Conserved Protein Domain Family
PX_SNX4

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cd06864: PX_SNX4 
The phosphoinositide binding Phox Homology domain of Sorting Nexin 4
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.
Statistics
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PSSM-Id: 132774
View PSSM: cd06864
Aligned: 10 rows
Threshold Bit Score: 202.984
Threshold Setting Gi: 195999222
Created: 10-Jul-2008
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
phosphoinosit..
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
  • Comment:A majority of PX domain containing proteins binds phosphatidylinositol-3-phosphate (PI3P) at this site. In some cases, other phosphoinositides, such as PI4P or PI(3,4)P2, are the preferred substrates.
  • Comment:based on the structures of phosphatidylinositol-3-phosphate bound to other members of this superfamily
  • Comment:Two basic residues are key in binding with phosphoinositides: one forms hydrogen bonds with the 3-phosphate of PI(3)P and another forms hydrogen bonds with the 4-and 5-hydroxyl groups of PI(3)P.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                           ###                       ## 
gi 118093806  42 MEITVSEAEKRTGRnamnmqETYTAYLIETRAVesqne--gqcspVDSLWRRYSEFELLRNYLLVTYPHIVVPPLPEKRa 119
gi 62900919   58 IEISVSEAEKRTGRnamnmqETYTAYLIETRSIehtdg---qsvlTDSLWRRYSEFELLRSYLLVYYPHIVVPPLPEKRa 134
gi 169153748  41 MEISVAEAEKRTGKnavnmqETYTVYLIETRPVdaase--gtspvPDSLWRRYSEFELLRNYLLVTYPFVVVPPLPEKRa 118
gi 189234487  27 LEISVAESEKRANGtln-lrEFYTVYLIETKSVltdsefqnkfpkLTTVWRRYTEFEQLRGYLEVTYPYIILPPLPEKRv 105
gi 72084412   47 VEINVTEQEKRTGNaamgikDVYTVYLVETCRVkdnsniakltmdSSSLWRRYSEFELLRNYLVVTFPHVVLPPLPEKRm 126
gi 193695266  14 ASIGITEADKRMNSals-lkEYYTVYIIETKIDsetwaetkgmqkLSLATRRYTDFVTLHNHLGDKYPWVVIPPLPEKKq 92
gi 156363427  25 MILSITDSEKRASEyi---kEPFTVYLIESKYIdggppa-gdpdmSCNLWRRYSEFELLRNYLVATYPAVIVPPLPEKRi 100
gi 198434825  42 FKITVSDPEKRTKPsgikmqETFVVYLIETTPKnaess---lieeVTSLWRRYSEFELLRNYLVVIYPAVIVPPLPEKRa 118
gi 215506163  16 VEITITDTERRCAGsavplqDIYVAYQVESVIRepe-------ktPYIVWRRYSDFEVLHSHLQDSFPYVIIPPLPERKv 88
gi 195999222   1 MDITVTEPEKRVVNtdm-lkDTFMVYLVQTKCTghggpd-dfekgTHSVWRRYSEFDLLRNYFNVTYPYIIIPPIPEKKl 78
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
Feature 1                              #                              
gi 118093806 120 dfvw---hklsaDNMDPDFVERRRIGLENFLLRVASHPVLCQDKIFYSFLTQE 169
gi 62900919  135 efvw---hklsaDNMDPDFVERRRIGLENFLLRIASHPLLCRDKIFYLFLTQE 184
gi 169153748 119 efvw---hklsaDNMDPDFVERRRVGLENFLLRVASHPVLARDNIFYLFLTEE 168
gi 189234487 106 mfgw---qkissDTFDPNFVDRRRAGLENFLLRVASHPVLSWDKHFIEFLQHE 155
gi 72084412  127 mamwq--qlatvDNFDADFVERRRVALEGFLQRVAAHPLLCQDELFHGFLQDA 177
gi 193695266  93 sfmwn--seavsDTMDPDFVDRRRAGLESFLKRIAGHSEIGYDECFLKFLGEC 143
gi 156363427 101 nlsa---lrlaaDKFDPDFIEKRRTGLENFLLRCAAHGQLSQDPIFLGFLNMV 150
gi 198434825 119 nfiwn--kitatDTFDIDFLERRRAGLESFLHRIAGHRKLGKDKIVKHFITKE 169
gi 215506163  89 myrw---qklpsDRLDPDFVERRRASLELFLRRVAGHPELCTNVLFLEFLKHE 138
gi 195999222  79 psfhmswknittDTFDQDFIERRRSGLEAFLHRVAQHPTLCQDRIFHSFLQKE 131

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