Conserved Protein Domain Family
PX_IRAS

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cd06875: PX_IRAS 
The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected
The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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.
Statistics
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PSSM-Id: 132785
View PSSM: cd06875
Aligned: 13 rows
Threshold Bit Score: 183.25
Threshold Setting Gi: 156396482
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                                               ###                       ##            # 
EAW65231       14 EPAKEARVVGSELv---DTYTVYIIQVTDGshEWTVKHRYSDFHDLHEKLVAEr-kIDKNLLPPKKiIGKNSRSLVEKRE 89   human
XP_414245      12 EPLRSARVLGSELv---ETYTVYIIQVSVGnhQWTVKHRYSDFHDLHEKLVSEk-kIDKNLLPPKKiIGKNSKSLVEKRQ 87   chicken
NP_001091209    5 EGPRDIRVVGSELv---ETYTVYIIEVYVGsfQWKVKHRYSDFFDLHEKLTLEn-kVDKNLLPPKKmIGKNSKSLVEKRQ 80   African clawe...
XP_394619       8 QENVHIKIPSADTv---EGITYYCIEVRIAsiKWTVKHRYNDFAELHDKLVLEn-yVKKDILPPKKlIGNKCEAFVEKRR 83   honey bee
XP_001605947    8 QEDVQLSIPSFETt---DGVTFYVVEVKIGtvEWTVKHRYSEFAELHDTLVLDh-cVEKDILPPKKlIGNKSETFVEKRR 83   jewel wasp
NP_611017       8 HADTTVTVPKFSNesssGGVTYYDIKVRVGkvEWLVERRYRDFANLHEKLVGEi-sISKKLLPPKKlVGNKQPSFLEQRR 86   fruit fly
XP_001945341    8 CHECNIAICKAETd--tDGVTYYHIKVNVGgvTWSVQKRYNQFLELHKKLVNEh-tVTKDILPGKKiIGNKDPNFIERRR 84   pea aphid
XP_001637422    1 MKIRKIEVPAAEVi---DGYAVYYVEVFITeySWLVRKRYREFRELHDKLVKEy-hIDQSLLPPKKyFGNLDPDYIETRR 76   starlet sea a...
XP_001656018    8 SNETSISIPRIITv---DSVNYYEVLIKCGhvMWTVNRRYRDFDDLHNKLVQEr-sVAKDKLPPKKvIGNKSPTFLKKRQ 83   yellow fever ...
XP_002241912   12 LGAKTARIASAEQv---ENYTVYVIEVTAGtnTWTVRHRYSEFSELHEKLLSEk-kVDKNALPPKKlLGNMSKSFVEKRQ 87   Florida lancelet
EEC06558       12 KASEAVKIIGTEHg---EGFTVYIIQVSVApyRWTAKHRYSDFKDLHDKLTASy-hVDKALLPPKKlFGNQSEAFVQQRQ 87   black-legged ...
EEB13859        8 CDKLKITIPRVEEk---NKFTVYEIQIEVDdvKWSVFHRFRDFAQLHDVLVASh-sVAKDLLPPKKvIGNKEPTFIEKRR 83   human body louse
XP_002123643    4 KPETQVFINSVEQv---EDYTEYTIEVHHNgfMWKIKHRYSEFRKLHNALRNHnpdLEKNLLPPKKiIGKMSTSFIDKRR 80   Ciona intesti...
Feature 1                                                  
EAW65231       90 KDLEVYLQKLLAAFpg-vtPRVLAHFLHFHFYEINGITAAL 129  human
XP_414245      88 KELEVYLQTLLVKFsv-taPKVLSHFLHFHFYEINGITAAL 127  chicken
NP_001091209   81 KELEMYLQTLLGLFpl-avPRAMSSFLHFHLYEIHGIAAVL 120  African clawed frog
XP_394619      84 LSLEIYLNEVYNYLkk-amPRELAVFLDMHIYDIFFLLQSM 123  honey bee
XP_001605947   84 LGLETYLNSVYIYLkk-imPRPLAIFLELNVYEIFFLLQNL 123  jewel wasp
NP_611017      87 EQLEIYLQELLIYFrt-elPRALAEFLDFNKYDIIYLLQDL 126  fruit fly
XP_001945341   85 VGLEIYLQTVLSFLqk-smPEELLEFLEFHKYDVILIVKKL 124  pea aphid
XP_001637422   77 LLLEIYLHKLLEKFed-nlPDQLDNFLEGFKYDVCGVTYNL 116  starlet sea anemone
XP_001656018   84 EALEQYLKEMLTFLkv-tmPKEFVEFLEFHRYDIIFLSQNL 123  yellow fever mosquito
XP_002241912   88 KELEAYLQMLLEKHqd-ciPKVLERFLDFHLYEIFGVTHAL 127  Florida lancelet
EEC06558       88 AELEHYLQTLVHQFsa-glPLSLAHFLDFPKYEVRTIVDDL 127  black-legged tick
EEB13859       84 NGLENYLITVVRFLqk-tmPRELAHFLDFQYYDIQFLLYSL 123  human body louse
XP_002123643   81 EELELYLQTLMSQKfsggvPRTLGVFLDFHHYEVERLTQDL 121  Ciona intestinalis

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