RVLFDLNEIPKRVppdsplaPQWYRLEDRK-GDKVRGELML 157
Cdd:cd08377   81 KVAIPLLSIKNGE-------RKWYALKDKKlRTRAKGSILL 114

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: 83.08 E-value: 5.66e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKM---GNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDFVKDDFM 116
Cdd:cd04036    2 LTVRVLRATNITKGDLLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDDHL 81

                         90
                 ....*....|.
gi 641838788 117 GRVLFDLNEIP 127
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: 81.23 E-value: 3.56e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKD---RIQSSVLEVTVKDK--DFVKDD 114
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSdpsRLSNLVLEVYVYNDrrSGRRRS 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 641838788 115 FMGRVLFDLNEipkrVPPDSPLAPQWYRLEDRK-GDKVRGELMLAVWM 161
Cdd:cd04022   82 FLGRVRISGTS----FVPPSEAVVQRYPLEKRGlFSRVRGEIGLKVYI 125

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: 80.19 E-value: 4.01e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGN-QALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKV-VKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79

                         90       100
                 ....*....|....*....|....*.
gi 641838788 281 GKCMIPLQYVDKRldhKPVNTRWYNL 306
Cdd:cd00030   80 GEVEIPLSELLDS---GKEGELWLPL 102

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: 80.55 E-value: 6.85e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDV--TGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKD-FVKDDFM 116
Cdd:cd04024    3 LRVHVVEAKDLAAKDRsgKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDrFAGKDYL 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 641838788 117 GRVLFDLNEIpkRVPPDSPLAPQWYRLEDRKGDK---VRGELML 157
Cdd:cd04024   83 GEFDIALEEV--FADGKTGQSDKWITLKSTRPGKtsvVSGEIHL 124

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: 78.44 E-value: 3.43e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKM-----GNYKGTTRHFEKKTNPEWNQVFAFS---KDRIQSSVLEVTVKDKD-F 110
Cdd:cd04031   18 LIVTVLQARDLPPRDDGSLRNPYVKVYLlpdrsEKSKRRTKTVKKTLNPEWNQTFEYSnvrRETLKERTLEVTVWDYDrD 97

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 641838788 111 VKDDFMGRVLFDLNeipkrvppDSPL--APQWYRLE 144
Cdd:cd04031   98 GENDFLGEVVIDLA--------DALLddEPHWYPLQ 125

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

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 75.22 E-value: 2.03e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788   201 YLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQ---ALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKD 277
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKV-VKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRD 79

                           90       100
                   ....*....|....*....|.
gi 641838788   278 EVLGKCMIPLQYVDKRLDHKP 298
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRHEK 100

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: 2.24e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDFV-KDDFMGR 118
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVsKNDFLGK 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 641838788 119 VLFDLNEIPKRVPPDSplapqWYRL------EDRKGDKVrGELMLAV 159
Cdd:cd04025   82 VVFSIQTLQQAKQEEG-----WFRLlpdpraEEESGGNL-GSLRLKV 122

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: 75.06 E-value: 8.78e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGScDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSkdrIQS--SVLEVTVKDKD-FVKDDFM 116
Cdd:cd04038    4 LKVRVVRGTNLAVRDFTSS-DPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLS---VPNpmAPLKLEVFDKDtFSKDDSM 79


                 ....*..
gi 641838788 117 GRVLFDL 123
Cdd:cd04038   80 GEAEIDL 86

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: 73.87 E-value: 1.19e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKD------VTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDFVKD 113
Cdd:cd08391    3 LRIHVIEAQDLVAKDkfvgglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPDKD 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 641838788 114 DFMGRVLFDLNEIPKrvppdSPLAPQWYRLED 145
Cdd:cd08391   83 DFLGRLSIDLGSVEK-----KGFIDEWLPLED 109

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: 73.06 E-value: 1.59e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  44 VVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDF-VKDDFMGRVLFD 122
Cdd:cd08376    6 LVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTgKKDEFIGRCEID 85


                 ....*.
gi 641838788 123 LNEIPK 128
Cdd:cd08376   86 LSALPR 91

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: 72.41 E-value: 5.14e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKdVTGSCDPYVEVKMGN-YKGTTRHFE--KKTN-PEWNQVFAF------SKDRIQS---------SV 100
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFARVTLNYsSKTDTKRTKvkKKTNnPRFDEAFYFeltigfSYEKKSFkveeedlekSE 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 641838788 101 LEVTVKDKDFV-KDDFMGRVLFDLNEIPKRVPPDSplapqWYRLEDR 146
Cdd:cd08675   80 LRVELWHASMVsGDDFLGEVRIPLQGLQQAGSHQA-----WYFLQPR 121

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: 69.99 E-value: 2.78e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  26 KLTSTYDlvEQMQYLYVRVVKAKDLPPKDVTGSCDPYVEVKM--GNYKGTTR--HFEKKT-NPEWNQVFAF--SKDRIQS 98
Cdd:cd04030    6 QLTIRYS--SQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLlpDKSKSTRRktSVKKDNlNPVFDETFEFpvSLEELKR 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 641838788  99 SVLEVTVKDKD--FVKD-DFMGRVLFDLNEIpkrvpPDSPLAPQWYRLE 144
Cdd:cd04030   84 RTLDVAVKNSKsfLSREkKLLGQVLIDLSDL-----DLSKGFTQWYDLT 127

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: 69.28 E-value: 4.77e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKM---GNYKGTTRHFEKKTNPEWNQVFAF---SKDRIQSSVLEVTVKDKD-FVK 112
Cdd:cd08386   18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFegfPYEKLQQRVLYLQVLDYDrFSR 97

                         90
                 ....*....|....
gi 641838788 113 DDFMGRVLFDLNEI 126
Cdd:cd08386   98 NDPIGEVSLPLNKV 111

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: 67.72 E-value: 1.14e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKD-VTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWN-QVFAFSKD--RIQSSVLEVTVKDKD-FVKDD 114
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNsEWFRFEVDdeELQDEPLQIRVMDHDtYSAND 80

                         90
                 ....*....|
gi 641838788 115 FMGRVLFDLN 124
Cdd:cd08688   81 AIGKVYIDLN 90

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: 67.57 E-value: 2.03e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  42 VR--VVKAKDLPPKDVTGSCDPYVEVKMGNYK-GTTRHFEKKT-NPEWNQVFAFSKDRIQSSVLEVTVKDKDFV-KDDFM 116
Cdd:cd04037    2 VRvyVVRARNLQPKDPNGKSDPYLKIKLGKKKiNDRDNYIPNTlNPVFGKMFELEATLPGNSILKISVMDYDLLgSDDLI 81


                 ....*..
gi 641838788 117 GRVLFDL 123
Cdd:cd04037   82 GETVIDL 88

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: 67.27 E-value: 2.25e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 198 KLWY------LRVNVIEAQDLQPTDKGRFPEVYVKAQL------GNQAlRTRVSAsRTINPMWNEDLMF--VAAEPFEEH 263
Cdd:cd04031    8 QLWYdkvtsqLIVTVLQARDLPPRDDGSLRNPYVKVYLlpdrseKSKR-RTKTVK-KTLNPEWNQTFEYsnVRRETLKER 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 641838788 264 LI-LTVEDRVAPNKDEVLGKCMIPLQyvDKRLDHKPvntRWYNLE 307
Cdd:cd04031   86 TLeVTVWDYDRDGENDFLGEVVIDLA--DALLDDEP---HWYPLQ 125

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: 67.41 E-value: 2.65e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKD-FVKDDFMGR 118
Cdd:cd08375   17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDfFSPDDFLGR 96

                         90
                 ....*....|
gi 641838788 119 VLFDLNEIPK 128
Cdd:cd08375   97 TEIRVADILK 106

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: 66.32 E-value: 2.95e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 364 LELGILNAQGLMPMktkDGRGTTDAYCVAKYG-QKWVRTRTIIDSPTPKWNEQYTWEVFDP-CTVITIGVFdnchlhggD 441
Cdd:cd00030    1 LRVTVIEARNLPAK---DLNGKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPeSDTLTVEVW--------D 69

                         90       100       110
                 ....*....|....*....|....*....|...
gi 641838788 442 KAGGARDSRIGKVRIRLSTLETDR-VYTHSYPL 473
Cdd:cd00030   70 KDRFSKDDFLGEVEIPLSELLDSGkEGELWLPL 102

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

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 66.13 E-value: 6.57e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKM-----GNYKGTTRHFEKKTNPEWNQVFAFS-KDRIQSSVLEVTVKDKD-FVK 112
Cdd:cd04026   15 LTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDlKPADKDRRLSIEVWDWDrTTR 94

