PPIP1_HUMAN
ID PPIP1_HUMAN Reviewed; 416 AA.
AC O43586; B5BU74; B5BUK4; O43585; O95657;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Proline-serine-threonine phosphatase-interacting protein 1;
DE Short=PEST phosphatase-interacting protein 1;
DE AltName: Full=CD2-binding protein 1;
DE AltName: Full=H-PIP;
GN Name=PSTPIP1; Synonyms=CD2BP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP CD2 AND PTPN12, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9857189; DOI=10.1093/emboj/17.24.7320;
RA Li J., Nishizawa K., An W., Hussey R.E., Lialios F.E., Salgia R.,
RA Sunder-Plassmann R., Reinherz E.L.;
RT "A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic
RT domain and regulates CD2-triggered adhesion.";
RL EMBO J. 17:7320-7336(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS HIS-48; LYS-106;
RP HIS-146; LEU-149; SER-151; ASP-155 AND HIS-156.
RA Wilson L.A., Fields D., Cruz L., Lasky L., Friesen J., Siminovitch K.A.;
RT "The human homologue of mouse PTP-PIP interactor protein.";
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
RP INTERACTION WITH MEFV, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANTS
RP PAPAS THR-230 AND GLN-250, AND MUTAGENESIS OF TRP-232 AND TYR-345.
RX PubMed=14595024; DOI=10.1073/pnas.2135380100;
RA Shoham N.G., Centola M., Mansfield E., Hull K.M., Wood G., Wise C.A.,
RA Kastner D.L.;
RT "Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean
RT fever and PAPA syndrome as disorders in the same pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13501-13506(2003).
RN [7]
RP FUNCTION, SUBUNIT, INTERACTION WITH MEFV, AND CHARACTERIZATION OF VARIANTS
RP THR-230 AND GLN-250.
RX PubMed=17964261; DOI=10.1016/j.molcel.2007.08.029;
RA Yu J.W., Fernandes-Alnemri T., Datta P., Wu J., Juliana C., Solorzano L.,
RA McCormick M., Zhang Z., Alnemri E.S.;
RT "Pyrin activates the ASC pyroptosome in response to engagement by
RT autoinflammatory PSTPIP1 mutants.";
RL Mol. Cell 28:214-227(2007).
RN [8]
RP FUNCTION, INTERACTION WITH DNM2, AND SUBCELLULAR LOCATION.
RX PubMed=18480402; DOI=10.1091/mbc.e08-02-0225;
RA Cooper K.M., Bennin D.A., Huttenlocher A.;
RT "The PCH family member proline-serine-threonine phosphatase-interacting
RT protein 1 targets to the leukocyte uropod and regulates directed cell
RT migration.";
RL Mol. Biol. Cell 19:3180-3191(2008).
RN [9]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MEFV.
RX PubMed=19109554; DOI=10.3181/0806-rm-184;
RA Waite A.L., Schaner P., Hu C., Richards N., Balci-Peynircioglu B., Hong A.,
RA Fox M., Gumucio D.L.;
RT "Pyrin and ASC co-localize to cellular sites that are rich in polymerizing
RT actin.";
RL Exp. Biol. Med. (Maywood) 234:40-52(2009).
RN [11]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS
RP THR-230 AND GLN-250, AND MUTAGENESIS OF TRP-232 AND ASP-266.
RX PubMed=19584923; DOI=10.1371/journal.pone.0006147;
RA Waite A.L., Schaner P., Richards N., Balci-Peynircioglu B., Masters S.L.,
RA Brydges S.D., Fox M., Hong A., Yilmaz E., Kastner D.L., Reinherz E.L.,
RA Gumucio D.L.;
RT "Pyrin Modulates the Intracellular Distribution of PSTPIP1.";
RL PLoS ONE 4:E6147-E6147(2009).
RN [12]
RP STRUCTURE BY NMR OF 358-416.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3 domain of the human proline-serine-threonine
RT phosphatase-interacting protein 1.";
RL Submitted (FEB-2007) to the PDB data bank.
