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Conserved domains on  [gi|578832411|ref|XP_006722489|]
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E3 ubiquitin-protein ligase NEDD4-like isoform X11 [Homo sapiens]

Protein Classification

WW domain-containing protein( domain architecture ID 11559386)

WW domain-containing protein; the WW domain mediates protein-protein interaction via proline-rich motifs, such as PPxY; similar to mammalian Yes-associated protein 1 (YAP1) which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 686-1015 2.17e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


:

Pssm-ID: 214523  Cd Length: 328  Bit Score: 514.09  E-value: 2.17e-175
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    686 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 765
Cdd:smart00119    1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    766 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 842
Cdd:smart00119   80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    843 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 922
Cdd:smart00119  160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    923 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 1001
Cdd:smart00119  240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                           330
                    ....*....|....
gi 578832411   1002 REKLLMAVENAQGF 1015
Cdd:smart00119  315 REKLLLAINEGKGF 328
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-179 9.86e-79

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: 252.66  E-value: 9.86e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLYVADENRELALVQTKTIKKTLNPKW 100
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGAS--------------------------DPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKW 54

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578832411  101 NEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 179
Cdd:cd04033    55 NEEFFFRVNPREHRLLFEVFDENRLTRDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 413-442 1.57e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


:

Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 62.52  E-value: 1.57e-12
                           10        20        30
                   ....*....|....*....|....*....|
gi 578832411   413 LPSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 526-556 7.00e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


:

Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 60.62  E-value: 7.00e-12
                          10        20        30
                  ....*....|....*....|....*....|.
gi 578832411  526 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 556
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 224-250 1.27e-09

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


:

Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.05  E-value: 1.27e-09
                           10        20
                   ....*....|....*....|....*..
gi 578832411   224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:pfam00397    4 GWEERWDPDGRVYYYNHETGETQWEKP 30
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 575-625 8.52e-07

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


:

Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 46.05  E-value: 8.52e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 578832411    575 PLPPGWEERIHLDGRTFYIDHssqvlcgendtresvpsyDSKITQWEDPRL 625
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNH------------------ETKETQWEKPRE 33
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 345-528 6.38e-04

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 44.16  E-value: 6.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  345 PDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGeeptpsvayvHTTPGLPSGWEERKDAK 424
Cdd:PHA03247 2589 PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPH----------PPPTVPPPERPRDDPAP 2658

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  425 GRtyyVNHNNRTTTWTRPimqlaedgASGSATnsnnhliePQIRRPRSLSSPTVTLSAplegakdspvrravkdtLSNPQ 504
Cdd:PHA03247 2659 GR---VSRPRRARRLGRA--------AQASSP--------PQRPRRRAARPTVGSLTS-----------------LADPP 2702

                         170       180
                  ....*....|....*....|....
gi 578832411  505 SPQPSPynSPKPQHKVTQSFLPPG 528
Cdd:PHA03247 2703 PPPPTP--EPAPHALVSATPLPPG 2724
 
Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 686-1015 2.17e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


Pssm-ID: 214523  Cd Length: 328  Bit Score: 514.09  E-value: 2.17e-175
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    686 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 765
Cdd:smart00119    1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    766 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 842
Cdd:smart00119   80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    843 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 922
Cdd:smart00119  160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    923 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 1001
Cdd:smart00119  240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                           330
                    ....*....|....
gi 578832411   1002 REKLLMAVENAQGF 1015
Cdd:smart00119  315 REKLLLAINEGKGF 328
HECTc cd00078
HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It ...
 662-1016 7.33e-167

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.


Pssm-ID: 238033 [Multi-domain]  Cd Length: 352  Bit Score: 492.85  E-value: 7.33e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  662 FEMKLHRNNIFEESYRRIMSVKRPDvLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINP 741
Cdd:cd00078     1 LKITVRRDRILEDALRQLSKVSSSD-LKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  742 NSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPT--ELDLMF 819
Cdd:cd00078    80 SSFA-DEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGDedDLELTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  820 CIDEEN-FGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCG 898
Cdd:cd00078   159 TIELDSsFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELLICG 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  899 LGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELygsngPQLFTIEQWGSP- 977
Cdd:cd00078   239 SEDIDLEDLKKNTEYKGGYSSDSPTIQWFWEVLESFTNEERKKFLQFVTGSSRLPVGGFADL-----NPKFTIRRVGSPd 313

                         330       340       350
                  ....*....|....*....|....*....|....*....
gi 578832411  978 EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 1016
Cdd:cd00078   314 DRLPTAHTCFNLLKLPPYSSKEILREKLLYAINEGAGFG 352
HUL4 COG5021
Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];
413-1015 1.36e-164

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227354 [Multi-domain]  Cd Length: 872  Bit Score: 506.23  E-value: 1.36e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  413 LPSGWEERKDAKGRTYYVNHNNRTTTWTRPImqlaedgASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEgaKDSPV 492
Cdd:COG5021   299 LNSLFSTRADSFGRTYYLDHDRILTQYSRPL-------LEETLGESTSFLVVNNDDSSSIKDLPHQVGSNPFL--EAHPE 369

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  493 RRAVKDTLSNpqspqpspynspkpQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDP-RLKFPVHMRSKTSLNPN 571
Cdd:COG5021   370 FSELLKNQSR--------------GTTRDFRNKPTGWSSSIEDLGQFLFSDFLTSSSTYEDLrREQLGRESDESFYVASN 435

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  572 -------DLGPLPPGWEERIHLDGRTFYIDHSsqvlcgendtresvpsydSKITQWEDPRLQNPA--ITGPAVPYSREFK 642
Cdd:COG5021   436 vqqqrasREGPLLSGWKTRLNNLYRFYFVEHR------------------KKTLTKNDSRLGSFIslNKLDIRRIKEDKR 497

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  643 QKYDYFRKKLKKPADIPnrFEMKLHRNNIFEESYRRIMSvKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNP 722
Cdd:COG5021   498 RKLFYSLKQKAKIFDPY--LHIKVRRDRVFEDSYREIMD-ESGDDLKKTLEIEFVGEEGIDAGGLTREWLFLLSKEMFNP 574

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  723 YYGLFEYSATDNYTLQINPNSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYN 802
Cdd:COG5021   575 DYGLFEYITEDLYTLPINPLSSI-NPEHLSYFKFLGRVIGKAIYDSRILDVQFSKAFYKKLLGKPVSLVDLESLDPELYR 653

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  803 SLKWILEN--DPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLP 880
Cdd:COG5021   654 SLVWLLNNdiDETILDLTFTVEDDSFGESRTVELIPNGRNISVTNENKKEYVKKVVDYKLNKRVEKQFSAFKSGFSEIIP 733

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  881 IDLIKIFDENELELLMCGLGD-VDVNDWRQHSIYKnGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAE 959
Cdd:COG5021   734 PDLLQIFDESELELLIGGIPEdIDIDDWKSNTAYH-GYTEDSPIIVWFWEIISEFDFEERAKLLQFVTGTSRIPINGFKD 812

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411  960 LYGSNGPQLFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGF 1015
Cdd:COG5021   813 LQGSDGVRKFTIEKGGTDdDRLPSAHTCFNRLKLPEYSSKEKLRSKLLTAINEGAGF 869
HECT pfam00632
HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl ...
 713-1016 8.29e-132

HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl Terminus.