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 641838788 113 DDFMGRVLFDLNEIPKRvPPDSplapqWYRLEDRK 147
Cdd:cd04026   95 NDFMGSLSFGVSELIKM-PVDG-----WYKLLNQE 123

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: 64.43 E-value: 1.22e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788   363 VLELGILNAQGLMPMktkDGRGTTDAYCVAKYGQ---KWVRTRTIIDSPTPKWNEQYTWEVFDPCT-VITIGVFDNCHLH 438
Cdd:smart00239   1 TLTVKIISARNLPPK---DKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPELaELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|....*
gi 641838788   439 ggdkaggaRDSRIGKVRIRLSTLET 463
Cdd:smart00239  78 --------RDDFIGQVTIPLSDLLL 94

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: 65.34 E-value: 1.26e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  38 QYLYVRVVKAKDLPPKDVTGSCDPYVEVKM-------GNYKGTTRhFEKKT-NPEWNQVFAFS----KDRIQSSVLEVTV 105
Cdd:cd04009   16 QSLRVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQ-VKKKTlFPLFDESFEFNvppeQCSVEGALLLFTV 94

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 641838788 106 KDKDFV-KDDFMGRVLFDLNEIPKRVPPDSPLAPQ 139
Cdd:cd04009   95 KDYDLLgSNDFEGEAFLPLNDIPGVEDTSSAQGFG 129

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: 65.26 E-value: 1.46e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  39 YLYvrvvKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF-------SKDRIQSS----VLEVTvkD 107
Cdd:cd04017    6 YIY----QARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFdevelygSPEEIAQNpplvVVELF--D 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 641838788 108 KDFV-KDDFMGRVLFDlnEIPKRVP-PDSPLAPQWYRLedRKGDKVRGELMLAV 159
Cdd:cd04017   80 QDSVgKDEFLGRSVAK--PLVKLDLeEDFPPKLQWFPI--YKGGQSAGELLAAF 129

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 64.60 E-value: 1.78e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGN---YKGTTRHfeKKTNPEWNQVFAFSKDRIqSSVLEVTVKDKDFV-KDDF 115
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGktvYKSKTIY--KNLNPVWDEKFTLPIEDV-TQPLYIKVFDYDRGlTDDF 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 641838788 116 MGRVLFDLNEIPKRVPPDSPLapqwyRLEDRKGDKVRGELMLAV 159
Cdd:cd04042   79 MGSAFVDLSTLELNKPTEVKL-----KLEDPNSDEDLGYISLVV 117

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: 64.53 E-value: 3.07e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEV-------KMGNYKGTTRHfeKKTNPEWNQVFAF--SKDRIQSSVLEVTVKDKD- 109
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVsllqggkKLKKKKTSVKK--GTLNPVFNEAFSFdvPAEQLEEVSLVITVVDKDs 93

                         90
                 ....*....|....*
gi 641838788 110 FVKDDFMGRVLFDLN 124
Cdd:cd00276   94 VGRNEVIGQVVLGPD 108

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

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 63.91 E-value: 3.89e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGT-------TRHFEKKTNPEWNQVFAFSKDRIQSSVLeVTVKDKD-FV 111
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNgeidsvqTKTIKKTLNPKWNEEFFFRVNPREHRLL-FEVFDENrLT 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 641838788 112 KDDFMGRVLFDLNEIPKRVP-PDSPLAPQWYRLEDR--KGdKVRGELML 157
Cdd:cd04033   81 RDDFLGQVEVPLNNLPTETPgNERRYTFKDYLLRPRssKS-RVKGHLRL 128

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

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 62.97 E-value: 8.62e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF----SKDRIQSSVLEVTVKDKDFVK--- 112
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFechnSSDRIKVRVWDEDDDIKSRLKqkf 82

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 641838788 113 ----DDFMGRVLFDLNEIpkrvppdSPLAPQWYRLEDR 146
Cdd:cd04027   83 tresDDFLGQTIIEVRTL-------SGEMDVWYNLEKR 113

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: 62.30 E-value: 1.32e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKM--GNYKGT---TRHFEKKTNPEWNQVFAF---SKDRIQSSVLEVTVKDKDFV 111
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpGASKATklrTKTVHKTRNPEFNETLTYygiTEEDIQRKTLRLLVLDEDRF 96

                         90       100
                 ....*....|....*....|
gi 641838788 112 KDDFMGRVLFDL-NEIPKRV 130
Cdd:cd04035   97 GNDFLGETRIPLkKLKPNQT 116

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: 62.35 E-value: 1.52e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 368 ILNAQGLMPmktKDGRGTTDAYCVAKY-GQKwVRTRTIIDSPTPKWNEQYTWEVFDPCT----VITIGVFDnchlhggDK 442
Cdd:cd04022    6 VVDAQDLMP---KDGQGSSSAYVELDFdGQK-KRTRTKPKDLNPVWNEKLVFNVSDPSRlsnlVLEVYVYN-------DR 74

                         90       100       110
                 ....*....|....*....|....*....|...
gi 641838788 443 AGGARDSRIGKVRIRLSTL--ETDRVYTHsYPL 473
Cdd:cd04022   75 RSGRRRSFLGRVRISGTSFvpPSEAVVQR-YPL 106

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: 62.77 E-value: 1.76e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPY----------------VEVKMGNYKGT-TRHFEKKT------------NPEWNQVFA 90
Cdd:cd08676   30 LKVTVIEAKGLLAKDVNGFSDPYcmlgivpasrernsekSKKRKSHRKKAvLKDTVPAKsikvtevkpqtlNPVWNETFR 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 641838788  91 FSKDRIQSSVLEVTVKDKDfvkDDFMGRVLFDLNEIPkrvppdSPLAPQWYRL 143
Cdd:cd08676  110 FEVEDVSNDQLHLDIWDHD---DDFLGCVNIPLKDLP------SCGLDSWFKL 153

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: 61.51 E-value: 2.41e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  31 YDLveQMQYLYVRVVKAKDLPPKDVTGSCDPYVEVKMGN---YKGTTRHFEKKTNPEWNQVFAFS--KDRIQSSVLEVTV 105
Cdd:cd08385   11 YDF--QSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPdkkKKFETKVHRKTLNPVFNETFTFKvpYSELGNKTLVFSV 88

                         90       100
                 ....*....|....*....|..
gi 641838788 106 KDKD-FVKDDFMGRVLFDLNEI 126
Cdd:cd08385   89 YDFDrFSKHDLIGEVRVPLLTV 110

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: 61.15 E-value: 3.49e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEV------YVKAQLGNQALRTRVSASrTINPMWNEdlMFVAAEPFEEHLILTVE----Dr 271
Cdd:cd08391    3 LRIHVIEAQDLVAKDKFVGGLVkgksdpYVIVRVGAQTFKSKVIKE-NLNPKWNE--VYEAVVDEVPGQELEIElfdeD- 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 641838788 272 vaPNKDEVLGKCMIPLQYVDKrldhKPVNTRWYNLE 307
Cdd:cd08391   79 --PDKDDFLGRLSIDLGSVEK----KGFIDEWLPLE 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: 61.06 E-value: 3.91e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQALRTRVSASR--TINPMWNEDLMF-VAAEPFEE-HLILTVEDRVAPN 275
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSLlqGGKKLKKKKTSVKkgTLNPVFNEAFSFdVPAEQLEEvSLVITVVDKDSVG 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 641838788 276 KDEVLGKCMIPLQYVDKRLDH---------KPVnTRWYNL 306
Cdd:cd00276   96 RNEVIGQVVLGPDSGGEELEHwnemlasprKPI-ARWHKL 134

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

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 61.28 E-value: 4.36e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMgNYKGttRHFEKKT--------NPEWNQVFAFS--KDRIQSSVLEVTVKDKD 109
Cdd:cd08405   17 ITVNIIKARNLKAMDINGTSDPYVKVWL-MYKD--KRVEKKKtvikkrtlNPVFNESFIFNipLERLRETTLIITVMDKD 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 641838788 110 FV-KDDFMGRVLFDLNEIPKRVP--------PDSPLApQWYRL 143
Cdd:cd08405   94 RLsRNDLIGKIYLGWKSGGLELKhwkdmlskPRQPVA-QWHRL 135

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: 59.57 E-value: 1.06e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  39 YLYVRVVKAKDLPPKDVTGSCDPYVEVKMGnykgttrHFEKKT--------NPEWNQVFAFSKDRIQSSVLEVTVKDKDF 110
Cdd:cd08681    2 TLVVVVLKARNLPNKRKLDKQDPYCVLRIG-------GVTKKTktdfrggqHPEWDEELRFEITEDKKPILKVAVFDDDK 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 641838788 111 VKDDFMGRVLFDLNEIPKRVPPDsplapQWYRLeDRKGdKVRGELML 157
Cdd:cd08681   75 RKPDLIGDTEVDLSPALKEGEFD-----DWYEL-TLKG-RYAGEVYL 114