RN [13]
RP VARIANTS PAPAS THR-230 AND GLN-250, AND CHARACTERIZATION OF VARIANTS PAPAS
RP THR-230 AND GLN-250.
RX PubMed=11971877; DOI=10.1093/hmg/11.8.961;
RA Wise C.A., Gillum J.D., Seidman C.E., Lindor N.M., Veile R., Bashiardes S.,
RA Lovett M.;
RT "Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for
RT PAPA syndrome, an autoinflammatory disorder.";
RL Hum. Mol. Genet. 11:961-969(2002).
RN [14]
RP VARIANTS PAPAS THR-230; GLN-250 AND LYS-250.
RX PubMed=22161697; DOI=10.1002/art.34332;
RA Demidowich A.P., Freeman A.F., Kuhns D.B., Aksentijevich I., Gallin J.I.,
RA Turner M.L., Kastner D.L., Holland S.M.;
RT "Brief report: genotype, phenotype, and clinical course in five patients
RT with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and
RT acne).";
RL Arthritis Rheum. 64:2022-2027(2012).
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 (By
CC similarity). Down-regulates CD2-stimulated adhesion through the
CC coupling of PTPN12 to CD2. Also has a role in innate immunity and the
CC inflammatory response. Recruited to inflammasomes by MEFV. Induces
CC formation of pyroptosomes, large supramolecular structures composed of
CC oligomerized PYCARD dimers which form prior to inflammatory apoptosis.
CC Binding to MEFV allows MEFV to bind to PYCARD and facilitates
CC pyroptosome formation. Regulates endocytosis and cell migration in
CC neutrophils. {ECO:0000250, ECO:0000269|PubMed:17964261,
CC ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:19109554,
CC ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:9857189}.
CC -!- SUBUNIT: Homodimer (PubMed:19584923). Homotrimer (PubMed:17964261).
CC Interacts (via coiled-coil domain) with CD2AP, PTPN12 and PTPN18.
CC Interacts (via SH3 domain) with ABL1 and WAS. Interacts (via SH3 and
CC coiled-coil domains) with MEFV (via B-box zinc finger); the interaction
CC allows binding of MEFV to PYCARD and facilitates formation of PYCARD
CC pyroptosomes. Interacts with CD2, DNM2 and FASLG.
CC {ECO:0000269|PubMed:14595024, ECO:0000269|PubMed:17964261,
CC ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:19109554,
CC ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:9857189}.
CC -!- INTERACTION:
CC O43586; O15169: AXIN1; NbExp=3; IntAct=EBI-1050964, EBI-710484;
CC O43586; O43684: BUB3; NbExp=3; IntAct=EBI-1050964, EBI-1050987;
CC O43586; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-1050964, EBI-5453285;
CC O43586; Q8IX18: DHX40; NbExp=3; IntAct=EBI-1050964, EBI-2514301;
CC O43586; Q08426: EHHADH; NbExp=3; IntAct=EBI-1050964, EBI-2339219;
CC O43586; Q86YD7: FAM90A1; NbExp=6; IntAct=EBI-1050964, EBI-6658203;
CC O43586; P48023: FASLG; NbExp=5; IntAct=EBI-1050964, EBI-495538;
CC O43586; Q96D16: FBXL18; NbExp=3; IntAct=EBI-1050964, EBI-744419;
CC O43586; Q9GZV7: HAPLN2; NbExp=3; IntAct=EBI-1050964, EBI-11956675;
CC O43586; Q03014: HHEX; NbExp=3; IntAct=EBI-1050964, EBI-747421;
CC O43586; O75031: HSF2BP; NbExp=3; IntAct=EBI-1050964, EBI-7116203;
CC O43586; Q14005-2: IL16; NbExp=3; IntAct=EBI-1050964, EBI-17178971;
CC O43586; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-1050964, EBI-2556193;
