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Conserved domains on  [gi|2553878300|ref|NP_001116758|]
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copine Va isoform 2 [Danio rerio]

Protein Classification

copine family protein( domain architecture ID 10134306)

copine family protein is a C2 domain-containing, calcium-dependent, phospholipid-binding protein that is involved in membrane trafficking, protein-protein interactions, and cell division and growth

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. ...
279-539 4.47e-133

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: 387.88  E-value: 4.47e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 279 KKRRYINSGTVTLLSFLVEaeHTFLDYIKAGLQIHFTVAIDFTASNGNPSQSTSLHYMNPYQMNAYAMALKAVGEIIQDY 358
Cdd:cd01459     1 IKKVYKSSGEVTLTDCRVQ--PTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPY 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 359 DSDKMFPALGFGAKLPPDGRVSHEFPLNGNvdNPYCNGMEGILEAYHESLKTVQLYGPTNFAPVINHVARYAAAVQDGSQ 438
Cdd:cd01459    79 DSDKLIPAFGFGAIVTKDQSVFSFFPGYSE--SPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSK 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 439 YFVLLIITDGVISDMAQTKEAIVNAAKLPMSIIIVGVGQAEFDAMVELDGDDVRISSRGKLAERDIVQFVPFRDYMDRTG 518
Cdd:cd01459   157 YHILLIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAG 236
                         250       260
                  ....*....|....*....|.
gi 2553878300 519 NhvlSMARLAKDVLAEIPDQL 539
Cdd:cd01459   237 N---PEAALATAALAEIPSQL 254
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
28-149 3.69e-66

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: 210.89  E-value: 3.69e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  28 TKVEITVSCRNLLDRDTFSKSDPLCILYTQGAESKQWREFGRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSK 107
Cdd:cd04048     1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2553878300 108 SPDLAKHDFLGQTFCTLGEIVGSPGSRLEKPLggIPGKNCGT 149
Cdd:cd04048    81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
164-273 4.61e-59

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: 191.62  E-value: 4.61e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 164 ATMQFCANKLDKKDFFGRSDPFMVFYRSNEDGTFTICHKTEVVKNTLNPIWQPFTIPVRALCNGDYDRSIKVEVYDWDRD 243
Cdd:cd04047     3 VELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSS 82
                          90       100       110
                  ....*....|....*....|....*....|
gi 2553878300 244 GSHDFIGEFTTSYRELSrgQSQFNVYEVVN 273
Cdd:cd04047    83 GKHDLIGEFETTLDELL--KSSPLEFELIN 110
 
Name Accession Description Interval E-value
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
279-539 4.47e-133

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: 387.88  E-value: 4.47e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 279 KKRRYINSGTVTLLSFLVEaeHTFLDYIKAGLQIHFTVAIDFTASNGNPSQSTSLHYMNPYQMNAYAMALKAVGEIIQDY 358
Cdd:cd01459     1 IKKVYKSSGEVTLTDCRVQ--PTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPY 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 359 DSDKMFPALGFGAKLPPDGRVSHEFPLNGNvdNPYCNGMEGILEAYHESLKTVQLYGPTNFAPVINHVARYAAAVQDGSQ 438
Cdd:cd01459    79 DSDKLIPAFGFGAIVTKDQSVFSFFPGYSE--SPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSK 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 439 YFVLLIITDGVISDMAQTKEAIVNAAKLPMSIIIVGVGQAEFDAMVELDGDDVRISSRGKLAERDIVQFVPFRDYMDRTG 518
Cdd:cd01459   157 YHILLIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAG 236
                         250       260
                  ....*....|....*....|.
gi 2553878300 519 NhvlSMARLAKDVLAEIPDQL 539
Cdd:cd01459   237 N---PEAALATAALAEIPSQL 254
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
332-547 7.52e-122

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: 357.80  E-value: 7.52e-122
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 332 SLHYMNPYQMNAYAMALKAVGEIIQDYDSDKMFPALGFGAKLPPDGRVSHEFPLNGNVDNPYCNGMEGILEAYHESLKTV 411
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 412 QLYGPTNFAPVINHVARYAAA-VQDGSQYFVLLIITDGVISDMAQTKEAIVNAAKLPMSIIIVGVGQAEFDAMVELDGDD 490
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARIAKAsTQNAGQYHVLLIITDGVVTDMKATIDAIVNASHLPLSIIIVGVGDGDFSDMRELDDDD 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2553878300 491 VRISSRGKLAERDIVQFVPFRDYMDrtgNHVLSMARLAKDVLAEIPDQLILYMKSRG 547
Cdd:pfam07002 161 RLRSSDGRIAARDIVQFVPFRDIMS---NADLKEAALALAVLAEIPDQYVAYMELRG 214
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
28-149 3.69e-66

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: 210.89  E-value: 3.69e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  28 TKVEITVSCRNLLDRDTFSKSDPLCILYTQGAESKQWREFGRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSK 107
Cdd:cd04048     1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2553878300 108 SPDLAKHDFLGQTFCTLGEIVGSPGSRLEKPLggIPGKNCGT 149
Cdd:cd04048    81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
164-273 4.61e-59