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: 58.42 E-value: 3.08e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  31 YDLVEQmqYLYVRVVKAKDLPPKDVT-GSCDPYVEVKM----GNYKGTtrHFEKKT-NPEWNQVFAF--SKDRIQSSVLE 102
Cdd:cd08390    9 YDLEEE--QLTVSLIKARNLPPRTKDvAHCDPFVKVCLlpdeRRSLQS--KVKRKTqNPNFDETFVFqvSFKELQRRTLR 84

                         90       100
                 ....*....|....*....|....
gi 641838788 103 VTVKDKD-FVKDDFMGRVLFDLNE 125
Cdd:cd08390   85 LSVYDVDrFSRHCIIGHVLFPLKD 108

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: 58.08 E-value: 3.23e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 201 YLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRvSASRTINPMWNEDLMFvAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:cd08377    2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTH-TIYKTLNPEWNKIFTF-PIKDIHDVLEVTVYDEDKDKKPEFL 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 641838788 281 GKCMIPLqyvdkrLDHKPVNTRWYNLekhivvegekkKDTKFASRIHMRICLE 333
Cdd:cd08377   80 GKVAIPL------LSIKNGERKWYAL-----------KDKKLRTRAKGSILLE 115

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: 58.06 E-value: 3.60e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  42 VRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIQSSVLeVTVKDKDFVKDDFMGRVLF 121
Cdd:cd04046    7 VHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIK-IQVWNSNLLCDEFLGQATL 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 641838788 122 DLNEIPKRVPPDSPLAPQwyrlEDRKGDKVRGELMLAV 159
Cdd:cd04046   86 SADPNDSQTLRTLPLRKR----GRDAAGEVPGTISVKV 119

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: 58.23 E-value: 4.22e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  42 VRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF-----SKDRIQSSVLEVTVKDKDFV-KDDF 115
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFelpglLSGNGNRATLQLTVMHRNLLgLDKF 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 641838788 116 MGRVLFDLNEI------PKRvppdsplapQWYRLEDRKG--DKVRGELMLAV 159
Cdd:cd08682   83 LGQVSIPLNDLdedkgrRRT---------RWFKLESKPGkdDKERGEIEVDI 125

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: 57.74 E-value: 5.63e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  34 VEQMQYLYVRVVKAKDLPPKDVTGSCDPYVEV-------KMGNYKGTTRhfeKKT-NPEWNQVFAF--SKDRIQSSVLEV 103
Cdd:cd08384    9 NTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLylkpdagKKSKHKTQVK---KKTlNPEFNEEFFYdiKHSDLAKKTLEI 85

                         90       100
                 ....*....|....*....|..
gi 641838788 104 TVKDKDFVK-DDFMGRVLFDLN 124
Cdd:cd08384   86 TVWDKDIGKsNDYIGGLQLGIN 107

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: 57.82 E-value: 6.11e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMgnYKGTTRHFEKKT-------NPEWNQVFAFS--KDRIQSSVLEVTVKDKDF 110
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNL--YYGKKRISKKKThvkkctlNPVFNESFVFDipSEELEDISVEFLVLDSDR 94

                         90
                 ....*....|.
gi 641838788 111 V-KDDFMGRVL 120
Cdd:cd08404   95 VtKNEVIGRLV 105

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: 57.27 E-value: 7.19e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVsASRTINPMWNE--DLMFvaaepFEEH---LILTVEDRVAPNK 276
Cdd:cd08376    2 VTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKV-CSKTLNPQWLEqfDLHL-----FDDQsqiLEIEVWDKDTGKK 75

                         90       100       110
                 ....*....|....*....|....*....|..
gi 641838788 277 DEVLGKCMIPLQyvdkRLDHKPVNTRWYNLEK 308
Cdd:cd08376   76 DEFIGRCEIDLS----ALPREQTHSLELELED 103

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: 56.64 E-value: 1.10e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  30 TYDlvEQMQYLYVRVVKAKDLPPKDVTGSCDPYVEVKM----GNYKGTTRHfeKKT-NPEWNQVFAF--SKDRIQSSVLE 102
Cdd:cd08387   10 EYD--KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLlpdrSNTKQSKIH--KKTlNPEFDESFVFevPPQELPKRTLE 85

                         90       100
                 ....*....|....*....|....*
gi 641838788 103 VTVKDKD-FVKDDFMGRVLFDLNEI 126
Cdd:cd08387   86 VLLYDFDqFSRDECIGVVELPLAEV 110

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: 56.02 E-value: 1.79e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 361 IGVLELGILNAQGLMPMKTKDgrGTTDAYCVAKYGQKWV--RTRTIIDSPTPKWNEQ-YtwevfdpctvITIGVF-DNCH 436
Cdd:cd04044    1 IGVLAVTIKSARGLKGSDIIG--GTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETkY----------ILVNSLtEPLN 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 641838788 437 LHGGDKAGGARDSRIGKVRIRLSTLETDRVYTH-SYPLLvlypNGVKKMGEIHLAVRF 493
Cdd:cd04044   69 LTVYDFNDKRKDKLIGTAEFDLSSLLQNPEQENlTKNLL----RNGKPVGELNYDLRF 122

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: 55.65 E-value: 2.51e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGN---YKGTTrhfEKKT-NPEWNQVFAFSKDRIQSSVLEVTVKDKDFV-KDD 114
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNGekvFKTKT---IKKTlNPVWNESFEVPVPSRVRAVLKVEVYDWDRGgKDD 77

                         90
                 ....*....|..
gi 641838788 115 FMGRVLFDLNEI 126
Cdd:cd04040   78 LLGSAYIDLSDL 89

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: 56.18 E-value: 2.86e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTD-KGRFPevYVKAQLGNQALRTRVsASRTINPMWNEDLMFVAAEPfeeHLILTVE--DRVAPNKDE 278
Cdd:cd04038    4 LKVRVVRGTNLAVRDfTSSDP--YVVLTLGNQKVKTRV-IKKNLNPVWNEELTLSVPNP---MAPLKLEvfDKDTFSKDD 77

                         90
                 ....*....|
gi 641838788 279 VLGKCMIPLQ 288
Cdd:cd04038   78 SMGEAEIDLE 87

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: 55.35 E-value: 3.28e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  39 YLY-VRVVKAKDLPPKDVTGSCDPYVEVKMGNYK---GTTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDFVKD- 113
Cdd:cd04043    1 HLFtIRIVRAENLKADSSNGLSDPYVTLVDTNGKrriAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKh 80

                         90
                 ....*....|....*.
gi 641838788 114 DFMGRVLFDLNeiPKR 129
Cdd:cd04043   81 DLCGRASLKLD--PKR 94

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

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 54.64 E-value: 1.13e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 641838788 384 GTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNCHLHGGDKAGGA 446
Cdd:cd04038   20 TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKDTFSKDDSMGEA 82

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: 53.94 E-value: 1.46e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYveVKMGNYKGTTRHFEKKT-------NPEWNQVFAF--SKDRIQSSVLEVTVKDKDF 110
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLSDPY--VKIHLMQNGKRLKKKKTtikkrtlNPYYNESFSFevPFEQIQKVHLIVTVLDYDR 94

                         90
                 ....*....|.
gi 641838788 111 V-KDDFMGRVL 120
Cdd:cd08402   95 IgKNDPIGKVV 105

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

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 53.23 E-value: 1.90e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 203 RVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVsASRTINPMWNEDLMF----VAAEPFEEH-LILTVEDRVAPNKD 277
Cdd:cd08682    2 QVTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSV-KEKTTSPVWKEECSFelpgLLSGNGNRAtLQLTVMHRNLLGLD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 641838788 278 EVLGKCMIPLQYVDKRLDHKpvNTRWYNLekhivvEGEKKKDTKFASRIHMRI 330
Cdd:cd08682   81 KFLGQVSIPLNDLDEDKGRR--RTRWFKL------ESKPGKDDKERGEIEVDI 125

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: 52.66 E-value: 2.65e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 380 KDGRGTTDAYCVAKYGQKWV-RTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNchlhggDKagGARDSRIGKVRIRL 458
Cdd:cd04042   15 RDRGGTSDPYVKFKYGGKTVyKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDY------DR--GLTDDFMGSAFVDL 86

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 641838788 459 STLETDRVYTHSYPLlvLYPNGVKKMGEIHLAVRFT 494
Cdd:cd04042   87 STLELNKPTEVKLKL--EDPNSDEDLGYISLVVTLT 120

