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Conserved domains on  [gi|568941302|ref|XP_006505915|]
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copine-9 isoform X3 [Mus musculus]

Protein Classification

copine family protein( domain architecture ID 10134296)

copine family protein similar to copines, a class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
118-374 9.53e-122

VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding.


:

Pssm-ID: 238736  Cd Length: 254  Bit Score: 352.83  E-value: 9.53e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 118 YTNSGTVTLLSFSVdsEFTFVDYIKGGTQLNFTVAIDFTASNGNPLQPTSLHYMSPYQLSAYAMALKAVGEIIQDYDSDK 197
Cdd:cd01459    5 YKSSGEVTLTDCRV--QPTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 198 LFPAYGFGAKLPPEGRISHQFPLNnnDEDPNCAGIEGVLESYFQSLRTVQLYGPTYFAPVINQVARAAAKISDGSQYYVL 277
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFFPGY--SESPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSKYHIL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 278 LIITDGVISDMTQTKEAIVSASSLPMSIIIVGVGPAMFEAMEELDGDDVRVSSRGRYAERDIVQFVPFRDYVDRSGNqvl 357
Cdd:cd01459  161 LIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAGN--- 237
                        250
                 ....*....|....*..
gi 568941302 358 SMARLAKDVLAEIPEQL 374
Cdd:cd01459  238 PEAALATAALAEIPSQL 254
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1-108 2.83e-60

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


:

Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.83e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   1 MQLCANKLDKKDFFGKSDPFLVFYRSNEDGTFTICHKTEVVKNTLNPVWQPFSIPVRALCNGDYDRTVKIDVYDWDRDGS 80
Cdd:cd04047    5 LQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSSGK 84
                         90       100
                 ....*....|....*....|....*...
gi 568941302  81 HDFIGEFTTSYRELSKaqNQFTVYEVLN 108
Cdd:cd04047   85 HDLIGEFETTLDELLK--SSPLEFELIN 110
 
Name Accession Description Interval E-value
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
118-374 9.53e-122

VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding.


Pssm-ID: 238736  Cd Length: 254  Bit Score: 352.83  E-value: 9.53e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 118 YTNSGTVTLLSFSVdsEFTFVDYIKGGTQLNFTVAIDFTASNGNPLQPTSLHYMSPYQLSAYAMALKAVGEIIQDYDSDK 197
Cdd:cd01459    5 YKSSGEVTLTDCRV--QPTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 198 LFPAYGFGAKLPPEGRISHQFPLNnnDEDPNCAGIEGVLESYFQSLRTVQLYGPTYFAPVINQVARAAAKISDGSQYYVL 277
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFFPGY--SESPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSKYHIL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 278 LIITDGVISDMTQTKEAIVSASSLPMSIIIVGVGPAMFEAMEELDGDDVRVSSRGRYAERDIVQFVPFRDYVDRSGNqvl 357
Cdd:cd01459  161 LIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAGN--- 237
                        250
                 ....*....|....*..
gi 568941302 358 SMARLAKDVLAEIPEQL 374
Cdd:cd01459  238 PEAALATAALAEIPSQL 254
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
167-381 5.00e-111

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.


Pssm-ID: 462064  Cd Length: 214  Bit Score: 324.29  E-value: 5.00e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  167 SLHYMSPYQLSAYAMALKAVGEIIQDYDSDKLFPAYGFGAKLPPEGRISHQFPLNNNDEDPNCAGIEGVLESYFQSLRTV 246
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  247 QLYGPTYFAPVINQVAR-AAAKISDGSQYYVLLIITDGVISDMTQTKEAIVSASSLPMSIIIVGVGPAMFEAMEELDGDD 325
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARiAKASTQNAGQYHVLLIITDGVVTDMKATIDAIVNASHLPLSIIIVGVGDGDFSDMRELDDDD 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568941302  326 VRVSSRGRYAERDIVQFVPFRDYVDrsgNQVLSMARLAKDVLAEIPEQLLSYMRTR 381
Cdd:pfam07002 161 RLRSSDGRIAARDIVQFVPFRDIMS---NADLKEAALALAVLAEIPDQYVAYMELR 213
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1-108 2.83e-60

