SHIP2_HUMAN
ID SHIP2_HUMAN Reviewed; 1258 AA.
AC O15357; B2RTX5; Q13577; Q13578;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 {ECO:0000305};
DE EC=3.1.3.86 {ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:9660833};
DE AltName: Full=Inositol polyphosphate phosphatase-like protein 1;
DE Short=INPPL-1;
DE AltName: Full=Protein 51C;
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 2;
DE Short=SH2 domain-containing inositol phosphatase 2;
DE Short=SHIP-2;
GN Name=INPPL1; Synonyms=SHIP2;
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] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=8530088; DOI=10.1006/geno.1995.1247;
RA Hejna J.A., Saito H., Merkens L.S., Tittle T.V., Jakobs P.M., Whitney M.A.,
RA Grompe M., Friedberg A.S., Moses R.E.;
RT "Cloning and characterization of a human cDNA (INPPL1) sharing homology
RT with inositol polyphosphate phosphatases.";
RL Genomics 29:285-287(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP GLY-1114.
RC TISSUE=Hippocampus;
RX PubMed=9367831; DOI=10.1006/bbrc.1997.7538;
RA Pesesse X., Deleu S., De Smedt F., Drayer L., Erneux C.;
RT "Identification of a second SH2-domain-containing protein closely related
RT to the phosphatidylinositol polyphosphate 5-phosphatase SHIP.";
RL Biochem. Biophys. Res. Commun. 239:697-700(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-1114.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-1114.
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 FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, PHOSPHORYLATION, AND
RP INTERACTION WITH SHC1.
RX PubMed=9660833; DOI=10.1074/jbc.273.29.18605;
RA Habib T., Hejna J.A., Moses R.E., Decker S.J.;
RT "Growth factors and insulin stimulate tyrosine phosphorylation of the
RT 51C/SHIP2 protein.";
RL J. Biol. Chem. 273:18605-18609(1998).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, PHOSPHORYLATION,
RP AND INTERACTION WITH SHC1 AND ABL1.
RX PubMed=10194451;
RA Wisniewski D., Strife A., Swendeman S., Erdjument-Bromage H., Geromanos S.,
RA Kavanaugh W.M., Tempst P., Clarkson B.;
RT "A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-
RT phosphatase (SHIP2) is constitutively tyrosine phosphorylated and
RT associated with src homologous and collagen gene (SHC) in chronic
RT myelogenous leukemia progenitor cells.";
RL Blood 93:2707-2720(1999).
RN [8]
RP INTERACTION WITH FCGR2B.
RX PubMed=11016922; DOI=10.1074/jbc.m003518200;
RA Bruhns P., Vely F., Malbec O., Fridman W.H., Vivier E., Daeeron M.;
RT "Molecular basis of the recruitment of the SH2 domain-containing inositol
RT 5-phosphatases SHIP1 and SHIP2 by fcgamma RIIB.";
RL J. Biol. Chem. 275:37357-37364(2000).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EGFR AND SHC1, AND
RP PHOSPHORYLATION AT TYR-986.
RX PubMed=11349134; DOI=10.1074/jbc.m103537200;
RA Pesesse X., Dewaste V., De Smedt F., Laffargue M., Giuriato S., Moreau C.,
RA Payrastre B., Erneux C.;
RT "The Src homology 2 domain containing inositol 5-phosphatase SHIP2 is
RT recruited to the epidermal growth factor (EGF) receptor and
RT dephosphorylates phosphatidylinositol 3,4,5-trisphosphate in EGF-stimulated
RT COS-7 cells.";
RL J. Biol. Chem. 276:28348-28355(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FLNA AND FLNB.
RX PubMed=11739414; DOI=10.1083/jcb.200104005;
RA Dyson J.M., O'Malley C.J., Becanovic J., Munday A.D., Berndt M.C.,
RA Coghill I.D., Nandurkar H.H., Ooms L.M., Mitchell C.A.;
RT "The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds
RT filamin and regulates submembraneous actin.";
RL J. Cell Biol. 155:1065-1079(2001).
RN [11]
RP PHOSPHORYLATION, INTERACTION WITH BCAR1, AND MUTAGENESIS OF ARG-47.
RX PubMed=11158326; DOI=10.1128/mcb.21.4.1416-1428.2001;
RA Prasad N., Topping R.S., Decker S.J.;
RT "SH2-containing inositol 5'-phosphatase SHIP2 associates with the p130(Cas)
RT adapter protein and regulates cellular adhesion and spreading.";
RL Mol. Cell. Biol. 21:1416-1428(2001).
RN [12]
RP PHOSPHORYLATION AT TYR-1162.
RX PubMed=11687594; DOI=10.1074/jbc.m109992200;
RA Steen H., Kuster B., Fernandez M., Pandey A., Mann M.;
RT "Tyrosine phosphorylation mapping of the epidermal growth factor receptor
RT signaling pathway.";
RL J. Biol. Chem. 277:1031-1039(2002).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT TYR-986, AND MUTAGENESIS OF 986-TYR-TYR-987.