Pssm-ID: 459880  Cd Length: 304  Bit Score: 400.45  E-value: 8.29e-132
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   713 FLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCN-EDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLN 791
Cdd:pfam00632    1 TLLSKELFDPNYGLFEYETEDDRTYWFNPSSSESPdLELLDYFKFLGKLLGKAIYNGILLDLPFPPFFYKKLLGEPLTLE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   792 DMESVDSEYYNSLKWIL---ENDPTELDLMFCIDEenFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQM 868
Cdd:pfam00632   81 DLESIDPELYKSLKSLLnmdNDDDEDLGLTFTIPV--FGESKTIELIPNGRNIPVTNENKEEYIRLYVDYRLNKSIEPQL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   869 NAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTG 948
Cdd:pfam00632  159 EAFRKGFYSVIPKEALSLFTPEELELLICGSPEIDVEDLKKNTEYDGGYTKNSPTIQWFWEILEEFSPEQRRLFLKFVTG 238

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   949 TSRVPMNGFAELygsngpQLFTIEQWGS--PEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 1016
Cdd:pfam00632  239 SSRLPVGGFKSL------PKFTIVRKGGddDDRLPTAHTCFNRLKLPDYSSKEILKEKLLIAIEEGEGFG 302
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-179 9.86e-79

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: 252.66  E-value: 9.86e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLYVADENRELALVQTKTIKKTLNPKW 100
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGAS--------------------------DPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKW 54

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578832411  101 NEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 179
Cdd:cd04033    55 NEEFFFRVNPREHRLLFEVFDENRLTRDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
C2 pfam00168
C2 domain;
21-149 1.19e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 99.32  E-value: 1.19e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyVADENRelalVQTKTIKKTLNPKW 100
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTS--------------------------DPYVKVYL-LDGKQK----KKTKVVKNTLNPVW 50

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 578832411   101 NEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPTEDPTME 149
Cdd:pfam00168   51 NETFTFSVPDPENAVLeIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 21-147 3.50e-24

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 97.94  E-value: 3.50e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411     21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLYVADENRelalVQTKTIKKTLNPKW 100
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKS--------------------------DPYVKVSLDGDPKEK----KKTKVVKNTLNPVW 50

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*...
gi 578832411    101 NEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:smart00239   51 NETFEFEVPPPELAELeIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRH 98
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 413-442 1.57e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 62.52  E-value: 1.57e-12
                           10        20        30
                   ....*....|....*....|....*....|
gi 578832411   413 LPSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 412-442 3.58e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 61.46  E-value: 3.58e-12
                            10        20        30
                    ....*....|....*....|....*....|.
gi 578832411    412 GLPSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKP 31
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 526-556 7.00e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 60.62  E-value: 7.00e-12
                          10        20        30
                  ....*....|....*....|....*....|.
gi 578832411  526 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 556
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 414-442 9.11e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 60.23  E-value: 9.11e-12
                          10        20
                  ....*....|....*....|....*....
gi 578832411  414 PSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDP 29
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 525-556 9.40e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 60.31  E-value: 9.40e-12
                            10        20        30
                    ....*....|....*....|....*....|..
gi 578832411    525 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 556
Cdd:smart00456    2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 525-554 9.49e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 60.21  E-value: 9.49e-12
                           10        20        30
                   ....*....|....*....|....*....|
gi 578832411   525 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP 554
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 224-250 1.27e-09

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.05  E-value: 1.27e-09
                           10        20
                   ....*....|....*....|....*..
gi 578832411   224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:pfam00397    4 GWEERWDPDGRVYYYNHETGETQWEKP 30
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 224-250 3.64e-09

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 52.92  E-value: 3.64e-09
                          10        20
                  ....*....|....*....|....*..
gi 578832411  224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:cd00201     3 GWEERWDPDGRVYYYNHNTKETQWEDP 29
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
63-149 4.77e-09

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 60.54  E-value: 4.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   63 SDNSNDPYVKLslYVADENrelaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:COG5038  1057 ENGYSDPFVKL--FLNEKS----VYKTKVVKKTLNPVWNEEFTIEVlNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKL 1130


                  ....*...
gi 578832411  142 PTEDPTME 149
Cdd:COG5038  1131 EPGGTTNS 1138
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 224-250 1.38e-08

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 51.06  E-value: 1.38e-08
                            10        20
                    ....*....|....*....|....*..
gi 578832411    224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:smart00456    5 GWEERKDPDGRPYYYNHETKETQWEKP 31
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 575-625 8.52e-07

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 46.05  E-value: 8.52e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 578832411    575 PLPPGWEERIHLDGRTFYIDHssqvlcgendtresvpsyDSKITQWEDPRL 625
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNH------------------ETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 576-623 2.89e-06

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 44.42  E-value: 2.89e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 578832411   576 LPPGWEERIHLDGRTFYIDHSsqvlcgendTREsvpsydskiTQWEDP 623
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHE---------TGE---------TQWEKP 30
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 577-625 4.36e-06

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 44.06  E-value: 4.36e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 578832411  577 PPGWEERIHLDGRTFYIDHssqvlcgendtresvpsyDSKITQWEDPRL 625
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNH------------------NTKETQWEDPRE 31
PHA03247 PHA03247
large tegument protein UL36; Provisional
 345-528 6.38e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 44.16  E-value: 6.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  345 PDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGeeptpsvayvHTTPGLPSGWEERKDAK 424
Cdd:PHA03247 2589 PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPH----------PPPTVPPPERPRDDPAP 2658

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  425 GRtyyVNHNNRTTTWTRPimqlaedgASGSATnsnnhliePQIRRPRSLSSPTVTLSAplegakdspvrravkdtLSNPQ 504
Cdd:PHA03247 2659 GR---VSRPRRARRLGRA--------AQASSP--------PQRPRRRAARPTVGSLTS-----------------LADPP 2702

                         170       180
                  ....*....|....*....|....
gi 578832411  505 SPQPSPynSPKPQHKVTQSFLPPG 528
Cdd:PHA03247 2703 PPPPTP--EPAPHALVSATPLPPG 2724
PLN02952 PLN02952
phosphoinositide phospholipase C
 59-141 5.11e-03

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 40.75  E-value: 5.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   59 TKCESDNSNDPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVN-PSNHRLLFEVFDENRLTRDDFLGQVDVP 137
Cdd:PLN02952  489 THFDSYSPPDFYTKM--YIVGVPADNAKKKTKIIEDNWYPAWNEEFSFPLTvPELALLRIEVREYDMSEKDDFGGQTCLP 566


                  ....
gi 578832411  138 LSHL 141
Cdd:PLN02952  567 VSEL 570
 
Name Accession Description Interval E-value
HECTc smart00119
Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to ...
 686-1015 2.17e-175

Domain Homologous to E6-AP Carboxyl Terminus with; E3 ubiquitin-protein ligases. Can bind to E2 enzymes.


Pssm-ID: 214523  Cd Length: 328  Bit Score: 514.09  E-value: 2.17e-175
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    686 DVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDnYTLQINPNSGLCNEDHLSYFTFIGRVAGLAV 765
Cdd:smart00119    1 DLKKRVLEIEFEGEEGLDGGGVTREFFFLLSKELFNPDYGLFRYSPND-YLLYPNPRSGFANEEHLSYFRFIGRVLGKAL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    766 FHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWI-LENDPTE-LDLMFCIDEEN-FGQTYQVDLKPNGSEIM 842
Cdd:smart00119   80 YDNRLLDLFFARPFYKKLLGKPVTLHDLESLDPELYKSLKWLlLNNDTSEeLDLTFSIVLTSeFGQVKVVELKPGGSNIP 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    843 VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHP 922
Cdd:smart00119  160 VTEENKKEYVHLVIEYRLNKGIEKQLEAFREGFSEVIPENLLKLFDPEELELLICGSPEIDVDDLKSNTEYKGGYSANSQ 239

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    923 VIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSngpqlFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDL 1001
Cdd:smart00119  240 TIKWFWEVVESFTNEERRKLLQFVTGSSRLPVGGFAALSPK-----FTIRKAGSDdERLPTAHTCFNRLKLPPYSSKEIL 314

                           330
                    ....*....|....
gi 578832411   1002 REKLLMAVENAQGF 1015
Cdd:smart00119  315 REKLLLAINEGKGF 328
HECTc cd00078
HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It ...
 662-1016 7.33e-167

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.


