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Protein

Proline-serine-threonine phosphatase-interacting protein 1

Gene

Pstpip1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

GO - Molecular functioni

  • actin binding Source: MGI
  • protein phosphatase binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell adhesion, Endocytosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_317454. The NLRP3 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Proline-serine-threonine phosphatase-interacting protein 1
Short name:
PEST phosphatase-interacting protein 1
Gene namesi
Name:Pstpip1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1321396. Pstpip1.

Subcellular locationi

  • 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).By similarity

GO - Cellular componenti

  • actomyosin contractile ring Source: MGI
  • cleavage furrow Source: MGI
  • lamellipodium Source: UniProtKB-SubCell
  • membrane Source: MGI
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • stress fiber Source: MGI
  • uropod Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi344 – 3441Y → F: Complete loss of protein phosphorylation. 3 Publications
Mutagenesisi367 – 3671Y → F: No effect on phosphorylation. 3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 415415Proline-serine-threonine phosphatase-interacting protein 1PRO_0000058540Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei344 – 3441Phosphotyrosine; by ABL11 Publication

Post-translational modificationi

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.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP97814.
PRIDEiP97814.

PTM databases

PhosphoSiteiP97814.

Expressioni

Tissue specificityi

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).2 Publications

Developmental stagei

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

Gene expression databases

BgeeiP97814.
GenevisibleiP97814. MM.

Interactioni

Subunit structurei

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.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Abl1P005205EBI-7484574,EBI-914519
Ptpn12P358315EBI-7484574,EBI-2642957
Ptpn18Q611523EBI-7484574,EBI-7074223

Protein-protein interaction databases

BioGridi202439. 2 interactions.
IntActiP97814. 6 interactions.
MINTiMINT-444743.
STRINGi10090.ENSMUSP00000055823.

Structurei

3D structure databases

ProteinModelPortaliP97814.
SMRiP97814. Positions 7-285, 326-415.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 264260F-BARPROSITE-ProRule annotationAdd
BLAST
Domaini358 – 41558SH3PROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili94 – 13340Sequence AnalysisAdd
BLAST
Coiled coili162 – 21554Sequence AnalysisAdd
BLAST

Domaini

The F-BAR domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod (By similarity).By similarity

Sequence similaritiesi

Contains 1 F-BAR domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

eggNOGiNOG303711.
HOGENOMiHOG000294218.
HOVERGENiHBG052960.
InParanoidiP97814.
KOiK12804.
OrthoDBiEOG7BCNBS.
PhylomeDBiP97814.
TreeFamiTF313677.

Family and domain databases

InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR030777. PSTPIP1.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PANTHERiPTHR23065:SF3. PTHR23065:SF3. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTiSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P97814-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMAQLQFRDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDVE ELLRQRAQAE
60 70 80 90 100
ERYGKELVQI ARKAGGQTEM NSLRTSFDSL KQQTENVGSA HIQLALALRE
110 120 130 140 150
ELRSLEEFRE RQKEQRKKYE AIMDRVQKSK LSLYKKTMES KKAYDQKCRD
160 170 180 190 200
ADDAEQAFER VSANGHQKQV EKSQNKAKQC KESATEAERV YRQNIEQLER
210 220 230 240 250
ARTEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHCNQLSM QCVKDDELYE
260 270 280 290 300
EVRLTLEGCD VEGDINGFIQ SKSTGREPPA PVPYQNYYDR EVTPLIGSPS
310 320 330 340 350
IQPSCGVIKR FSGLLHGSPK TTPSAPAAST ETLTPTPERN ELVYASIEVQ
360 370 380 390 400
ATQGNLNSSA QDYRALYDYT AQNSDELDIS AGDILAVILE GEDGWWTVER
410
NGQRGFVPGS YLEKL
Length:415
Mass (Da):47,590
Last modified:May 1, 1997 - v1
Checksum:i16C0329284D2739C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti301 – 3011I → V in AAH96761 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87814 mRNA. Translation: AAB48483.1.
BC096761 mRNA. Translation: AAH96761.1.
CCDSiCCDS40645.1.
RefSeqiNP_035323.2. NM_011193.2.
UniGeneiMm.2534.

Genome annotation databases

GeneIDi19200.
KEGGimmu:19200.
UCSCiuc009psv.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87814 mRNA. Translation: AAB48483.1.
BC096761 mRNA. Translation: AAH96761.1.
CCDSiCCDS40645.1.
RefSeqiNP_035323.2. NM_011193.2.
UniGeneiMm.2534.

3D structure databases

ProteinModelPortaliP97814.
SMRiP97814. Positions 7-285, 326-415.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202439. 2 interactions.
IntActiP97814. 6 interactions.
MINTiMINT-444743.
STRINGi10090.ENSMUSP00000055823.

PTM databases

PhosphoSiteiP97814.

Proteomic databases

PaxDbiP97814.
PRIDEiP97814.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi19200.
KEGGimmu:19200.
UCSCiuc009psv.2. mouse.

Organism-specific databases

CTDi9051.
MGIiMGI:1321396. Pstpip1.

Phylogenomic databases

eggNOGiNOG303711.
HOGENOMiHOG000294218.
HOVERGENiHBG052960.
InParanoidiP97814.
KOiK12804.
OrthoDBiEOG7BCNBS.
PhylomeDBiP97814.
TreeFamiTF313677.

Enzyme and pathway databases

ReactomeiREACT_317454. The NLRP3 inflammasome.

Miscellaneous databases

NextBioi295916.
PROiP97814.
SOURCEiSearch...

Gene expression databases

BgeeiP97814.
GenevisibleiP97814. MM.

Family and domain databases

InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR030777. PSTPIP1.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PANTHERiPTHR23065:SF3. PTHR23065:SF3. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTiSM00055. FCH. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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 AT TYR-344, 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.

Entry informationi

Entry nameiPPIP1_MOUSE
AccessioniPrimary (citable) accession number: P97814
Secondary accession number(s): Q4V9R4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: May 1, 1997
Last modified: July 22, 2015
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.