Conserved Protein Domain Family
PX_SNX19

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cd06893: PX_SNX19 
The phosphoinositide binding Phox Homology domain of Sorting Nexin 19
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. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.
Statistics
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PSSM-Id: 132803
View PSSM: cd06893
Aligned: 6 rows
Threshold Bit Score: 200.846
Threshold Setting Gi: 212507842
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 2495726    532 NLRITGTITAREHsgtgfhPYTLYTVKYEtaldgens---------------sglqqlaYHTVNRRYREFLNLQTRLEEK 596
gi 49118298   434 NLRITGTITAKEHsgtgshPYTLYTIKYDtvldsqsl---------------gslqpmaYHTVNRRYREFLNLQTRLEER 498
gi 123208197  484 NLQITKTITAKEQrsssthPYTLYTVKYEtggdsess---------------asdqpvpCHMVNRRYSEFLNLQTRLEER 548
gi 219458062  797 NVRIPKTQTAVEYkgmgtrKYTLYRVQYEttilvpmegel---------gqeavepittTMSVRRRFREFITLHVALEEN 867
gi 198424915  427 HIRIHEAVTVDEAfeg-ggRYTLYKITYFapphkqinkrrtsnfnlsnsssntmeadlkEFQVQRRFREFLTLQDRLNEK 505
gi 212507842  648 NICIPKAELVTDYk----sPHVVYTVQYDgiymvkqeqn----------pnaepefvlqTTIIKKKFMDFLHLQTKLEEN 713
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
Feature 1                              ##         #                              
gi 2495726    597 PDlrkfiknvkgPKKLFPDLPFGNmdsDRVEARKSLLESFLKQLCAIpEIANSEEVQEFLALN 659
gi 49118298   499 ADlrkfvkhikgPKKFLPELPFGNmdsDKVEARKSLLETFLKQLCAVpEVANSEEVQEFLALN 561
gi 123208197  549 TDlkkaiknvkgPKKLFPDLPFSNpdsDKVEARRSQLESFLRKLCTIpEAANSEEVQEFLALN 611
gi 219458062  868 PKfrkim-knvkGPNRLFYLPFGNmdkNTIRQRRGQLQDFLGELCSRpELCQSKELQEFLAYG 929
gi 198424915  506 QKirklm-tkirGPSRMFPMPIGNldkQYIEKRRKLLQAFMRELCSYpEISETVELRQFLAYT 567
gi 212507842  714 SNfrsi---mkgPSKWLNLYSSGK---SEEASRKGMLETFLRQICSNvEISNSPEVHEFLAYG 770

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