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 02-SEP-2026, entry version 176. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 FunCoup; P97814; 70. DR IntAct; P97814; 5. DR MINT; P97814; -. DR STRING; 10090.ENSMUSP00000055823; -. DR GlyGen; P97814; 1 site. DR iPTMnet; P97814; -. DR PhosphoSitePlus; P97814; -. DR jPOST; P97814; -. DR PaxDb; 10090-ENSMUSP00000055823; -. DR PeptideAtlas; P97814; -. DR ProteomicsDB; 289736; -. DR DNASU; 19200; -. DR GeneID; 19200; -. DR UCSC; uc009psv.2; mouse. DR AGR; MGI:1321396; -. DR CTD; 9051; -. DR MGI; MGI:1321396; Pstpip1. DR eggNOG; KOG2398; Eukaryota. DR InParanoid; P97814; -. DR OrthoDB; 10255964at2759; -. DR PhylomeDB; P97814; -. DR Reactome; R-MMU-844456; The NLRP3 inflammasome. DR BioGRID-ORCS; 19200; 2 hits in 77 CRISPR screens. DR PRO; PR:P97814; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P97814; protein. 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; EXP:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. 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; ISS:UniProtKB. 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:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0019903; F:protein phosphatase binding; IDA:MGI. DR CDD; cd11824; SH3_PSTPIP1; 1. DR FunFam; 1.20.1270.60:FF:000037; Proline-serine-threonine phosphatase interacting protein 1; 1. DR FunFam; 2.30.30.40:FF:000150; Proline-serine-threonine phosphatase interacting protein 1; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR027267; AH/BAR_dom_sf. DR InterPro; IPR031160; F_BAR_dom. DR InterPro; IPR001060; FCH_dom. DR InterPro; IPR030777; PSTPIP1_SH3. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR23065; PROLINE-SERINE-THREONINE PHOSPHATASE INTERACTING PROTEIN 1; 1. DR PANTHER; PTHR23065:SF51; PROLINE-SERINE-THREONINE PHOSPHATASE-INTERACTING PROTEIN 1; 1. DR Pfam; PF00611; FCH; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR01887; SPECTRNALPHA. DR SMART; SM00055; FCH; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF103657; BAR/IMD domain-like; 1. DR SUPFAM; SSF50044; SH3-domain; 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 //