RX PubMed=12235291; DOI=10.1242/jcs.00070;
RA Prasad N., Topping R.S., Decker S.J.;
RT "Src family tyrosine kinases regulate adhesion-dependent tyrosine
RT phosphorylation of 5'-inositol phosphatase SHIP2 during cell attachment and
RT spreading on collagen I.";
RL J. Cell Sci. 115:3807-3815(2002).
RN [14]
RP INTERACTION WITH CBL AND SORBS1.
RX PubMed=12504111; DOI=10.1016/s0006-291x(02)02894-2;
RA Vandenbroere I., Paternotte N., Dumont J.E., Erneux C., Pirson I.;
RT "The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-
RT containing inositol polyphosphate 5-phosphatase SHIP2.";
RL Biochem. Biophys. Res. Commun. 300:494-500(2003).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP ACTIN; FILAMIN AND GPIB.
RX PubMed=12676785; DOI=10.1182/blood-2002-09-2897;
RA Dyson J.M., Munday A.D., Kong A.M., Huysmans R.D., Matzaris M.,
RA Layton M.J., Nandurkar H.H., Berndt M.C., Mitchell C.A.;
RT "SHIP-2 forms a tetrameric complex with filamin, actin, and GPIb-IX-V:
RT localization of SHIP-2 to the activated platelet actin cytoskeleton.";
RL Blood 102:940-948(2003).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, PHOSPHORYLATION, INTERACTION WITH
RP FCGR2A, AND MUTAGENESIS OF ARG-47 AND ASP-607.
RX PubMed=12690104; DOI=10.1074/jbc.m302907200;
RA Pengal R.A., Ganesan L.P., Fang H., Marsh C.B., Anderson C.L.,
RA Tridandapani S.;
RT "SHIP-2 inositol phosphatase is inducibly expressed in human monocytes and
RT serves to regulate Fcgamma receptor-mediated signaling.";
RL J. Biol. Chem. 278:22657-22663(2003).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1135, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [19]
RP ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=16824732; DOI=10.1016/j.cellsig.2006.05.010;
RA Vandeput F., Backers K., Villeret V., Pesesse X., Erneux C.;
RT "The influence of anionic lipids on SHIP2 phosphatidylinositol 3,4,5-
RT trisphosphate 5-phosphatase activity.";
RL Cell. Signal. 18:2193-2199(2006).
RN [20]
RP INTERACTION WITH SORBS3.
RX PubMed=16302969; DOI=10.1111/j.1742-4658.2005.04996.x;
RA Paternotte N., Zhang J., Vandenbroere I., Backers K., Blero D., Kioka N.,
RA Vanderwinden J.-M., Pirson I., Erneux C.;
RT "SHIP2 interaction with the cytoskeletal protein Vinexin.";
RL FEBS J. 272:6052-6066(2005).
RN [21]
RP FUNCTION.
RX PubMed=15668240; DOI=10.1074/jbc.m410289200;
RA Prasad N.K., Decker S.J.;
RT "SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton
RT organization and ligand-dependent down-regulation of the epidermal growth
RT factor receptor.";
RL J. Biol. Chem. 280:13129-13136(2005).
RN [22]
RP INTERACTION WITH MET.
RX PubMed=15735664; DOI=10.1038/sj.onc.1208558;
RA Koch A., Mancini A., El Bounkari O., Tamura T.;
RT "The SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met
RT directly via tyrosine residue 1356 and involves hepatocyte growth factor
RT (HGF)-induced lamellipodium formation, cell scattering and cell
RT spreading.";
RL Oncogene 24:3436-3447(2005).
RN [23]
RP INTERACTION WITH CENTD3.
RX PubMed=17314030; DOI=10.1016/j.cellsig.2006.12.015;
RA Raaijmakers J.H., Deneubourg L., Rehmann H., de Koning J., Zhang Z.,
RA Krugmann S., Erneux C., Bos J.L.;
RT "The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2
RT in a SAM domain-dependent manner.";
RL Cell. Signal. 19:1249-1257(2007).
RN [24]
RP FUNCTION, AND INTERACTION WITH EPHA2.
RX PubMed=17135240; DOI=10.1074/jbc.m608509200;
RA Zhuang G., Hunter S., Hwang Y., Chen J.;
RT "Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via
RT phosphatidylinositol 3-Kinase-dependent Rac1 activation.";
RL J. Biol. Chem. 282:2683-2694(2007).
RN [25]
RP PHOSPHORYLATION AT THR-958, AND MUTAGENESIS OF THR-958.
RX PubMed=17219406; DOI=10.1002/jcp.20965;
RA Artemenko Y., Gagnon A., Ibrahim S., Sorisky A.;
RT "Regulation of PDGF-stimulated SHIP2 tyrosine phosphorylation and
RT association with Shc in 3T3-L1 preadipocytes.";
RL J. Cell. Physiol. 211:598-607(2007).
RN [26]
RP INVOLVEMENT IN NIDDM.