CC O43586; Q96GY3: LIN37; NbExp=3; IntAct=EBI-1050964, EBI-748884;
CC O43586; Q9Y4Z0: LSM4; NbExp=6; IntAct=EBI-1050964, EBI-372521;
CC O43586; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-1050964, EBI-348259;
CC O43586; O15553: MEFV; NbExp=4; IntAct=EBI-1050964, EBI-7644532;
CC O43586; P00540: MOS; NbExp=3; IntAct=EBI-1050964, EBI-1757866;
CC O43586; Q09161: NCBP1; NbExp=3; IntAct=EBI-1050964, EBI-464743;
CC O43586; Q9Y5E9: PCDHB14; NbExp=6; IntAct=EBI-1050964, EBI-10329013;
CC O43586; Q96T60: PNKP; NbExp=3; IntAct=EBI-1050964, EBI-1045072;
CC O43586; Q8WWY3: PRPF31; NbExp=9; IntAct=EBI-1050964, EBI-1567797;
CC O43586; P0CG20: PRR35; NbExp=3; IntAct=EBI-1050964, EBI-11986293;
CC O43586; O43586: PSTPIP1; NbExp=4; IntAct=EBI-1050964, EBI-1050964;
CC O43586; Q05209: PTPN12; NbExp=5; IntAct=EBI-1050964, EBI-2266035;
CC O43586; Q99952: PTPN18; NbExp=4; IntAct=EBI-1050964, EBI-1384210;
CC O43586; Q9Y2R2: PTPN22; NbExp=6; IntAct=EBI-1050964, EBI-1211241;
CC O43586; Q15287: RNPS1; NbExp=3; IntAct=EBI-1050964, EBI-395959;
CC O43586; P32969: RPL9P9; NbExp=3; IntAct=EBI-1050964, EBI-358122;
CC O43586; Q14D33: RTP5; NbExp=6; IntAct=EBI-1050964, EBI-10217913;
CC O43586; P28702-3: RXRB; NbExp=3; IntAct=EBI-1050964, EBI-16429492;
CC O43586; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-1050964, EBI-748391;
CC O43586; O00560: SDCBP; NbExp=3; IntAct=EBI-1050964, EBI-727004;
CC O43586; Q9H788: SH2D4A; NbExp=3; IntAct=EBI-1050964, EBI-747035;
CC O43586; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-1050964, EBI-358489;
CC O43586; Q9UQ90: SPG7; NbExp=3; IntAct=EBI-1050964, EBI-717201;
CC O43586; P17752: TPH1; NbExp=3; IntAct=EBI-1050964, EBI-3956833;
CC O43586; Q9Y228: TRAF3IP3; NbExp=3; IntAct=EBI-1050964, EBI-765817;
CC O43586; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-1050964, EBI-10241197;
CC O43586; O75386: TULP3; NbExp=6; IntAct=EBI-1050964, EBI-5357290;
CC O43586; Q96B02: UBE2W; NbExp=4; IntAct=EBI-1050964, EBI-716589;
CC O43586; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-1050964, EBI-14104088;
CC O43586; Q9Y473: ZNF175; NbExp=3; IntAct=EBI-1050964, EBI-3438881;
CC O43586; Q9H9D4: ZNF408; NbExp=3; IntAct=EBI-1050964, EBI-347633;
CC O43586; Q9UK33: ZNF580; NbExp=3; IntAct=EBI-1050964, EBI-746277;
CC O43586; A0A0S2Z5X4: ZNF688; NbExp=3; IntAct=EBI-1050964, EBI-16429014;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9857189}. Cell
CC membrane {ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:9857189};
CC Peripheral membrane protein {ECO:0000269|PubMed:9857189}. Cell
CC projection, uropodium {ECO:0000269|PubMed:18480402}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:19109554,
CC ECO:0000269|PubMed:19584923}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P97814}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P97814}. Cleavage furrow
CC {ECO:0000250|UniProtKB:P97814}. Note=Mainly cytoplasmic in T-cells
CC (PubMed:9857189). Colocalizes in cluster with CD2 near the cell surface
CC membrane in activated T-cells (PubMed:9857189). In monocytes, forms a
CC branched filamentous network in the cytoplasm (PubMed:19584923). In