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: 191.62  E-value: 4.61e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 164 ATMQFCANKLDKKDFFGRSDPFMVFYRSNEDGTFTICHKTEVVKNTLNPIWQPFTIPVRALCNGDYDRSIKVEVYDWDRD 243
Cdd:cd04047     3 VELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSS 82
                          90       100       110
                  ....*....|....*....|....*....|
gi 2553878300 244 GSHDFIGEFTTSYRELSrgQSQFNVYEVVN 273
Cdd:cd04047    83 GKHDLIGEFETTLDELL--KSSPLEFELIN 110
C2 pfam00168
C2 domain;
170-263 2.48e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.14  E-value: 2.48e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEdgtfTICHKTEVVKNTLNPIW-QPFTIPVRAlcngDYDRSIKVEVYDWDRDGSHDF 248
Cdd:pfam00168  10 AKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRDDF 81
                          90
                  ....*....|....*
gi 2553878300 249 IGEFTTSYRELSRGQ 263
Cdd:pfam00168  82 IGEVRIPLSELDSGE 96
C2 pfam00168
C2 domain;
29-139 2.95e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 77.36  E-value: 2.95e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  29 KVEITV-SCRNLLDRDTFSKSDPLCILYTQGAESKQwrefgRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSK 107
Cdd:pfam00168   2 RLTVTViEAKNLPPKDGNGTSDPYVKVYLLDGKQKK-----KTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76
                          90       100       110
                  ....*....|....*....|....*....|..
gi 2553878300 108 SpdlaKHDFLGQTFCTLGEIVGSPGSRLEKPL 139
Cdd:pfam00168  77 G----RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
168-265 9.07e-17

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 75.99  E-value: 9.07e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  168 FCANKLDKKDFFGRSDPFMVFYRsneDGTFTICHKTEVVKNTLNPIW-QPFTIPVRALCngdyDRSIKVEVYDWDRDGSH 246
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79
                           90
                   ....*....|....*....
gi 2553878300  247 DFIGEFTTSYRELSRGQSQ 265
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRH 98
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
29-133 3.31e-13

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: 65.59  E-value: 3.31e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300   29 KVEItVSCRNLLDRDTFSKSDPLCILYTQGAESKQwrefGRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSKS 108
Cdd:smart00239   3 TVKI-ISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77
                           90       100
                   ....*....|....*....|....*
gi 2553878300  109 PDlakhDFLGQTFCTLGEIVGSPGS 133
Cdd:smart00239  78 RD----DFIGQVTIPLSDLLLGGRH 98
VWA smart00327
von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins ...
313-478 2.47e-10

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: 59.78  E-value: 2.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  313 HFTVAIDFTASngnpsqstslhyMNPYQMNAYAMALKAVGEIIQDYDSDKMFPALGFGaklppdGRVSHEFPLNGnvdnp 392
Cdd:smart00327   1 DVVFLLDGSGS------------MGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFS------DDARVLFPLND----- 57
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  393 yCNGMEGILEAYHESlkTVQLYGPTNFAPVINHVARYAAAVQDGSQYF---VLLIITDGVISD-MAQTKEAIVNAAKLPM 468
Cdd:smart00327  58 -SRSKDALLEALASL--SYKLGGGTNLGAALQYALENLFSKSAGSRRGapkVVILITDGESNDgPKDLLKAAKELKRSGV 134
                          170
                   ....*....|
gi 2553878300  469 SIIIVGVGQA 478
Cdd:smart00327 135 KVFVVGVGND 144
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
180-287 5.35e-07

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 52.84  E-value: 5.35e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  180 GRSDPFMVFYRSNEDgtftiCHKTEVVKNTLNPIW-QPFTIPV--RALCNgdydrsIKVEVYDWDRDGSHDFIG------ 250
Cdd:COG5038   1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLGtaeidl 1127
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2553878300  251 -----EFTTSYRELSRGQSQFNVYEVVNPKKKLKKRRYINSG 287
Cdd:COG5038   1128 sklepGGTTNSNIPLDGKTFIVLDGTLHPGFNFRSKYALNVS 1169
 
Name Accession Description Interval E-value
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
279-539 4.47e-133

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: 387.88  E-value: 4.47e-133
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 279 KKRRYINSGTVTLLSFLVEaeHTFLDYIKAGLQIHFTVAIDFTASNGNPSQSTSLHYMNPYQMNAYAMALKAVGEIIQDY 358
Cdd:cd01459     1 IKKVYKSSGEVTLTDCRVQ--PTFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPY 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 359 DSDKMFPALGFGAKLPPDGRVSHEFPLNGNvdNPYCNGMEGILEAYHESLKTVQLYGPTNFAPVINHVARYAAAVQDGSQ 438
Cdd:cd01459    79 DSDKLIPAFGFGAIVTKDQSVFSFFPGYSE--SPECQGFEGVLRAYREALPNVSLSGPTNFAPVIRAAANIAKASNSQSK 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 439 YFVLLIITDGVISDMAQTKEAIVNAAKLPMSIIIVGVGQAEFDAMVELDGDDVRISSRGKLAERDIVQFVPFRDYMDRTG 518
Cdd:cd01459   157 YHILLIITDGEITDMNETIKAIVEASKYPLSIVIVGVGDGPFDAMERLDDDDGLESSDGRIATRDIVQFVPFTEFMSNAG 236
                         250       260
                  ....*....|....*....|.
gi 2553878300 519 NhvlSMARLAKDVLAEIPDQL 539
Cdd:cd01459   237 N---PEAALATAALAEIPSQL 254
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
332-547 7.52e-122

