Conserved Protein Domain Family
PX_PI3K_C2_gamma

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cd06896: PX_PI3K_C2_gamma 
The phosphoinositide binding Phox Homology Domain of the Gamma 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 gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. 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: 132806
Aligned: 3 rows
Threshold Bit Score: 194.359
Created: 10-Jul-2008
Updated: 2-Oct-2020
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:
Feature 1                                     ###                      ##           #          
O75747    1206 ERAILGFSKKSSNLYLIQVTHSNNETSLTEKSFEQFSKLHSQLQKQFASLTLPEFPHWWHLPFTNSDHRRFRDLNHYMEQ 1285 human
XP_416412 1178 RATILGFNKKSDYLYLVQVVQTCSLVTFVEKSFDQFSELHSNLQKQFPSHALPEFPHSWHIPFTDLEHKRVKDLNLYLKQ 1257 chicken
NP_997566 1268 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 1347 house mouse
Feature 1                           
O75747    1286 ILNVshEVTNSDCVLSFFLSE 1306 human
XP_416412 1258 LLSGsrKLANNELVLSFFLNW 1278 chicken
NP_997566 1348 VLRGsyEVANSDCVLSFFLSE 1368 house mouse

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