CC transfected cells, forms relatively straight filaments radiating out
CC from the nucleus (PubMed:19584923). Filament formation requires an
CC intact tubulin cytoskeleton (PubMed:19584923). In migrating
CC neutrophils, colocalizes with PIP5K1C and DNM2 to the trailing edge of
CC the uropod in a actin-dependent manner (PubMed:18480402). Colocalized
CC with PTPN12 in the cytoplasm and the perinuclear region. During
CC interphase, colocalizes with F-actin in the cortical cytoskeleton,
CC lamellipodia, and stress fibers. In dividing cells, colocalizes with
CC the F-actin rich cytokinetic cleavage furrow. Colocalized with CD2AP
CC and WAS in the actin cytoskeleton within the cytoplasm. Colocalized
CC with CD2, CD2AP and WAS at the site of T-cell:APC contact (By
CC similarity). {ECO:0000250|UniProtKB:P97814,
CC ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:19584923,
CC ECO:0000269|PubMed:9857189}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CD2BP1L;
CC IsoId=O43586-1; Sequence=Displayed;
CC Name=2; Synonyms=CD2BP1S;
CC IsoId=O43586-2; Sequence=VSP_015627;
CC -!- TISSUE SPECIFICITY: Highly expressed in the peripheral blood
CC leukocytes, granulocytes and monocytes, namely in T-cells and natural
CC killer cells, and in spleen. Weakly expressed in the thymus, small
CC intestine, lung and placenta. {ECO:0000269|PubMed:14595024,
CC ECO:0000269|PubMed:9857189}.
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.
CC -!- PTM: Dephosphorylated on Tyr-345 by PTPN18, this event negatively
CC regulates the association of PSTPIP1 with SH2 domain-containing
CC proteins as tyrosine kinase. Phosphorylation of Tyr-345 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 (By similarity). {ECO:0000250}.
CC -!- DISEASE: PAPA syndrome (PAPAS) [MIM:604416]: Characterized by autosomal
CC dominant inheritance of early-onset, primarily affecting skin and joint
CC tissues. Recurring inflammatory episodes lead to accumulation of
CC sterile, pyogenic, neutrophil-rich material within the affected joints,
CC ultimately resulting in significant destruction.
CC {ECO:0000269|PubMed:11971877, ECO:0000269|PubMed:14595024,
CC ECO:0000269|PubMed:22161697}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary
CC autoinflammatory disorders mutations;
CC URL="https://infevers.umai-montpellier.fr/web/search.php?n=5";
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DR EMBL; AF038602; AAD11958.1; -; mRNA.
DR EMBL; AF038603; AAD11959.1; -; mRNA.
DR EMBL; U94778; AAD00762.1; -; mRNA.
DR EMBL; AB451310; BAG70124.1; -; mRNA.
DR EMBL; AB451440; BAG70254.1; -; mRNA.
DR EMBL; CH471136; EAW99213.1; -; Genomic_DNA.
DR EMBL; BC008602; AAH08602.1; -; mRNA.
DR CCDS; CCDS45312.1; -. [O43586-1]
DR CCDS; CCDS81910.1; -. [O43586-2]
DR RefSeq; NP_001308064.1; NM_001321135.1. [O43586-2]
DR RefSeq; NP_001308066.1; NM_001321137.1.
DR RefSeq; NP_003969.2; NM_003978.4. [O43586-1]
DR PDB; 2DIL; NMR; -; A=361-416.
DR PDB; 7AAL; X-ray; 1.97 A; A/B=1-289.
DR PDB; 7AAM; X-ray; 2.15 A; A/B=1-289.
DR PDB; 7AAN; X-ray; 2.14 A; A/B=1-289.
DR PDBsum; 2DIL; -.
DR PDBsum; 7AAL; -.
DR PDBsum; 7AAM; -.
DR PDBsum; 7AAN; -.
