Conserved Protein Domain Family
PX_PLD1

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cd07296: PX_PLD1 
The phosphoinositide binding Phox Homology domain of Phospholipase D1
The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Phospholipase D (PLD) catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine to generate membrane-bound phosphatidic acid and choline. PLDs are implicated in many cellular functions like signaling, cytoskeletal reorganization, vesicular transport, stress responses, and the control of differentiation, proliferation, and survival. PLD1 contains PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. It acts as an effector of Rheb in the signaling of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that transduces nutrients and other stimuli to regulate many cellular processes. PLD1 also regulates the secretion of the procoagulant von Willebrand factor (VWF) in endothelial cells. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of PLD1 specifically binds to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3], which enables PLD1 to mediate signals via the ERK1/2 pathway.
Statistics
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PSSM-Id: 132829
View PSSM: cd07296
Aligned: 4 rows
Threshold Bit Score: 250.997
Threshold Setting Gi: 161611818
Created: 23-Feb-2009
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 19861153    78 GCPVKAQVLEVERFTSts-----------rMPSVNLYTIELTHGEFTWQVKRKFKHFQEFHRELLKYKAFIRIPIPTKRH 146
gi 118095292   74 GCPVRVRVLEVERFTStk-----------kVPSLNVYTIELTHGEFTWHVKRKFRHFQEFHRELLRYKAFVRIPIPTRSH 142
gi 161611818   70 ALPITAKILEVERFTSaqdrfnitaqrsvsKVLPAVFKIEMKHGNFTWMVKRKEKHFMELHRELRAYKTFLRIPLPSRSH 149
gi 50414498    77 GCPIKVRVLEVERFASsss---------skAPVLNIYTIELTHGEFTWQVKRKYKHFQDLHRELLRYKAFIRIPIPIRSH 147
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
Feature 1                            ##             #                              
gi 19861153   147 TFRRQnvk-eepREMPSLPRSSEna-iqEEQFFGRRKQLEDYLTKILKMPMYRNYHATTEFLDVS 209
gi 118095292  143 TVRRQsikrgepRQMPSLPHTAEst-vrEEHFSSRRKQLEDYLSKILKMPMYRNYHGTKRFRLDI 206
gi 161611818  150 TERRQtinrnleRHMPTLPRGGGeelarEEQVSSRKRQLEDYLNKLLKMPMYRNYHATMEFIDVS 214
gi 50414498   148 TVRRQtvkrgdvRSMPNLPRNAEiv--rEEQSSSRRKQLEDYISALLKMPMYRNYHATREFIDVS 210

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