RX PubMed=12086927; DOI=10.2337/diabetes.51.7.2012;
RA Marion E., Kaisaki P.J., Pouillon V., Gueydan C., Levy J.C., Bodson A.,
RA Krzentowski G., Daubresse J.-C., Mockel J., Behrends J., Servais G.,
RA Szpirer C., Kruys V., Gauguier D., Schurmans S.;
RT "The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for
RT type 2 diabetes in rat and man.";
RL Diabetes 51:2012-2017(2002).
RN [27]
RP INVOLVEMENT IN METABOLIC SYNDROME.
RX PubMed=15220217; DOI=10.2337/diabetes.53.7.1900;
RA Kaisaki P.J., Delepine M., Woon P.Y., Sebag-Montefiore L., Wilder S.P.,
RA Menzel S., Vionnet N., Marion E., Riveline J.-P., Charpentier G.,
RA Schurmans S., Levy J.C., Lathrop M., Farrall M., Gauguier D.;
RT "Polymorphisms in type II SH2 domain-containing inositol 5-phosphatase
RT (INPPL1, SHIP2) are associated with physiological abnormalities of the
RT metabolic syndrome.";
RL Diabetes 53:1900-1904(2004).
RN [28]
RP INVOLVEMENT IN NIDDM, AND VARIANTS ILE-632; MET-721; SER-982 AND GLY-1083.
RX PubMed=15687335; DOI=10.1210/jc.2004-1724;
RA Kagawa S., Sasaoka T., Yaguchi S., Ishihara H., Tsuneki H., Murakami S.,
RA Fukui K., Wada T., Kobayashi S., Kimura I., Kobayashi M.;
RT "Impact of SRC homology 2-containing inositol 5'-phosphatase 2 gene
RT polymorphisms detected in a Japanese population on insulin signaling.";
RL J. Clin. Endocrinol. Metab. 90:2911-2919(2005).
RN [29]
RP INVOLVEMENT IN METABOLIC SYNDROME.
RX PubMed=17557929; DOI=10.1136/jmg.2007.049718;
RA Braga Marcano A.C., Burke B., Gungadoo J., Wallace C., Kaisaki P.J.,
RA Woon P.Y., Farrall M., Clayton D., Brown M., Dominiczak A., Connell J.M.,
RA Webster J., Lathrop M., Caulfield M., Samani N., Gauguier D., Munroe P.B.;
RT "Genetic association analysis of inositol polyphosphate phosphatase-like 1
RT (INPPL1, SHIP2) variants with essential hypertension.";
RL J. Med. Genet. 44:603-605(2007).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-165 AND SER-241, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [34]
RP INTERACTION WITH FCRL6.
RX PubMed=20933011; DOI=10.1016/j.imlet.2010.09.023;
RA Kulemzin S.V., Zamoshnikova A.Y., Yurchenko M.Y., Vitak N.Y.,
RA Najakshin A.M., Fayngerts S.A., Chikaev N.A., Reshetnikova E.S.,
RA Kashirina N.M., Peclo M.M., Rutkevich P.N., Shevelev A.Y.,
RA Yanushevskaya E.V., Baranov K.O., Mamonkin M., Vlasik T.N., Sidorenko S.P.,
RA Taranin A.V., Mechetina L.V.;
RT "FCRL6 receptor: expression and associated proteins.";
RL Immunol. Lett. 134:174-182(2011).
RN [35]
RP FUNCTION, INTERACTION WITH SH3YL1, AND MUTAGENESIS OF 140-PRO-LEU-141.
RX PubMed=21624956; DOI=10.1083/jcb.201012161;
RA Hasegawa J., Tokuda E., Tenno T., Tsujita K., Sawai H., Hiroaki H.,
RA Takenawa T., Itoh T.;
RT "SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-
RT binding domain.";
RL J. Cell Biol. 193:901-916(2011).
RN [36]
RP FUNCTION, AND VARIANTS OPSMD TRP-401; SER-659; CYS-688 AND ILE-722.
RX PubMed=23273569; DOI=10.1016/j.ajhg.2012.11.015;
RA Huber C., Faqeih E.A., Bartholdi D., Bole-Feysot C., Borochowitz Z.,
RA Cavalcanti D.P., Frigo A., Nitschke P., Roume J., Santos H.G., Shalev S.A.,
RA Superti-Furga A., Delezoide A.L., Le Merrer M., Munnich A.,
RA Cormier-Daire V.;
RT "Exome sequencing identifies INPPL1 mutations as a cause of
RT opsismodysplasia.";
RL Am. J. Hum. Genet. 92:144-149(2013).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-352; TYR-886;
RP SER-890; THR-958; SER-1131; TYR-1135; TYR-1162 AND SER-1257, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically
CC hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate
CC (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively
CC regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a
CC central role in regulation of PI3K-dependent insulin signaling,
CC although the precise molecular mechanisms and signaling pathways remain
CC unclear. While overexpression reduces both insulin-stimulated MAP
CC kinase and Akt activation, its absence does not affect insulin
CC signaling or GLUT4 trafficking. Confers resistance to dietary obesity.