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: 357.80  E-value: 7.52e-122
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 332 SLHYMNPYQMNAYAMALKAVGEIIQDYDSDKMFPALGFGAKLPPDGRVSHEFPLNGNVDNPYCNGMEGILEAYHESLKTV 411
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVLNFNPENPECEGIEGVLEAYRSALPNL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 412 QLYGPTNFAPVINHVARYAAA-VQDGSQYFVLLIITDGVISDMAQTKEAIVNAAKLPMSIIIVGVGQAEFDAMVELDGDD 490
Cdd:pfam07002  81 QLYGPTNFAPIIDAAARIAKAsTQNAGQYHVLLIITDGVVTDMKATIDAIVNASHLPLSIIIVGVGDGDFSDMRELDDDD 160
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2553878300 491 VRISSRGKLAERDIVQFVPFRDYMDrtgNHVLSMARLAKDVLAEIPDQLILYMKSRG 547
Cdd:pfam07002 161 RLRSSDGRIAARDIVQFVPFRDIMS---NADLKEAALALAVLAEIPDQYVAYMELRG 214
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
28-149 3.69e-66

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: 210.89  E-value: 3.69e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  28 TKVEITVSCRNLLDRDTFSKSDPLCILYTQGAESKQWREFGRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSK 107
Cdd:cd04048     1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2553878300 108 SPDLAKHDFLGQTFCTLGEIVGSPGSRLEKPLggIPGKNCGT 149
Cdd:cd04048    81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
164-273 4.61e-59

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: 191.62  E-value: 4.61e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 164 ATMQFCANKLDKKDFFGRSDPFMVFYRSNEDGTFTICHKTEVVKNTLNPIWQPFTIPVRALCNGDYDRSIKVEVYDWDRD 243
Cdd:cd04047     3 VELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYDSS 82
                          90       100       110
                  ....*....|....*....|....*....|
gi 2553878300 244 GSHDFIGEFTTSYRELSrgQSQFNVYEVVN 273
Cdd:cd04047    83 GKHDLIGEFETTLDELL--KSSPLEFELIN 110
C2 pfam00168
C2 domain;
170-263 2.48e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.14  E-value: 2.48e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEdgtfTICHKTEVVKNTLNPIW-QPFTIPVRAlcngDYDRSIKVEVYDWDRDGSHDF 248
Cdd:pfam00168  10 AKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRDDF 81
                          90
                  ....*....|....*
gi 2553878300 249 IGEFTTSYRELSRGQ 263
Cdd:pfam00168  82 IGEVRIPLSELDSGE 96
C2 pfam00168
C2 domain;
29-139 2.95e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 77.36  E-value: 2.95e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  29 KVEITV-SCRNLLDRDTFSKSDPLCILYTQGAESKQwrefgRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSK 107
Cdd:pfam00168   2 RLTVTViEAKNLPPKDGNGTSDPYVKVYLLDGKQKK-----KTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76
                          90       100       110
                  ....*....|....*....|....*....|..
gi 2553878300 108 SpdlaKHDFLGQTFCTLGEIVGSPGSRLEKPL 139
Cdd:pfam00168  77 G----RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
168-265 9.07e-17

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 75.99  E-value: 9.07e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  168 FCANKLDKKDFFGRSDPFMVFYRsneDGTFTICHKTEVVKNTLNPIW-QPFTIPVRALCngdyDRSIKVEVYDWDRDGSH 246
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79
                           90
                   ....*....|....*....
gi 2553878300  247 DFIGEFTTSYRELSRGQSQ 265
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRH 98
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
169-253 1.89e-15

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 72.10  E-value: 1.89e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 169 CANKLDKKDFFGRSDPFMVFYRSNEdgtftICHKTEVVKNTLNPIW-QPFTIPVralcNGDYDRSIKVEVYDWDRDGSHD 247
Cdd:cd00030     7 EARNLPAKDLNGKSDPYVKVSLGGK-----QKFKTKVVKNTLNPVWnETFEFPV----LDPESDTLTVEVWDKDRFSKDD 77

                  ....*.
gi 2553878300 248 FIGEFT 253
Cdd:cd00030    78 FLGEVE 83
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
180-251 2.03e-15

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: 72.60  E-value: 2.03e-15
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2553878300 180 GRSDPFMVFYRSNEDgtftiCHKTEVVKNTLNPIW-QPFTIPVralcNGDYDRSIKVEVYDWDRDGSHDFIGE 251
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 ...
166-264 4.97e-14

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: 68.75  E-value: 4.97e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 166 MQFCANKLDKKDFFGRSDPF-MVFYRSNEDGTFTICHKTEVVKNTLNPIW-QPFTIpvralcngDY----DRSIKVEVYD 239
Cdd:cd04048     5 LSISCRNLLDKDVLSKSDPFvVVYVKTGGSGQWVEIGRTEVIKNNLNPDFvTTFTV--------DYyfeeVQKLRFEVYD 76
                          90       100       110
                  ....*....|....*....|....*....|.
gi 2553878300 240 WD----RDGSHDFIGEFTTSYREL--SRGQS 264
Cdd:cd04048    77 VDskskDLSDHDFLGEAECTLGEIvsSPGQK 107
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
29-134 5.99e-14

