Conserved Protein Domain Family
PX_RICS_like

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cd07278: PX_RICS_like 
The phosphoinositide binding Phox Homology domain of PX-RICS-like proteins
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this family include PX-RICS, TCGAP (Tc10/Cdc42 GTPase-activating protein), and similar proteins. They contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. They act as Rho GTPase-activating proteins. PX-RICS is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. The PX domain of PX-RICS specifically binds phosphatidylinositol 3-phosphate (PI3P), PI4P, and PI5P. TCGAP is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. 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: 132811
View PSSM: cd07278
Aligned: 4 rows
Threshold Bit Score: 186.929
Threshold Setting Gi: 68846537
Created: 13-Jan-2009
Updated: 17-Jan-2013
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:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                         ###                         ##  
gi 68846537    56 NVDFGHIQLLLSpdreg-----pslsgENELVFGVQVTCQGRsWPVLRSYDDFRSLDAHLHRCIFDRRFSCLPELPPPPE 130
gi 219432261   14 YVDIGQLQVAMGdespdplkhngvpepHKDTLYLVSVECQGKcWTVQHSYEDFRFLDKHLHSCIYDRKFSQLTELPKGEA 93
gi 212511218   69 HVEIGSLQVVIIddgslk----syknsGEEKWWSLNVQSQNKsWLVKRSYDNFKMLDKQLHQCIYDRKFSELMELPEECI 144
gi 206558298  127 NVEFGSIQLSLSeeqnev---mkngceSKELVYLVQIACQGKsWIVKRSYEDFRVLDKHLHLCIYDRRFSQLTELPRSDV 203
                          90       100       110
                  ....*....|....*....|....*....|....*...
Feature 1                #                              
gi 68846537   131 garAAQMLVPLLLQYLETLSGLVDSNLNCGPVLTWMEL 168
gi 219432261   94 mkeNIQAVKQVLSRYLARLSQITGNLLNCGPVLNWLEL 131
gi 212511218  145 e--EQENLHKVLSDYMKRFSSIAGNLINCGPILNWLEL 180
gi 206558298  204 lkdSPESVTQMLTAYLSRLSTIAGNKINCGPALTWMEI 241

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