CC May act by regulating AKT2, but not AKT1, phosphorylation at the plasma
CC membrane. Part of a signaling pathway that regulates actin cytoskeleton
CC remodeling. Required for the maintenance and dynamic remodeling of
CC actin structures as well as in endocytosis, having a major impact on
CC ligand-induced EGFR internalization and degradation. Participates in
CC regulation of cortical and submembraneous actin by hydrolyzing
CC PtdIns(3,4,5)P3 thereby regulating membrane ruffling (PubMed:21624956).
CC Regulates cell adhesion and cell spreading. Required for HGF-mediated
CC lamellipodium formation, cell scattering and spreading. Acts as a
CC negative regulator of EPHA2 receptor endocytosis by inhibiting via
CC PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis
CC by regulating PtdIns(3,4,5)P3 level and is required to form an initial
CC protrusive pattern, and later, maintain proper neurite outgrowth. Acts
CC as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A).
CC Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a
CC central role in terminating signal transduction from activating
CC immune/hematopoietic cell receptor systems. Involved in EGF signaling
CC pathway. Upon stimulation by EGF, it is recruited by EGFR and
CC dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating
CC the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-
CC regulates Fc-gamma-R-mediated phagocytosis in macrophages independently
CC of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent
CC gene transcription by regulating macrophage colony-stimulating factor
CC (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and
CC could thus affect the levels of the higher inositol polyphosphates like
CC InsP6. Involved in endochondral ossification.
CC {ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414,
CC ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12676785,
CC ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15668240,
CC ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:17135240,
CC ECO:0000269|PubMed:21624956, ECO:0000269|PubMed:23273569,
CC ECO:0000269|PubMed:9660833}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:57836; EC=3.1.3.86;
CC Evidence={ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:16824732,
CC ECO:0000269|PubMed:9660833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305|PubMed:10194451};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43548,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416,
CC ChEBI:CHEBI:83417; Evidence={ECO:0000269|PubMed:16824732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43549;
CC Evidence={ECO:0000305|PubMed:16824732};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-
CC 3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-
CC (1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43556,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420,
CC ChEBI:CHEBI:83422; Evidence={ECO:0000269|PubMed:16824732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43557;
CC Evidence={ECO:0000305|PubMed:16824732};
CC -!- ACTIVITY REGULATION: Activated upon translocation to the sites of
CC synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is
CC enhanced in the presence of phosphatidylserine.
CC {ECO:0000269|PubMed:16824732}.
CC -!- SUBUNIT: Interacts with tyrosine phosphorylated form of SHC1
CC (PubMed:9660833, PubMed:10194451, PubMed:11349134). Interacts with EGFR
CC (PubMed:11349134). Upon stimulation by the EGF signaling pathway, it
CC forms a complex with SHC1 and EGFR (PubMed:11349134). Interacts with
CC cytoskeletal protein SORBS3/vinexin, promoting its localization to the
CC periphery of cells (PubMed:16302969). Forms a complex with filamin
CC (FLNA or FLNB), actin, GPIb (GP1BA or GP1BB) that regulates cortical
CC and submembraneous actin (PubMed:11739414, PubMed:12676785). Interacts
CC with c-Met/MET, when c-Met/MET is phosphorylated on 'Tyr-1356'
CC (PubMed:15735664). Interacts with p130Cas/BCAR1 (PubMed:11158326).
CC Interacts with CENTD3/ARAP3 via its SAM domain (PubMed:17314030).
CC Interacts with c-Cbl/CBL and CAP/SORBS1 (PubMed:12504111). Interacts
CC with activated EPHA2 receptor (PubMed:17135240). Interacts with
CC receptor FCGR2A (PubMed:12690104). Interacts with receptor FCGR2B
CC (PubMed:11016922). Interacts with tyrosine kinase ABL1
CC (PubMed:10194451). Interacts with tyrosine kinase TEC (By similarity).
CC Interacts with CSF1R (By similarity). Interacts (via N-terminus) with
CC SH3YL1 (via SH3 domain) (PubMed:21624956). Interacts with FCRL6
CC (tyrosine phosphorylated form) (PubMed:20933011). Interacts (via SH2
CC domain) with tyrosine phosphorylated KLRC1 (via ITIM).
CC {ECO:0000250|UniProtKB:Q6P549, ECO:0000269|PubMed:10194451,
CC ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11158326,
CC ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11739414,
CC ECO:0000269|PubMed:12504111, ECO:0000269|PubMed:12676785,
CC ECO:0000269|PubMed:12690104, ECO:0000269|PubMed:15735664,
CC ECO:0000269|PubMed:16302969, ECO:0000269|PubMed:17135240,
CC ECO:0000269|PubMed:17314030, ECO:0000269|PubMed:20933011,
CC ECO:0000269|PubMed:9660833}.