Pssm-ID: 238033 [Multi-domain]  Cd Length: 352  Bit Score: 492.85  E-value: 7.33e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  662 FEMKLHRNNIFEESYRRIMSVKRPDvLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINP 741
Cdd:cd00078     1 LKITVRRDRILEDALRQLSKVSSSD-LKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  742 NSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPT--ELDLMF 819
Cdd:cd00078    80 SSFA-DEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGDedDLELTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  820 CIDEEN-FGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCG 898
Cdd:cd00078   159 TIELDSsFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELLICG 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  899 LGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELygsngPQLFTIEQWGSP- 977
Cdd:cd00078   239 SEDIDLEDLKKNTEYKGGYSSDSPTIQWFWEVLESFTNEERKKFLQFVTGSSRLPVGGFADL-----NPKFTIRRVGSPd 313

                         330       340       350
                  ....*....|....*....|....*....|....*....
gi 578832411  978 EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 1016
Cdd:cd00078   314 DRLPTAHTCFNLLKLPPYSSKEILREKLLYAINEGAGFG 352
HUL4 COG5021
Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];
413-1015 1.36e-164

Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227354 [Multi-domain]  Cd Length: 872  Bit Score: 506.23  E-value: 1.36e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  413 LPSGWEERKDAKGRTYYVNHNNRTTTWTRPImqlaedgASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEgaKDSPV 492
Cdd:COG5021   299 LNSLFSTRADSFGRTYYLDHDRILTQYSRPL-------LEETLGESTSFLVVNNDDSSSIKDLPHQVGSNPFL--EAHPE 369

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  493 RRAVKDTLSNpqspqpspynspkpQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDP-RLKFPVHMRSKTSLNPN 571
Cdd:COG5021   370 FSELLKNQSR--------------GTTRDFRNKPTGWSSSIEDLGQFLFSDFLTSSSTYEDLrREQLGRESDESFYVASN 435

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  572 -------DLGPLPPGWEERIHLDGRTFYIDHSsqvlcgendtresvpsydSKITQWEDPRLQNPA--ITGPAVPYSREFK 642
Cdd:COG5021   436 vqqqrasREGPLLSGWKTRLNNLYRFYFVEHR------------------KKTLTKNDSRLGSFIslNKLDIRRIKEDKR 497

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  643 QKYDYFRKKLKKPADIPnrFEMKLHRNNIFEESYRRIMSvKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNP 722
Cdd:COG5021   498 RKLFYSLKQKAKIFDPY--LHIKVRRDRVFEDSYREIMD-ESGDDLKKTLEIEFVGEEGIDAGGLTREWLFLLSKEMFNP 574

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  723 YYGLFEYSATDNYTLQINPNSGLcNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYN 802
Cdd:COG5021   575 DYGLFEYITEDLYTLPINPLSSI-NPEHLSYFKFLGRVIGKAIYDSRILDVQFSKAFYKKLLGKPVSLVDLESLDPELYR 653

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  803 SLKWILEN--DPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLP 880
Cdd:COG5021   654 SLVWLLNNdiDETILDLTFTVEDDSFGESRTVELIPNGRNISVTNENKKEYVKKVVDYKLNKRVEKQFSAFKSGFSEIIP 733

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  881 IDLIKIFDENELELLMCGLGD-VDVNDWRQHSIYKnGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAE 959
Cdd:COG5021   734 PDLLQIFDESELELLIGGIPEdIDIDDWKSNTAYH-GYTEDSPIIVWFWEIISEFDFEERAKLLQFVTGTSRIPINGFKD 812

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411  960 LYGSNGPQLFTIEQWGSP-EKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGF 1015
Cdd:COG5021   813 LQGSDGVRKFTIEKGGTDdDRLPSAHTCFNRLKLPEYSSKEKLRSKLLTAINEGAGF 869
HECT pfam00632
HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl ...
 713-1016 8.29e-132

HECT-domain (ubiquitin-transferase); The name HECT comes from Homologous to the E6-AP Carboxyl Terminus.


Pssm-ID: 459880  Cd Length: 304  Bit Score: 400.45  E-value: 8.29e-132
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   713 FLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCN-EDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLN 791
Cdd:pfam00632    1 TLLSKELFDPNYGLFEYETEDDRTYWFNPSSSESPdLELLDYFKFLGKLLGKAIYNGILLDLPFPPFFYKKLLGEPLTLE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   792 DMESVDSEYYNSLKWIL---ENDPTELDLMFCIDEenFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQM 868
Cdd:pfam00632   81 DLESIDPELYKSLKSLLnmdNDDDEDLGLTFTIPV--FGESKTIELIPNGRNIPVTNENKEEYIRLYVDYRLNKSIEPQL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   869 NAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTG 948
Cdd:pfam00632  159 EAFRKGFYSVIPKEALSLFTPEELELLICGSPEIDVEDLKKNTEYDGGYTKNSPTIQWFWEILEEFSPEQRRLFLKFVTG 238

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   949 TSRVPMNGFAELygsngpQLFTIEQWGS--PEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE 1016
Cdd:pfam00632  239 SSRLPVGGFKSL------PKFTIVRKGGddDDRLPTAHTCFNRLKLPDYSSKEILKEKLLIAIEEGEGFG 302
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 21-179 9.86e-79

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: 252.66  E-value: 9.86e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLYVADENRELALVQTKTIKKTLNPKW 100
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGAS--------------------------DPYVKISLYDPDGNGEIDSVQTKTIKKTLNPKW 54

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578832411  101 NEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYM 179
Cdd:cd04033    55 NEEFFFRVNPREHRLLFEVFDENRLTRDDFLGQVEVPLNNLPTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAYL 133
C2 pfam00168
C2 domain;
21-149 1.19e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 99.32  E-value: 1.19e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyVADENRelalVQTKTIKKTLNPKW 100
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTS--------------------------DPYVKVYL-LDGKQK----KKTKVVKNTLNPVW 50

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 578832411   101 NEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPTEDPTME 149
Cdd:pfam00168   51 NETFTFSVPDPENAVLeIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 22-153 1.96e-24

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: 98.68  E-value: 1.96e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyvadenRELALVQTKTIKKTLNPKWN 101
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKS--------------------------DPYVKVSL------GGKQKFKTKVVKNTLNPVWN 48

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 578832411  102 EEFYFRV-NPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYT 153
Cdd:cd00030    49 ETFEFPVlDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELWLP 101
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 21-147 3.50e-24

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 97.94  E-value: 3.50e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411     21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLYVADENRelalVQTKTIKKTLNPKW 100
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKS--------------------------DPYVKVSLDGDPKEK----KKTKVVKNTLNPVW 50

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*...
gi 578832411    101 NEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:smart00239   51 NETFEFEVPPPELAELeIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRH 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 ...
 68-141 4.00e-18

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: 81.54  E-value: 4.00e-18
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   68 DPYVKLSLYVADENRelALVQTKTIKKTLNPKWNEEFYFRVNPSNH--RLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd04026    35 DPYVKLKLIPDPKNE--TKQKTKTIKKTLNPVWNETFTFDLKPADKdrRLSIEVWDWDRTTRNDFMGSLSFGVSEL 108
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 22-147 3.98e-16

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 75.30  E-value: 3.98e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyvadENRELAlvQTKTIKKTLNPKWN 101
Cdd:cd04040     1 LTVDVISAENLPSADRNGKS--------------------------DPFVKFYL----NGEKVF--KTKTIKKTLNPVWN 48

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 578832411  102 EEFYFRVNP-SNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:cd04040    49 ESFEVPVPSrVRAVLKVEVYDWDRGGKDDLLGSAYIDLSDLEPEETT 95
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 63-147 7.52e-16

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: 74.97  E-value: 7.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   63 SDNSNDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR-----LLFEVFDENRLTRDDFLGQVDVP 137
Cdd:cd04009    33 SNGSSDPFVKVELLPRHLFPDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCSvegalLLFTVKDYDLLGSNDFEGEAFLP 112

                          90
                  ....*....|
gi 578832411  138 LSHLPTEDPT 147
Cdd:cd04009   113 LNDIPGVEDT 122
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 21-138 6.44e-15

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: 72.74  E-value: 6.44e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFgasfcsiavelffgrdirkitkcesdnSNDPYVKLSLyvADENrelalVQTKTIKKTLNPKW 100
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFT---------------------------SSDPYVVLTL--GNQK-----VKTRVIKKNLNPVW 48

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 578832411  101 NEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPL 138
Cdd:cd04038    49 NEELTLSVPNPMAPLKLEVFDKDTFSKDDSMGEAEIDL 86
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 64-180 3.67e-14

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: 69.89  E-value: 3.67e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   64 DNSNDPYVKLSLyvaDENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLpT 143
Cdd:cd04044    21 GGTVDPYVTFSI---SNRRELA--RTKVKKDTSNPVWNETKYILVNSLTEPLNLTVYDFNDKRKDKLIGTAEFDLSSL-L 94