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


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.83e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   1 MQLCANKLDKKDFFGKSDPFLVFYRSNEDGTFTICHKTEVVKNTLNPVWQPFSIPVRALCNGDYDRTVKIDVYDWDRDGS 80
Cdd:cd04047    5 LQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSSGK 84
                         90       100
                 ....*....|....*....|....*...
gi 568941302  81 HDFIGEFTTSYRELSKaqNQFTVYEVLN 108
Cdd:cd04047   85 HDLIGEFETTLDELLK--SSPLEFELIN 110
C2 pfam00168
C2 domain;
3-94 1.02e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 80.83  E-value: 1.02e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302    3 LCANKLDKKDFFGKSDPFLVFYRSNEdgtfTICHKTEVVKNTLNPVW-QPFSIPVRAlcngDYDRTVKIDVYDWDRDGSH 81
Cdd:pfam00168   8 IEAKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRD 79
                          90
                  ....*....|...
gi 568941302   82 DFIGEFTTSYREL 94
Cdd:pfam00168  80 DFIGEVRIPLSEL 92
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
3-94 1.76e-16

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: 74.45  E-value: 1.76e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302     3 LCANKLDKKDFFGKSDPFLVFYRsneDGTFTICHKTEVVKNTLNPVW-QPFSIPVRALCngdyDRTVKIDVYDWDRDGSH 81
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79
                           90
                   ....*....|...
gi 568941302    82 DFIGEFTTSYREL 94
Cdd:smart00239  80 DFIGQVTIPLSDL 92
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
15-102 1.69e-08

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 56.69  E-value: 1.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   15 GKSDPFLVFYRSNEDgtftiCHKTEVVKNTLNPVW-QPFSIPV--RALCNgdydrtVKIDVYDWDRDGSHDFIGeftTSY 91
Cdd:COG5038  1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLG---TAE 1124
                          90
                  ....*....|.
gi 568941302   92 RELSKAQNQFT 102
Cdd:COG5038  1125 IDLSKLEPGGT 1135
VWA smart00327
von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins ...
148-343 5.91e-07

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.


Pssm-ID: 214621 [Multi-domain]  Cd Length: 175  Bit Score: 49.38  E-value: 5.91e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   148 NFTVAIDFTASngnplqptslhyMSPYQLSAYAMALKAVGEIIQDYDSDKLFPAYGFGaklppeGRISHQFPLNNndeDP 227
Cdd:smart00327   1 DVVFLLDGSGS------------MGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFS------DDARVLFPLND---SR 59
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   228 NCAgiegVLESYFQSLRtVQLYGPTYFAPVINQVARAAAKISDGSQYY---VLLIITDGVISD-MTQTKEAIVSASSLPM 303
Cdd:smart00327  60 SKD----ALLEALASLS-YKLGGGTNLGAALQYALENLFSKSAGSRRGapkVVILITDGESNDgPKDLLKAAKELKRSGV 134
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 568941302   304 SIIIVGVGPAMFEA-MEELDGDDVRVSSRGRYAERDIVQFV 343
Cdd:smart00327 135 KVFVVGVGNDVDEEeLKKLASAPGGVYVFLPELLDLLIDLL 175
 
Name Accession Description Interval E-value
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
118-374 9.53e-122

VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding.


Pssm-ID: 238736  Cd Length: 254  Bit Score: 352.83  E-value: 9.53e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 118 YTNSGTVTLLSFSVdsEFTFVDYIKGGTQLNFTVAIDFTASNGNPLQPTSLHYMSPYQLSAYAMALKAVGEIIQDYDSDK 197
Cdd:cd01459    5 YKSSGEVTLTDCRV--QPTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 198 LFPAYGFGAKLPPEGRISHQFPLNnnDEDPNCAGIEGVLESYFQSLRTVQLYGPTYFAPVINQVARAAAKISDGSQYYVL 277
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFFPGY--SESPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSKYHIL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302 278 LIITDGVISDMTQTKEAIVSASSLPMSIIIVGVGPAMFEAMEELDGDDVRVSSRGRYAERDIVQFVPFRDYVDRSGNqvl 357
Cdd:cd01459  161 LIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAGN--- 237
                        250
                 ....*....|....*..
gi 568941302 358 SMARLAKDVLAEIPEQL 374
Cdd:cd01459  238 PEAALATAALAEIPSQL 254
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
167-381 5.00e-111

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.