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: 53.48 E-value: 4.06e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEV-----KMGNYKGTTRHFEKKTNPEWNQVFAFSKDR---IQSSVLEVTVKDKD-F 110
Cdd:cd04020   29 LHVWVKEAKNLPALKSGGTSDSFVKCyllpdKSKKSKQKTPVVKKSVNPVWNHTFVYDGVSpedLSQACLELTVWDHDkL 108


                 ....*..
gi 641838788 111 VKDDFMG 117
Cdd:cd04020  109 SSNDFLG 115

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: 52.00 E-value: 6.85e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVLG 281
Cdd:cd08375   17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKV-VSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPDDFLG 95


                 ....*.
gi 641838788 282 KCMIPL 287
Cdd:cd08375   96 RTEIRV 101

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: 9.32e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  42 VRVVKAKDLppKDVTGSC--DPYVEVKM-GNYKGTTR-HFEKKTNPEWNQVFAFSKD----RIQSSVLEVTVKDKD-FVK 112
Cdd:cd04051    4 ITIISAEDL--KNVNLFGkmKVYAVVWIdPSHKQSTPvDRDGGTNPTWNETLRFPLDerllQQGRLALTIEVYCERpSLG 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 641838788 113 DDFMGRVLFDLNEIPKRVPPDSPLAPQWYRLEDRKGdKVRG 153
Cdd:cd04051   82 DKLIGEVRVPLKDLLDGASPAGELRFLSYQLRRPSG-KPQG 121

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 51.18 E-value: 1.11e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGN--YKGTTRHfEKKTNPEWNQVFAFSKDRIQSSV---LEVTVKDKD-FVKD 113
Cdd:cd04049    3 LEVLLISAKGLQDTDFLGKIDPYVIIQCRTqeRKSKVAK-GDGRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDnFSDD 81

                         90
                 ....*....|...
gi 641838788 114 DFMGRVLFDLNEI 126
Cdd:cd04049   82 DFIGEATIHLKGL 94

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: 50.80 E-value: 1.41e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSaSRTINPMWNEDLMFVAAEPfEEHLILTVE-----DRVAPNK 276
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTK-PKDLNPVWNEKLVFNVSDP-SRLSNLVLEvyvynDRRSGRR 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 641838788 277 DEVLGKCMIPLQYVdkrLDHKPVNTRWYNLEK 308
Cdd:cd04022   80 RSFLGRVRISGTSF---VPPSEAVVQRYPLEK 108

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: 50.26 E-value: 1.42e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 209 AQDLQPTDKGRFPEVYVKAQLGNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRvapNKDEVLGKCMIPLq 288
Cdd:cd04050    9 AKNLPLAKSTKEPSPYVELTVGKTTQKSKV-KERTNNPVWEEGFTFLVRNPENQELEIEVKDD---KTGKSLGSLTLPL- 83

                         90       100
                 ....*....|....*....|..
gi 641838788 289 yvdKRLDHKPVNT--RWYNLEK 308
Cdd:cd04050   84 ---SELLKEPDLTldQPFPLDN 102

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: 49.95 E-value: 1.96e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 371 AQGLMPMktkDGRGTTDAYCVAKYG-QKWvRTRTIIDSPTPKWNEQYTWEVF-DPCTVITIGVFdnchlhggDKAGGARD 448
Cdd:cd08376    9 GKNLPPM---DDNGLSDPYVKFRLGnEKY-KSKVCSKTLNPQWLEQFDLHLFdDQSQILEIEVW--------DKDTGKKD 76

                         90       100
                 ....*....|....*....|....*
gi 641838788 449 SRIGKVRIRLSTLETDRVYTHSYPL 473
Cdd:cd08376   77 EFIGRCEIDLSALPREQTHSLELEL 101

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: 50.86 E-value: 2.32e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDvtGSCDPYVEVKM--GNYKGTTRHFE--KKTN-PEWNQVFAF------SKDRIQS-------SVL 101
Cdd:cd04010    2 LSVRVIECSDLALKN--GTCDPYASVTLiySNKKQDTKRTKvkKKTNnPQFDEAFYFdvtidsSPEKKQFempeedaEKL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 641838788 102 EVTVK---DKDFVKDDFMGRVlfdlnEIPKRVPPDSPLAPQ-WYRLEDR 146
Cdd:cd04010   80 ELRVDlwhASMGGGDVFLGEV-----RIPLRGLDLQAGSHQaWYFLQPR 123

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 50.71 E-value: 2.46e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKD----------VTGS----CDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSK------DRIQss 99
Cdd:cd04018    2 FIFKIYRAEDLPQMDsgimanvkkaFLGEkkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEmfpplcERIK-- 79

                         90       100
                 ....*....|....*....|....*...
gi 641838788 100 vleVTVKDKDFV-KDDFMGRVLFDLNEI 126
Cdd:cd04018   80 ---IQIRDWDRVgNDDVIGTHFIDLSKI 104

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: 49.98 E-value: 2.46e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 362 GVLELGILNAQGLMpmkTKD------GRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYtwEVF---DPCTVITIGVF 432
Cdd:cd08391    1 GVLRIHVIEAQDLV---AKDkfvgglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVY--EAVvdeVPGQELEIELF 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 641838788 433 DNchlhggDkagGARDSRIGKVRIRLSTLETDRVYTHSYPLlvlypNGVKKmGEIHL 489
Cdd:cd08391   76 DE------D---PDKDDFLGRLSIDLGSVEKKGFIDEWLPL-----EDVKS-GRLHL 117

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: 49.73 E-value: 4.01e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRF--PEVYVKAQLGNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEV 279
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSGKgkSDPYAILSVGAQRFKTQT-IPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 641838788 280 LGKCMIPLQyvDKRLDHK-PVNTRWYNLE-----KHIVVEGEK 316
Cdd:cd04024   82 LGEFDIALE--EVFADGKtGQSDKWITLKstrpgKTSVVSGEI 122

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 53.99 E-value: 4.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788   32 DLVEQMQYLYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKG-TTRHFEKKTNPEWNQVFAFSKDRIQSSVLEVTVKDKDF 110
Cdd:COG5038  1034 EMVENSGYLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVyKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDS 1113

                          90       100
                  ....*....|....*....|..
gi 641838788  111 V-KDDFMGRVLFDLNEIPKRVP 131
Cdd:COG5038  1114 GeKNDLLGTAEIDLSKLEPGGT 1135

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: 49.34 E-value: 5.68e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 362 GVLELGILNAQGLMPmKTKDGRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDP-CTVITIGVFDNCHLHGG 440
Cdd:cd04024    1 GVLRVHVVEAKDLAA-KDRSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAqNQLLKLILWDKDRFAGK 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 641838788 441 DKAGGARDSrIGKVRIRLSTLETDRVYThsypllvLYPNGVKKM----GEIHLavRFT 494
Cdd:cd04024   80 DYLGEFDIA-LEEVFADGKTGQSDKWIT-------LKSTRPGKTsvvsGEIHL--QFS 127

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

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 48.83 E-value: 7.15e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDvtGSC-DPYVEVkmgnY---------KGTTRHFEKKTNPEWNQVFA---FSKDRIQSSVLEVTVK 106
Cdd:cd08381   15 LFVMVMHAKNLPLLD--GSDpDPYVKT----YllpdpqkttKRKTKVVRKTRNPTFNEMLVydgLPVEDLQQRVLQVSVW 88

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 641838788 107 DKD-FVKDDFMGRVLFDLNEIPKRVPPDsplapQWYRLE 144
Cdd:cd08381   89 SHDsLVENEFLGGVCIPLKKLDLSQETE-----KWYPLG 122

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: 48.77 E-value: 8.29e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL-GNQALRTRVSASRTINPMWNEDLMFV--AAEPFEEHLILTVE--DRVAPNK 276
Cdd:cd04051    2 LEITIISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRDGGTNPTWNETLRFPldERLLQQGRLALTIEvyCERPSLG 81

                         90
                 ....*....|....
gi 641838788 277 DEVLGKCMIPLQYV 290
Cdd:cd04051   82 DKLIGEVRVPLKDL 95

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

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 48.03 E-value: 1.09e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 364 LELGILNAQGLMPmktkdgRGTTDAYCVAKYGQKWV-RTRTIIDsPTPKWNEQYTWEVFdPCTVitigVFDNCHLHGGDK 442
Cdd:cd08383    2 LRLRILEAKNLPS------KGTRDPYCTVSLDQVEVaRTKTVEK-LNPFWGEEFVFDDP-PPDV----TFFTLSFYNKDK 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 641838788 443 AGGARDSRIGKVriRLSTLETDRVYTHSYPLLVLYPNGVkKMGEIHLAVRF 493
Cdd:cd08383   70 RSKDRDIVIGKV--ALSKLDLGQGKDEWFPLTPVDPDSE-VQGSVRLRARY 117