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 578832411  144 EDPTMERPYtfKDFLlrpRSHKSRvkGFLRLKMAYMP 180
Cdd:cd04044    95 QNPEQENLT--KNLL---RNGKPV--GELNYDLRFFP 124
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 43-141 4.54e-14

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: 69.88  E-value: 4.54e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   43 CSIAVELFFGRDIRKITKCESDNSnDPYVKLSLYVADENRElALVQTKTIKK-TLNPKWNEEFYFRV-NPSNHRLLFEVF 120
Cdd:cd00275     2 LTLTIKIISGQQLPKPKGDKGSIV-DPYVEVEIHGLPADDS-AKFKTKVVKNnGFNPVWNETFEFDVtVPELAFLRFVVY 79

                          90       100
                  ....*....|....*....|.
gi 578832411  121 DENRlTRDDFLGQVDVPLSHL 141
Cdd:cd00275    80 DEDS-GDDDFLGQACLPLDSL 99
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 21-176 1.12e-13

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: 68.48  E-value: 1.12e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyvadENRELalvQTKTIKKTLNPKW 100
Cdd:cd08377     2 FLQVKVIRASGLAAADIGGKS--------------------------DPFCVLEL----VNARL---QTHTIYKTLNPEW 48

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411  101 NEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLpteDPTMERPYTFKDfllrpRSHKSRVKGFLRLKM 176
Cdd:cd08377    49 NKIFTFPIKDIHDVLEVTVYDEDKDKKPEFLGKVAIPLLSI---KNGERKWYALKD-----KKLRTRAKGSILLEM 116
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 21-139 1.24e-13

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: 68.47  E-value: 1.24e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFgasfcsiavelffgrdIRKITKCESDnsndPYVKLSlyVADEnrelaLVQTKTIKKTLNPKW 100
Cdd:cd08391     2 VLRIHVIEAQDLVAKDKF----------------VGGLVKGKSD----PYVIVR--VGAQ-----TFKSKVIKENLNPKW 54

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 578832411  101 NEEFYFRVNP-SNHRLLFEVFDENRlTRDDFLGQVDVPLS 139
Cdd:cd08391    55 NEVYEAVVDEvPGQELEIELFDEDP-DKDDFLGRLSIDLG 93
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 5-148 1.93e-13

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: 68.13  E-value: 1.93e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    5 LGEPVYGLSEDEGESrILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyVADENREL 84
Cdd:cd08386     2 LGRIQFSVSYDFQES-TLTLKILKAVELPAKDFSGTS--------------------------DPFVKIYL-LPDKKHKL 53

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578832411   85 alvQTKTIKKTLNPKWNEEFYFRVNPSN---HRLLF-EVFDENRLTRDDFLGQVDVPLSHLPTEDPTM 148
Cdd:cd08386    54 ---ETKVKRKNLNPHWNETFLFEGFPYEklqQRVLYlQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQT 118
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 5-139 2.96e-13

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: 67.29  E-value: 2.96e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    5 LGEPVYGLSEDEGESRiLRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyVADENREL 84
Cdd:cd08385     2 LGKLQFSLDYDFQSNQ-LTVGIIQAADLPAMDMGGTS--------------------------DPYVKVYL-LPDKKKKF 53

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 578832411   85 alvQTKTIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLS 139
Cdd:cd08385    54 ---ETKVHRKTLNPVFNETFTFKVPYSelgNKTLVFSVYDFDRFSKHDLIGEVRVPLL 108
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 21-166 4.73e-13

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: 67.06  E-value: 4.73e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGasfcsiavelffgrdirkITKCesdnsnDPYVKLSlyVADENRElalvqTKTIKKTLNPKW 100
Cdd:cd04024     2 VLRVHVVEAKDLAAKDRSG------------------KGKS------DPYAILS--VGAQRFK-----TQTIPNTLNPKW 50

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578832411  101 NEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHL----PTEDPTMerPYTFKDFLLRPRSHKS 166
Cdd:cd04024    51 NYWCEFPIFSAQNQLLkLILWDKDRFAGKDYLGEFDIALEEVfadgKTGQSDK--WITLKSTRPGKTSVVS 119
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 413-442 1.57e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 62.52  E-value: 1.57e-12
                           10        20        30
                   ....*....|....*....|....*....|
gi 578832411   413 LPSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 412-442 3.58e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 61.46  E-value: 3.58e-12
                            10        20        30
                    ....*....|....*....|....*....|.
gi 578832411    412 GLPSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKP 31
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 68-147 3.71e-12

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


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 64.15  E-value: 3.71e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSLyvadENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:cd04045    23 DPYVRVLV----NGIVKG--RTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMDYEKVGKDRSLGSVEINVSDLIKKNED 96
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 56-144 5.74e-12

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 64.14  E-value: 5.74e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSNDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVnPSNHR----LLFEVFDENRLTRDDFL 131
Cdd:cd00276    24 RNLPPSDGKGLSDPYVKVSLLQ--GGKKLKKKKTSVKKGTLNPVFNEAFSFDV-PAEQLeevsLVITVVDKDSVGRNEVI 100

                          90
                  ....*....|...
gi 578832411  132 GQVDVPLSHLPTE 144
Cdd:cd00276   101 GQVVLGPDSGGEE 113
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 526-556 7.00e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 60.62  E-value: 7.00e-12
                          10        20        30
                  ....*....|....*....|....*....|.
gi 578832411  526 PPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 556
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 56-142 7.19e-12

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 63.44  E-value: 7.19e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSNDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLtRDDFLGQV 134
Cdd:cd04036    10 TNITKGDLLSTPDCYVELWLPTASDEK----KRTKTIKNSINPVWNETFEFRIQSQVKNVLeLTVMDEDYV-MDDHLGTV 84


                  ....*...
gi 578832411  135 DVPLSHLP 142
Cdd:cd04036    85 LFDVSKLK 92
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 414-442 9.11e-12

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 60.23  E-value: 9.11e-12
                          10        20
                  ....*....|....*....|....*....
gi 578832411  414 PSGWEERKDAKGRTYYVNHNNRTTTWTRP 442
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDP 29
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 525-556 9.40e-12

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 60.31  E-value: 9.40e-12
                            10        20        30
                    ....*....|....*....|....*....|..
gi 578832411    525 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRL 556
Cdd:smart00456    2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 525-554 9.49e-12

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 60.21  E-value: 9.49e-12
                           10        20        30
                   ....*....|....*....|....*....|
gi 578832411   525 LPPGWEMRIAPNGRPFFIDHNTKTTTWEDP 554
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 13-144 1.01e-11

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: 63.93  E-value: 1.01e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   13 SEDEGESRILRVKVVSGIDLAKKDIFGAS--FCSIAVElfFGRDIRKITKCESDNSNDPYVKLSLYVADEnrelaLVQ-T 89
Cdd:cd08676    21 REAEPPIFVLKVTVIEAKGLLAKDVNGFSdpYCMLGIV--PASRERNSEKSKKRKSHRKKAVLKDTVPAK-----SIKvT 93

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   90 KTIKKTLNPKWNEEFYFRVNP-SNHRLLFEVFDENrltrDDFLGQVDVPLSHLPTE 144
Cdd:cd08676    94 EVKPQTLNPVWNETFRFEVEDvSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSC 145
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-175 1.95e-11

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 62.35  E-value: 1.95e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDifGASFCSIAVELFFgrdirkitkcesdnsndpyvklslyvaDENRelalVQTKTIKKTLNPKWN 101
Cdd:cd04022     2 LVVEVVDAQDLMPKD--GQGSSSAYVELDF---------------------------DGQK----KRTRTKPKDLNPVWN 48

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578832411  102 EEFYFRV-NPSNHRLLF---EVFDENRLTR-DDFLGQVDVPLSHLPTEDPTMERPYTfkdflLRPRSHKSRVKGFLRLK 175
Cdd:cd04022    49 EKLVFNVsDPSRLSNLVlevYVYNDRRSGRrRSFLGRVRISGTSFVPPSEAVVQRYP-----LEKRGLFSRVRGEIGLK 122
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 66-176 2.88e-11