Pssm-ID: 462064  Cd Length: 214  Bit Score: 324.29  E-value: 5.00e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  167 SLHYMSPYQLSAYAMALKAVGEIIQDYDSDKLFPAYGFGAKLPPEGRISHQFPLNNNDEDPNCAGIEGVLESYFQSLRTV 246
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  247 QLYGPTYFAPVINQVAR-AAAKISDGSQYYVLLIITDGVISDMTQTKEAIVSASSLPMSIIIVGVGPAMFEAMEELDGDD 325
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARiAKASTQNAGQYHVLLIITDGVVTDMKATIDAIVNASHLPLSIIIVGVGDGDFSDMRELDDDD 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568941302  326 VRVSSRGRYAERDIVQFVPFRDYVDrsgNQVLSMARLAKDVLAEIPEQLLSYMRTR 381
Cdd:pfam07002 161 RLRSSDGRIAARDIVQFVPFRDIMS---NADLKEAALALAVLAEIPDQYVAYMELR 213
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1-108 2.83e-60

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


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.83e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   1 MQLCANKLDKKDFFGKSDPFLVFYRSNEDGTFTICHKTEVVKNTLNPVWQPFSIPVRALCNGDYDRTVKIDVYDWDRDGS 80
Cdd:cd04047    5 LQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSSGK 84
                         90       100
                 ....*....|....*....|....*...
gi 568941302  81 HDFIGEFTTSYRELSKaqNQFTVYEVLN 108
Cdd:cd04047   85 HDLIGEFETTLDELLK--SSPLEFELIN 110
C2 pfam00168
C2 domain;
3-94 1.02e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 80.83  E-value: 1.02e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302    3 LCANKLDKKDFFGKSDPFLVFYRSNEdgtfTICHKTEVVKNTLNPVW-QPFSIPVRAlcngDYDRTVKIDVYDWDRDGSH 81
Cdd:pfam00168   8 IEAKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRD 79
                          90
                  ....*....|...
gi 568941302   82 DFIGEFTTSYREL 94
Cdd:pfam00168  80 DFIGEVRIPLSEL 92
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
3-94 1.76e-16

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: 74.45  E-value: 1.76e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302     3 LCANKLDKKDFFGKSDPFLVFYRsneDGTFTICHKTEVVKNTLNPVW-QPFSIPVRALCngdyDRTVKIDVYDWDRDGSH 81
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79
                           90
                   ....*....|...
gi 568941302    82 DFIGEFTTSYREL 94
Cdd:smart00239  80 DFIGQVTIPLSDL 92
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
15-86 1.81e-16

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: 74.91  E-value: 1.81e-16
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568941302  15 GKSDPFLVFYRSNEDgtftiCHKTEVVKNTLNPVW-QPFSIPVralcNGDYDRTVKIDVYDWDRDGSHDFIGE 86
Cdd:cd04040   18 GKSDPFVKFYLNGEK-----VFKTKTIKKTLNPVWnESFEVPV----PSRVRAVLKVEVYDWDRGGKDDLLGS 81
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
1-105 2.63e-16

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: 74.53  E-value: 2.63e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   1 MQLCANKLDKKDFFGKSDPFLVFY-RSNEDGTFTICHKTEVVKNTLNPVW-QPFSIpvralcngDY----DRTVKIDVYD 74
Cdd:cd04048    5 LSISCRNLLDKDVLSKSDPFVVVYvKTGGSGQWVEIGRTEVIKNNLNPDFvTTFTV--------DYyfeeVQKLRFEVYD 76
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568941302  75 WD----RDGSHDFIGEFTTSYRELSKAQNQFTVYE 105
Cdd:cd04048   77 VDskskDLSDHDFLGEAECTLGEIVSSPGQKLTLP 111
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
3-88 4.04e-16

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: 73.64  E-value: 4.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFLVFYRSNEdgtftICHKTEVVKNTLNPVW-QPFSIPVralcNGDYDRTVKIDVYDWDRDGSH 81
Cdd:cd00030    6 IEARNLPAKDLNGKSDPYVKVSLGGK-----QKFKTKVVKNTLNPVWnETFEFPV----LDPESDTLTVEVWDKDRFSKD 76

                 ....*..
gi 568941302  82 DFIGEFT 88
Cdd:cd00030   77 DFLGEVE 83
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
15-99 5.06e-11

