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P97814 (PPIP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proline-serine-threonine phosphatase-interacting protein 1

Short name=PEST phosphatase-interacting protein 1
Gene names
Name:Pstpip1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton. Cell projectionlamellipodium. Cell projectionuropodium By similarity. Cytoplasmperinuclear 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

Tissue specificity

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

Developmental stage

Highly expressed in the day 7 embryo (E7). Ref.1

Domain

The FCH domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod By similarity.

Post-translational modification

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

Sequence similarities

Contains 1 FCH domain.

Contains 1 SH3 domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 415415Proline-serine-threonine phosphatase-interacting protein 1
PRO_0000058540

Regions

Domain5 – 8278FCH
Domain358 – 41558SH3
Coiled coil94 – 13340 Potential
Coiled coil162 – 21554 Potential

Amino acid modifications

Modified residue3441Phosphotyrosine; by ABL1

Experimental info

Mutagenesis3441Y → F: Complete loss of protein phosphorylation. Ref.3 Ref.4 Ref.5
Mutagenesis3671Y → F: No effect on phosphorylation. Ref.3 Ref.4 Ref.5
Sequence conflict3011I → V in AAH96761. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P97814 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 16C0329284D2739C

FASTA41547,590
        10         20         30         40         50         60 
MMAQLQFRDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDVE ELLRQRAQAE ERYGKELVQI 

        70         80         90        100        110        120 
ARKAGGQTEM NSLRTSFDSL KQQTENVGSA HIQLALALRE ELRSLEEFRE RQKEQRKKYE 

       130        140        150        160        170        180 
AIMDRVQKSK LSLYKKTMES KKAYDQKCRD ADDAEQAFER VSANGHQKQV EKSQNKAKQC 

       190        200        210        220        230        240 
KESATEAERV YRQNIEQLER ARTEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHCNQLSM 

       250        260        270        280        290        300 
QCVKDDELYE EVRLTLEGCD VEGDINGFIQ SKSTGREPPA PVPYQNYYDR EVTPLIGSPS 

       310        320        330        340        350        360 
IQPSCGVIKR FSGLLHGSPK TTPSAPAAST ETLTPTPERN ELVYASIEVQ ATQGNLNSSA 

       370        380        390        400        410 
QDYRALYDYT AQNSDELDIS AGDILAVILE GEDGWWTVER NGQRGFVPGS YLEKL 

« Hide

References

« Hide 'large scale' references
[1]"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.
[2]"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].
Strain: C57BL/6NCr.
Tissue: Hematopoietic stem cell.
[3]"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.
[4]"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.
[5]"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.
[6]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U87814 mRNA. Translation: AAB48483.1.
BC096761 mRNA. Translation: AAH96761.1.
RefSeqNP_035323.2. NM_011193.2.
UniGeneMm.2534.

3D structure databases

ProteinModelPortalP97814.
SMRP97814. Positions 7-285, 326-415.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202439. 2 interactions.
IntActP97814. 6 interactions.
MINTMINT-444743.
STRING10090.ENSMUSP00000055823.

PTM databases

PhosphoSiteP97814.

Proteomic databases

PaxDbP97814.
PRIDEP97814.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000059206; ENSMUSP00000055823; ENSMUSG00000032322.
GeneID19200.
KEGGmmu:19200.
UCSCuc009psv.2. mouse.

Organism-specific databases

CTD9051.
MGIMGI:1321396. Pstpip1.

Phylogenomic databases

eggNOGNOG303711.
GeneTreeENSGT00730000110901.
HOGENOMHOG000294218.
HOVERGENHBG052960.
InParanoidP97814.
KOK12804.
OrthoDBEOG7BCNBS.
PhylomeDBP97814.
TreeFamTF313677.

Gene expression databases

BgeeP97814.
GenevestigatorP97814.

Family and domain databases

InterProIPR001060. FCH_dom.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PfamPF00611. FCH. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS50133. FCH. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio295916.
PROP97814.
SOURCESearch...

Entry information

Entry namePPIP1_MOUSE
AccessionPrimary (citable) accession number: P97814
Secondary accession number(s): Q4V9R4
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot