PPIP1_MOUSE
ID PPIP1_MOUSE Reviewed; 415 AA.
AC P97814; Q4V9R4;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Proline-serine-threonine phosphatase-interacting protein 1;
DE Short=PEST phosphatase-interacting protein 1;
GN Name=Pstpip1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PTPN18, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=9265651; DOI=10.1083/jcb.138.4.845;
RA Spencer S., Dowbenko D., Cheng J., Li W., Brush J., Utzig S., Simanis V.,
RA Lasky L.A.;
RT "PSTPIP: a tyrosine phosphorylated cleavage furrow-associated protein that
RT is a substrate for a PEST tyrosine phosphatase.";
RL J. Cell Biol. 138:845-860(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6NCr; TISSUE=Hematopoietic stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH WAS, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP TYR-344, AND MUTAGENESIS OF TYR-344 AND TYR-367.
RX PubMed=9488710; DOI=10.1074/jbc.273.10.5765;
RA Wu Y., Spencer S.D., Lasky L.A.;
RT "Tyrosine phosphorylation regulates the SH3-mediated binding of the
RT Wiskott-Aldrich syndrome protein to PSTPIP, a cytoskeletal-associated
RT protein.";
RL J. Biol. Chem. 273:5765-5770(1998).
RN [4]
RP FUNCTION, INTERACTION WITH ABL1, PHOSPHORYLATION, AND MUTAGENESIS OF
RP TYR-344 AND TYR-367.
RX PubMed=11163214; DOI=10.1016/s1097-2765(00)00138-6;
RA Cong F., Spencer S., Cote J.F., Wu Y., Tremblay M.L., Lasky L.A.,
RA Goff S.P.;
RT "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine
RT phosphatase to the c-Abl kinase to mediate Abl dephosphorylation.";
RL Mol. Cell 6:1413-1423(2000).
RN [5]
RP FUNCTION, INTERACTION WITH PTPN12, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-344 AND TYR-367.
RX PubMed=11711533; DOI=10.1074/jbc.m106428200;
RA Cote J.-F., Chung P.L., Theberge J.-F., Halle M., Spencer S., Lasky L.A.,
RA Tremblay M.L.;
RT "PSTPIP is a substrate of PTP-PEST and serves as a scaffold guiding PTP-
RT PEST toward a specific dephosphorylation of WASP.";
RL J. Biol. Chem. 277:2973-2986(2002).
RN [6]
RP FUNCTION, INTERACTION WITH CD2; CD2AP AND WAS, AND SUBCELLULAR LOCATION.
RX PubMed=12530983; DOI=10.1016/s1074-7613(02)00516-2;
RA Badour K., Zhang J., Shi F., McGavin M.K.H., Rampersad V., Hardy L.A.,
RA Field D., Siminovitch K.A.;
RT "The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP
RT and PSTPIP1 adaptors to promote formation of the immunological synapse.";
RL Immunity 18:141-154(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in regulation of the actin cytoskeleton. May
CC regulate WAS actin-bundling activity. Bridges the interaction between
CC ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a
CC scaffold protein between PTPN12 and WAS and allow PTPN12 to
CC dephosphorylate WAS. Has the potential to physically couple CD2 and
CC CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-
CC cell:APC contact site so as to promote the actin polymerization
CC required for synapse induction during T-cell activation. Down-regulates
CC CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has
CC a role in innate immunity and the inflammatory response. Recruited to
CC inflammasomes by MEFV. Induces formation of pyroptosomes, large
CC supramolecular structures composed of oligomerized PYCARD dimers which
CC form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to
CC bind to PYCARD and facilitates pyroptosome formation. Regulates
CC endocytosis and cell migration in neutrophils.
CC {ECO:0000269|PubMed:11163214, ECO:0000269|PubMed:11711533,
CC ECO:0000269|PubMed:12530983, ECO:0000269|PubMed:9265651,
CC ECO:0000269|PubMed:9488710}.
CC -!- SUBUNIT: Homodimer. Homotrimer. Interacts (via coiled-coil domain) with
CC CD2AP, PTPN12 and PTPN18. Interacts (via SH3 domain) with ABL1 and WAS.
CC Interacts (via SH3 and coiled-coil domains) with MEFV (via B-box zinc
CC finger); the interaction allows binding of MEFV to PYCARD and
CC facilitates formation of PYCARD pyroptosomes. Interacts with DNM2 and
CC FASLG (By similarity). Interacts with CD2. {ECO:0000250,
CC ECO:0000269|PubMed:11163214, ECO:0000269|PubMed:11711533,
CC ECO:0000269|PubMed:12530983, ECO:0000269|PubMed:9265651,
CC ECO:0000269|PubMed:9488710}.
CC -!- INTERACTION:
CC P97814; P00520: Abl1; NbExp=5; IntAct=EBI-7484574, EBI-914519;
CC P97814; P35831: Ptpn12; NbExp=5; IntAct=EBI-7484574, EBI-2642957;
CC P97814; Q61152: Ptpn18; NbExp=3; IntAct=EBI-7484574, EBI-7074223;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11711533,
CC ECO:0000269|PubMed:12530983}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:11711533}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:9265651}. Cleavage furrow
CC {ECO:0000269|PubMed:9265651}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9265651, ECO:0000269|PubMed:9488710}. Cell membrane
CC {ECO:0000250|UniProtKB:O43586}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O43586}. Cell projection, uropodium
CC {ECO:0000250|UniProtKB:O43586}. Note=Colocalized with PTPN12 in the
CC cytoplasm and the perinuclear region (PubMed:11711533). During
CC interphase, colocalizes with F-actin in the cortical cytoskeleton,
CC lamellipodia, and stress fibers (PubMed:9265651). In dividing cells,
CC colocalizes with the F-actin rich cytokinetic cleavage furrow
CC (PubMed:9265651). Colocalized with CD2AP and WAS in the actin
CC cytoskeleton within the cytoplasm (PubMed:12530983, PubMed:9488710).
CC Colocalized with CD2, CD2AP and WAS at the site of T-cell:APC contact
CC (PubMed:12530983). Mainly cytoplasmic in T cells. Colocalizes in
CC cluster with CD2 near the cell surface membrane in activated T-cells.
CC In monocytes, forms a branched filamentous network in the cytoplasm. In
CC transfected cells, forms relatively straight filaments radiating out
CC from the nucleus. Filament formation requires an intact tubulin
CC cytoskeleton. In migrating neutrophils, colocalizes with PIP5K1C and
CC DNM2 to the trailing edge of the uropod in a actin-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:O43586,
CC ECO:0000269|PubMed:11711533, ECO:0000269|PubMed:12530983,
CC ECO:0000269|PubMed:9265651, ECO:0000269|PubMed:9488710}.
CC -!- TISSUE SPECIFICITY: Highly expressed in adult lung and spleen, and
CC weakly expressed in testis, muscle, kidney, brain and heart. Highly
CC expressed in spleen and thymus, moderately in lung, brain and muscle,
CC and weakly expressed in heart and liver (at protein level).
CC {ECO:0000269|PubMed:11711533, ECO:0000269|PubMed:9265651}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in 7 dpc embryos.
CC {ECO:0000269|PubMed:9265651}.
CC -!- DOMAIN: The F-BAR domain is important for filament formation. The SH3
CC domain is not required for filament formation or localization to the
CC uropod (By similarity). {ECO:0000250}.
CC -!- PTM: Dephosphorylated on Tyr-344 by PTPN18, this event negatively
CC regulates the association of PSTPIP1 with SH2 domain-containing
CC proteins as tyrosine kinase. Phosphorylation of Tyr-344 is probably
CC required for subsequent phosphorylation at other tyrosine residues.