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


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 59.97  E-value: 5.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  15 GKSDPFlVFYRSNEDGTFTICHKTEVVKNTLNPVW-QPFSIPVRAlcnGDYDRTVKIDVYDWDRDGSHDFIGEFTTSYRE 93
Cdd:cd04026   32 GLSDPY-VKLKLIPDPKNETKQKTKTIKKTLNPVWnETFTFDLKP---ADKDRRLSIEVWDWDRTTRNDFMGSLSFGVSE 107

                 ....*.
gi 568941302  94 LSKAQN 99
Cdd:cd04026  108 LIKMPV 113
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
5-93 1.50e-08

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: 52.81  E-value: 1.50e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNEDGTFTIcHKTEVVKNTLNPVWQ---PFSIPVRALcngdYDRTVKIDVYDWDRDGSH 81
Cdd:cd08405   24 ARNLKAMDINGTSDPYVKVWLMYKDKRVEK-KKTVIKKRTLNPVFNesfIFNIPLERL----RETTLIITVMDKDRLSRN 98
                         90
                 ....*....|..
gi 568941302  82 DFIGEFTTSYRE 93
Cdd:cd08405   99 DLIGKIYLGWKS 110
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
15-102 1.69e-08

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 56.69  E-value: 1.69e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   15 GKSDPFLVFYRSNEDgtftiCHKTEVVKNTLNPVW-QPFSIPV--RALCNgdydrtVKIDVYDWDRDGSHDFIGeftTSY 91
Cdd:COG5038  1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLG---TAE 1124
                          90
                  ....*....|.
gi 568941302   92 RELSKAQNQFT 102
Cdd:COG5038  1125 IDLSKLEPGGT 1135
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
5-85 1.96e-08

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: 52.30  E-value: 1.96e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNED-GTFTIChktevvkNTLNPVW-QPFSIPVRalcngDYDRTVKIDVYDWDRDGSHD 82
Cdd:cd08377   10 ASGLAAADIGGKSDPFCVLELVNARlQTHTIY-------KTLNPEWnKIFTFPIK-----DIHDVLEVTVYDEDKDKKPE 77

                 ...
gi 568941302  83 FIG 85
Cdd:cd08377   78 FLG 80
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
13-94 4.35e-08

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


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 51.49  E-value: 4.35e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  13 FFGKSDPFL-VFYRSnedgtftICHKTEVVKNTLNPVW-QPFSIPVRAlcNGDYDRTVKIDVYDWDRDGSHDFIGEFTTS 90
Cdd:cd08373   11 LKGKGDRIAkVTFRG-------VKKKTRVLENELNPVWnETFEWPLAG--SPDPDESLEIVVKDYEKVGRNRLIGSATVS 81

                 ....
gi 568941302  91 YREL 94
Cdd:cd08373   82 LQDL 85
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
7-86 6.39e-08

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: 51.20  E-value: 6.39e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   7 KLDKKDFFGKSDPF--LVFYRSNEDGTFTICHkTEVVKNTLNPVW-QPFSIPVRALCNgdydrTVKIDVYDWDRDGSHDF 83
Cdd:cd04033   11 DLAKKDIFGASDPYvkISLYDPDGNGEIDSVQ-TKTIKKTLNPKWnEEFFFRVNPREH-----RLLFEVFDENRLTRDDF 84

                 ...
gi 568941302  84 IGE 86
Cdd:cd04033   85 LGQ 87
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
5-88 6.44e-08

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: 50.73  E-value: 6.44e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNE-DGTFtichKTEVVKNTLNPVWQP---FSIPVRALCNgdydRTVKIDVYDWDRDGS 80
Cdd:cd08385   25 AADLPAMDMGGTSDPYVKVYLLPDkKKKF----ETKVHRKTLNPVFNEtftFKVPYSELGN----KTLVFSVYDFDRFSK 96

                 ....*...
gi 568941302  81 HDFIGEFT 88
Cdd:cd08385   97 HDLIGEVR 104
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
5-98 8.00e-08

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: 50.37  E-value: 8.00e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFF------GKSDPFLVFYRSNEdgTFtichKTEVVKNTLNPVW-QPFSipvrALCNGDYDRTVKIDVYDWDR 77
Cdd:cd08391   10 AQDLVAKDKFvgglvkGKSDPYVIVRVGAQ--TF----KSKVIKENLNPKWnEVYE----AVVDEVPGQELEIELFDEDP 79
                         90       100
                 ....*....|....*....|.
gi 568941302  78 DgSHDFIGEFTTSYRELSKAQ 98
Cdd:cd08391   80 D-KDDFLGRLSIDLGSVEKKG 99
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
11-86 8.91e-08