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: 67.86  E-value: 5.99e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  29 KVEItVSCRNLLDRDTFSKSDPLCILYTQGAESKqwrefgRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSKS 108
Cdd:cd00030     2 RVTV-IEARNLPAKDLNGKSDPYVKVSLGGKQKF------KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFS 74
                          90       100
                  ....*....|....*....|....*.
gi 2553878300 109 PDlakhDFLGQTFCTLGEIVGSPGSR 134
Cdd:cd00030    75 KD----DFLGEVEIPLSELLDSGKEG 96
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
29-133 3.31e-13

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: 65.59  E-value: 3.31e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300   29 KVEItVSCRNLLDRDTFSKSDPLCILYTQGAESKQwrefGRTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSKS 108
Cdd:smart00239   3 TVKI-ISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77
                           90       100
                   ....*....|....*....|....*
gi 2553878300  109 PDlakhDFLGQTFCTLGEIVGSPGS 133
Cdd:smart00239  78 RD----DFIGQVTIPLSDLLLGGRH 98
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
180-259 2.33e-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: 61.51  E-value: 2.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 180 GRSDPFmVFYRSNEDGTFTICHKTEVVKNTLNPIW-QPFTIPVRAlcnGDYDRSIKVEVYDWDRDGSHDFIGEFTTSYRE 258
Cdd:cd04026    32 GLSDPY-VKLKLIPDPKNETKQKTKTIKKTLNPVWnETFTFDLKP---ADKDRRLSIEVWDWDRTTRNDFMGSLSFGVSE 107

                  .
gi 2553878300 259 L 259
Cdd:cd04026   108 L 108
VWA smart00327
von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins ...
313-478 2.47e-10

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: 59.78  E-value: 2.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  313 HFTVAIDFTASngnpsqstslhyMNPYQMNAYAMALKAVGEIIQDYDSDKMFPALGFGaklppdGRVSHEFPLNGnvdnp 392
Cdd:smart00327   1 DVVFLLDGSGS------------MGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFS------DDARVLFPLND----- 57
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  393 yCNGMEGILEAYHESlkTVQLYGPTNFAPVINHVARYAAAVQDGSQYF---VLLIITDGVISD-MAQTKEAIVNAAKLPM 468
Cdd:smart00327  58 -SRSKDALLEALASL--SYKLGGGTNLGAALQYALENLFSKSAGSRRGapkVVILITDGESNDgPKDLLKAAKELKRSGV 134
                          170
                   ....*....|
gi 2553878300  469 SIIIVGVGQA 478
Cdd:smart00327 135 KVFVVGVGND 144
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
172-251 2.29e-09

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: 55.82  E-value: 2.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 172 KLDKKDFFGRSDPFMV--FYRSNEDGTFTICHkTEVVKNTLNPIW-QPFTIPVRALCNgdydrSIKVEVYDWDRDGSHDF 248
Cdd:cd04033    11 DLAKKDIFGASDPYVKisLYDPDGNGEIDSVQ-TKTIKKTLNPKWnEEFFFRVNPREH-----RLLFEVFDENRLTRDDF 84

                  ...
gi 2553878300 249 IGE 251
Cdd:cd04033    85 LGQ 87
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
178-267 5.97e-09

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: 54.18  E-value: 5.97e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 178 FFGRSDPFM-VFYRSnedgtftICHKTEVVKNTLNPIW-QPFTIPVRAlcNGDYDRSIKVEVYDWDRDGSHDFIGEFTTS 255
Cdd:cd08373    11 LKGKGDRIAkVTFRG-------VKKKTRVLENELNPVWnETFEWPLAG--SPDPDESLEIVVKDYEKVGRNRLIGSATVS 81
                          90
                  ....*....|...
gi 2553878300 256 YREL-SRGQSQFN 267
Cdd:cd08373    82 LQDLvSEGLLEVT 94
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
173-257 2.15e-07

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


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 50.23  E-value: 2.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 173 LDKKDFfgrSDPF-MVFYRSNedgtftiCHKTEVVKNTLNPIW-QPFTIPVRALCNG--DYDR---SIKVEVYDWDRDGS 245
Cdd:cd04017    16 ADKSGL---SDPFaRVSFLNQ-------SQETEVIKETLSPTWdQTLIFDEVELYGSpeEIAQnppLVVVELFDQDSVGK 85
                          90
                  ....*....|..
gi 2553878300 246 HDFIGEFTTSYR 257
Cdd:cd04017    86 DEFLGRSVAKPL 97
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
203-253 2.29e-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: 49.94  E-value: 2.29e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2553878300 203 TEVVKNTLNPIW-QPFT---IPVRALcngdYDRSIKVEVYDWDRDGSHDFIGEFT 253
Cdd:cd04031    57 TKTVKKTLNPEWnQTFEysnVRRETL----KERTLEVTVWDYDRDGENDFLGEVV 107
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
170-258 2.72e-07

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: 49.72  E-value: 2.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEDGTFTIcHKTEVVKNTLNPIWQ---PFTIPVRALcngdYDRSIKVEVYDWDRDGSH 246
Cdd:cd08405    24 ARNLKAMDINGTSDPYVKVWLMYKDKRVEK-KKTVIKKRTLNPVFNesfIFNIPLERL----RETTLIITVMDKDRLSRN 98
                          90
                  ....*....|..
gi 2553878300 247 DFIGEFTTSYRE 258
Cdd:cd08405    99 DLIGKIYLGWKS 110
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
168-250 3.63e-07