DR AlphaFoldDB; O43586; -.
DR SMR; O43586; -.
DR BioGRID; 114513; 92.
DR IntAct; O43586; 54.
DR MINT; O43586; -.
DR STRING; 9606.ENSP00000452746; -.
DR iPTMnet; O43586; -.
DR PhosphoSitePlus; O43586; -.
DR SwissPalm; O43586; -.
DR BioMuta; PSTPIP1; -.
DR EPD; O43586; -.
DR jPOST; O43586; -.
DR MassIVE; O43586; -.
DR MaxQB; O43586; -.
DR PaxDb; O43586; -.
DR PeptideAtlas; O43586; -.
DR PRIDE; O43586; -.
DR ProteomicsDB; 49064; -. [O43586-1]
DR ProteomicsDB; 49065; -. [O43586-2]
DR Antibodypedia; 2771; 183 antibodies from 26 providers.
DR DNASU; 9051; -.
DR Ensembl; ENST00000558012.6; ENSP00000452746.1; ENSG00000140368.13. [O43586-1]
DR Ensembl; ENST00000559295.5; ENSP00000452743.1; ENSG00000140368.13. [O43586-2]
DR GeneID; 9051; -.
DR KEGG; hsa:9051; -.
DR MANE-Select; ENST00000558012.6; ENSP00000452746.1; NM_003978.5; NP_003969.2.
DR UCSC; uc002bcf.3; human. [O43586-1]
DR CTD; 9051; -.
DR DisGeNET; 9051; -.
DR GeneCards; PSTPIP1; -.
DR HGNC; HGNC:9580; PSTPIP1.
DR HPA; ENSG00000140368; Group enriched (bone marrow, lymphoid tissue).
DR MalaCards; PSTPIP1; -.
DR MIM; 604416; phenotype.
DR MIM; 606347; gene.
DR neXtProt; NX_O43586; -.
DR OpenTargets; ENSG00000140368; -.
DR Orphanet; 251523; Hyperzincemia and hypercalprotectinemia.
DR Orphanet; 69126; Pyogenic arthritis-pyoderma gangrenosum-acne syndrome.
DR PharmGKB; PA33931; -.
DR VEuPathDB; HostDB:ENSG00000140368; -.
DR eggNOG; KOG2398; Eukaryota.
DR GeneTree; ENSGT00940000156932; -.
DR InParanoid; O43586; -.
DR OMA; PIEYQNY; -.
DR OrthoDB; 727724at2759; -.
DR PhylomeDB; O43586; -.
DR TreeFam; TF313677; -.
DR PathwayCommons; O43586; -.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; O43586; -.
DR SIGNOR; O43586; -.
DR BioGRID-ORCS; 9051; 28 hits in 1069 CRISPR screens.
DR ChiTaRS; PSTPIP1; human.
DR EvolutionaryTrace; O43586; -.
DR GeneWiki; PSTPIP1; -.
DR GenomeRNAi; 9051; -.
DR Pharos; O43586; Tbio.
DR PRO; PR:O43586; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O43586; protein.
DR Bgee; ENSG00000140368; Expressed in granulocyte and 108 other tissues.
DR ExpressionAtlas; O43586; baseline and differential.