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: 48.02 E-value: 1.37e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVT-GSCDPYVEV-----KMGNYKGTTRHFEKKTNPEWNQVFAF--SKDRIQSSVLEVTVKDKD-F 110
Cdd:cd08521   16 LEVHIKECRNLAYADEKkKRSNPYVKVyllpdKSKQSKRKTSVKKNTTNPVFNETLKYhiSKSQLETRTLQLSVWHHDrF 95

                         90       100       110
                 ....*....|....*....|....*....|...
gi 641838788 111 VKDDFMGRVLFDLNEIPKrvppDSPlAPQWYRL 143
Cdd:cd08521   96 GRNTFLGEVEIPLDSWDL----DSQ-QSEWYPL 123

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: 47.86 E-value: 1.53e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVLG 281
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSV-VKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFLG 80

                         90       100
                 ....*....|....*....|....*
gi 641838788 282 KCMIPLQyvdkRLDHKPVNTRWYNL 306
Cdd:cd04025   81 KVVFSIQ----TLQQAKQEEGWFRL 101

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: 48.17 E-value: 1.54e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQALRTRVSA--SRTINPMWNEDLMFVAaePFEE----HLILTVEDRVA 273
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLSDPYVKIHLmqNGKRLKKKKTTikKRTLNPYYNESFSFEV--PFEQiqkvHLIVTVLDYDR 94

                         90
                 ....*....|..
gi 641838788 274 PNKDEVLGKCMI 285
Cdd:cd08402   95 IGKNDPIGKVVL 106

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: 47.26 E-value: 1.64e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKD-VTGSCDPYVEV---KMGNYKGTTRHFEKKTNPEWNQ--VFAFSKDRIQSSV-LEVTVKDKD-FV 111
Cdd:cd04041    3 LVVTIHRATDLPKADfGTGSSDPYVTAsfaKFGKPLYSTRIIRKDLNPVWEEtwFVLVTPDEVKAGErLSCRLWDSDrFT 82

                         90
                 ....*....|....*
gi 641838788 112 KDDFMGRVLFDLNEI 126
Cdd:cd04041   83 ADDRLGRVEIDLKEL 97

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: 46.83 E-value: 2.17e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  48 KDLPPKD-VTGSCDPYVEVKMGNYK-GTTRHFEKKTNPEWNQVF-AFSKDRiQSSVLEVTVKDKDFVKDDFMGRVLFDLN 124
Cdd:cd04052    1 KGLDTSEsKTGLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTeFLVTDR-RKSRVTVVVKDDRDRHDPVLGSVSISLN 79

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 641838788 125 EIPKRvppdSPLAPQWYRLEDRKGDKVRgelMLAVW 160
Cdd:cd04052   80 DLIDA----TSVGQQWFPLSGNGQGRIR---ISALW 108

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: 47.40 E-value: 2.51e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  50 LPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRIqSSVLEVTV-------KDKDFVKDDFMGRVLFD 122
Cdd:cd08379   15 LRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYDP-CTVLTVGVfdnsqshWKEAVQPDVLIGKVRIR 93

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 641838788 123 LN--EIPKRVPPDSPLapqwyRLEDRKGDKVRGELMLA 158
Cdd:cd08379   94 LStlEDDRVYAHSYPL-----LSLNPSGVKKMGELECA 126

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: 46.79 E-value: 2.56e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL-GNQALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKT-IKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLL 79

                         90
                 ....*....|.
gi 641838788 281 GKCMIPLQYVD 291
Cdd:cd04040   80 GSAYIDLSDLE 90

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: 47.05 E-value: 2.60e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 363 VLELGILNAQGLMPmkTKDGRGTTDAYCVAKYGQKWV-RTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNchlhggD 441
Cdd:cd08401    1 SLKIKIGEAKNLPP--RSGPNKMRDCYCTVNLDQEEVfRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDR------D 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 641838788 442 KAGgaRDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGvKKMGEIHLAVRF 493
Cdd:cd08401   73 VLR--RDSVIGKVAIKKEDLHKYYGKDTWFPLQPVDADS-EVQGKVHLELRL 121

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 46.40 E-value: 3.10e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF--SKDRIQSsvLEVTVKDKD 109
Cdd:cd04050    2 LFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFlvRNPENQE--LEIEVKDDK 71

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 46.94 E-value: 3.13e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSASRTINPMWNEDLMFVAAEPFEE---HLILTVEDRVAPNKDE 278
Cdd:cd04049    3 LEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGDGRNPEWNEKFKFTVEYPGWGgdtKLILRIMDKDNFSDDD 82

                         90
                 ....*....|
gi 641838788 279 VLGKCMIPLQ 288
Cdd:cd04049   83 FIGEATIHLK 92

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: 46.89 E-value: 3.36e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQA---LRTRvSASRTINPMWNEDLMFVAAEPFE---EHLILTV--EDR 271
Cdd:cd04035   17 LHCTIIRAKGLKAMDANGLSDPYVKLNLlpGASKatkLRTK-TVHKTRNPEFNETLTYYGITEEDiqrKTLRLLVldEDR 95

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 641838788 272 VapnKDEVLGKCMIPLqyvdKRLdhKPVNTRWYNL 306
Cdd:cd04035   96 F---GNDFLGETRIPL----KKL--KPNQTKQFNI 121

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: 47.15 E-value: 3.43e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 200 WYLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSASrTINPMWNEDLMF-----------VAAEPfeEHLILTV 268
Cdd:cd04017    1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKE-TLSPTWDQTLIFdevelygspeeIAQNP--PLVVVEL 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 641838788 269 EDRVAPNKDEVLGKCMI-PLQYVDKRLDHKPVnTRWYNLEKHIVVEGE 315
Cdd:cd04017   78 FDQDSVGKDEFLGRSVAkPLVKLDLEEDFPPK-LQWFPIYKGGQSAGE 124

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

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 46.41 E-value: 4.55e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRvSASRTINPMWNEDLMF----------VAAEPFEEHLILTVEDR 271
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTK-TIPQNLNPVWNEKFHFechnssdrikVRVWDEDDDIKSRLKQK 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 641838788 272 VAPNKDEVLGKCMIPLQYVDKRLDhkpvntRWYNLEK 308
Cdd:cd04027   82 FTRESDDFLGQTIIEVRTLSGEMD------VWYNLEK 112

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: 46.36 E-value: 5.04e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMGNYK-GTTRHFEKKTNPEWNQVFAFSKDRIQSSVlEVTVKDKDFV-KDDFMG 117
Cdd:cd04054    2 LYIRIVEGKNLPAKDITGSSDPYCIVKVDNEViIRTATVWKTLNPFWGEEYTVHLPPGFHTV-SFYVLDEDTLsRDDVIG 80


                 ..
gi 641838788 118 RV 119
Cdd:cd04054   81 KV 82

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: 49.34 E-value: 5.91e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  581 ICNWKNP-IT-TVLIHILFIILVLYPELILPTVFLYLFLIGVWYYRWRPRHPPHMDTRLSHADSAHPDELDEEFdtfpts 658
Cdd:pfam06398  35 ILTWTNPdYTlSFLLVYTFICLVPYLVLLSLPLGYLLFVVMVPGYLYRHSPLPRSSLEDANPSPAEGPTLDEAL------ 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  659 rPSDIVRMrydrLRSIAGRIQTVVGDLATQGERLQSLLSWRDPRATALFVIFCLIAAI----VLYVTPFQVVALLTGFYV 734
Cdd:pfam06398 109 -SMEIVLN----LRDLQNKMTLLLSPIDALEKFLYPFAGFKDEDLSTLLFLTLLLTPIyiflTLPLIPWRLILLVLGAFL 183


                  ....*...
gi 641838788  735 LR-HPRFR 741
Cdd:pfam06398 184 LTyHPSWR 191

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: 45.58 E-value: 1.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 191 SKVYLsPKLWYLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALR-----TRVSASrTINPMWNEDLMF-VAAEPFEE-H 263
Cdd:cd08403    6 SLCYL-PTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRlkkkkTSVKKN-TLNPTYNEALVFdVPPENVDNvS 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 641838788 264 LILTV--EDRVAPNkdEVLGKCMIPLQYVDKRLDH---------KPVnTRWYNL 306
Cdd:cd08403   84 LIIAVvdYDRVGHN--ELIGVCRVGPNADGQGREHwnemlanprKPI-AQWHQL 134