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: 49.22  E-value: 3.63e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 168 FCANKLDKKDFFGRSDPFMVFYRSNED-GTFTIChktevvkNTLNPIW-QPFTIPVRalcngDYDRSIKVEVYDWDRDGS 245
Cdd:cd08377     8 IRASGLAAADIGGKSDPFCVLELVNARlQTHTIY-------KTLNPEWnKIFTFPIK-----DIHDVLEVTVYDEDKDKK 75

                  ....*
gi 2553878300 246 HDFIG 250
Cdd:cd08377    76 PEFLG 80
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
176-251 4.28e-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: 49.63  E-value: 4.28e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2553878300 176 KDFFGrSDPFMVFYRSNEDGtftichKTEVVKNTLNPIWQP---FTIPvralcngDYDRSIKVEVYDWDRDGSHDFIGE 251
Cdd:cd04038    17 RDFTS-SDPYVVLTLGNQKV------KTRVIKKNLNPVWNEeltLSVP-------NPMAPLKLEVFDKDTFSKDDSMGE 81
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
180-287 5.35e-07

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 52.84  E-value: 5.35e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  180 GRSDPFMVFYRSNEDgtftiCHKTEVVKNTLNPIW-QPFTIPV--RALCNgdydrsIKVEVYDWDRDGSHDFIG------ 250
Cdd:COG5038   1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLGtaeidl 1127
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2553878300  251 -----EFTTSYRELSRGQSQFNVYEVVNPKKKLKKRRYINSG 287
Cdd:COG5038   1128 sklepGGTTNSNIPLDGKTFIVLDGTLHPGFNFRSKYALNVS 1169
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
34-128 6.62e-07

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: 48.44  E-value: 6.62e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  34 VSCRNLLDRDTF------SKSDPLCILYTqGAESkqwreFgRTEVIDNTLNPDFVRKY--ILDYffEEKQNLRFDIYDid 105
Cdd:cd08391     8 IEAQDLVAKDKFvgglvkGKSDPYVIVRV-GAQT-----F-KSKVIKENLNPKWNEVYeaVVDE--VPGQELEIELFD-- 76
                          90       100
                  ....*....|....*....|...
gi 2553878300 106 sksPDLAKHDFLGQTFCTLGEIV 128
Cdd:cd08391    77 ---EDPDKDDFLGRLSIDLGSVE 96
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
170-253 1.35e-06

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: 47.64  E-value: 1.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNE-DGTFtichKTEVVKNTLNPIWQP---FTIPVRALCNgdydRSIKVEVYDWDRDGS 245
Cdd:cd08385    25 AADLPAMDMGGTSDPYVKVYLLPDkKKKF----ETKVHRKTLNPVFNEtftFKVPYSELGN----KTLVFSVYDFDRFSK 96

                  ....*...
gi 2553878300 246 HDFIGEFT 253
Cdd:cd08385    97 HDLIGEVR 104
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
163-265 2.56e-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: 46.71  E-value: 2.56e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 163 CATMQfcANKLDKKDFFGRSDPFM-VFYRSNEdgtfticHKTEVVKNTLNPIW-QPFTIPVRalcnGDYDRSIKVEVYDW 240
Cdd:cd04025     4 CHVLE--ARDLAPKDRNGTSDPFVrVFYNGQT-------LETSVVKKSCYPRWnEVFEFELM----EGADSPLSVEVWDW 70
                          90       100
                  ....*....|....*....|....*
gi 2553878300 241 DRDGSHDFIGEFTTSYRELSRGQSQ 265
Cdd:cd04025    71 DLVSKNDFLGKVVFSIQTLQQAKQE 95
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
176-251 2.92e-06

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: 46.50  E-value: 2.92e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2553878300 176 KDFFGRSDPFMVFYRSNEdgtftICHKTEVVKNTLNPIW-QPFTIPVRalcngDYDRSIKVEVYDWDRDGSHDFIGE 251
Cdd:cd04042    15 RDRGGTSDPYVKFKYGGK-----TVYKSKTIYKNLNPVWdEKFTLPIE-----DVTQPLYIKVFDYDRGLTDDFMGS 81
vWA-TerF-like pfam10138
vWA found in TerF C terminus; vWA domain fused to TerD domain typified by the TerF protein. ...
398-487 3.05e-06

vWA found in TerF C terminus; vWA domain fused to TerD domain typified by the TerF protein. Some times found as solos.


Pssm-ID: 401947 [Multi-domain]  Cd Length: 200  Bit Score: 48.05  E-value: 3.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 398 EGILEAYHESLKTVQLYGP-TNFAPVINHVARYAAAVQDGSQYFVLLIiTDGVISDMAQTKEAIVNAAKLPMSIIIVGVG 476
Cdd:pfam10138  64 PGWVERLHLGRDRYRKLGGqNNEPPVMEAVIDYYRKNPADLPTLVLFI-TDGGVTDNAAIERLLREASREPIFWQFVGIG 142
                          90
                  ....*....|.
gi 2553878300 477 QAEFDAMVELD 487
Cdd:pfam10138 143 RSGYGFLEKLD 153
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
168-222 3.41e-06

