SHIP1_MOUSE
ID SHIP1_MOUSE Reviewed; 1191 AA.
AC Q9ES52; Q3UPF9; Q4U212; Q61034; Q61173; Q61181; Q9JKR7; Q9JLF9; Q9JLG0;
AC Q9QVN8; Q9WUC2;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 {ECO:0000305};
DE EC=3.1.3.86 {ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9341117};
DE AltName: Full=Inositol polyphosphate-5-phosphatase D;
DE EC=3.1.3.56 {ECO:0000250|UniProtKB:Q92835};
DE AltName: Full=Inositol polyphosphate-5-phosphatase of 145 kDa {ECO:0000303|PubMed:8643691};
DE Short=SIP-145 {ECO:0000303|PubMed:8643691};
DE AltName: Full=Phosphatidylinositol-4,5-bisphosphate 5-phosphatase;
DE EC=3.1.3.36 {ECO:0000269|PubMed:9367159};
DE AltName: Full=SH2 domain-containing inositol 5'-phosphatase 1;
DE Short=SH2 domain-containing inositol phosphatase 1;
DE Short=SHIP-1;
DE AltName: Full=p150Ship {ECO:0000303|PubMed:8654924};
GN Name=Inpp5d; Synonyms=7a33, Ship, Ship1;
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] (ISOFORM 2), PROTEIN SEQUENCE OF 2-9 AND
RP 1163-1173, FUNCTION, ENZYME ACTIVITY, PHOSPHORYLATION, TISSUE SPECIFICITY,
RP AND INTERACTION WITH SHC1.
RC STRAIN=DBA/2J;
RX PubMed=8654924; DOI=10.1101/gad.10.9.1084;
RA Lioubin M.N., Algate P.A., Tsai S., Carlberg K., Aebersold A.,
RA Rohrschneider L.R.;
RT "p150Ship, a signal transduction molecule with inositol polyphosphate-5-
RT phosphatase activity.";
RL Genes Dev. 10:1084-1095(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 902-916, ENZYME
RP ACTIVITY, TISSUE SPECIFICITY, AND INTERACTION WITH GRB2 AND SHC1.
RX PubMed=8643691; DOI=10.1073/pnas.93.4.1689;
RA Damen J.E., Liu L., Rosten P., Humphries R.K., Jefferson A.B.,
RA Majerus P.W., Krystal G.;
RT "The 145-kDa protein induced to associate with Shc by multiple cytokines is
RT an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-
RT phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1689-1693(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9027494; DOI=10.1006/geno.1996.4374;
RA Liu Q., Dumont D.J.;
RT "Molecular cloning and chromosomal localization in human and mouse of the
RT SH2-containing inositol phosphatase, INPP5D (SHIP).";
RL Genomics 39:109-112(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PHOSPHORYLATION, INTERACTION WITH
RP SHC1 AND GRB2, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ;
RX PubMed=10068665;
RA Lucas D.M., Rohrschneider L.R.;
RT "A novel spliced form of SH2-containing inositol phosphatase is expressed
RT during myeloid development.";
RL Blood 93:1922-1933(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 4).
RC STRAIN=129/Sv;
RX PubMed=11013080; DOI=10.1006/geno.2000.6324;
RA Wolf I., Lucas D.M., Algate P.A., Rohrschneider L.R.;
RT "Cloning of the genomic locus of mouse SH2 containing inositol 5-
RT phosphatase (SHIP) and a novel 110-kDa splice isoform, SHIPdelta.";
RL Genomics 69:104-112(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND SUBCELLULAR LOCATION (ISOFORM
RP 5).
RX PubMed=11567986; DOI=10.1182/blood.v98.7.2028;
RA Tu Z., Ninos J.M., Ma Z., Wang J.-W., Lemos M.P., Desponts C., Ghansah T.,
RA Howson J.M., Kerr W.G.;
RT "Embryonic and hematopoietic stem cells express a novel SH2-containing
RT inositol 5'-phosphatase isoform that partners with the Grb2 adapter
RT protein.";
RL Blood 98:2028-2038(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thyroid;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-106.
RX PubMed=8632995; DOI=10.1073/pnas.93.9.3947;
RA Kerr W.G., Heller M., Herzenberg L.A.;
RT "Analysis of lipopolysaccharide-response genes in B-lineage cells
RT demonstrates that they can have differentiation stage-restricted expression
RT and contain SH2 domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:3947-3952(1996).
