Conserved Protein Domain Family
PX_SNX5

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cd07291: PX_SNX5 
The phosphoinositide binding Phox Homology domain of Sorting Nexin 5
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. SNX5, abundantly expressed in macrophages, regulates macropinocytosis, a process that enables cells to internalize large amounts of external solutes. It may also be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p. It also binds the Fanconi anaemia complementation group A protein (FANCA). SNX5 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to other sorting nexins including SNX1-2. The PX-BAR structural unit helps determine the specific membrane-targeting of some SNXs. The PX domain of SNX5 binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,4)P2. SNX5 is localized to a subdomain of early endosome and is recruited to the plasma membrane following EGF stimulation and elevation of PI(3,4)P2 levels.
Statistics
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PSSM-Id: 132824
View PSSM: cd07291
Aligned: 3 rows
Threshold Bit Score: 310.839
Threshold Setting Gi: 87244960
Created: 23-Jan-2009
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
putative
Feature 1:putative 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 10720289   29 PSLQIDIPDALSERDKVKFTVHTKTTLPTFqsPEFSVTRQHEDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQK 108
gi 213627155  25 PSLQIDIPDALSERDKVKFTVHTKTKLPNFksPDFSVTRLHEDFIWLHDSLIETEDYAGLIIPPAPAKPDFDGPREKMQK 104
gi 87244960   24 ASLLIDIPDALCERDKVKFTVHTKTTLSSFqkPDFSVPRQHEDFIWLHDAIVETEEYAGLIIPPAPPKPDFEGPREKMHK 103
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
Feature 1                                      #                              
gi 10720289  109 LGEGEGsMTKEEFAKMKQELEAEYLAVFKKTVSSHEVFLQRLSSHPVLSKDRNFHVFLEYD 169
gi 213627155 105 LGEGEGsMTKDEFSKMKQELEAEYLAVFKKTVAVHEVFLQRIASHPILCKDTNFHIFLEYD 165
gi 87244960  104 LGEGESsMTKEEYAKMKQELEAEYLAVFKKTVQVHEVFLQRLSSHPSFSKDRNFHIFLEYD 164

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