2NSQ,3B7Y


Conserved Protein Domain Family
C2_NEDD4_NEDD4L

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cd04033: C2_NEDD4_NEDD4L 
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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.
Statistics
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PSSM-Id: 175999
View PSSM: cd04033
Aligned: 13 rows
Threshold Bit Score: 189.872
Threshold Setting Gi: 32563663
Created: 11-Jan-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Ca2+ binding
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:Ca2+ binding site [ion binding site]
Evidence:
  • Structure:3B7Y, human Nedd4 C2 Domain with bound calcium
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                              #                                                         #
2NSQ_A         22 ILRVKVVSGIDLAKkDIFGASDPYVKLSLyvad-----enrELALVQTKTIKKTLNPKWNEEFYFRVNpsnHRLLFEVFD 96   human
3B7Y_A         21 IVRVRVIAGIGLAKkDILGASDPYVRVTLydp------mngVLTSVQTKTIKKSLNPKWNEEILFRVHpqqHRLLFEVFD 94   human
2347056        18 ILRVKIVSGTDLAKkDIFGASDPYVKLSLyvad-----enrELALVQTKTIKKTLNPKWNEEFFFRVHptnHRLLFEVFD 92   African clawe...
NP_648993      71 HLRIVVLTGQSLAKkDIFGASDPYVRIDLntin-----gdiNIDSVLTKTKKKTLNPTWNEEFIFRVKpseHKLVFQVFD 145  fruit fly
NP_490865      20 LLRVRLLRGTKLGKrDLLGVCSPYCMIRLens------ngdTVDEVQVETKKKTRNPTWNSVFTFRVTr-aCQMKILVYD 92   nematode
CAF99574        6 ILKVKVIEGIGLAKkDILGASDPYTKLSLydp------atgESNSFHTKTIKKTLDPKWNEEFFFQVDprkHRLLFEVFD 79   spotted green...
AAL87621       11 ILRVKVVSGIDLAKkDIFGASDPYVKLSLyvad-----enrELALVQTKTIKKTLNPKWNEEFYFRVNptnHRLLFEVFD 85   chicken
NP_001029358   22 ILRVKIIAGIGLAKkDILGASDPYTRISLydp------vngEITSLQTKTIKKTLDPKWNEEFFFRVHprrHRLLLEVFD 95   zebrafish
XP_001638134   32 ILRVKVVAGIDLAKkDIFGLSDPYCKIRLfrgd----rtagEIDSITTETIKKTLTPKWNEEFLFRVNpidNRLLFEVFD 107  starlet sea a...
XP_002125074   18 LVRIQVLSGHNLAKkDIFGASDPYVSVSLykpkrsasgsskTITCVNTKTKKRTLNPSWNEKFLFRVVpreNRLLFEVFD 97   Ciona intesti...
EEC15222       18 LLRLRIVAGHSLAKkDIFGASDPYVRIDLvkakg---dgytVLDSLYTKTKKKTLHPKWDEEFVIKVDpqeHKIIMEVFD 94   black-legged ...
XP_002161041   39 ILRVKILKGTNLAKkDIFGLSDPYCVIKLfdrr-----ranLVTKLQTNVQKKTLNPQWNCSFYLRVNtlnHKLLLELFD 113  green hydra
CAZ36865       32 LLRVRVIRALDLMKkDIFGASDPYCKLCIyktqr---stlpLCSPVPTKTVKRSLNPIWNEEFIFRVNpseNRLVFELYD 108  Schistosoma m...
Feature 1          #    #                                                     
2NSQ_A         97 ENRLTRDDFLGQVDVPLSHLPTEdptme-rpytFKDFLLr-PRSHKSRVKGFLRLKMAYM 154  human
3B7Y_A         95 ENRLTRDDFLGQVDVPLYPLPTEnprle-rpytFKDFVLh-PRSHKSRVKGYLRLKMTYL 152  human
2347056        93 ENRLTRDDFLGQVDVPLNHLPTEdptme-rpytFKDFLLr-PRSHKSRVKGFLRLKMAYL 150  African clawed frog
NP_648993     146 ENRLTRDDFLGMVELTLVNLPTEqegrtigeqsYTLRPRr-SVGAKSRIKGTLRIYHAFI 204  fruit fly
NP_490865      93 ENRLRKDVLMGFVSRTLNDGLITtqa-----pnPEEYALqsGTASKGKSIGSLFLSFHFM 147  nematode
CAF99574       80 ENRLGIALSADYAALPQLSSVFIpgvna-ggctKKSVLQi-SLQPRGKVGAELEASTEDG 137  spotted green pufferfish
AAL87621       86 ENRLTRDDFLGQVDVPLSHLPTEdpsme-rpytFKDFLLr-PRSHKSRVKGFLRLKMAYM 143  chicken
NP_001029358   96 ENRLTRDDFLGQVDVPLHQIPTEhpnne-rpytFKDFLLh-PRSHKSRVKGHLRLKMTYL 153  zebrafish
XP_001638134  108 ENRLTRDDFLGEVEIPSLGSYPTerrn--vrilDKDYRLr-KRSERSRVKGHLRLRLSFL 164  starlet sea anemone
XP_002125074   98 ENRLTRDDFLGQVDIPINASYISndde--tgtpHREFPLr-PRSSKSRVKGHLRLKLSYA 154  Ciona intestinalis
EEC15222       95 ENRLTRDDFLGLVELSLAGLPVEqpgr---hipHKYYLLr-RRSNKSRVKGHLQVYHAFL 150  black-legged tick
XP_002161041  114 ENRITRDDFLGEVEIPLNNLPNEgneqdiervaTKDYILq-QRSAKSHVRGNIRVYIAVV 172  green hydra
CAZ36865      109 ENRITRDDFLGVVTVFLPYLEIGtegsn-crlmAKSFLLr-PRSSRSRVRGNLHLYLAYL 166  Schistosoma mansoni

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