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: 61.82  E-value: 2.88e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   66 SNDPYVklSLYVADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDEN---------RLTR--DDFLGQV 134
Cdd:cd04027    21 TSDPYV--TVQVGKTKK-----RTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDddiksrlkqKFTResDDFLGQT 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 578832411  135 DVPLSHLPTEdptMERPYTfkdflLRPRSHKSRVKGFLRLKM 176
Cdd:cd04027    94 IIEVRTLSGE---MDVWYN-----LEKRTDKSAVSGAIRLHI 127
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 22-147 3.24e-11

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: 61.52  E-value: 3.24e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyvadENRELalVQTKTIKKTLNPKWN 101
Cdd:cd04042     2 LDIHLKEGRNLAARDRGGTS--------------------------DPYVKFKY----GGKTV--YKSKTIYKNLNPVWD 49

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 578832411  102 EEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:cd04042    50 EKFTLPIEDVTQPLYIKVFDYDRGLTDDFMGSAFVDLSTLELNKPT 95
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 65-139 6.68e-11

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


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 60.73  E-value: 6.68e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578832411   65 NSNDPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLS 139
Cdd:cd08390    34 AHCDPFVKVCL-LPDERRSL---QSKVKRKTQNPNFDETFVFQVSFKelqRRTLRLSVYDVDRFSRHCIIGHVLFPLK 107
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 68-156 8.26e-11

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


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 59.89  E-value: 8.26e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSlyVADENRElalvqTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLTRddfLGQVDVPLSHLPT-ED 145
Cdd:cd04050    22 SPYVELT--VGKTTQK-----SKVKERTNNPVWEEGFTFLVrNPENQELEIEVKDDKTGKS---LGSLTLPLSELLKePD 91

                          90
                  ....*....|.
gi 578832411  146 PTMERPYTFKD 156
Cdd:cd04050    92 LTLDQPFPLDN 102
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 66-141 2.39e-10

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 58.81  E-value: 2.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   66 SNDPYVKLSLYVADEnrelALVQTKTIKKTLNPKWNEEFYFRVNP----SNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd04041    22 SSDPYVTASFAKFGK----PLYSTRIIRKDLNPVWEETWFVLVTPdevkAGERLSCRLWDSDRFTADDRLGRVEIDLKEL 97
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 88-180 2.42e-10

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 59.30  E-value: 2.42e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   88 QTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLshlpteDPTMERPYTFKDFLLRPR-SHKS 166
Cdd:cd08678    34 QSSTQKNTSNPFWDEHFLFELSPNSKELLFEVYDNGKKSDSKFLGLAIVPF------DELRKNPSGRQIFPLQGRpYEGD 107

                          90
                  ....*....|....
gi 578832411  167 RVKGFLRLKMAYMP 180
Cdd:cd08678   108 SVSGSITVEFLFME 121
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 68-141 3.25e-10

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


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 58.57  E-value: 3.25e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411   68 DPYVKLSLyVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPSN-HRLLFEV--FDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd08387    38 DPYCKVRL-LPDRSNTK---QSKIHKKTLNPEFDESFVFEVPPQElPKRTLEVllYDFDQFSRDECIGVVELPLAEV 110
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 68-158 4.79e-10

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 58.06  E-value: 4.79e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSLY-VADENRELalvQTKTIKKTLNPKWNEEF-YFRVNPSNHR---LLFEVFDENRLtRDDFLGQVDVPLSHLp 142
Cdd:cd04035    37 DPYVKLNLLpGASKATKL---RTKTVHKTRNPEFNETLtYYGITEEDIQrktLRLLVLDEDRF-GNDFLGETRIPLKKL- 111

                          90
                  ....*....|....*.
gi 578832411  143 tedpTMERPYTFKDFL 158
Cdd:cd04035   112 ----KPNQTKQFNICL 123
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 67-146 6.10e-10

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


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 57.65  E-value: 6.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   67 NDPYVKLSLyvADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPTED 145
Cdd:cd08376    21 SDPYVKFRL--GNEKY-----KSKVCSKTLNPQWLEQFDLHLFDDQSQILeIEVWDKDTGKKDEFIGRCEIDLSALPREQ 93


                  .
gi 578832411  146 P 146
Cdd:cd08376    94 T 94
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 56-144 9.40e-10

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


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 57.80  E-value: 9.40e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSNDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVNP---SNHRLLFEVFDENRLTRDDFLG 132
Cdd:cd08402    25 KNLKKMDVGGLSDPYVKIHLMQ--NGKRLKKKKTTIKKRTLNPYYNESFSFEVPFeqiQKVHLIVTVLDYDRIGKNDPIG 102

                          90
                  ....*....|..
gi 578832411  133 QVDVPLSHLPTE 144
Cdd:cd08402   103 KVVLGCNATGAE 114
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 224-250 1.27e-09

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 54.05  E-value: 1.27e-09
                           10        20
                   ....*....|....*....|....*..
gi 578832411   224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:pfam00397    4 GWEERWDPDGRVYYYNHETGETQWEKP 30
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 55-141 1.37e-09

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 56.90  E-value: 1.37e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   55 IRKITKCESDNSNDPYVKLSLYvADENRElALVQTKTIKKTLNPKWNEEFYFRVNPS--NHRLLfEVFDEN---RLTRD- 128
Cdd:cd04030    25 CRNLPPCDSSDIPDPYVRLYLL-PDKSKS-TRRKTSVKKDNLNPVFDETFEFPVSLEelKRRTL-DVAVKNsksFLSREk 101

                          90
                  ....*....|...
gi 578832411  129 DFLGQVDVPLSHL 141
Cdd:cd04030   102 KLLGQVLIDLSDL 114
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 22-163 1.88e-09

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: 56.55  E-value: 1.88e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFgasfcsiavelffgrdirkitkcesdNSNDPYVKLSlyVADENRElalvQTKTIKKTLNPKWN 101
Cdd:cd08382     2 VRLTVLCADGLAKRDLF--------------------------RLPDPFAVIT--VDGGQTH----STDVAKKTLDPKWN 49

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578832411  102 EEFYFRVNPSNhRLLFEVFDENRLTRDD--FLGQVDVPL-SHLPTEDPTMERpytfkdFLLRPRS 163
Cdd:cd08382    50 EHFDLTVGPSS-IITIQVFDQKKFKKKDqgFLGCVRIRAnAVLPLKDTGYQR------LDLRKLK 107
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 6-149 1.90e-09

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


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 56.49  E-value: 1.90e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411    6 GEPVYGLSEDEgESRILRVKVVSGIDLAKKDifgasfcsiavelffgrdirkitkcESDNSNDPYVKLSLyVADENRELA 85
Cdd:cd08521     1 GEIEFSLSYNY-KTGSLEVHIKECRNLAYAD-------------------------EKKKRSNPYVKVYL-LPDKSKQSK 53

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411   86 LvQTKTIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTME 149
Cdd:cd08521    54 R-KTSVKKNTTNPVFNETLKYHISKSqleTRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSE 119
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 68-140 2.20e-09

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: 56.49  E-value: 2.20e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSLY---VADENRelalvQTKTIKKTLNPKWNEEFYFRvNPSNHRLL-----FEVFDENRLTRDDFLGQVDVPLS 139
Cdd:cd04031    38 NPYVKVYLLpdrSEKSKR-----RTKTVKKTLNPEWNQTFEYS-NVRRETLKertleVTVWDYDRDGENDFLGEVVIDLA 111


                  .
gi 578832411  140 H 140
Cdd:cd04031   112 D 112
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 56-141 2.41e-09

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: 56.61  E-value: 2.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSnDPYVKLSLYVADENRELalvQTKTIKKTLNPKWNEEFYFRVNPSNHR----------------LLFEV 119
Cdd:cd08675     9 RDLALKSNGTC-DPFARVTLNYSSKTDTK---RTKVKKKTNNPRFDEAFYFELTIGFSYekksfkveeedlekseLRVEL 84

                          90       100
                  ....*....|....*....|..
gi 578832411  120 FDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd08675    85 WHASMVSGDDFLGEVRIPLQGL 106
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 224-250 3.64e-09

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 52.92  E-value: 3.64e-09
                          10        20
                  ....*....|....*....|....*..
gi 578832411  224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:cd00201     3 GWEERWDPDGRVYYYNHNTKETQWEDP 29
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
63-149 4.77e-09