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: 46.53  E-value: 3.41e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2553878300 168 FCANKLDKKDFFGRSDPFMVFyrSNEDGTftiCHKTEVVKNTLNPIW-QPFTIPVR 222
Cdd:cd08382     7 LCADGLAKRDLFRLPDPFAVI--TVDGGQ---THSTDVAKKTLDPKWnEHFDLTVG 57
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
29-120 3.65e-06

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 46.02  E-value: 3.65e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  29 KVEItVSCRNLLDRDTFSKSDPLCILYTQGaeskqwREFGRTEVIDNTLNPDFvrkyilDYFFEE------KQNLRFDIY 102
Cdd:cd04040     2 TVDV-ISAENLPSADRNGKSDPFVKFYLNG------EKVFKTKTIKKTLNPVW------NESFEVpvpsrvRAVLKVEVY 68
                          90
                  ....*....|....*...
gi 2553878300 103 DIDSKSPDlakhDFLGQT 120
Cdd:cd04040    69 DWDRGGKD----DLLGSA 82
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
170-264 4.77e-06

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: 45.75  E-value: 4.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFF------GRSDPFMVFYRSNEdgTFtichKTEVVKNTLNPIW-QPFtipvRALCNGDYDRSIKVEVYDWDR 242
Cdd:cd08391    10 AQDLVAKDKFvgglvkGKSDPYVIVRVGAQ--TF----KSKVIKENLNPKWnEVY----EAVVDEVPGQELEIELFDEDP 79
                          90       100
                  ....*....|....*....|..
gi 2553878300 243 DgSHDFIGEFTTSYRELSRGQS 264
Cdd:cd08391    80 D-KDDFLGRLSIDLGSVEKKGF 100
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
169-250 6.03e-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: 45.80  E-value: 6.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 169 CANkLDKKDFFGRSDPFMVFYRSnEDGTFTICHKTEVVKNTLNPIWQP---FTIPVRALCNgdydRSIKVEVYDWDRDGS 245
Cdd:cd08384    22 CVN-LAAMDANGYSDPFVKLYLK-PDAGKKSKHKTQVKKKTLNPEFNEeffYDIKHSDLAK----KTLEITVWDKDIGKS 95

                  ....*
gi 2553878300 246 HDFIG 250
Cdd:cd08384    96 NDYIG 100
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
170-251 3.04e-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: 43.93  E-value: 3.04e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSnEDGTFTICHKTEVVKNTLNPIWQP---FTIPVRALcngdYDRSIKVEVYDWDRDGSH 246
Cdd:cd08402    24 AKNLKKMDVGGLSDPYVKIHLM-QNGKRLKKKKTTIKKRTLNPYYNEsfsFEVPFEQI----QKVHLIVTVLDYDRIGKN 98

                  ....*
gi 2553878300 247 DFIGE 251
Cdd:cd08402    99 DPIGK 103
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
170-252 3.43e-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: 43.57  E-value: 3.43e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFF--GRSDPFMVFYRSNEDgtfticHKTEVVKNTLNPIWQPFT-IPVRALCNGdydrSIKVEVYDWDRDGSH 246
Cdd:cd04024    10 AKDLAAKDRSgkGKSDPYAILSVGAQR------FKTQTIPNTLNPKWNYWCeFPIFSAQNQ----LLKLILWDKDRFAGK 79

                  ....*.
gi 2553878300 247 DFIGEF 252
Cdd:cd04024    80 DYLGEF 85
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
183-265 5.28e-05

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: 42.63  E-value: 5.28e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 183 DPF--MVFYRSnedgTFtichKTEVVKNTLNPIW-QPFTIPVRALcngDYDRSIKVEVYDWDRDGSHDFIGEFTTSYREL 259
Cdd:cd04039    27 DPFviISFGRR----VF----RTSWRRHTLNPVFnERLAFEVYPH---EKNFDIQFKVLDKDKFSFNDYVATGSLSVQEL 95

                  ....*.
gi 2553878300 260 SRGQSQ 265
Cdd:cd04039    96 LNAAPQ 101
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
201-262 7.15e-05

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


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 42.53  E-value: 7.15e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2553878300 201 HKTEVVK-NTLNPIW-QPFTIPVR----ALcngdydrsIKVEVYDWDrDGSHDFIGEFTTSYRELSRG 262
Cdd:cd00275    44 FKTKVVKnNGFNPVWnETFEFDVTvpelAF--------LRFVVYDED-SGDDDFLGQACLPLDSLRQG 102
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
170-265 8.96e-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: 42.32  E-value: 8.96e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEDGtfticHK--TEVVKNTLNPIW-QPFTI---PVRALcngdYDRSIKVEVYDWDRD 243
Cdd:cd08386    25 AVELPAKDFSGTSDPFVKIYLLPDKK-----HKleTKVKRKNLNPHWnETFLFegfPYEKL----QQRVLYLQVLDYDRF 95
                          90       100
                  ....*....|....*....|..
gi 2553878300 244 GSHDFIGEFTTSYRELSRGQSQ 265
Cdd:cd08386    96 SRNDPIGEVSLPLNKVDLTEEQ 117
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
30-110 1.06e-04

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


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 42.16  E-value: 1.06e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  30 VEITV-SCRNLLDRDTFSKS-DPLCILYTQGAeskqwREFGRTEVIDNTLNPDFVR-KYILDYFFEEKqnLRFDIYDIDS 106
Cdd:cd04044     4 LAVTIkSARGLKGSDIIGGTvDPYVTFSISNR-----RELARTKVKKDTSNPVWNEtKYILVNSLTEP--LNLTVYDFND 76