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: 44.98 E-value: 1.22e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 641838788 362 GVLELGILNAQGLMpmkTKDGRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFD 433
Cdd:cd08377    1 GFLQVKVIRASGLA---AADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYD 69

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: 45.23 E-value: 1.25e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 203 RVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSA-SRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVLG 281
Cdd:cd04037    3 RVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYiPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDLIG 82


                 ....*.
gi 641838788 282 KCMIPL 287
Cdd:cd04037   83 ETVIDL 88

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: 1.41e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 364 LELGILNAQGLMpmkTKDGRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFD 433
Cdd:cd04027    3 ISITVVCAQGLI---AKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWD 69

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: 44.95 E-value: 1.70e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 204 VNVIEAQDLQPTDKGRFPEVYVkaQLGNQALRTRVSASRTI----NPMWNEDlmFVAAEPFEEHLIL--TVEDRVAPNKD 277
Cdd:cd04043    5 IRIVRAENLKADSSNGLSDPYV--TLVDTNGKRRIAKTRTIydtlNPRWDEE--FELEVPAGEPLWIsaTVWDRSFVGKH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 641838788 278 EVLGKCMIPLqyvDKRLDHKPVNTR--WYNLEK------HIVVEGEKK 317
Cdd:cd04043   81 DLCGRASLKL---DPKRFGDDGLPReiWLDLDTqgrlllRVSMEGERD 125

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: 44.67 E-value: 1.80e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 364 LELGILNAQGLmPMKTkdgrgTTDAYCVAKYGQ-KWVRTRTIIDsPTPKWNEQYtweVFD--PCTV--ITIGVFDnchlh 438
Cdd:cd08400    6 LQLNVLEAHKL-PVKH-----VPHPYCVISLNEvKVARTKVREG-PNPVWSEEF---VFDdlPPDVnsFTISLSN----- 70

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 641838788 439 ggdKAGGARDSRIGKVRIRLSTLETDRVYTHSYPLLVLYPNGVKKMGEIHLAVRFT 494
Cdd:cd08400   71 ---KAKRSKDSEIAEVTVQLSKLQNGQETDEWYPLSSASPLKGGEWGSLRIRARYS 123

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: 45.03 E-value: 1.88e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL----GNQALRTRVSASRTINPMWNEDLMFVAAEP--FEEHLILTVEDRVAPN 275
Cdd:cd08384   15 LIVGIIRCVNLAAMDANGYSDPFVKLYLkpdaGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSdlAKKTLEITVWDKDIGK 94

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 641838788 276 KDEVLGKCMIPLQYVDKRLDH-----KPVN---TRWYNL 306
Cdd:cd08384   95 SNDYIGGLQLGINAKGERLRHwldclKNPDkkiEAWHTL 133

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: 44.45 E-value: 2.58e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLP-PKDVTGS-CDPYVEVKM------GNYKGTTRHFEKKT-NPEWNQVFAFSKDRIQSSVLEVTVKDKDF 110
Cdd:cd00275    4 LTIKIISGQQLPkPKGDKGSiVDPYVEVEIhglpadDSAKFKTKVVKNNGfNPVWNETFEFDVTVPELAFLRFVVYDEDS 83


                 ....*..
gi 641838788 111 VKDDFMG 117
Cdd:cd00275   84 GDDDFLG 90

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

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 44.19 E-value: 2.83e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 201 YLRVNVIEAQDLQPTDKGR-----FPEV-----YVKAQLGNQALRTRVSASRTINPMWNEDlmFVAAEPFEEHLILTVED 270
Cdd:cd04014    5 TLKIKICEAVDLKPTDWSTrhavpKKGSqlldpYVSIDVDDTHIGKTSTKPKTNSPVWNEE--FTTEVHNGRNLELTVFH 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 641838788 271 RVAPNKDEVLGKCMIPLQYVDKRLDHKpvNTRWYNLEKHivvegekkkdtkfaSRIHMRICLEGG 335
Cdd:cd04014   83 DAAIGPDDFVANCTISFEDLIQRGSGS--FDLWVDLEPQ--------------GKLHVKIELKGS 131

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: 43.33 E-value: 4.19e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  42 VRVVKAKDLPpkdvTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF----SKDRIQSSVLEVTVKDKD-FVKDDFM 116
Cdd:cd04011    8 VRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFnfheSPDELFDKIIKISVYDSRsLRSDTLI 83


                 ....*..
gi 641838788 117 GRVLFDL 123
Cdd:cd04011   84 GSFKLDV 90

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 47.06 E-value: 4.24e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788   40 LYVRVVKAKDLPPKD--VTGSCDPYVEVKM-GNYKGTTRHFEKKTNPEWNQVFaFSKDRIQSSVLEVTVKDK-DFVKDDF 115
Cdd:COG5038   438 VEVKIKSAEGLKKSDstINGTVDPYITVTFsDRVIGKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFnSFKSDKV 516

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  116 MGRVLFDLNEIPKRVPPDSPLApqwyrlEDRKGDKVRGELmlavwmgtqadeAFPEAWHSDAAT----VTGIEGLANIRS 191
Cdd:COG5038   517 VGSTQLDLALLHQNPVKKNELY------EFLRNTKNVGRL------------TYDLRFFPVIEDkkelKGSVEPLEDSNT 578

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  192 KVylspklwyLRVNVIEAQDLQpTDKGRFPEVYVKAQLGNQALRTRVSASRTINPMWNEDLMFVAAEPFEEHLILTVEDR 271
Cdd:COG5038   579 GI--------LKVTLREVKALD-ELSSKKDNKSAELYTNAKEVYSTGKLKFTNHPSWNLQYNVLVTDRKNSSIKVVTFDV 649

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 641838788  272 vapNKDEVLGKCMIPLQ-YVDKRLDhkpvNTRWY------------NLEKHIVVEGEKKKDTKFASRIHMrICL 332
Cdd:COG5038   650 ---QSGKVIATEGSTLPdLIDRTLD----TFLVFplrnpkgrifitNYWKPIYNAGGSSSKTVYDTPIGA-IRV 715

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: 43.81 E-value: 4.46e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 368 ILNAQGLmpmKTKDGRGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNCHLhggdkaggaR 447
Cdd:cd04046    9 VHSAEGL---SKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSNLL---------C 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 641838788 448 DSRIGKVriRLSTLETDRVYTHSYPllvLYPNGVKKMGEI--HLAVRFTCS 496
Cdd:cd04046   77 DEFLGQA--TLSADPNDSQTLRTLP---LRKRGRDAAGEVpgTISVKVTSS 122

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: 43.42 E-value: 4.80e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQAlrtrVSASRTI----NPMWNEDLMfVAAEPFEEHLILTVEDRVAPNKD 277
Cdd:cd04042    2 LDIHLKEGRNLAARDRGGTSDPYVKFKYGGKT----VYKSKTIyknlNPVWDEKFT-LPIEDVTQPLYIKVFDYDRGLTD 76

                         90
                 ....*....|
gi 641838788 278 EVLGKCMIPL 287
Cdd:cd04042   77 DFMGSAFVDL 86

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: 5.14e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQAL-RTRVSASrTINPMWNEdLMFVAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:cd04045    3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKgRTVTISN-TLNPVWDE-VLYVPVTSPNQKITLEVMDYEKVGKDRSL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 641838788 281 GKCMIPLQ-YVDKRLDHKPVNtrwYNLEKHIVVEGEKKKDTK 321
Cdd:cd04045   81 GSVEINVSdLIKKNEDGKYVE---YDDEEERLKRLLSLKGVK 119

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: 43.18 E-value: 7.73e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQALRTR--VSASRTINPMWNEDLMF-VAAEPFEE-HLILTVEDRVAPN 275
Cdd:cd08405   17 ITVNIIKARNLKAMDINGTSDPYVKVWLmyKDKRVEKKktVIKKRTLNPVFNESFIFnIPLERLREtTLIITVMDKDRLS 96

                         90
                 ....*....|.
gi 641838788 276 KDEVLGKCMIP 286
Cdd:cd08405   97 RNDLIGKIYLG 107

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: 42.58 E-value: 1.01e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 641838788  42 VRVVKAKDLPPKDVTGSCDPYVEVKMGNY-KGTTRHFEKKTNPEWNQVF 89
Cdd:cd04045    5 LHIRKANDLKNLEGVGKIDPYVRVLVNGIvKGRTVTISNTLNPVWDEVL 53

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

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 42.54 E-value: 1.19e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDK-GRFPEVYVKAQLGNQA--LRTRVsASRTINPMWNEDLMFVAAEpFEEHLILTVEDRVAPNKDE 278
Cdd:cd04044    4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRelARTKV-KKDTSNPVWNETKYILVNS-LTEPLNLTVYDFNDKRKDK 81