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: 50.35  E-value: 8.91e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568941302  11 KDFFGKSDPFLVFYRSNEdgtftICHKTEVVKNTLNPVW-QPFSIPVRalcngDYDRTVKIDVYDWDRDGSHDFIGE 86
Cdd:cd04042   15 RDRGGTSDPYVKFKYGGK-----TVYKSKTIYKNLNPVWdEKFTLPIE-----DVTQPLYIKVFDYDRGLTDDFMGS 81
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
11-86 2.08e-07

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: 50.02  E-value: 2.08e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568941302  11 KDFFGkSDPFLVFYRSNEDGtftichKTEVVKNTLNPVWQP---FSIPvralcngDYDRTVKIDVYDWDRDGSHDFIGE 86
Cdd:cd04038   17 RDFTS-SDPYVVLTLGNQKV------KTRVIKKNLNPVWNEeltLSVP-------NPMAPLKLEVFDKDTFSKDDSMGE 81
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
3-98 3.66e-07

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: 48.78  E-value: 3.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFLVFY----RSNEdgtfticHK--TEVVKNTLNPVW-QPF---SIPVRALcngdYDRTVKIDV 72
Cdd:cd04031   23 LQARDLPPRDDGSLRNPYVKVYllpdRSEK-------SKrrTKTVKKTLNPEWnQTFeysNVRRETL----KERTLEVTV 91
                         90       100
                 ....*....|....*....|....*.
gi 568941302  73 YDWDRDGSHDFIGEFTTsyrELSKAQ 98
Cdd:cd04031   92 WDYDRDGENDFLGEVVI---DLADAL 114
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
3-49 4.37e-07

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


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 48.46  E-value: 4.37e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 568941302   3 LCANKLDKKDFFGKSDPFLVFyrSNEDGTftiCHKTEVVKNTLNPVW 49
Cdd:cd08382    7 LCADGLAKRDLFRLPDPFAVI--TVDGGQ---THSTDVAKKTLDPKW 48
VWA smart00327
von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins ...
148-343 5.91e-07

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.


Pssm-ID: 214621 [Multi-domain]  Cd Length: 175  Bit Score: 49.38  E-value: 5.91e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   148 NFTVAIDFTASngnplqptslhyMSPYQLSAYAMALKAVGEIIQDYDSDKLFPAYGFGaklppeGRISHQFPLNNndeDP 227
Cdd:smart00327   1 DVVFLLDGSGS------------MGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFS------DDARVLFPLND---SR 59
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   228 NCAgiegVLESYFQSLRtVQLYGPTYFAPVINQVARAAAKISDGSQYY---VLLIITDGVISD-MTQTKEAIVSASSLPM 303
Cdd:smart00327  60 SKD----ALLEALASLS-YKLGGGTNLGAALQYALENLFSKSAGSRRGapkVVILITDGESNDgPKDLLKAAKELKRSGV 134
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 568941302   304 SIIIVGVGPAMFEA-MEELDGDDVRVSSRGRYAERDIVQFV 343
Cdd:smart00327 135 KVFVVGVGNDVDEEeLKKLASAPGGVYVFLPELLDLLIDLL 175
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
3-100 2.16e-06

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 46.32  E-value: 2.16e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFL-VFYRSNEdgtfticHKTEVVKNTLNPVW-QPFSIPVRalcnGDYDRTVKIDVYDWDRDGS 80
Cdd:cd04025    7 LEARDLAPKDRNGTSDPFVrVFYNGQT-------LETSVVKKSCYPRWnEVFEFELM----EGADSPLSVEVWDWDLVSK 75
                         90       100
                 ....*....|....*....|
gi 568941302  81 HDFIGEFTTSYRELSKAQNQ 100
Cdd:cd04025   76 NDFLGKVVFSIQTLQQAKQE 95
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
4-85 3.10e-06

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: 46.19  E-value: 3.10e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   4 CANkLDKKDFFGKSDPFLVFYRSnEDGTFTICHKTEVVKNTLNPVWQP---FSIPVRALCNgdydRTVKIDVYDWDRDGS 80
Cdd:cd08384   22 CVN-LAAMDANGYSDPFVKLYLK-PDAGKKSKHKTQVKKKTLNPEFNEeffYDIKHSDLAK----KTLEITVWDKDIGKS 95