                  ....
gi 2553878300 107 KSPD 110
Cdd:cd04044    77 KRKD 80
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
174-261 1.31e-04

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: 42.62  E-value: 1.31e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 174 DKKDFfgrSDPFMVFYRSNEDGtftichKTEVVKNTLNPIW-QPFTIPVR--ALCngdydRSIKVEVYDWDRDGSHDFIG 250
Cdd:cd04018    30 EKKEL---VDPYVEVSFAGQKV------KTSVKKNSYNPEWnEQIVFPEMfpPLC-----ERIKIQIRDWDRVGNDDVIG 95
                          90
                  ....*....|.
gi 2553878300 251 eftTSYRELSR 261
Cdd:cd04018    96 ---THFIDLSK 103
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
170-276 1.36e-04

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: 42.19  E-value: 1.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEDGtFTICHKTEVVKNTLNPIWQP---FTIPVRALCNgdydRSIKVEVYDWDRDGSH 246
Cdd:cd00276    23 ARNLPPSDGKGLSDPYVKVSLLQGGK-KLKKKKTSVKKGTLNPVFNEafsFDVPAEQLEE----VSLVITVVDKDSVGRN 97
                          90       100       110
                  ....*....|....*....|....*....|.
gi 2553878300 247 DFIGEFTTSYRELSRGQSQFNvyEVV-NPKK 276
Cdd:cd00276    98 EVIGQVVLGPDSGGEELEHWN--EMLaSPRK 126
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
29-131 1.81e-04

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 41.64  E-value: 1.81e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  29 KVEItVSCRNLL--DRDTFSKSDPLCILYTqGAEskqwrEFgRTEVIDNTLNPDFvrkyilDYFFE----EKQNLRFDI- 101
Cdd:cd04024     4 RVHV-VEAKDLAakDRSGKGKSDPYAILSV-GAQ-----RF-KTQTIPNTLNPKW------NYWCEfpifSAQNQLLKLi 69
                          90       100       110
                  ....*....|....*....|....*....|.
gi 2553878300 102 -YDIDskspDLAKHDFLGQTFCTLGEIVGSP 131
Cdd:cd04024    70 lWDKD----RFAGKDYLGEFDIALEEVFADG 96
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
170-251 2.28e-04

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: 41.45  E-value: 2.28e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEDgTFTICH--KTEVVKNTLNPIW-QPFTIPVRALCNGDYDRSIKVEVYDWDRDGSH 246
Cdd:cd04009    25 ARNLLPLDSNGSSDPFVKVELLPRH-LFPDVPtpKTQVKKKTLFPLFdESFEFNVPPEQCSVEGALLLFTVKDYDLLGSN 103

                  ....*
gi 2553878300 247 DFIGE 251
Cdd:cd04009   104 DFEGE 108
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
97-250 2.55e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 43.98  E-value: 2.55e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300   97 LRFDIYDIdsksPDLAKhdFL-GQTFCTLGEIVGSPGS---RLEKPLGGIPGKNCGTIILTAEElgncrdcatmqfcANK 172
Cdd:COG5038    387 FGVDIFAI----PGLSR--FIqEIINSTLGPMLLPPNSltiDISQIMAGDSGTAIGVVEVKIKS-------------AEG 447
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  173 LDKKDFF--GRSDPFMVFyrsnedGTFTICH-KTEVVKNTLNPIW-QPFTIPVRALcngdyDRSIKVEVYDWDRDGSHDF 248
Cdd:COG5038    448 LKKSDSTinGTVDPYITV------TFSDRVIgKTRVKKNTLNPVWnETFYILLNSF-----TDPLNLSLYDFNSFKSDKV 516

                   ..
gi 2553878300  249 IG 250
Cdd:COG5038    517 VG 518
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
169-260 4.42e-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: 4.42e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 169 CANKLDKKDFFGRSDPFMVFYRSNEDgtfticHKTEVVKNTLNPIW-QPFTIPvralCNGDYDRsIKVEVYDWDRD---- 243
Cdd:cd04027     9 CAQGLIAKDKTGTSDPYVTVQVGKTK------KRTKTIPQNLNPVWnEKFHFE----CHNSSDR-IKVRVWDEDDDiksr 77
                          90       100
                  ....*....|....*....|....
gi 2553878300 244 -------GSHDFIGEFTTSYRELS 260
Cdd:cd04027    78 lkqkftrESDDFLGQTIIEVRTLS 101
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
179-250 7.37e-04

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: 39.55  E-value: 7.37e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2553878300 179 FGRSDPFMVFyrSNEDGTFTIChKTEVVKNTLNPIW-QPFTIPVRalcnGDYDRSIKVEVYDWDRDGSHDFIG 250
Cdd:cd04043    19 NGLSDPYVTL--VDTNGKRRIA-KTRTIYDTLNPRWdEEFELEVP----AGEPLWISATVWDRSFVGKHDLCG 84
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
12-118 8.09e-04