DR Genevisible; O43586; HS.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001931; C:uropod; IEA:UniProtKB-SubCell.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030041; P:actin filament polymerization; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
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 GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Cytoskeleton; Disease variant;
KW Endocytosis; Immunity; Inflammatory response; Innate immunity; Membrane;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..416
FT /note="Proline-serine-threonine phosphatase-interacting
FT protein 1"
FT /id="PRO_0000058539"
FT DOMAIN 5..264
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 359..416
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT COILED 166..212
FT /evidence="ECO:0000255"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97814"
FT MOD_RES 345
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P97814"
FT VAR_SEQ 280..309
FT /note="APVPYQNYYDREVTPLTSSPGIQPSCGMIK -> GEVRLADSAAS (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:9857189"
FT /id="VSP_015627"
FT VARIANT 48
FT /note="Q -> H (in dbSNP:rs1141038)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023515"
FT VARIANT 106
FT /note="E -> K (in dbSNP:rs1141039)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023516"
FT VARIANT 146
FT /note="Q -> H (in dbSNP:rs1141041)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023517"
FT VARIANT 149
FT /note="R -> L (in dbSNP:rs1141042)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023518"
FT VARIANT 151
FT /note="A -> S (in dbSNP:rs1141043)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023519"
FT VARIANT 155
FT /note="E -> D (in dbSNP:rs1141044)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023520"
FT VARIANT 156
FT /note="Q -> H (in dbSNP:rs1141045)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023521"
FT VARIANT 230
FT /note="A -> T (in PAPAS; severely reduced binding with
FT PTPN12; markedly increased binding to MEFV; accentuates
FT IL1B secretion; no effect on filament formation; increased
FT induction of MEFV in response to retroviral infection;
FT dbSNP:rs121908130)"
FT /evidence="ECO:0000269|PubMed:11971877,
FT ECO:0000269|PubMed:14595024, ECO:0000269|PubMed:17964261,
FT ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:22161697"
FT /id="VAR_023522"
FT VARIANT 250
FT /note="E -> K (in PAPAS; dbSNP:rs28939089)"
FT /evidence="ECO:0000269|PubMed:22161697"
FT /id="VAR_070635"
FT VARIANT 250
FT /note="E -> Q (in PAPAS; severely reduced binding with
FT PTPN12; markedly increased binding to MEFV; accentuates
FT IL1B secretion; increased induction of MEFV in response to
FT retroviral infection; dbSNP:rs28939089)"
FT /evidence="ECO:0000269|PubMed:11971877,
FT ECO:0000269|PubMed:14595024, ECO:0000269|PubMed:17964261,
FT ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:22161697"
FT /id="VAR_023523"
FT MUTAGEN 232
FT /note="W->A: Abolishes binding to MEFV. Cytoplasmic
FT filaments are finer with fewer branches."
FT /evidence="ECO:0000269|PubMed:14595024,
FT ECO:0000269|PubMed:19584923"
FT MUTAGEN 266
FT /note="D->N: No effect on filament formation."
FT /evidence="ECO:0000269|PubMed:19584923"
FT MUTAGEN 345
FT /note="Y->F: Decreases binding to MEFV."
FT /evidence="ECO:0000269|PubMed:14595024"
FT CONFLICT 367
FT /note="L -> F (in Ref. 2; AAD00762)"
FT /evidence="ECO:0000305"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:2DIL"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:2DIL"
FT STRAND 385..390
FT /evidence="ECO:0007829|PDB:2DIL"
FT STRAND 393..401
FT /evidence="ECO:0007829|PDB:2DIL"
FT STRAND 404..409
FT /evidence="ECO:0007829|PDB:2DIL"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:2DIL"
SQ SEQUENCE 416 AA; 47591 MW; 97818150B3D5D600 CRC64;
MMPQLQFKDA FWCRDFTAHT GYEVLLQRLL DGRKMCKDME ELLRQRAQAE ERYGKELVQI
ARKAGGQTEI NSLRASFDSL KQQMENVGSS HIQLALTLRE ELRSLEEFRE RQKEQRKKYE
AVMDRVQKSK LSLYKKAMES KKTYEQKCRD ADDAEQAFER ISANGHQKQV EKSQNKARQC
KDSATEAERV YRQSIAQLEK VRAEWEQEHR TTCEAFQLQE FDRLTILRNA LWVHSNQLSM
QCVKDDELYE EVRLTLEGCS IDADIDSFIQ AKSTGTEPPA PVPYQNYYDR EVTPLTSSPG
IQPSCGMIKR FSGLLHGSPK TTSLAASAAS TETLTPTPER NEGVYTAIAV QEIQGNPASP
AQEYRALYDY TAQNPDELDL SAGDILEVIL EGEDGWWTVE RNGQRGFVPG SYLEKL