                 ....*....
gi 641838788 279 VLGKCMIPL 287
Cdd:cd04044   82 LIGTAEFDL 90

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 42.24 E-value: 1.24e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 641838788  44 VVKAKDLPPKdvTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAFSKDRI--QSSVLEVTVKD 107
Cdd:cd08373    2 VVSLKNLPGL--KGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSpdPDESLEIVVKD 65

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: 42.44 E-value: 1.27e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  37 MQYLYVRVVKAK-DLPPkdvtGSCDPYVEVKMGNYKGTTRHFeKKTNPEWNQVFAFSKDRIQSSvLEVTVKDKDFVKDDF 115
Cdd:cd08394    1 MSLLCVLVKKAKlDGAP----DKFNTYVTLKVQNVKSTTIAV-RGSQPCWEQDFMFEINRLDLG-LVIELWNKGLIWDTL 74

                         90
                 ....*....|..
gi 641838788 116 MGRVLFDLNEIP 127
Cdd:cd08394   75 VGTVWIPLSTIR 86

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: 42.36 E-value: 1.59e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGR---FPEVYVKAQLGNQALRTRVSaSRTINPMWNEDLMFVAAEPFEEHLILT-VEDRVAPN-- 275
Cdd:cd08675    1 LSVRVLECRDLALKSNGTcdpFARVTLNYSSKTDTKRTKVK-KKTNNPRFDEAFYFELTIGFSYEKKSFkVEEEDLEKse 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 641838788 276 ------------KDEVLGKCMIPLQyvdkRLDHKPVNTRWYNL 306
Cdd:cd08675   80 lrvelwhasmvsGDDFLGEVRIPLQ----GLQQAGSHQAWYFL 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: 41.77 E-value: 2.16e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDL-PPKDVTGSCDPYVEVKMGNYK--GTTRHFEKKTNPEWNQVFAFskdrIQSS---VLEVTVKDK-DFVK 112
Cdd:cd04044    4 LAVTIKSARGLkGSDIIGGTVDPYVTFSISNRRelARTKVKKDTSNPVWNETKYI----LVNSltePLNLTVYDFnDKRK 79

                         90
                 ....*....|....
gi 641838788 113 DDFMGRVLFDLNEI 126
Cdd:cd04044   80 DKLIGTAEFDLSSL 93

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: 41.02 E-value: 2.31e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 197 PKLWYLRVNVIEAQDLQ-----PtdkgrfpevYVKAQLGNQALRTRVSASrTINPMWNEDLMF----VAAEPFEEHLILT 267
Cdd:cd04011    1 PQDFQVRVRVIEARQLVggnidP---------VVKVEVGGQKKYTSVKKG-TNCPFYNEYFFFnfheSPDELFDKIIKIS 70

                         90       100
                 ....*....|....*....|....*....
gi 641838788 268 VEDRVAPNKDEVLGKCMIPLQYVDKRLDH 296
Cdd:cd04011   71 VYDSRSLRSDTLIGSFKLDVGTVYDQPDH 99

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: 41.48 E-value: 2.96e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPpKDVTGSCDPYVEVKMGNYKGTTRHFEKKTNPEWNQVFAF-SKDRIQSSVLEVTVKDKD-FVKDDFMG 117
Cdd:cd04032   30 LTVTVLRATGLW-GDYFTSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFgSVELSPGGKLRFEVWDRDnGWDDDLLG 108


                 .
gi 641838788 118 R 118
Cdd:cd04032  109 T 109

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: 41.23 E-value: 3.01e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL---GNQALRTRVSaSRTINPMWNEDLMF-VAAEPFEEHlilTVE----DRVA 273
Cdd:cd08387   18 LNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIH-KKTLNPEFDESFVFeVPPQELPKR---TLEvllyDFDQ 93

                         90
                 ....*....|....*...
gi 641838788 274 PNKDEVLGKCMIPLQYVD 291
Cdd:cd08387   94 FSRDECIGVVELPLAEVD 111

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: 41.50 E-value: 3.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQpTDKGRF---PEVYVKAQLGNQALRTRVSASR----TINPMWNEDLMF------VAAEPFEehliLTV 268
Cdd:cd08407   17 LLVVVIKAKNLH-SDQLKLllgIDVSVKVTLKHQNAKLKKKQTKrakhKINPVWNEMIMFelpselLAASSVE----LEV 91

                         90       100
                 ....*....|....*....|....*...
gi 641838788 269 EDRVAPNKDEVLGKCMIPLQYVDKRLDH 296
Cdd:cd08407   92 LNQDSPGQSLPLGRCSLGLHTSGTERQH 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: 40.71 E-value: 3.74e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKdvtGSCDPYVEVKMGNYK-GTTRHFEKKtNPEWNQVFAFS--KDRIQSSVLEVTVKDKD-FVKDDF 115
Cdd:cd08383    2 LRLRILEAKNLPSK---GTRDPYCTVSLDQVEvARTKTVEKL-NPFWGEEFVFDdpPPDVTFFTLSFYNKDKRsKDRDIV 77


                 ....*..
gi 641838788 116 MGRVLFD 122
Cdd:cd08383   78 IGKVALS 84

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 43.98 E-value: 4.27e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  201 YLRVNVIEAQDLQPTDKGRFPEVYVKAQLGNQALRTRVSASRTINPMWNEDLMFVAAEPFEEHLILTVEDRVAPNKDEVL 280
Cdd:COG5038  1041 YLTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLL 1120

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 641838788  281 GKCMIPLQYVDKRLDHK---PVNTRW-----------YNLE-KHIVVEGEK-KKDTKFASRIHMRI 330
Cdd:COG5038  1121 GTAEIDLSKLEPGGTTNsniPLDGKTfivldgtlhpgFNFRsKYALNVSRKeGILGDIAKKVGTGL 1186

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 40.49 E-value: 5.01e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 196 SPKLWYLRVNVIEAQDLQPTD--KGRfPEVYVKAQL----GNQALRTRVSASRTINPMWNEDLMFVA--AEPFEEHLILT 267
Cdd:cd08393   11 DPKLRELHVHVIQCQDLAAADpkKQR-SDPYVKTYLlpdkSNRGKRKTSVKKKTLNPVFNETLRYKVerEELPTRVLNLS 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 641838788 268 VEDRVAPNKDEVLGKCMIPLQYVDkrLDHKPVNtrWYNLE 307
Cdd:cd08393   90 VWHRDSLGRNSFLGEVEVDLGSWD--WSNTQPT--WYPLQ 125

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: 40.45 E-value: 7.38e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 352 TAKQLWKSSIGVLELGILNAQGLMPMKTKdgrGTTDAYCVAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFD-PCTVITIG 430
Cdd:cd08375    5 LARSQRASGIGRLMVVIVEGRDLKPCNSN---GKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDlEQDVLCIT 81

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 641838788 431 VFDNCHLhggdkaggARDSRIGKVRIRLSTLETDR 465
Cdd:cd08375   82 VFDRDFF--------SPDDFLGRTEIRVADILKET 108

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

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 39.72 E-value: 8.84e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  32 DLVEQMQYLYVRVVKAKDLPPKDV-TGSCDPYVEV-------KMGNYKGTTRhfeKKT-NPEWNQVFAFS--KDRIQSSV 100
Cdd:cd08393    9 DYDPKLRELHVHVIQCQDLAAADPkKQRSDPYVKTyllpdksNRGKRKTSVK---KKTlNPVFNETLRYKveREELPTRV 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 641838788 101 LEVTVKDKD-FVKDDFMGRVLFDLNEIpkrvppD-SPLAPQWYRLE 144
Cdd:cd08393   86 LNLSVWHRDsLGRNSFLGEVEVDLGSW------DwSNTQPTWYPLQ 125

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: 40.01 E-value: 8.95e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 641838788 362 GVLELGILNAQGLmpmKTKDGRGTTDAYCVAKYGQKwVRTRTII--DSPTPKWNEQYTWEVFDP 423
Cdd:cd04049    1 GTLEVLLISAKGL---QDTDFLGKIDPYVIIQCRTQ-ERKSKVAkgDGRNPEWNEKFKFTVEYP 60

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 39.47 E-value: 1.07e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 364 LELGILNAQGLMPMktkDGRGTTDAYCVAKY-GQKWVRTRTIIDSPTPKWNEQYTWEVfdPC---TVITIGVFDnchlhg 439
Cdd:cd04040    1 LTVDVISAENLPSA---DRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPV--PSrvrAVLKVEVYD------ 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 641838788 440 GDkAGGARDSrIGKVRIRLSTLETDRVYTHSYPllvLYPNGVKKMGEIHL 489
Cdd:cd04040   70 WD-RGGKDDL-LGSAYIDLSDLEPEETTELTLP---LDGQGGGKLGAVFL 114