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


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 40.05  E-value: 8.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  12 MASVCEFDPitgniPATKVEITV-SCRNLLDRDTFSKSDPLCILYTQGAESKQWREFG---------------------- 68
Cdd:cd08676    17 LERVREAEP-----PIFVLKVTViEAKGLLAKDVNGFSDPYCMLGIVPASRERNSEKSkkrkshrkkavlkdtvpaksik 91
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2553878300  69 RTEVIDNTLNPDFVRKYILDYFFEEKQNLRFDIYDIDSkspdlakhDFLG 118
Cdd:cd08676    92 VTEVKPQTLNPVWNETFRFEVEDVSNDQLHLDIWDHDD--------DFLG 133
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
201-250 8.63e-04

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: 40.38  E-value: 8.63e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2553878300 201 HKTEVVKNTLNPIWQpFTIPVRALCNGDY-DRSIKVEVYDWDRDGSHDFIG 250
Cdd:cd04020    66 QKTPVVKKSVNPVWN-HTFVYDGVSPEDLsQACLELTVWDHDKLSSNDFLG 115
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
170-251 1.20e-03

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: 39.07  E-value: 1.20e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFyrsnEDGTFTICHKTEVVKNTLNPIwqpF--------TIPVRALcngdydrsIKVEVYDWD 241
Cdd:cd04037     9 ARNLQPKDPNGKSDPYLKI----KLGKKKINDRDNYIPNTLNPV---FgkmfeleaTLPGNSI--------LKISVMDYD 73
                          90
                  ....*....|
gi 2553878300 242 RDGSHDFIGE 251
Cdd:cd04037    74 LLGSDDLIGE 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 ...
160-276 1.60e-03

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: 1.60e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 160 CRDCATMQFCANkLDKKDFFGRSDPFMVFYRSNEdGTFTICHKTEVVKNTLNPIWQP---FTIPVRalcNGDyDRSIKVE 236
Cdd:cd08403    14 GRLTLTIIKARN-LKAMDITGFSDPYVKVSLMCE-GRRLKKKKTSVKKNTLNPTYNEalvFDVPPE---NVD-NVSLIIA 87
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2553878300 237 VYDWDRDGSHDFIGEFTTSYRELSRGQSQFNvyEVV-NPKK 276
Cdd:cd08403    88 VVDYDRVGHNELIGVCRVGPNADGQGREHWN--EMLaNPRK 126
vWFA cd00198
Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation ...
412-490 1.90e-03

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.


Pssm-ID: 238119 [Multi-domain]  Cd Length: 161  Bit Score: 39.09  E-value: 1.90e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 412 QLYGPTNFAPVINHVARYAAAVQDGSQYFVLLIITDGVISDMAQTKEAIVNAAK-LPMSIIIVGVG-QAEFDAMVELDGD 489
Cdd:cd00198    75 GLGGGTNIGAALRLALELLKSAKRPNARRVIILLTDGEPNDGPELLAEAARELRkLGITVYTIGIGdDANEDELKEIADK 154

                  .
gi 2553878300 490 D 490
Cdd:cd00198   155 T 155
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
180-259 3.10e-03

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: 38.12  E-value: 3.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 180 GRSDPFM-VFYRSnedGTFTICHKTEVVKNTLNPIW---------QPFTIPVR--ALCNGDYDRS-IKVEVYDWDRDGSH 246
Cdd:cd08675    17 GTCDPFArVTLNY---SSKTDTKRTKVKKKTNNPRFdeafyfeltIGFSYEKKsfKVEEEDLEKSeLRVELWHASMVSGD 93
                          90
                  ....*....|...
gi 2553878300 247 DFIGEFTTSYREL 259
Cdd:cd08675    94 DFLGEVRIPLQGL 106
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
201-250 4.51e-03

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: 37.29  E-value: 4.51e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2553878300 201 HKTEVVKNTLNPIWQP----FTIPVRALcngdYDRSIKVEVYDWDRDGSHDFIG 250
Cdd:cd08688    34 YKTDVVKKSLNPVWNSewfrFEVDDEEL----QDEPLQIRVMDHDTYSANDAIG 83
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
170-265 5.19e-03

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


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 37.24  E-value: 5.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300 170 ANKLDKKDFFGRSDPFMVFYRSNEDgtfticHKTEVVKNTLNPIW-QPFTIpvrALCNgDYDRSIKVEVYDWDRDGSHDF 248
Cdd:cd08376     9 GKNLPPMDDNGLSDPYVKFRLGNEK------YKSKVCSKTLNPQWlEQFDL---HLFD-DQSQILEIEVWDKDTGKKDEF 78
                          90
                  ....*....|....*..
gi 2553878300 249 IGEFTTSYRELSRGQSQ 265
Cdd:cd08376    79 IGRCEIDLSALPREQTH 95
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
27-120 5.78e-03

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


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 37.14  E-value: 5.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2553878300  27 ATKVEITV-SCRNL--LDRDTFSKSDPLCILYTQGAESKQWREFgRTEVI-DNTLNPDFVRKYILDYFFEEKQNLRFDIY 102
Cdd:cd00275     1 PLTLTIKIiSGQQLpkPKGDKGSIVDPYVEVEIHGLPADDSAKF-KTKVVkNNGFNPVWNETFEFDVTVPELAFLRFVVY 79
                          90
                  ....*....|....*...
gi 2553878300 103 DIDSKspdlaKHDFLGQT 120
Cdd:cd00275    80 DEDSG-----DDDFLGQA 92
 
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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