CC -!- INTERACTION:
CC O15357; P10275: AR; NbExp=3; IntAct=EBI-1384248, EBI-608057;
CC O15357; P56945: BCAR1; NbExp=2; IntAct=EBI-1384248, EBI-702093;
CC O15357; P46108: CRK; NbExp=2; IntAct=EBI-1384248, EBI-886;
CC O15357; Q13480: GAB1; NbExp=2; IntAct=EBI-1384248, EBI-517684;
CC O15357; Q8IV36: HID1; NbExp=2; IntAct=EBI-1384248, EBI-743438;
CC O15357; Q15811-2: ITSN1; NbExp=9; IntAct=EBI-1384248, EBI-8052395;
CC O15357; P08581: MET; NbExp=2; IntAct=EBI-1384248, EBI-1039152;
CC O15357; Q9BX66: SORBS1; NbExp=5; IntAct=EBI-1384248, EBI-433642;
CC O15357; O60504-1: SORBS3; NbExp=2; IntAct=EBI-1384248, EBI-1222953;
CC O15357; A0A061I5T4: H671_4g13114; Xeno; NbExp=2; IntAct=EBI-1384248, EBI-2504267;
CC O15357-1; P29317: EPHA2; NbExp=3; IntAct=EBI-15963021, EBI-702104;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11349134}.
CC Cytoplasm, cytoskeleton. Membrane {ECO:0000269|PubMed:11739414};
CC Peripheral membrane protein. Cell projection, filopodium
CC {ECO:0000269|PubMed:12676785}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:12676785}. Nucleus {ECO:0000250|UniProtKB:D7PF45}.
CC Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Note=Translocates to
CC membrane ruffles when activated, translocation is probably due to
CC different mechanisms depending on the stimulus and cell type. Partly
CC translocated via its SH2 domain which mediates interaction with
CC tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor
CC (FCGR2B). Tyrosine phosphorylation may also participate in membrane
CC localization. Insulin specifically stimulates its redistribution from
CC the cytosol to the plasma membrane. Recruited to the membrane following
CC M-CSF stimulation. In activated spreading platelets, localizes with
CC actin at filopodia, lamellipodia and the central actin ring.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15357-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15357-2; Sequence=VSP_027985;
CC -!- TISSUE SPECIFICITY: Widely expressed, most prominently in skeletal
CC muscle, heart and brain. Present in platelets. Expressed in transformed
CC myeloid cells and in primary macrophages, but not in peripheral blood
CC monocytes. {ECO:0000269|PubMed:12676785, ECO:0000269|PubMed:12690104,
CC ECO:0000269|PubMed:8530088, ECO:0000269|PubMed:9367831,
CC ECO:0000269|PubMed:9660833}.
CC -!- INDUCTION: By bacterial lipopolysaccharides (LPS).
CC {ECO:0000269|PubMed:12690104}.
CC -!- DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of
CC proteins such as SHC1 or FCGR2A. It also mediates the interaction with
CC p130Cas/BCAR1.
CC -!- DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated
CC proteins is required for the specific binding of the PID domain.
CC {ECO:0000250}.
CC -!- PTM: Tyrosine phosphorylated by the members of the SRC family after
CC exposure to a diverse array of extracellular stimuli such as insulin,
CC growth factors such as EGF or PDGF, chemokines, integrin ligands and
CC hypertonic and oxidative stress. May be phosphorylated upon IgG
CC receptor FCGR2B-binding. Phosphorylated at Tyr-986 following cell
CC attachment and spreading. Phosphorylated at Tyr-1162 following EGF
CC signaling pathway stimulation. Phosphorylated at Thr-958 in response to
CC PDGF. {ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:11158326,
CC ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11687594,
CC ECO:0000269|PubMed:12235291, ECO:0000269|PubMed:12690104,
CC ECO:0000269|PubMed:17219406, ECO:0000269|PubMed:9660833}.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:12086927, ECO:0000269|PubMed:15687335}.
CC Note=Disease susceptibility may be associated with variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Note=Genetic variations in INPPL1 may be a cause of
CC susceptibility to metabolic syndrome. Metabolic syndrome is
CC characterized by diabetes, insulin resistance, hypertension, and
CC hypertriglyceridemia is absent. {ECO:0000269|PubMed:15220217,
CC ECO:0000269|PubMed:17557929}.
CC -!- DISEASE: Opsismodysplasia (OPSMD) [MIM:258480]: A rare skeletal
CC dysplasia involving delayed bone maturation. Clinical signs observed at
CC birth include short limbs, small hands and feet, relative macrocephaly
CC with a large anterior fontanel, and characteristic craniofacial
CC abnormalities including a prominent brow, depressed nasal bridge, a
CC small anteverted nose, and a relatively long philtrum. Death secondary
CC to respiratory failure during the first few years of life has been
CC reported, but there can be long-term survival. Typical radiographic
CC findings include shortened long bones with very delayed epiphyseal
CC ossification, severe platyspondyly, metaphyseal cupping, and
CC characteristic abnormalities of the metacarpals and phalanges.
CC {ECO:0000269|PubMed:23273569}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Its ability to confer resistance to dietary obesity
CC suggests that it may serve as a possible therapeutic target in cases of
CC type 2 diabetes and obesity.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA50503.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA96658.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/INPPL1ID40984ch11q13.html";
CC ---------------------------------------------------------------------------
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DR EMBL; L24444; AAA50503.1; ALT_FRAME; mRNA.