RN [10]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=8723348; DOI=10.1016/s0960-9822(02)00511-0;
RA Kavanaugh W.M., Pot D.A., Chin S.M., Deuter-Reinhard M., Jefferson A.B.,
RA Norris F.A., Masiarz F.R., Cousens L.S., Majerus P.W., Williams L.T.;
RT "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling
RT complexes with Shc and Grb2.";
RL Curr. Biol. 6:438-445(1996).
RN [11]
RP FUNCTION.
RX PubMed=8805703; DOI=10.1038/383263a0;
RA Ono M., Bolland S., Tempst P., Ravetch J.V.;
RT "Role of the inositol phosphatase SHIP in negative regulation of the immune
RT system by the receptor Fc(gamma)RIIB.";
RL Nature 383:263-266(1996).
RN [12]
RP PHOSPHORYLATION.
RX PubMed=8805618;
RA Chacko G.W., Tridandapani S., Damen J.E., Liu L., Krystal G.,
RA Coggeshall K.M.;
RT "Negative signaling in B lymphocytes induces tyrosine phosphorylation of
RT the 145-kDa inositol polyphosphate 5-phosphatase, SHIP.";
RL J. Immunol. 157:2234-2238(1996).
RN [13]
RP FUNCTION.
RX PubMed=9244303; DOI=10.1016/s0092-8674(00)80337-2;
RA Ono M., Okada H., Bolland S., Yanagi S., Kurosaki T., Ravetch J.V.;
RT "Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory
RT signaling.";
RL Cell 90:293-301(1997).
RN [14]
RP DOMAIN SH2, AND INTERACTION WITH SHC1.
RX PubMed=9083021; DOI=10.1074/jbc.272.14.8983;
RA Liu L., Damen J.E., Hughes M.R., Babic I., Jirik F.R., Krystal G.;
RT "The Src homology 2 (SH2) domain of SH2-containing inositol phosphatase
RT (SHIP) is essential for tyrosine phosphorylation of SHIP, its association
RT with Shc, and its induction of apoptosis.";
RL J. Biol. Chem. 272:8983-8988(1997).
RN [15]
RP PHOSPHORYLATION AT TYR-918 AND TYR-1021, INTERACTION WITH SHC1, AND
RP MUTAGENESIS OF TYR-918 AND TYR-1021.
RX PubMed=9099679; DOI=10.1074/jbc.272.16.10396;
RA Lamkin T.D., Walk S.F., Liu L., Damen J.E., Krystal G., Ravichandran K.S.;
RT "Shc interaction with Src homology 2 domain containing inositol phosphatase
RT (SHIP) in vivo requires the Shc-phosphotyrosine binding domain and two
RT specific phosphotyrosines on SHIP.";
RL J. Biol. Chem. 272:10396-10401(1997).
RN [16]
RP INTERACTION WITH PTPN11.
RX PubMed=9110989; DOI=10.1074/jbc.272.17.10998;
RA Liu L., Damen J.E., Ware M.D., Krystal G.;
RT "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP
RT with SHP2.";
RL J. Biol. Chem. 272:10998-11001(1997).
RN [17]
RP CATALYTIC ACTIVITY.
RX PubMed=9367159; DOI=10.1038/36621;
RA Rameh L.E., Tolias K.F., Duckworth B.C., Cantley L.C.;
RT "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate.";
RL Nature 390:192-196(1997).
RN [18]
RP INTERACTION WITH KLRC1.
RX PubMed=9485206;
RX DOI=10.1002/(sici)1521-4141(199801)28:01<264::aid-immu264>3.0.co;2-o;
RA Le Drean E., Vely F., Olcese L., Cambiaggi A., Guia S., Krystal G.,
RA Gervois N., Moretta A., Jotereau F., Vivier E.;
RT "Inhibition of antigen-induced T cell response and antibody-induced NK cell
RT cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-
RT tyrosine phosphatases.";
RL Eur. J. Immunol. 28:264-276(1998).
RN [19]
RP INTERACTION WITH DAB2.
RX PubMed=11247302; DOI=10.1034/j.1600-0854.2001.020206.x;
RA Morris S.M., Cooper J.A.;
RT "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts
RT with AP-2.";
RL Traffic 2:111-123(2001).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-935 AND TYR-945, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-935; THR-964;
RP SER-967 AND SER-972, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
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).