                 ....*
gi 568941302  81 HDFIG 85
Cdd:cd08384   96 NDYIG 100
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
8-92 1.44e-05

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: 44.46  E-value: 1.44e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   8 LDKKDFfgkSDPFL-VFYRSNedgtftiCHKTEVVKNTLNPVW-QPFSIPVRALCNG--DYDR---TVKIDVYDWDRDGS 80
Cdd:cd04017   16 ADKSGL---SDPFArVSFLNQ-------SQETEVIKETLSPTWdQTLIFDEVELYGSpeEIAQnppLVVVELFDQDSVGK 85
                         90
                 ....*....|..
gi 568941302  81 HDFIGEFTTSYR 92
Cdd:cd04017   86 DEFLGRSVAKPL 97
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
5-110 1.54e-05

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: 44.31  E-value: 1.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSnEDGTFTICHKTEVVKNTLNPVWQP---FSIPVRALcngdYDRTVKIDVYDWDRDGSH 81
Cdd:cd08402   24 AKNLKKMDVGGLSDPYVKIHLM-QNGKRLKKKKTTIKKRTLNPYYNEsfsFEVPFEQI----QKVHLIVTVLDYDRIGKN 98
                         90       100       110
                 ....*....|....*....|....*....|
gi 568941302  82 DFIGEFTTSYRELSKAQNQFTvyEVL-NPR 110
Cdd:cd08402   99 DPIGKVVLGCNATGAELRHWS--DMLaSPR 126
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
5-86 2.27e-05

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: 43.47  E-value: 2.27e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNEDGtfticHK--TEVVKNTLNPVW-QPFSI---PVRALcngdYDRTVKIDVYDWDRD 78
Cdd:cd08386   25 AVELPAKDFSGTSDPFVKIYLLPDKK-----HKleTKVKRKNLNPHWnETFLFegfPYEKL----QQRVLYLQVLDYDRF 95

                 ....*...
gi 568941302  79 GSHDFIGE 86
Cdd:cd08386   96 SRNDPIGE 103
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
5-110 2.77e-05

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: 43.34  E-value: 2.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNEDGtFTICHKTEVVKNTLNPVWQP---FSIPVRALCNgdydRTVKIDVYDWDRDGSH 81
Cdd:cd00276   23 ARNLPPSDGKGLSDPYVKVSLLQGGK-KLKKKKTSVKKGTLNPVFNEafsFDVPAEQLEE----VSLVITVVDKDSVGRN 97
                         90       100       110
                 ....*....|....*....|....*....|
gi 568941302  82 DFIGEFTTSYRELSKAQNQFtvYEVL-NPR 110
Cdd:cd00276   98 EVIGQVVLGPDSGGEELEHW--NEMLaSPR 125
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
15-110 3.08e-05

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: 43.52  E-value: 3.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  15 GKSDPF-LVFYRSnedGTFTICHKTEVVKNTLNPVW---------QPFSIPVRALCNGDYD---RTVKIDVYDWDRDGSH 81
Cdd:cd08675   17 GTCDPFaRVTLNY---SSKTDTKRTKVKKKTNNPRFdeafyfeltIGFSYEKKSFKVEEEDlekSELRVELWHASMVSGD 93
                         90       100
                 ....*....|....*....|....*....
gi 568941302  82 DFIGEFTTSYRELSKAqNQFTVYEVLNPR 110
Cdd:cd08675   94 DFLGEVRIPLQGLQQA-GSHQAWYFLQPR 121
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
5-87 5.00e-05

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: 42.80  E-value: 5.00e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFF--GKSDPFLVFYRSNEDgtfticHKTEVVKNTLNPVWQP-FSIPVRALCNGdydrTVKIDVYDWDRDGSH 81
Cdd:cd04024   10 AKDLAAKDRSgkGKSDPYAILSVGAQR------FKTQTIPNTLNPKWNYwCEFPIFSAQNQ----LLKLILWDKDRFAGK 79

                 ....*.
gi 568941302  82 DFIGEF 87
Cdd:cd04024   80 DYLGEF 85
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
5-86 5.34e-05