DR EMBL; L36818; AAA96658.1; ALT_FRAME; mRNA.
DR EMBL; Y14385; CAA74743.1; -; mRNA.
DR EMBL; AP000593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74855.1; -; Genomic_DNA.
DR EMBL; BC140853; AAI40854.1; -; mRNA.
DR CCDS; CCDS8213.1; -. [O15357-1]
DR PIR; JC5765; JC5765.
DR RefSeq; NP_001558.3; NM_001567.3. [O15357-1]
DR RefSeq; XP_011543301.1; XM_011544999.2. [O15357-1]
DR PDB; 2K4P; NMR; -; A=1194-1258.
DR PDB; 2KSO; NMR; -; B=1200-1258.
DR PDB; 2MK2; NMR; -; A=20-117.
DR PDB; 3NR8; X-ray; 2.80 A; A/B=419-732.
DR PDB; 4A9C; X-ray; 2.10 A; A/B=419-732.
DR PDB; 5OKM; X-ray; 1.96 A; A/B/C/D/E/F/G/H=420-878.
DR PDB; 5OKN; X-ray; 2.65 A; A/B/C/D/E/F/G/H=420-878.
DR PDB; 5OKO; X-ray; 1.94 A; A/B=420-878.
DR PDB; 5OKP; X-ray; 1.85 A; A=420-878.
DR PDB; 6SQU; X-ray; 2.27 A; A/B=419-732.
DR PDB; 6SRR; X-ray; 2.45 A; A/B=419-732.
DR PDBsum; 2K4P; -.
DR PDBsum; 2KSO; -.
DR PDBsum; 2MK2; -.
DR PDBsum; 3NR8; -.
DR PDBsum; 4A9C; -.
DR PDBsum; 5OKM; -.
DR PDBsum; 5OKN; -.
DR PDBsum; 5OKO; -.
DR PDBsum; 5OKP; -.
DR PDBsum; 6SQU; -.
DR PDBsum; 6SRR; -.
DR AlphaFoldDB; O15357; -.
DR BMRB; O15357; -.
DR SMR; O15357; -.
DR BioGRID; 109848; 164.
DR DIP; DIP-39733N; -.
DR IntAct; O15357; 120.
DR MINT; O15357; -.
DR STRING; 9606.ENSP00000298229; -.
DR BindingDB; O15357; -.
DR ChEMBL; CHEMBL2331064; -.
DR GuidetoPHARMACOLOGY; 1459; -.
DR SwissLipids; SLP:000000953; -.
DR DEPOD; INPPL1; -.
DR GlyGen; O15357; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; O15357; -.
DR MetOSite; O15357; -.
DR PhosphoSitePlus; O15357; -.
DR BioMuta; INPPL1; -.
DR EPD; O15357; -.
DR jPOST; O15357; -.
DR MassIVE; O15357; -.
DR MaxQB; O15357; -.
DR PaxDb; O15357; -.
DR PeptideAtlas; O15357; -.
DR PRIDE; O15357; -.
DR ProteomicsDB; 48609; -. [O15357-1]
DR ProteomicsDB; 48610; -. [O15357-2]
DR Antibodypedia; 30825; 357 antibodies from 33 providers.
DR DNASU; 3636; -.
DR Ensembl; ENST00000298229.7; ENSP00000298229.2; ENSG00000165458.15. [O15357-1]
DR Ensembl; ENST00000538751.5; ENSP00000444619.1; ENSG00000165458.15. [O15357-2]
DR GeneID; 3636; -.
DR KEGG; hsa:3636; -.
DR MANE-Select; ENST00000298229.7; ENSP00000298229.2; NM_001567.4; NP_001558.3.
DR UCSC; uc001osf.4; human. [O15357-1]
DR CTD; 3636; -.
DR DisGeNET; 3636; -.
DR GeneCards; INPPL1; -.
DR HGNC; HGNC:6080; INPPL1.
DR HPA; ENSG00000165458; Low tissue specificity.
DR MalaCards; INPPL1; -.
DR MIM; 125853; phenotype.
DR MIM; 258480; phenotype.
DR MIM; 600829; gene.
DR neXtProt; NX_O15357; -.
DR OpenTargets; ENSG00000165458; -.
DR Orphanet; 2746; Opsismodysplasia.
DR Orphanet; 3144; Schneckenbecken dysplasia.
DR PharmGKB; PA29888; -.
DR VEuPathDB; HostDB:ENSG00000165458; -.
DR eggNOG; KOG0565; Eukaryota.
DR eggNOG; KOG4384; Eukaryota.
DR GeneTree; ENSGT00940000156576; -.
DR HOGENOM; CLU_007493_1_1_1; -.
DR InParanoid; O15357; -.
DR OMA; EWISVDQ; -.
DR OrthoDB; 311217at2759; -.
DR PhylomeDB; O15357; -.
DR TreeFam; TF323475; -.
DR BioCyc; MetaCyc:HS09233-MON; -.
DR BRENDA; 3.1.3.56; 2681.
DR BRENDA; 3.1.3.86; 2681.
DR PathwayCommons; O15357; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR SABIO-RK; O15357; -.
