2IWL,2AR5


Conserved Protein Domain Family
PX_PI3K_C2_alpha

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cd07289: PX_PI3K_C2_alpha 
Click on image for an interactive view with Cn3D
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.
Statistics
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PSSM-Id: 132822
View PSSM: cd07289
Aligned: 5 rows
Threshold Bit Score: 229.818
Threshold Setting Gi: 118137305
Created: 15-Jan-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphoinosit..
Conserved site includes 6 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
  • Comment:The PX domain of PI3K-C2alpha preferentially binds phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2).
  • 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                                             ###                       ##             #  
2IWL_X         22 EVSVFTYHKKynpDKHYIYVVRILREGQIePSFVFRTFDEFQELHNKLSIIFPLWKLPGFPNRMVLGRthikDVAAKRKI 101  human
2AR5_A          7 EVSVFTYHKKynpDKHYIYVVRILREGQIePSFVFRTFDEFQELHNKLSIIFPLWKLPGFPNRMVLGRthikDVAAKRKI 86   human
XP_421003    1430 QVSVFTYQKRynpDKHYIYVVRVLREGQAePTFVFRTFDEFQELHNKLGILFPLWKLPGFPNKMVLGRthikDVAAKRKV 1509 chicken
CAK10814     1462 DASVFSFQKRynpDKHYTYVIRILREGQSePQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRthikDVASKRKV 1541 zebrafish
NP_001128289 1427 EATIFTYHKRynpDKYYIYVVRVVREGQDnSAFIFRTFDEFQELHNKLSILFPLWKLPGFPSKVVLGRthikEVAAKRKV 1506 western clawe...
Feature 1                                      
2IWL_X        102 ELNSYLQSLMNAstDVAECDLVCTFFHPL 130  human
2AR5_A         87 ELNSYLQSLMNAstDVAECDLVCTFFHGS 115  human
XP_421003    1510 ELNSYIQSLMNSspEVAECDLVYTFFHPL 1538 chicken
CAK10814     1542 ELNSYVHNLMRSstEVAQCDLIYTFFHPI 1570 zebrafish
NP_001128289 1507 ELNSYIQSLMGStpEVAECDLIYTFFHPL 1535 western clawed frog

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