P97814 (PPIP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 101. History...
Names and origin
|Protein names||Recommended name:|
Proline-serine-threonine phosphatase-interacting protein 1
Short name=PEST phosphatase-interacting protein 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||415 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allow PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation. Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has a role in innate immunity and the inflammatory response. Recruited to inflammasomes by MEFV. Induces formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to bind to PYCARD and facilitates pyroptosome formation. Regulates endocytosis and cell migration in neutrophils. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6
Homodimer. Homotrimer. Interacts (via coiled-coil domain) with CD2AP, PTPN12 and PTPN18. Interacts (via SH3 domain) with ABL1 and WAS. Interacts (via SH3 and coiled-coil domains) with MEFV (via B-box zinc finger); the interaction allows binding of MEFV to PYCARD and facilitates formation of PYCARD pyroptosomes. Interacts with DNM2 and FASLG By similarity. Interacts with CD2. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6
Cytoplasm. Cytoplasm › cytoskeleton. Cell projection › lamellipodium. Cell projection › uropodium By similarity. Cytoplasm › perinuclear region. Cleavage furrow. Note: During interphase, colocalizes with F-actin in the cortical cytoskeleton, lamellipodia, and stress fibers. In dividing cells, colocalizes with the F-actin rich cytokinetic cleavage furrow. Colocalized with WAS to filamentous structures within the cytoplasm. Colocalized with PTPN12 in the cytoplasm and the perinuclear region. Colocalized with CD2AP and WAS in the actin cytoskeleton. Colocalized with CD2, CD2AP and WAS at the site of T-cell:APC contact. In monocytes, forms a branched filamentous network in the cytoplasm By similarity. In migrating neutrophils, localizes most strongly to the trailing edge of the uropod where it colocalizes with PIP5K1C By similarity. In transfected cells, forms relatively straight filaments radiating out from the nucleus By similarity. Colocalizes with MEFV, particularly at the branch point of filaments By similarity. Filament formation requires an intact tubulin cytoskeleton By similarity. Ref.1 Ref.3 Ref.5 Ref.6
Highly expressed in adult lung and spleen, and weakly expressed in testis, muscle, kidney, brain and heart. Highly expressed in spleen and thymus, moderately in lung, brain and muscle, and weakly expressed in heart and liver (at protein level). Ref.1 Ref.5
Highly expressed in the day 7 embryo (E7). Ref.1
The FCH domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod By similarity.
Dephosphorylated on Tyr-344 by PTPN18, this event negatively regulates the association of PSTPIP1 with SH2 domain-containing proteins as tyrosine kinase. Phosphorylation of Tyr-344 is probably required for subsequent phosphorylation at other tyrosine residues. Phosphorylation is induced by activation of the EGFR and PDGFR in a ABL1 dependent manner. The phosphorylation regulates the interaction with WAS and with MEFV. Ref.1 Ref.3 Ref.4 Ref.5
Contains 1 FCH domain.
Contains 1 SH3 domain.
|Biological process||Cell adhesion|
|Cellular component||Cell projection|
|Technical term||Complete proteome|
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: UniProtKB-KW
|Cellular_component||actomyosin contractile ringcleavage furrowlamellipodium|
Inferred from electronic annotation. Source: UniProtKB-SubCellperinuclear region of cytoplasm
Inferred from electronic annotation. Source: UniProtKB-SubCellstress fiber
|Molecular_function||actin bindingprotein phosphatase binding|
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 415||415||Proline-serine-threonine phosphatase-interacting protein 1||PRO_0000058540|
|Domain||5 – 82||78||FCH|
|Domain||358 – 415||58||SH3|
|Coiled coil||94 – 133||40||Potential|
|Coiled coil||162 – 215||54||Potential|
Amino acid modifications
|Modified residue||344||1||Phosphotyrosine; by ABL1|
|Mutagenesis||344||1||Y → F: Complete loss of protein phosphorylation. Ref.3 Ref.4 Ref.5|
|Mutagenesis||367||1||Y → F: No effect on phosphorylation. Ref.3 Ref.4 Ref.5|
|Sequence conflict||301||1||I → V in AAH96761. Ref.2|
|||"PSTPIP: a tyrosine phosphorylated cleavage furrow-associated protein that is a substrate for a PEST tyrosine phosphatase."|
Spencer S., Dowbenko D., Cheng J., Li W., Brush J., Utzig S., Simanis V., Lasky L.A.
J. Cell Biol. 138:845-860(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PTPN18, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Hematopoietic stem cell.
|||"Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated protein."|
Wu Y., Spencer S.D., Lasky L.A.
J. Biol. Chem. 273:5765-5770(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH WAS, SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF TYR-344 AND TYR-367.
|||"Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation."|
Cong F., Spencer S., Cote J.F., Wu Y., Tremblay M.L., Lasky L.A., Goff S.P.
Mol. Cell 6:1413-1423(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ABL1, PHOSPHORYLATION, MUTAGENESIS OF TYR-344 AND TYR-367.
|||"PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-PEST toward a specific dephosphorylation of WASP."|
Cote J.-F., Chung P.L., Theberge J.-F., Halle M., Spencer S., Lasky L.A., Tremblay M.L.
J. Biol. Chem. 277:2973-2986(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PTPN12, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, MUTAGENESIS OF TYR-344 AND TYR-367.
|||"The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse."|
Badour K., Zhang J., Shi F., McGavin M.K.H., Rampersad V., Hardy L.A., Field D., Siminovitch K.A.
Immunity 18:141-154(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CD2; CD2AP AND WAS, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|U87814 mRNA. Translation: AAB48483.1.|
BC096761 mRNA. Translation: AAH96761.1.
|RefSeq||NP_035323.2. NM_011193.2. |
3D structure databases
|SMR||P97814. Positions 7-285, 326-415. |
Protein-protein interaction databases
|BioGrid||202439. 2 interactions.|
|IntAct||P97814. 6 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000059206; ENSMUSP00000055823; ENSMUSG00000032322. |
|UCSC||uc009psv.2. mouse. |
|MGI||MGI:1321396. Pstpip1. |
Gene expression databases
Family and domain databases
|InterPro||IPR001060. FCH_dom. |
|Pfam||PF00611. FCH. 1 hit. |
|PRINTS||PR00452. SH3DOMAIN. |
|SMART||SM00055. FCH. 1 hit. |
SM00326. SH3. 1 hit.
|SUPFAM||SSF50044. SSF50044. 1 hit. |
|PROSITE||PS50133. FCH. 1 hit. |
PS50002. SH3. 1 hit.
|Accession||Primary (citable) accession number: P97814|
Secondary accession number(s): Q4V9R4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|