DR SignaLink; O15357; -.
DR SIGNOR; O15357; -.
DR BioGRID-ORCS; 3636; 29 hits in 1096 CRISPR screens.
DR ChiTaRS; INPPL1; human.
DR EvolutionaryTrace; O15357; -.
DR GeneWiki; INPPL1; -.
DR GenomeRNAi; 3636; -.
DR Pharos; O15357; Tchem.
DR PRO; PR:O15357; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O15357; protein.
DR Bgee; ENSG00000165458; Expressed in mucosa of stomach and 145 other tissues.
DR ExpressionAtlas; O15357; baseline and differential.
DR Genevisible; O15357; HS.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IBA:GO_Central.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; TAS:Reactome.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:UniProtKB.
DR GO; GO:0001958; P:endochondral ossification; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0097178; P:ruffle assembly; IEA:Ensembl.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell adhesion;
KW Cell projection; Cytoplasm; Cytoskeleton; Diabetes mellitus;
KW Disease variant; Hydrolase; Immunity; Lipid metabolism; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; SH2 domain; SH3-binding.
FT CHAIN 1..1258
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 2"
FT /id="PRO_0000302870"
FT DOMAIN 21..117
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 1196..1258
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 119..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 897..1118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 944..949
FT /note="SH3-binding"
FT MOTIF 983..986
FT /note="NPXY motif"
FT COMPBIAS 120..140
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 938..954
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1048..1073
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1088..1105
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 886
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 958
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17219406,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 986
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:11349134,
FT ECO:0000269|PubMed:12235291"
FT MOD_RES 1131
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1135
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1162
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11687594,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1257
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..242
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8530088"
FT /id="VSP_027985"
FT VARIANT 401
FT /note="R -> W (in OPSMD; dbSNP:rs397514511)"
FT /evidence="ECO:0000269|PubMed:23273569"
FT /id="VAR_069586"
FT VARIANT 632
FT /note="L -> I (associated with susceptibility to NIDDM;
FT dbSNP:rs61749195)"
FT /evidence="ECO:0000269|PubMed:15687335"
FT /id="VAR_034980"
FT VARIANT 659
FT /note="P -> S (in OPSMD; dbSNP:rs397514510)"
FT /evidence="ECO:0000269|PubMed:23273569"
FT /id="VAR_069587"
FT VARIANT 688
FT /note="W -> C (in OPSMD)"
FT /evidence="ECO:0000269|PubMed:23273569"
FT /id="VAR_069588"
FT VARIANT 721
FT /note="V -> M (in dbSNP:rs116848359)"
FT /evidence="ECO:0000269|PubMed:15687335"
FT /id="VAR_034981"
FT VARIANT 722
FT /note="F -> I (in OPSMD; dbSNP:rs397514512)"
FT /evidence="ECO:0000269|PubMed:23273569"
FT /id="VAR_069589"
FT VARIANT 982
FT /note="N -> S (associated with susceptibility to NIDDM;
FT dbSNP:rs70940821)"
FT /evidence="ECO:0000269|PubMed:15687335"
FT /id="VAR_034982"
FT VARIANT 1083
FT /note="A -> G (in dbSNP:rs11548491)"
FT /evidence="ECO:0000269|PubMed:15687335"
FT /id="VAR_034983"
FT VARIANT 1114
FT /note="A -> G (in dbSNP:rs1049472)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9367831, ECO:0000269|Ref.4"
FT /id="VAR_034984"
FT MUTAGEN 47
FT /note="R->G: Abolishes interaction with p130Cas/BCAR1 and
FT its ability to induce increased adhesion. Abolishes
FT phosphorylation upon FCGR2A clustering."
FT /evidence="ECO:0000269|PubMed:11158326,
FT ECO:0000269|PubMed:12690104"
FT MUTAGEN 140..141
FT /note="PL->AA: Abolishes interaction with SH3YL1."
FT /evidence="ECO:0000269|PubMed:21624956"
FT MUTAGEN 607
FT /note="D->A: Abolishes enzyme activity but not
FT phosphorylation upon FCGR2A clustering."
FT /evidence="ECO:0000269|PubMed:12690104"
FT MUTAGEN 958
FT /note="T->A: Reduces PDGF-stimulated tyrosine
FT phosphorylation and association with SHC1."
FT /evidence="ECO:0000269|PubMed:17219406"
FT MUTAGEN 986..987
FT /note="YY->FF: Inducer a strong reduction of
FT phosphorylation upon re-plating on collagen I."