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 60.54  E-value: 4.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   63 SDNSNDPYVKLslYVADENrelaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:COG5038  1057 ENGYSDPFVKL--FLNEKS----VYKTKVVKKTLNPVWNEEFTIEVlNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKL 1130


                  ....*...
gi 578832411  142 PTEDPTME 149
Cdd:COG5038  1131 EPGGTTNS 1138
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 66-134 7.55e-09

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: 55.12  E-value: 7.55e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578832411   66 SNDPYVKLSLYVADenRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENRLTRDDFLGQV 134
Cdd:cd08405    35 TSDPYVKVWLMYKD--KRVEKKKTVIKKRTLNPVFNESFIFNIPLERLRettLIITVMDKDRLSRNDLIGKI 104
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 62-134 9.43e-09

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: 54.66  E-value: 9.43e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   62 ESDNSNDPYVKLSLYVADENRELALVQTKtiKKTLNPKWNEEFYFRVNPSN---HRLLFEVFDENRLTRDDFLGQV 134
Cdd:cd08384    29 DANGYSDPFVKLYLKPDAGKKSKHKTQVK--KKTLNPEFNEEFFYDIKHSDlakKTLEITVWDKDIGKSNDYIGGL 102
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 224-250 1.38e-08

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 51.06  E-value: 1.38e-08
                            10        20
                    ....*....|....*....|....*..
gi 578832411    224 GWEEKVDNLGRTYYVNHNNRTTQWHRP 250
Cdd:smart00456    5 GWEERKDPDGRPYYYNHETKETQWEKP 31
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 22-134 1.43e-08

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 54.06  E-value: 1.43e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPY--VKlslyVADEnrelALVQTKTIKKTLNPK 99
Cdd:cd04054     2 LYIRIVEGKNLPAKDITGSS--------------------------DPYciVK----VDNE----VIIRTATVWKTLNPF 47

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 578832411  100 WNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQV 134
Cdd:cd04054    48 WGEEYTVHLPPGFHTVSFYVLDEDTLSRDDVIGKV 82
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 88-177 1.98e-08

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 53.59  E-value: 1.98e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   88 QTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVplshlPTEDPTMerpYTFKD--FLLRPRSHK 165
Cdd:cd08401    37 RTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIYDRDVLRRDSVIGKVAI-----KKEDLHK---YYGKDtwFPLQPVDAD 108

                          90
                  ....*....|..
gi 578832411  166 SRVKGFLRLKMA 177
Cdd:cd08401   109 SEVQGKVHLELR 120
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 22-141 2.56e-08

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 53.26  E-value: 2.56e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSLyvadENRELalvQTKTIKKTLNPKWN 101
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTS--------------------------DPFVRVFY----NGQTL---ETSVVKKSCYPRWN 48

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 578832411  102 EEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd04025    49 EVFEFELMEGADSPLsVEVWDWDLVSKNDFLGKVVFSIQTL 89
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 56-160 6.91e-08

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


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 52.39  E-value: 6.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSNDPYVKLSLYVADEnrelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-FEVFDENRLTRDDFLGQV 134
Cdd:cd08375    25 RDLKPCNSNGKSDPYCEVSMGSQEH-------KTKVVSDTLNPKWNSSMQFFVKDLEQDVLcITVFDRDFFSPDDFLGRT 97

                          90       100
                  ....*....|....*....|....*.
gi 578832411  135 DVPLSHLPTEDPTMERPYTfKDFLLR 160
Cdd:cd08375    98 EIRVADILKETKESKGPIT-KRLLLH 122
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 27-141 8.07e-08

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: 51.41  E-value: 8.07e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   27 VSGIDLAKKDIFGasfcsiavelffgrdirkitkcesdnSNDPYVKLSLYVADeNRELALVQTKTIKKTLNPKWNEefyF 106
Cdd:cd04047     7 FSGKKLDKKDFFG--------------------------KSDPFLEISRQSED-GTWVLVYRTEVIKNTLNPVWKP---F 56

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 578832411  107 RV--------NPSNHrLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd04047    57 TIplqklcngDYDRP-IKIEVYDYDSSGKHDLIGEFETTLDEL 98
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 68-137 8.99e-08

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 51.90  E-value: 8.99e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578832411   68 DPYVKLSlyvaDENRElalVQTKTIKKTLNPKWNEEFYF-RVNPSNhRLLFEVFDENRLtRDDFLGQVDVP 137
Cdd:cd04046    25 DPYVIIK----CEGES---VRSPVQKDTLSPEFDTQAIFyRKKPRS-PIKIQVWNSNLL-CDEFLGQATLS 86
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 68-143 1.02e-07

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: 51.42  E-value: 1.02e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSLYVADENRELALVQTKTIKKTLNPKWNE----EFYFrvnPSNHRLLFEVFD----ENRLTRDDFLGQVDVPLS 139
Cdd:cd04048    22 DPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTtftvDYYF---EEVQKLRFEVYDvdskSKDLSDHDFLGEAECTLG 98


                  ....
gi 578832411  140 HLPT 143
Cdd:cd04048    99 EIVS 102
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 67-134 1.10e-07

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


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 51.81  E-value: 1.10e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578832411   67 NDPYVKLSLYVAdenreLALVQTK---TIKKTLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQV 134
Cdd:cd08410    35 SDPFVKIQLVHG-----LKLIKTKktsCMRGTIDPFYNESFSFKVPQEeleNVSLVFTVYGHNVKSSNDFIGRI 103
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 68-141 1.31e-07

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 51.12  E-value: 1.31e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578832411   68 DPYVKLSlyVADENRElalvQTKTIKKTLNPKWNEEFYFRVNPSNHrLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd04021    23 DPYVEVT--VDGQPPK----KTEVSKKTSNPKWNEHFTVLVTPQST-LEFKVWSHHTLKADVLLGEASLDLSDI 89
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 22-134 1.91e-07

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: 51.94  E-value: 1.91e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   22 LRVKVVSGIDLAKKDIFGASFCSIAVELffgRDIRKITKCESDNSNDPYVKLSLyVADENRELALvQTKTIKKTLNPKWN 101
Cdd:cd04020     6 VALKYVPPESEGALKSKKPSTGELHVWV---KEAKNLPALKSGGTSDSFVKCYL-LPDKSKKSKQ-KTPVVKKSVNPVWN 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 578832411  102 EEFYFR-VNPS--NHRLL-FEVFDENRLTRDDFLGQV 134
Cdd:cd04020    81 HTFVYDgVSPEdlSQACLeLTVWDHDKLSSNDFLGGV 117
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 68-178 2.20e-07

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


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 50.34  E-value: 2.20e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSLyvadENRELAlvQTKTIKKtLNPKWNEEFYFRVNPSN---HRLLFEVFDENRLTRDDFLGQvdVPLSHLPTe 144
Cdd:cd08383    19 DPYCTVSL----DQVEVA--RTKTVEK-LNPFWGEEFVFDDPPPDvtfFTLSFYNKDKRSKDRDIVIGK--VALSKLDL- 88

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 578832411  145 dptmerpYTFKD--FLLRPRSHKSRVKGFLRLKMAY 178
Cdd:cd08383    89 -------GQGKDewFPLTPVDPDSEVQGSVRLRARY 117
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 68-139 3.97e-07

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


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 49.74  E-value: 3.97e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578832411   68 DPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENRLTRDDFLGQVDVPLS 139
Cdd:cd08393    38 DPYVKT--YLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREELPtrvLNLSVWHRDSLGRNSFLGEVEVDLG 110
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 57-176 3.99e-07

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 50.47  E-value: 3.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   57 KITKCE----SDNSNDPYVKLSLYVAdeNRELALVQTKTIKKTLNPKWNEEFYFRV--NPSNHRLLFEVFDE-------- 122
Cdd:cd04010     5 RVIECSdlalKNGTCDPYASVTLIYS--NKKQDTKRTKVKKKTNNPQFDEAFYFDVtiDSSPEKKQFEMPEEdaeklelr 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  123 ------NRLTRDDFLGQVDVPLSHLPTEDPTMERPYtfkdfLLRPRSHKSRVK----------GFLRLKM 176
Cdd:cd04010    83 vdlwhaSMGGGDVFLGEVRIPLRGLDLQAGSHQAWY-----FLQPREEKSTPPgtrsskdnslGSLRLKI 147
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 58-132 4.07e-07