RN [23]
RP INTERACTION WITH MILR1.
RX PubMed=20526344; DOI=10.1038/ni.1886;
RA Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T.,
RA Shibayama S., Shibuya K., Shibuya A.;
RT "An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-
RT mediated immediate hypersensitivity reactions.";
RL Nat. Immunol. 11:601-607(2010).
RN [24]
RP ENZYME ACTIVITY.
RX PubMed=9341117; DOI=10.1074/jbc.272.43.26857;
RA Giuriato S., Payrastre B., Drayer A.L., Plantavid M., Woscholski R.,
RA Parker P., Erneux C., Chap H.;
RT "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in
RT thrombin-stimulated human blood platelets.";
RL J. Biol. Chem. 272:26857-26863(1997).
RN [25]
RP INTERACTION WITH PTPN11.
RX PubMed=9393882; DOI=10.1038/sj.onc.1201422;
RA Sattler M., Salgia R., Shrikhande G., Verma S., Choi J.-L.,
RA Rohrschneider L.R., Griffin J.D.;
RT "The phosphatidylinositol polyphosphate 5-phosphatase SHIP and the protein
RT tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can
RT be regulated by BCR/ABL and growth factors.";
RL Oncogene 15:2379-2384(1997).
RN [26]
RP SUBCELLULAR LOCATION.
RX PubMed=9694708;
RA Damen J.E., Liu L., Ware M.D., Ermolaeva M., Majerus P.W., Krystal G.;
RT "Multiple forms of the SH2-containing inositol phosphatase, SHIP, are
RT generated by C-terminal truncation.";
RL Blood 92:1199-1205(1998).
RN [27]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9531585;
RA Liu Q., Shalaby F., Jones J., Bouchard D., Dumont D.J.;
RT "The SH2-containing inositol polyphosphate 5-phosphatase, ship, is
RT expressed during hematopoiesis and spermatogenesis.";
RL Blood 91:2753-2759(1998).
RN [28]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9857188; DOI=10.1093/emboj/17.24.7311;
RA Huber M., Helgason C.D., Scheid M.P., Duronio V., Humphries R.K.,
RA Krystal G.;
RT "Targeted disruption of SHIP leads to Steel factor-induced degranulation of
RT mast cells.";
RL EMBO J. 17:7311-7319(1998).
RN [29]
RP FUNCTION.
RX PubMed=9763612; DOI=10.1084/jem.188.7.1333;
RA Liu Q., Oliveira-Dos-Santos A.J., Mariathasan S., Bouchard D., Jones J.,
RA Sarao R., Kozieradzki I., Ohashi P.S., Penninger J.M., Dumont D.J.;
RT "The inositol polyphosphate 5-phosphatase ship is a crucial negative
RT regulator of B cell antigen receptor signaling.";
RL J. Exp. Med. 188:1333-1342(1998).
RN [30]
RP FUNCTION.
RX PubMed=9736736; DOI=10.1073/pnas.95.19.11330;
RA Huber M., Helgason C.D., Damen J.E., Liu L., Humphries R.K., Krystal G.;
RT "The src homology 2-containing inositol phosphatase (SHIP) is the
RT gatekeeper of mast cell degranulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11330-11335(1998).
RN [31]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9620849; DOI=10.1101/gad.12.11.1610;
RA Helgason C.D., Damen J.E., Rosten P., Grewal R., Sorensen P., Chappel S.M.,
RA Borowski A., Jirik F., Krystal G., Humphries R.K.;
RT "Targeted disruption of SHIP leads to hemopoietic perturbations, lung
RT pathology, and a shortened life span.";
RL Genes Dev. 12:1610-1620(1998).
RN [32]
RP INTERACTION WITH SHC1 AND FCGR2B, AND PHOSPHORYLATION.
RX PubMed=10395202; DOI=10.1016/s0161-5890(98)00097-2;
RA Tridandapani S., Phee H., Shivakumar L., Kelley T.W., Coggeshall K.M.;
RT "Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B
RT cells.";
RL Mol. Immunol. 35:1135-1146(1998).
RN [33]
RP INTERACTION WITH SRC.
RX PubMed=10794720; DOI=10.1042/bj3480107;
RA Giuriato S., Bodin S., Erneux C., Woscholski R., Plantavid M., Chap H.,
RA Payrastre B.;
RT "pp60c-src associates with the SH2-containing inositol-5-phosphatase SHIP1
RT and is involved in its tyrosine phosphorylation downstream of alphaIIbbeta3
RT integrin in human platelets.";
RL Biochem. J. 348:107-112(2000).