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 42.82 E-value: 1.07e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  344 HYSSDLRPTAKQLWKSSIGVLELGILNAQGLmpmktKDGR----GTTDAYCVAKYGQKWV-RTRTIIDSPTPKWNEQYTW 418
Cdd:COG5038   418 SLTIDISQIMAGDSGTAIGVVEVKIKSAEGL-----KKSDstinGTVDPYITVTFSDRVIgKTRVKKNTLNPVWNETFYI 492

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 641838788  419 EVFDPCTVITIGVFdnchlhggDKAGGARDSRIGKVRIRLSTLETDRVYTHsypLLVLYPNGVKKMGEIHLAVRF 493
Cdd:COG5038   493 LLNSFTDPLNLSLY--------DFNSFKSDKVVGSTQLDLALLHQNPVKKN---ELYEFLRNTKNVGRLTYDLRF 556

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: 39.47 E-value: 1.07e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  45 VKAKDLPPKDVTGSCDPYVEVKM--GNYKGTTRHF-----EKKTNPEWNQVFAF-----SKDRIQSSVLEVTVKDKDFVK 112
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVktGGSGQWVEIGrteviKNNLNPDFVTTFTVdyyfeEVQKLRFEVYDVDSKSKDLSD 86

                         90
                 ....*....|....
gi 641838788 113 DDFMGRVLFDLNEI 126
Cdd:cd04048   87 HDFLGEAECTLGEI 100

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: 39.98 E-value: 1.24e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  60 DPYVEVKMGNYK-GTTRHFEKKTNPEWNQVFafskdRI----QSSVLEVTVKDKDFVKDDFMGRVlfdlneipkRVPPDS 134
Cdd:cd04015   59 DPYATVDLAGARvARTRVIENSENPVWNESF-----HIycahYASHVEFTVKDNDVVGAQLIGRA---------YIPVED 124

                         90
                 ....*....|....*....
gi 641838788 135 PLAPQ----WYRLEDRKGD 149
Cdd:cd04015  125 LLSGEpvegWLPILDSNGK 143

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: 38.77 E-value: 1.55e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPP-KDVTGS---CDPYVEVKMGNYKGTTRhFEKKT-NPEWNQVFAFS-KDRIQSSVLEVTVKDKD-FVK 112
Cdd:cd04039    3 VFMEIKSITDLPPlKNMTRTgfdMDPFVIISFGRRVFRTS-WRRHTlNPVFNERLAFEvYPHEKNFDIQFKVLDKDkFSF 81

                         90       100
                 ....*....|....*....|...
gi 641838788 113 DDFMGRVLFDLNEIPKRVPPDSP 135
Cdd:cd04039   82 NDYVATGSLSVQELLNAAPQPDP 104

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: 38.65 E-value: 2.46e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 380 KDGRGTTDAYCVAKYGQKWV-RTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNCHLhggdkaggARDSRIGKVRIRL 458
Cdd:cd04054   15 KDITGSSDPYCIVKVDNEVIiRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDEDTL--------SRDDVIGKVSLTR 86

                         90       100       110
                 ....*....|....*....|....*....|....
gi 641838788 459 STLETDRVYTHSYPLLVLYPNGVKKMGEIHLAVR 492
Cdd:cd04054   87 EVISAHPRGIDGWMNLTEVDPDEEVQGEIHLELS 120

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: 37.52 E-value: 5.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLqPTDKGRFPEV---YVKAQL------GNQALRTRVSASRTINPMWNEDLMFVAAEPFEEHLILTVEDRV 272
Cdd:cd00275    4 LTIKIISGQQL-PKPKGDKGSIvdpYVEVEIhglpadDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDED 82

                         90
                 ....*....|....*
gi 641838788 273 aPNKDEVLGKCMIPL 287
Cdd:cd00275   83 -SGDDDFLGQACLPL 96

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: 37.56 E-value: 5.99e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 194 YLsPKLWYLRVNVIEAQDLQPTDKGRFPEVYVKAQL--GNQALRTRVSASR--TINPMWNEDLMF-VAAEPFEE-HLILT 267
Cdd:cd08410    9 YL-PSAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLvhGLKLIKTKKTSCMrgTIDPFYNESFSFkVPQEELENvSLVFT 87

                         90
                 ....*....|....*...
gi 641838788 268 VEDRVAPNKDEVLGKCMI 285
Cdd:cd08410   88 VYGHNVKSSNDFIGRIVI 105

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: 37.56 E-value: 6.34e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEVKMgnYKGTTRHFEKKT-------NPEWNQVFAF--SKDRIQSSVLEVTVKDKDF 110
Cdd:cd08410   16 LNVDIIRAKQLLQTDMSQGSDPFVKIQL--VHGLKLIKTKKTscmrgtiDPFYNESFSFkvPQEELENVSLVFTVYGHNV 93

                         90
                 ....*....|.
gi 641838788 111 -VKDDFMGRVL 120
Cdd:cd08410   94 kSSNDFIGRIV 104

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: 37.49 E-value: 7.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788  40 LYVRVVKAKDLPPKDVTGSCDPYVEV------KMGNYKGTTrhFEKKT-NPEWNQ--VFAFSKDRIQSSVLEVTVKDKDF 110
Cdd:cd08403   16 LTLTIIKARNLKAMDITGFSDPYVKVslmcegRRLKKKKTS--VKKNTlNPTYNEalVFDVPPENVDNVSLIIAVVDYDR 93


                 .
gi 641838788 111 V 111
Cdd:cd08403   94 V 94

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

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 36.81 E-value: 7.51e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 222 EVYVKAQLgnqALRTRVsASRTINPMWNEDLMFVAAEPFEEHLILTV-EDRVApnKDEVLGKCMIPLQYVdkrLDHKPVN 300
Cdd:cd04052   18 ELYLNGKL---VYTTRV-KKKTNNPSWNASTEFLVTDRRKSRVTVVVkDDRDR--HDPVLGSVSISLNDL---IDATSVG 88


                 ....*.
gi 641838788 301 TRWYNL 306
Cdd:cd04052   89 QQWFPL 94

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: 37.33 E-value: 8.30e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQLgNQALRTRVSAS-------RTINPMWNEDLMFvAAEPFEEHLILTVEDRVAP 274
Cdd:cd04033    2 LRVKVLAGIDLAKKDIFGASDPYVKISL-YDPDGNGEIDSvqtktikKTLNPKWNEEFFF-RVNPREHRLLFEVFDENRL 79

                         90
                 ....*....|...
gi 641838788 275 NKDEVLGKCMIPL 287
Cdd:cd04033   80 TRDDFLGQVEVPL 92

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: 37.33 E-value: 8.33e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTD-KGRFPEVYVKAQL---GNQALRTRVsASRTINPMWNEDLMFVAAEPFEE-----HLILTVEDRV 272
Cdd:cd08388   18 LLVNIIECRDLPAMDeQSGTSDPYVKLQLlpeKEHKVKTRV-LRKTRNPVYDETFTFYGIPYNQLqdlslHFAVLSFDRY 96

                         90
                 ....*....|....*....
gi 641838788 273 ApnKDEVLGKCMIPLQYVD 291
Cdd:cd08388   97 S--RDDVIGEVVCPLAGAD 113

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: 36.92 E-value: 8.34e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 202 LRVNVIEAQDLQPTDKGRFPEVYVKAQL---GNQALRTRVSaSRTINPMWNEDLMFvaaEPF------EEHLILTVEDRV 272
Cdd:cd08386   18 LTLKILKAVELPAKDFSGTSDPFVKIYLlpdKKHKLETKVK-RKNLNPHWNETFLF---EGFpyeklqQRVLYLQVLDYD 93

                         90       100       110
                 ....*....|....*....|....*....|....
gi 641838788 273 APNKDEVLGKCMIPLQYVDkrLDHKPvnTRWYNL 306
Cdd:cd08386   94 RFSRNDPIGEVSLPLNKVD--LTEEQ--TFWKDL 123

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: 36.80 E-value: 9.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 641838788 362 GVLELGILNAQGLmpmKTKDGRGTTDAYC-VAKYGQKWVRTRTIIDSPTPKWNEQYTWEVFDPCTVITIGVFDNchlhgg 440
Cdd:cd04045    1 GVLRLHIRKANDL---KNLEGVGKIDPYVrVLVNGIVKGRTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMDY------ 71

                         90
                 ....*....|....*....
gi 641838788 441 DKAGgaRDSRIGKVRIRLS 459
Cdd:cd04045   72 EKVG--KDRSLGSVEINVS 88