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


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 49.95  E-value: 4.07e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   58 ITKCESDNSNDPYVKLSlyvaDENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR-LLFEVFDENRLTRDDFLG 132
Cdd:cd04043    13 LKADSSNGLSDPYVTLV----DTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLwISATVWDRSFVGKHDLCG 84
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 58-151 4.58e-07

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


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 49.66  E-value: 4.58e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   58 ITKC-------ESDNSNDPYVKLSLYVADENRelalVQTKTIKKTLNPKWNEEF-YFRVNPS---NHRLLFEVFDENRLT 126
Cdd:cd08388    22 IIECrdlpamdEQSGTSDPYVKLQLLPEKEHK----VKTRVLRKTRNPVYDETFtFYGIPYNqlqDLSLHFAVLSFDRYS 97

                          90       100
                  ....*....|....*....|....*...
gi 578832411  127 RDDFLGQVDVPLSHLPTEDP---TMERP 151
Cdd:cd08388    98 RDDVIGEVVCPLAGADLLNEgelLVSRE 125
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 69-141 8.06e-07

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


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 48.75  E-value: 8.06e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 578832411   69 PYVKLSLyvadeNRELaLVQTKTIKKTLNPKWNEEFYFRV-NPSNHRLLFEVFDEnRLTRDDFLGQVDVPLSHL 141
Cdd:cd04052    15 PYAELYL-----NGKL-VYTTRVKKKTNNPSWNASTEFLVtDRRKSRVTVVVKDD-RDRHDPVLGSVSISLNDL 81
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 68-145 8.39e-07

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


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 49.19  E-value: 8.39e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578832411   68 DPYVKLSLyvaDENRelaLVQTKTIKKTLNPKWNEEFYFRVNpSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTED 145
Cdd:cd04014    36 DPYVSIDV---DDTH---IGKTSTKPKTNSPVWNEEFTTEVH-NGRNLELTVFHDAAIGPDDFVANCTISFEDLIQRG 106
WW smart00456
Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds ...
 575-625 8.52e-07

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.


Pssm-ID: 197736 [Multi-domain]  Cd Length: 33  Bit Score: 46.05  E-value: 8.52e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|.
gi 578832411    575 PLPPGWEERIHLDGRTFYIDHssqvlcgendtresvpsyDSKITQWEDPRL 625
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNH------------------ETKETQWEKPRE 33
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 60-141 1.94e-06

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


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 47.83  E-value: 1.94e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   60 KCESDN-SNDPYVKLSLyvadeNRELalVQTKTIKKTLNPKWNEEFYFRV------NPSNHRLLFEVFDENRLTRDDFLG 132
Cdd:cd08682    12 LCKGKSgTNDAYVIIQL-----GKEK--YSTSVKEKTTSPVWKEECSFELpgllsgNGNRATLQLTVMHRNLLGLDKFLG 84


                  ....*....
gi 578832411  133 QVDVPLSHL 141
Cdd:cd08682    85 QVSIPLNDL 93
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 89-148 2.30e-06

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: 47.25  E-value: 2.30e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   89 TKTIKKTLNPKWNEEFYFRVNP--SNHRLLFEVFDENRLTRDDFLGQVDVPLSHL----PTEDPTM 148
Cdd:cd04039    41 TSWRRHTLNPVFNERLAFEVYPheKNFDIQFKVLDKDKFSFNDYVATGSLSVQELlnaaPQPDPET 106
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 68-137 2.32e-06

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 47.19  E-value: 2.32e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411   68 DPYVKLSlyVADENRelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLL-----FEVFDENRLTRDDFLG--QVDVP 137
Cdd:cd04011    22 DPVVKVE--VGGQKK-----YTSVKKGTNCPFYNEYFFFNFHESPDELFdkiikISVYDSRSLRSDTLIGsfKLDVG 91
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 62-150 2.43e-06

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


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 47.82  E-value: 2.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   62 ESDNSNDPYVKLSLyVADENRElalVQTKTIKK--TLNPKWNEEFYFRVNPS---NHRLLFEVFDENRLTRDDFLGQVDV 136
Cdd:cd04029    32 EAKKRSNPYVKTYL-LPDKSRQ---SKRKTSIKrnTTNPVYNETLKYSISHSqleTRTLQLSVWHYDRFGRNTFLGEVEI 107

                          90
                  ....*....|....
gi 578832411  137 PLSHLPTEDPTMER 150
Cdd:cd04029   108 PLDSWNFDSQHEEC 121
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 21-133 2.49e-06

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: 47.54  E-value: 2.49e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDIFGASfcsiavelffgrdirkitkcesdnsnDPYVKLSL-YVADENRElalvqtKTIKKTLNPK 99
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKS--------------------------DPYLKIKLgKKKINDRD------NYIPNTLNPV 48

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 578832411  100 WNEEFYFRVN-PSNHRLLFEVFDENRLTRDDFLGQ 133
Cdd:cd04037    49 FGKMFELEATlPGNSILKISVMDYDLLGSDDLIGE 83
WW pfam00397
WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds ...
 576-623 2.89e-06

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.


Pssm-ID: 459800 [Multi-domain]  Cd Length: 30  Bit Score: 44.42  E-value: 2.89e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 578832411   576 LPPGWEERIHLDGRTFYIDHSsqvlcgendTREsvpsydskiTQWEDP 623
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHE---------TGE---------TQWEKP 30
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 63-146 4.14e-06

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


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 46.92  E-value: 4.14e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   63 SDNSNDPYVKLSL--YVAdenrelalvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLfEVFDENRLT-RDDFLGQVDVPLS 139
Cdd:cd08378    13 PANSNDPVVEVKLgnYKG---------STKAIERTSNPEWNQVFAFSKDRLQGSTL-EVSVWDKDKaKDDFLGGVCFDLS 82


                  ....*..
gi 578832411  140 HLPTEDP 146
Cdd:cd08378    83 EVPTRVP 89
WW cd00201
Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; ...
 577-625 4.36e-06

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.


Pssm-ID: 238122 [Multi-domain]  Cd Length: 31  Bit Score: 44.06  E-value: 4.36e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 578832411  577 PPGWEERIHLDGRTFYIDHssqvlcgendtresvpsyDSKITQWEDPRL 625
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNH------------------NTKETQWEDPRE 31
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 65-131 6.18e-06

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 46.29  E-value: 6.18e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578832411   65 NSNDPYVKLSLYVADENRELAlvQTKTIKKTLNPKWNEEFYFRVN--PSNHRLLFEVFDENRLTRDDFL 131
Cdd:cd08685    30 GTCNSYVKISLSPDKEVRFRQ--KTSTVPDSANPLFHETFSFDVNerDYQKRLLVTVWNKLSKSRDSGL 96
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 97-144 1.11e-05

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


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 45.79  E-value: 1.11e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 578832411   97 NPKWNEEFYFRVNPSN----HRLLFEVFDENRLTRDDFLGQVDVPLSHLPTE 144
Cdd:cd04049    46 NPEWNEKFKFTVEYPGwggdTKLILRIMDKDNFSDDDFIGEATIHLKGLFEE 97
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
64-155 1.77e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 48.99  E-value: 1.77e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   64 DNSNDPYVKLSLyvadENRELAlvQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPT 143
Cdd:COG5038   456 NGTVDPYITVTF----SDRVIG--KTRVKKNTLNPVWNETFYILLNSFTDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQ 529

                          90
                  ....*....|..
gi 578832411  144 EDPTMERPYTFK 155
Cdd:COG5038   530 NPVKKNELYEFL 541
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 67-136 5.82e-05

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: 44.04  E-value: 5.82e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578832411   67 NDPYVKLSLYVadENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENRLTRDDFLGQVDV 136
Cdd:cd08403    35 SDPYVKVSLMC--EGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVDnvsLIIAVVDYDRVGHNELIGVCRV 105
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 68-141 6.01e-05

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


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 43.44  E-value: 6.01e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578832411   68 DPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNP----SNHRLLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd08381    34 DPYVKT--YLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPvedlQQRVLQVSVWSHDSLVENEFLGGVCIPLKKL 109
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 56-133 6.21e-05

