Conserved Protein Domain Family
PX_FISH

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cd06888: PX_FISH 
The phosphoinositide binding Phox Homology domain of Five SH protein
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. Five SH (FISH), also called Tks5, is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. 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: 132798
View PSSM: cd06888
Aligned: 9 rows
Threshold Bit Score: 215.75
Threshold Setting Gi: 167516036
Created: 11-Jul-2008
Updated: 2-Oct-2020
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:
Feature 1                                                             ###                         
Q5TCZ1          6 VQDATVVDVEKRr---------------nPSKHYVYIINVTWSDsTSQTIYRRYSKFFDLQMQLLDKFPIEGGQkdpkqR 70   human
AAH88911        7 IVQVCVQDVQKRr---------------sPNKHYVYIIKVTWSNgTTEVIYRRYSKFFDLQMQILDKFPVEGGQkdpkqR 71   African clawe...
XP_421741      22 KQSAMCCYYPKQsgwqlqargfhwrslyaWGFLKVYIINVTWSDlTSQIIYRRYSKFFDLQMQLLDKFPIEGGQkdpkqR 101  chicken
Q1LYG0          6 VLDVKVVDVEKRr---------------nPSKHYVYLINVTYSDsTSHIIYRRYSKFFDLQMQILDKFPIEGGQkdpkkR 70   zebrafish
XP_001624740    6 IKDVKIVDVQKRk---------------iPSKHYVYVISVTWSDgSVNVVYRRYSKFFDLQTKLLEEFPDEGGVkdpsaR 70   starlet sea a...
XP_783086       6 VVNANVTDIEKRr---------------ePTKHYVYIIHVTWSDgSVNVVYRRYSTFFDFQNKLLSKFPEEAGAnnpssR 70   purple urchin
NP_001029000    6 LKSVKVIDIEKRr---------------lPSKHYVYLIEIKWSDgSLCTVGRRFSAFFMMHMTLLEKFPLEGGQkdpsrR 70   Ciona intesti...
XP_001742359    5 VKNVTVIDYQRRr---------------aPSKHYVYVITVVWSDgSEVTIYRRYSQLFEFHTSLLDRFPEAAGAtg-eeR 68   Monosiga brev...
XP_002125414    9 ITAVNVNRAEKRr---------------vPSKHYVYVIEVSWDDgSDTVIFRRYSKFFDLQISLLETFPKEGGMkdpstR 73   Ciona intesti...
Feature 1               ##              #                               
Q5TCZ1         71 IIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPpHISQCDEVFRFFEAR 124  human
AAH88911       72 IIPFLPGKILFRRSHIRDVAVRRLIPIDEYCKALIRLPaYISQCDEVLQFFEAR 125  African clawed frog
XP_421741     102 IIPFLPGKILFRRSHVRDVAVKRLKPIDEYCRALVRLPpHISQCDEVFRFFEAR 155  chicken
Q1LYG0         71 IIPFLPGKILFRRSHVRDVAMKRLRFIDDYCRALVRLPpQISQSEEVLRFFETK 124  zebrafish
XP_001624740   71 VLPFLPGKILFGRSHVRDVAVKRKEPIQEYCSKLVELPpKISQSGLVLKFFEPK 124  starlet sea anemone
XP_783086      71 CIPFLPGKKLFGRSHIREVALKRLSPIDEYCTALVKLPgKISDSKEVINFFTPT 124  purple urchin
NP_001029000   71 ILPFLPGKILFKRSHTRDVTLKRLGSISEYCESLLLLPeHISQCDTILRFFETS 124  Ciona intestinalis
XP_001742359   69 IIPFLPGKKIFGRSHTHKVAQSRAKPIDEYLKVLISLPaELSRCDLALELFEAT 122  Monosiga brevicollis MX1
XP_002125414   74 IIPFLPGKILFRRSNIRDVAMKRVLSIGEYCKDLIKLPsYIVQHSLILDFFETK 127  Ciona intestinalis

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