RN [34]
RP INTERACTION WITH EPOR, AND PHOSPHORYLATION.
RX PubMed=10660611; DOI=10.1074/jbc.275.6.4398;
RA Mason J.M., Beattie B.K., Liu Q., Dumont D.J., Barber D.L.;
RT "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent
RT manner to the erythropoietin receptor.";
RL J. Biol. Chem. 275:4398-4406(2000).
RN [35]
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 [36]
RP INTERACTION WITH FCGR2B.
RX PubMed=10779347; DOI=10.1128/mcb.20.10.3576-3589.2000;
RA Aman M.J., Walk S.F., March M.E., Su H.-P., Carver D.J., Ravichandran K.S.;
RT "Essential role for the C-terminal noncatalytic region of SHIP in
RT FcgammaRIIB1-mediated inhibitory signaling.";
RL Mol. Cell. Biol. 20:3576-3589(2000).
RN [37]
RP FUNCTION, AND MUTAGENESIS OF ASP-676; TYR-918 AND TYR-1021.
RX PubMed=11222379; DOI=10.1182/blood.v97.5.1343;
RA Damen J.E., Ware M.D., Kalesnikoff J., Hughes M.R., Krystal G.;
RT "SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition
RT of mast cell degranulation.";
RL Blood 97:1343-1351(2001).
RN [38]
RP INTERACTION WITH DOK1 AND CRKL, AND MUTAGENESIS OF TYR-918 AND TYR-1021.
RX PubMed=11031258; DOI=10.1074/jbc.m006250200;
RA Sattler M., Verma S., Pride Y.B., Salgia R., Rohrschneider L.R.,
RA Griffin J.D.;
RT "SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates
RT migration through two critical tyrosine residues and forms a novel
RT signaling complex with DOK1 and CRKL.";
RL J. Biol. Chem. 276:2451-2458(2001).
RN [39]
RP FUNCTION.
RX PubMed=11359765; DOI=10.1074/jbc.m011094200;
RA Malbec O., Schmitt C., Bruhns P., Krystal G., Fridman W.H., Daeeron M.;
RT "Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell
RT cycle arrest by FcgammaRIIB.";
RL J. Biol. Chem. 276:30381-30391(2001).
RN [40]
RP FUNCTION.
RX PubMed=11136821; DOI=10.1084/jem.193.1.61;
RA Cox D., Dale B.M., Kashiwada M., Helgason C.D., Greenberg S.;
RT "A regulatory role for Src homology 2 domain-containing inositol 5'-
RT phosphatase (SHIP) in phagocytosis mediated by Fc gamma receptors and
RT complement receptor 3 (alpha(M)beta(2); CD11b/CD18).";
RL J. Exp. Med. 193:61-71(2001).
RN [41]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH FCGR3.
RX PubMed=12393695; DOI=10.1182/blood-2002-04-1058;
RA Galandrini R., Tassi I., Mattia G., Lenti L., Piccoli M., Frati L.,
RA Santoni A.;
RT "SH2-containing inositol phosphatase (SHIP-1) transiently translocates to
RT raft domains and modulates CD16-mediated cytotoxicity in human NK cells.";
RL Blood 100:4581-4589(2002).
RN [42]
RP FUNCTION, INTERACTION WITH FCGR2A, AND PHOSPHORYLATION.
RX PubMed=12370370; DOI=10.4049/jimmunol.169.8.4370;
RA Tridandapani S., Wang Y., Marsh C.B., Anderson C.L.;
RT "Src homology 2 domain-containing inositol polyphosphate phosphatase
RT regulates NF-kappa B-mediated gene transcription by phagocytic Fc gamma Rs
RT in human myeloid cells.";
RL J. Immunol. 169:4370-4378(2002).
RN [43]
RP FUNCTION, AND INDUCTION.
RX PubMed=12447389; DOI=10.1038/ncb885;
RA Valderrama-Carvajal H., Cocolakis E., Lacerte A., Lee E.-H., Krystal G.,
RA Ali S., Lebrun J.-J.;
RT "Activin/TGF-beta induce apoptosis through Smad-dependent expression of the
RT lipid phosphatase SHIP.";
RL Nat. Cell Biol. 4:963-969(2002).