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


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 43.96  E-value: 6.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   56 RKITKCESDNSNDPYVKLSLYVADENrelaLVQTKT-IKK-TLNPKWNEEFYFRVnPS----NHRLLFEVFDENRLTRDD 129
Cdd:cd08404    25 RHLPKMDVSGLADPYVKVNLYYGKKR----ISKKKThVKKcTLNPVFNESFVFDI-PSeeleDISVEFLVLDSDRVTKNE 99


                  ....
gi 578832411  130 FLGQ 133
Cdd:cd08404   100 VIGR 103
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 66-139 9.18e-05

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 43.02  E-value: 9.18e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578832411   66 SNDPYVKlslyVADENRElalVQTKTIKKTLNPKWNEEFYF-RVN-PSNHRLLFEVFDENRLTRDDFLGQVDVPLS 139
Cdd:cd04032    47 STDGYVK----VFFGGQE---KRTEVIWNNNNPRWNATFDFgSVElSPGGKLRFEVWDRDNGWDDDLLGTCSVVPE 115
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 89-149 1.03e-04

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 42.68  E-value: 1.03e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578832411   89 TKTIKKTLNPKWN-EEFYFRVNP---SNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTME 149
Cdd:cd08688    36 TDVVKKSLNPVWNsEWFRFEVDDeelQDEPLQIRVMDHDTYSANDAIGKVYIDLNPLLLKDSVSQ 100
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 21-132 1.70e-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: 43.01  E-value: 1.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   21 ILRVKVVSGIDLAKKDifgaSFCSIAVELFFGRDIRKITkcesdnsnDPYVKLSLyvADENrelalVQTKTIKKTLNPKW 100
Cdd:cd04018     1 RFIFKIYRAEDLPQMD----SGIMANVKKAFLGEKKELV--------DPYVEVSF--AGQK-----VKTSVKKNSYNPEW 61

                          90       100       110
                  ....*....|....*....|....*....|....
gi 578832411  101 NEEFYFRVN-PS-NHRLLFEVFDENRLTRDDFLG 132
Cdd:cd04018    62 NEQIVFPEMfPPlCERIKIQIRDWDRVGNDDVIG 95
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
 68-177 3.10e-04

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 42.01  E-value: 3.10e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   68 DPYVKLSlyVADENRELALVQ--------TKTIKKTLNPKW-NEEFYFRVNPSNhRLLFEV---FDENRLTRDDFLGQVD 135
Cdd:cd08691    22 DPYVKIS--IQPGKRHIFPALphhgqecrTSIVENTINPVWhREQFVFVGLPTD-VLEIEVkdkFAKSRPIIRRFLGKLS 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 578832411  136 VPLSHLPTEDPTMERPYTFKdflLRPRSHKSRVKGFLRLKMA 177
Cdd:cd08691    99 IPVQRLLERHAIGDQELSYT---LGRRTPTDHVSGQLTFRFE 137
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 97-174 4.91e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 41.06  E-value: 4.91e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   97 NPKWNEEFYFRVNPS----NHRLL-FEVFDENRLTRDDFLGQVDVPLSHLPtEDPTMERPYTFKDFLLRPRShkSRVKGF 171
Cdd:cd04051    46 NPTWNETLRFPLDERllqqGRLALtIEVYCERPSLGDKLIGEVRVPLKDLL-DGASPAGELRFLSYQLRRPS--GKPQGV 122


                  ...
gi 578832411  172 LRL 174
Cdd:cd04051   123 LNF 125
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 68-141 5.59e-04

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: 41.09  E-value: 5.59e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 578832411   68 DPYVKLSLyvadenRELALvQTKTIKKTLNPKWNEEFYFRVNPSNHR---LLFEVFDENRLTRDDFLGQVDVPLSHL 141
Cdd:cd08373    16 DRIAKVTF------RGVKK-KTRVLENELNPVWNETFEWPLAGSPDPdesLEIVVKDYEKVGRNRLIGSATVSLQDL 85
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 54-178 5.80e-04

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 40.69  E-value: 5.80e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   54 DIRKITKcesdnsNDPYVKLSlyVADENRelalvQTKTIKKT-LNPKWNEEFYFRVNPS-NHRLLFEVFDENRlTRDDFL 131
Cdd:cd08681    15 NKRKLDK------QDPYCVLR--IGGVTK-----KTKTDFRGgQHPEWDEELRFEITEDkKPILKVAVFDDDK-RKPDLI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 578832411  132 GQVDVPLShlptedPTMERpYTFKDFLlrPRSHKSRVKGFLRLKMAY 178
Cdd:cd08681    81 GDTEVDLS------PALKE-GEFDDWY--ELTLKGRYAGEVYLELTF 118
PHA03247 PHA03247
large tegument protein UL36; Provisional
 345-528 6.38e-04

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 44.16  E-value: 6.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  345 PDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGeeptpsvayvHTTPGLPSGWEERKDAK 424
Cdd:PHA03247 2589 PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPH----------PPPTVPPPERPRDDPAP 2658

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411  425 GRtyyVNHNNRTTTWTRPimqlaedgASGSATnsnnhliePQIRRPRSLSSPTVTLSAplegakdspvrravkdtLSNPQ 504
Cdd:PHA03247 2659 GR---VSRPRRARRLGRA--------AQASSP--------PQRPRRRAARPTVGSLTS-----------------LADPP 2702

                         170       180
                  ....*....|....*....|....
gi 578832411  505 SPQPSPynSPKPQHKVTQSFLPPG 528
Cdd:PHA03247 2703 PPPPTP--EPAPHALVSATPLPPG 2724
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 61-134 7.85e-04

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: 40.60  E-value: 7.85e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   61 CESDNSNDPYVKLSLyvADENRElalvqTKTIKKTLNPKWNEEFYFrvnpsNHRLLF---------------EVFDENRL 125
Cdd:cd04017    16 ADKSGLSDPFARVSF--LNQSQE-----TEVIKETLSPTWDQTLIF-----DEVELYgspeeiaqnpplvvvELFDQDSV 83


                  ....*....
gi 578832411  126 TRDDFLGQV 134
Cdd:cd04017    84 GKDEFLGRS 92
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 69-148 1.83e-03

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 39.68  E-value: 1.83e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   69 PYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVF-DENRLTRDDFLGQVDVPLSHLPTEDPT 147
Cdd:cd04028    53 PYVKV--YLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSPTGKTLQVIVWgDYGRMDKKVFMGVAQILLDDLDLSNLV 130


                  .
gi 578832411  148 M 148
Cdd:cd04028   131 I 131
C2D_MCTP_PRT_plant cd08379
C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 87-143 2.07e-03

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 176025 [Multi-domain]  Cd Length: 126  Bit Score: 39.31  E-value: 2.07e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 578832411   87 VQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLT------RDDFLGQVDVPLSHLPT 143
Cdd:cd08379    37 VRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFDNSQSHwkeavqPDVLIGKVRIRLSTLED 99
PLN02952 PLN02952
phosphoinositide phospholipase C
 59-141 5.11e-03

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 40.75  E-value: 5.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578832411   59 TKCESDNSNDPYVKLslYVADENRELALVQTKTIKKTLNPKWNEEFYFRVN-PSNHRLLFEVFDENRLTRDDFLGQVDVP 137
Cdd:PLN02952  489 THFDSYSPPDFYTKM--YIVGVPADNAKKKTKIIEDNWYPAWNEEFSFPLTvPELALLRIEVREYDMSEKDDFGGQTCLP 566


                  ....
gi 578832411  138 LSHL 141
Cdd:PLN02952  567 VSEL 570
C2A_Munc13 cd08394
C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 89-142 5.39e-03

C2 domain first repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176040 [Multi-domain]  Cd Length: 127  Bit Score: 38.20  E-value: 5.39e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 578832411   89 TKTIKKTLnPKWNEEFYFRVNPSNHRLLFEVFDENrLTRDDFLGQVDVPLSHLP 142
Cdd:cd08394    35 TIAVRGSQ-PCWEQDFMFEINRLDLGLVIELWNKG-LIWDTLVGTVWIPLSTIR 86
 
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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