FT /evidence="ECO:0000269|PubMed:12235291"
FT CONFLICT 307
FT /note="I -> M (in Ref. 1; AAA96658)"
FT /evidence="ECO:0000305"
FT CONFLICT 1142
FT /note="R -> A (in Ref. 1; AAA50503/AAA96658)"
FT /evidence="ECO:0000305"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:2MK2"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:2MK2"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:2MK2"
FT STRAND 422..432
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 443..446
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 450..453
FT /evidence="ECO:0007829|PDB:5OKP"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 465..473
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 478..493
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 498..505
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 508..514
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 516..521
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 522..531
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 538..550
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 553..561
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 569..582
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 588..592
FT /evidence="ECO:0007829|PDB:5OKM"
FT HELIX 595..597
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 599..607
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 616..624
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 629..632
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 636..642
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 675..677
FT /evidence="ECO:0007829|PDB:4A9C"
FT STRAND 680..682
FT /evidence="ECO:0007829|PDB:4A9C"
FT STRAND 690..696
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 702..709
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 715..718
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 721..728
FT /evidence="ECO:0007829|PDB:5OKP"
FT TURN 732..734
FT /evidence="ECO:0007829|PDB:5OKO"
FT STRAND 747..758
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 765..770
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 774..776
FT /evidence="ECO:0007829|PDB:5OKO"
FT STRAND 784..787
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 793..799
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 800..802
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 813..816
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 820..827
FT /evidence="ECO:0007829|PDB:5OKP"
FT TURN 828..830
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 833..841
FT /evidence="ECO:0007829|PDB:5OKP"
FT TURN 842..844
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 845..848
FT /evidence="ECO:0007829|PDB:5OKO"
FT STRAND 850..858
FT /evidence="ECO:0007829|PDB:5OKP"
FT STRAND 861..873
FT /evidence="ECO:0007829|PDB:5OKP"
FT HELIX 1202..1206
FT /evidence="ECO:0007829|PDB:2K4P"
FT TURN 1207..1209
FT /evidence="ECO:0007829|PDB:2K4P"
FT HELIX 1211..1213
FT /evidence="ECO:0007829|PDB:2K4P"
FT HELIX 1214..1218
FT /evidence="ECO:0007829|PDB:2K4P"
FT TURN 1219..1221
FT /evidence="ECO:0007829|PDB:2K4P"
FT HELIX 1225..1228
FT /evidence="ECO:0007829|PDB:2K4P"
FT HELIX 1233..1238
FT /evidence="ECO:0007829|PDB:2K4P"
FT HELIX 1244..1256
FT /evidence="ECO:0007829|PDB:2K4P"
SQ SEQUENCE 1258 AA; 138599 MW; D76B5AA8ACDE8CBA CRC64;
MASACGAPGP GGALGSQAPS WYHRDLSRAA AEELLARAGR DGSFLVRDSE SVAGAFALCV
LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG LYAQPNQGLV CALLLPVEGE
REPDPPDDRD ASDGEDEKPP LPPRSGSTSI SAPTGPSSPL PAPETPTAPA AESAPNGLST
VSHDYLKGSY GLDLEAVRGG ASHLPHLTRT LATSCRRLHS EVDKVLSGLE ILSKVFDQQS
SPMVTRLLQQ QNLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPQPS
TRKAKTIPVQ AFEVKLDVTL GDLTKIGKSQ KFTLSVDVEG GRLVLLRRQR DSQEDWTTFT
HDRIRQLIKS QRVQNKLGVV FEKEKDRTQR KDFIFVSARK REAFCQLLQL MKNKHSKQDE
PDMISVFIGT WNMGSVPPPK NVTSWFTSKG LGKTLDEVTV TIPHDIYVFG TQENSVGDRE
WLDLLRGGLK ELTDLDYRPI AMQSLWNIKV AVLVKPEHEN RISHVSTSSV KTGIANTLGN
KGAVGVSFMF NGTSFGFVNC HLTSGNEKTA RRNQNYLDIL RLLSLGDRQL NAFDISLRFT
HLFWFGDLNY RLDMDIQEIL NYISRKEFEP LLRVDQLNLE REKHKVFLRF SEEEISFPPT
YRYERGSRDT YAWHKQKPTG VRTNVPSWCD RILWKSYPET HIICNSYGCT DDIVTSDHSP
VFGTFEVGVT SQFISKKGLS KTSDQAYIEF ESIEAIVKTA SRTKFFIEFY STCLEEYKKS
FENDAQSSDN INFLKVQWSS RQLPTLKPIL ADIEYLQDQH LLLTVKSMDG YESYGECVVA
LKSMIGSTAQ QFLTFLSHRG EETGNIRGSM KVRVPTERLG TRERLYEWIS IDKDEAGAKS
KAPSVSRGSQ EPRSGSRKPA FTEASCPLSR LFEEPEKPPP TGRPPAPPRA APREEPLTPR
LKPEGAPEPE GVAAPPPKNS FNNPAYYVLE GVPHQLLPPE PPSPARAPVP SATKNKVAIT
VPAPQLGHHR HPRVGEGSSS DEESGGTLPP PDFPPPPLPD SAIFLPPSLD PLPGPVVRGR
GGAEARGPPP PKAHPRPPLP PGPSPASTFL GEVASGDDRS CSVLQMAKTL SEVDYAPAGP
ARSALLPGPL ELQPPRGLPS DYGRPLSFPP PRIRESIQED LAEEAPCLQG GRASGLGEAG
MSAWLRAIGL ERYEEGLVHN GWDDLEFLSD ITEEDLEEAG VQDPAHKRLL LDTLQLSK