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: 42.61  E-value: 5.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNEDgTFTICH--KTEVVKNTLNPVW-QPFSIPVRALCNGDYDRTVKIDVYDWDRDGSH 81
Cdd:cd04009   25 ARNLLPLDSNGSSDPFVKVELLPRH-LFPDVPtpKTQVKKKTLFPLFdESFEFNVPPEQCSVEGALLLFTVKDYDLLGSN 103

                 ....*
gi 568941302  82 DFIGE 86
Cdd:cd04009  104 DFEGE 108
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
3-86 5.83e-05

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: 42.15  E-value: 5.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFLVFyrsnEDGTFTICHKTEVVKNTLNPVwqpF--------SIPVralcngdyDRTVKIDVYD 74
Cdd:cd04037    7 VRARNLQPKDPNGKSDPYLKI----KLGKKKINDRDNYIPNTLNPV---FgkmfeleaTLPG--------NSILKISVMD 71
                         90
                 ....*....|..
gi 568941302  75 WDRDGSHDFIGE 86
Cdd:cd04037   72 YDLLGSDDLIGE 83
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
9-96 9.80e-05

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: 42.23  E-value: 9.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   9 DKKDFfgkSDPFLVFYRSNEDGtftichKTEVVKNTLNPVW-QPFSIPVR--ALCngdydRTVKIDVYDWDRDGSHDFIG 85
Cdd:cd04018   30 EKKEL---VDPYVEVSFAGQKV------KTSVKKNSYNPEWnEQIVFPEMfpPLC-----ERIKIQIRDWDRVGNDDVIG 95
                         90
                 ....*....|.
gi 568941302  86 eftTSYRELSK 96
Cdd:cd04018   96 ---THFIDLSK 103
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
18-100 1.63e-04

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


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 40.70  E-value: 1.63e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302  18 DPFLV--FYRSnedgTFtichKTEVVKNTLNPVW-QPFSIPVRALcNGDYDrtVKIDVYDWDRDGSHDFIGEFTTSYREL 94
Cdd:cd04039   27 DPFVIisFGRR----VF----RTSWRRHTLNPVFnERLAFEVYPH-EKNFD--IQFKVLDKDKFSFNDYVATGSLSVQEL 95

                 ....*.
gi 568941302  95 SKAQNQ 100
Cdd:cd04039   96 LNAAPQ 101
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
3-109 2.25e-04

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: 40.87  E-value: 2.25e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFL-VFYRSNEDgtfTICHK-TEVVKNTLNPVWQP---FSIPvralCNGDYDRTVKIDVYDWDR 77
Cdd:cd08404   22 LKARHLPKMDVSGLADPYVkVNLYYGKK---RISKKkTHVKKCTLNPVFNEsfvFDIP----SEELEDISVEFLVLDSDR 94
                         90       100       110
                 ....*....|....*....|....*....|..
gi 568941302  78 DGSHDFIGEFTTSYRELSKAQNQftVYEVLNP 109
Cdd:cd08404   95 VTKNEVIGRLVLGPKASGSGGHH--WKEVCNP 124
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
5-85 3.31e-04

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: 40.08  E-value: 3.31e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPF----LVFYRSNEdgtfticHKTEVVKNTLNPVWQP-FSIPVRALCNGDydRTVKIDVYDWDRDG 79
Cdd:cd08387   25 ARNLQPRDFSGTADPYckvrLLPDRSNT-------KQSKIHKKTLNPEFDEsFVFEVPPQELPK--RTLEVLLYDFDQFS 95

                 ....*.
gi 568941302  80 SHDFIG 85
Cdd:cd08387   96 RDECIG 101
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
3-95 3.56e-04

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: 40.24  E-value: 3.56e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   3 LCANKLDKKDFFGKSDPFLVFYRSNEDgtfticHKTEVVKNTLNPVW-QPFSIPvralCNGDYDRtVKIDVYDWDRD--- 78
Cdd:cd04027    8 VCAQGLIAKDKTGTSDPYVTVQVGKTK------KRTKTIPQNLNPVWnEKFHFE----CHNSSDR-IKVRVWDEDDDiks 76
                         90       100
                 ....*....|....*....|....*
gi 568941302  79 --------GSHDFIGEFTTSYRELS 95
Cdd:cd04027   77 rlkqkftrESDDFLGQTIIEVRTLS 101
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
36-94 5.41e-04