CC Phosphorylation is induced by activation of the EGFR and PDGFR in a
CC ABL1 dependent manner. The phosphorylation regulates the interaction
CC with WAS and with MEFV. {ECO:0000269|PubMed:11163214,
CC ECO:0000269|PubMed:11711533, ECO:0000269|PubMed:9265651,
CC ECO:0000269|PubMed:9488710}.
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DR EMBL; U87814; AAB48483.1; -; mRNA.
DR EMBL; BC096761; AAH96761.1; -; mRNA.
DR CCDS; CCDS40645.1; -.
DR RefSeq; NP_035323.2; NM_011193.3.
DR AlphaFoldDB; P97814; -.
DR SMR; P97814; -.
DR BioGRID; 202439; 4.
DR IntAct; P97814; 5.
DR MINT; P97814; -.
DR STRING; 10090.ENSMUSP00000055823; -.
DR iPTMnet; P97814; -.
DR PhosphoSitePlus; P97814; -.
DR EPD; P97814; -.
DR jPOST; P97814; -.
DR MaxQB; P97814; -.
DR PaxDb; P97814; -.
DR PeptideAtlas; P97814; -.
DR PRIDE; P97814; -.
DR ProteomicsDB; 289736; -.
DR DNASU; 19200; -.
DR GeneID; 19200; -.
DR KEGG; mmu:19200; -.
DR UCSC; uc009psv.2; mouse.
DR CTD; 9051; -.
DR MGI; MGI:1321396; Pstpip1.
DR eggNOG; KOG2398; Eukaryota.
DR InParanoid; P97814; -.
DR OrthoDB; 727724at2759; -.
DR PhylomeDB; P97814; -.
DR TreeFam; TF313677; -.
DR Reactome; R-MMU-844456; The NLRP3 inflammasome.
DR BioGRID-ORCS; 19200; 2 hits in 72 CRISPR screens.
DR PRO; PR:P97814; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P97814; protein.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0005826; C:actomyosin contractile ring; IDA:MGI.
DR GO; GO:0032154; C:cleavage furrow; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001725; C:stress fiber; IDA:MGI.
DR GO; GO:0001931; C:uropod; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:MGI.
DR GO; GO:0030041; P:actin filament polymerization; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR CDD; cd11824; SH3_PSTPIP1; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR030777; PSTPIP1_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; Endocytosis; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..415
FT /note="Proline-serine-threonine phosphatase-interacting
FT protein 1"
FT /id="PRO_0000058540"
FT DOMAIN 5..264
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 358..415
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT COILED 94..133
FT /evidence="ECO:0000255"
FT COILED 162..215
FT /evidence="ECO:0000255"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 344
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000305|PubMed:9488710"
FT MUTAGEN 344
FT /note="Y->F: Complete loss of protein phosphorylation."
FT /evidence="ECO:0000269|PubMed:11163214,
FT ECO:0000269|PubMed:11711533, ECO:0000269|PubMed:9488710"
FT MUTAGEN 367
FT /note="Y->F: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:11163214,
FT ECO:0000269|PubMed:11711533, ECO:0000269|PubMed:9488710"
FT CONFLICT 301
FT /note="I -> V (in Ref. 2; AAH96761)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 47590 MW; 16C0329284D2739C CRC64;
MMAQLQFRDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDVE ELLRQRAQAE ERYGKELVQI
ARKAGGQTEM NSLRTSFDSL KQQTENVGSA HIQLALALRE ELRSLEEFRE RQKEQRKKYE
AIMDRVQKSK LSLYKKTMES KKAYDQKCRD ADDAEQAFER VSANGHQKQV EKSQNKAKQC
KESATEAERV YRQNIEQLER ARTEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHCNQLSM
QCVKDDELYE EVRLTLEGCD VEGDINGFIQ SKSTGREPPA PVPYQNYYDR EVTPLIGSPS
IQPSCGVIKR FSGLLHGSPK TTPSAPAAST ETLTPTPERN ELVYASIEVQ ATQGNLNSSA
QDYRALYDYT AQNSDELDIS AGDILAVILE GEDGWWTVER NGQRGFVPGS YLEKL
