Conserved Protein Domain Family
PX_SNX17_31

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cd06885: PX_SNX17_31 
The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.
Statistics
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PSSM-Id: 132795
View PSSM: cd06885
Aligned: 16 rows
Threshold Bit Score: 152.099
Threshold Setting Gi: 170582828
Created: 10-Jul-2008
Updated: 2-Oct-2020
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:
Feature 1                                           ###                        ##             #   
Q5R4A5          2 HFSIPETESrsgdsggsAYVAYNIHVNGVLHCRVRYSQLLGLREQLRKEYGan--vLPAFPPKKLFSLTp-AEVEQRREQ 78   Sumatran oran...
NP_001080742    2 HFSIPETESrsse-sgaQYLAYNIHVNGVLHCRVRYSQLLGLHEQLKKEYGnn--vVPAFPPKKLFTLTp-AEVEQRREQ 77   African clawe...
AAI62993        2 HFSIPETEVrsde-ngsSYVAYNIHVNGVLHCRVRYSQLLGLHEQIKKEYGnn--vVPAFPPKKIFTLTp-AEVDQRREQ 77   zebrafish
XP_001629235    2 HFSIPDTVEvkdr-sgsTFLAYNIHINGALHSAVRFSDLYQFNEQLKKEYGnr--iTARFPPRKILSLTa-VQVEERRDQ 77   starlet sea a...
XP_001744038    1 HLTLHRSQEerpa-qplKYVAYNIHINGTYHCSVRFSDLHKLHEKLKREFGag--aLEKFPPKNFRYMPp-EECVERRYY 76   Monosiga brev...
XP_001896306    3 HISIPTTQTlvemdgsrTYDAFDIYINGAYHASIRYSHLLKLHEKLRNHFGpk-lkTSDFPSKKLFRTLdqKALDERRLA 81   agent of lymp...
Q8N9S9          4 HFCIPVSQQrsda-lggRYVLYSVHLDGFLFCRVRYSQLHGWNEQLRRVFGn---cLPPFPPKYYLAMTt-AMADERRDQ 78   human
AAI06668        2 HICIPVTEElqdt-lgcRFVLYSVYLEGFLLFKVRYKDLHLWNEQIHRVFGn---gLPKFPPKHYLAMTk-NMANERRLQ 76   African clawe...
XP_795102     687 ILSDNGTQF--------VGAVYNVHVNGVFHCSVRYSQLHDFNEQVKKEFSnsftgYQKFPPKKFLSLTp-SQREERREK 757  purple urchin
XP_002124333    2 HFSIPDTEEieds-tgsSYKVFNVHVNGVLHCSVRYSQLHDLNNQFRKELKlk--tLPQFPPKKLLQLNd-SNLKERRVQ 77   Ciona intesti...
Feature 1                                     
Q5R4A5         79 LEKYMQAVRQDpLLGSSETFNSFLRRAQ 106  Sumatran orangutan
NP_001080742   78 LEKYMQAVRQDpVLGASETFNSFLRHSQ 105  African clawed frog
AAI62993       78 LEKYMQAVRQDpILGSSEMFNSFLRKAQ 105  zebrafish
XP_001629235   78 LEKYLQGICQDpDVANSSTFTDFLRNCQ 105  starlet sea anemone
XP_001744038   77 LQKWLQKVAQQpLICNGTTFQTFLLNAQ 104  Monosiga brevicollis MX1
XP_001896306   82 LARYFQTMVQLqSIAQHFITENAFLNFQ 109  agent of lymphatic filariasis
Q8N9S9         79 LEQYLQNVTMDpNVLRSDVFVEFLKLAQ 106  human
AAI06668       77 LEQYLQQIVTDpVVTSSDIFMDYFRKLQ 104  African clawed frog
XP_795102     758 LEKYIQIVSQDpRIANSDIFNGFLLTSQ 785  purple urchin
XP_002124333   78 LEKYIQEVSQDpMLSNSDIFNAFLRRAQ 105  Ciona intestinalis

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