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


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 39.83  E-value: 5.41e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568941302  36 HKTEVVK-NTLNPVW-QPFSIPVR----ALcngdydrtVKIDVYDWDrDGSHDFIGEFTTSYREL 94
Cdd:cd00275   44 FKTKVVKnNGFNPVWnETFEFDVTvpelAF--------LRFVVYDED-SGDDDFLGQACLPLDSL 99
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
36-85 7.79e-04

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: 38.83  E-value: 7.79e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568941302  36 HKTEVVKNTLNPVWQP----FSIPVRALcngdYDRTVKIDVYDWDRDGSHDFIG 85
Cdd:cd08688   34 YKTDVVKKSLNPVWNSewfrFEVDDEEL----QDEPLQIRVMDHDTYSANDAIG 83
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
5-85 9.44e-04

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: 39.03  E-value: 9.44e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFLVFYRSNEdGTFTICHKTEVVKNTLNPVWQP---FSIPVRalcNGDyDRTVKIDVYDWDRDGSH 81
Cdd:cd08403   23 ARNLKAMDITGFSDPYVKVSLMCE-GRRLKKKKTSVKKNTLNPTYNEalvFDVPPE---NVD-NVSLIIAVVDYDRVGHN 97

                 ....
gi 568941302  82 DFIG 85
Cdd:cd08403   98 ELIG 101
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
14-85 1.44e-03

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: 38.40  E-value: 1.44e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568941302  14 FGKSDPFLVFyrSNEDGTFTIChKTEVVKNTLNPVW-QPFSIPVRAlcngdyDRTVKIDVYDWDRD--GSHDFIG 85
Cdd:cd04043   19 NGLSDPYVTL--VDTNGKRRIA-KTRTIYDTLNPRWdEEFELEVPA------GEPLWISATVWDRSfvGKHDLCG 84
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
36-85 1.84e-03

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: 38.84  E-value: 1.84e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568941302  36 HKTEVVKNTLNPVW-QPFSIpvralcNGDY-----DRTVKIDVYDWDRDGSHDFIG 85
Cdd:cd04020   66 QKTPVVKKSVNPVWnHTFVY------DGVSpedlsQACLELTVWDHDKLSSNDFLG 115
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
5-87 2.02e-03

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


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 37.95  E-value: 2.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDFFGKSDPFlvfYRSNEDGTFTicHKTEVVKNTLNPVW-QPFSIPVRALcngdyDRTVKIDVYDWDRDGSHDF 83
Cdd:cd04045   10 ANDLKNLEGVGKIDPY---VRVLVNGIVK--GRTVTISNTLNPVWdEVLYVPVTSP-----NQKITLEVMDYEKVGKDRS 79

                 ....
gi 568941302  84 IGEF 87
Cdd:cd04045   80 LGSV 83
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
5-85 2.17e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 40.51  E-value: 2.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302    5 ANKLDKKDFF--GKSDPFLVFyrsnedGTFTICH-KTEVVKNTLNPVW-QPFSIPVRALcngdyDRTVKIDVYDWDRDGS 80
Cdd:COG5038   445 AEGLKKSDSTinGTVDPYITV------TFSDRVIgKTRVKKNTLNPVWnETFYILLNSF-----TDPLNLSLYDFNSFKS 513

                  ....*
gi 568941302   81 HDFIG 85
Cdd:COG5038   514 DKVVG 518
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
5-100 2.25e-03

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: 37.63  E-value: 2.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568941302   5 ANKLDKKDF-FGKSDPFLVFyrsnedgTFTICHK----TEVVKNTLNPVWQPFSIpvraLCNG----DYDRTVKIDVYDW 75
Cdd:cd04041   10 ATDLPKADFgTGSSDPYVTA-------SFAKFGKplysTRIIRKDLNPVWEETWF----VLVTpdevKAGERLSCRLWDS 78
                         90       100
                 ....*....|....*....|....*
gi 568941302  76 DRDGSHDFIGEFTTSYRELSKAQNQ 100
Cdd:cd04041   79 DRFTADDRLGRVEIDLKELIEDRNW 103
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
5-49 7.19e-03

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: 36.38  E-value: 7.19e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568941302   5 ANKLDKKDFFGKS-DPFLVFYRSNEDgtftICHKTEVVKNTLNPVW 49
Cdd:cd04044   11 ARGLKGSDIIGGTvDPYVTFSISNRR----ELARTKVKKDTSNPVW 52
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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