RN [44]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12161749; DOI=10.1038/nm752;
RA Takeshita S., Namba N., Zhao J.J., Jiang Y., Genant H.K., Silva M.J.,
RA Brodt M.D., Helgason C.D., Kalesnikoff J., Rauh M.J., Humphries R.K.,
RA Krystal G., Teitelbaum S.L., Ross F.P.;
RT "SHIP-deficient mice are severely osteoporotic due to increased numbers of
RT hyper-resorptive osteoclasts.";
RL Nat. Med. 8:943-949(2002).
RN [45]
RP FUNCTION, AND INTERACTION WITH MET.
RX PubMed=11896575; DOI=10.1038/sj.onc.1205224;
RA Mancini A., Koch A., Wilms R., Tamura T.;
RT "The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the
RT control of cell-cell junction and induces dissociation and dispersion of
RT MDCK cells.";
RL Oncogene 21:1477-1484(2002).
RN [46]
RP FUNCTION.
RX PubMed=12882960; DOI=10.1074/jbc.m305021200;
RA Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., Krystal G.,
RA Marsh C.B.;
RT "The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively
RT regulate macrophage colony-stimulating factor-induced Akt activity.";
RL J. Biol. Chem. 278:38628-38636(2003).
RN [47]
RP FUNCTION.
RX PubMed=15166241; DOI=10.1074/jbc.m400746200;
RA Maxwell M.J., Yuan Y., Anderson K.E., Hibbs M.L., Salem H.H., Jackson S.P.;
RT "SHIP1 and Lyn kinase negatively regulate integrin alpha IIb beta 3
RT signaling in platelets.";
RL J. Biol. Chem. 279:32196-32204(2004).
RN [48]
RP INTERACTION WITH FCGR2B.
RX PubMed=15456754; DOI=10.1074/jbc.m410261200;
RA Isnardi I., Lesourne R., Bruhns P., Fridman W.H., Cambier J.C., Daeeron M.;
RT "Two distinct tyrosine-based motifs enable the inhibitory receptor
RT FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and
RT the adapters Grb2/Grap.";
RL J. Biol. Chem. 279:51931-51938(2004).
RN [49]
RP INTERACTION WITH TEC.
RX PubMed=15492005; DOI=10.1074/jbc.m408141200;
RA Tomlinson M.G., Heath V.L., Turck C.W., Watson S.P., Weiss A.;
RT "SHIP family inositol phosphatases interact with and negatively regulate
RT the Tec tyrosine kinase.";
RL J. Biol. Chem. 279:55089-55096(2004).
RN [50]
RP FUNCTION, AND INTERACTION WITH DOK3.
RX PubMed=14993273; DOI=10.1128/mcb.24.6.2332-2343.2004;
RA Robson J.D., Davidson D., Veillette A.;
RT "Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid
RT phosphatase that interacts with the adaptor molecule Dok-3.";
RL Mol. Cell. Biol. 24:2332-2343(2004).
RN [51]
RP INTERACTION WITH PLCG1.
RX PubMed=16000869; DOI=10.1038/emm.2005.22;
RA Song M., Kim M.J., Ha S., Park J.B., Ryu S.H., Suh P.-G.;
RT "Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and
RT modulates EGF-induced PLC activity.";
RL Exp. Mol. Med. 37:161-168(2005).
RN [52]
RP SUBCELLULAR LOCATION.
RX PubMed=16406061; DOI=10.1016/j.imlet.2005.11.027;
RA Isnardi I., Bruhns P., Bismuth G., Fridman W.H., Daeeron M.;
RT "The SH2 domain-containing inositol 5-phosphatase SHIP1 is recruited to the
RT intracytoplasmic domain of human FcgammaRIIB and is mandatory for negative
RT regulation of B cell activation.";
RL Immunol. Lett. 104:156-165(2006).
RN [53]
RP FUNCTION.
RX PubMed=17142780; DOI=10.4049/jimmunol.177.12.8777;
RA Zhou P., Kitaura H., Teitelbaum S.L., Krystal G., Ross F.P., Takeshita S.;
RT "SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-
RT dependent alterations in D-type cyclins and p27.";
RL J. Immunol. 177:8777-8784(2006).
RN [54]
RP INTERACTION WITH IL6ST.
RX PubMed=17105399; DOI=10.1089/scd.2006.15.641;
RA Desponts C., Ninos J.M., Kerr W.G.;
RT "s-SHIP associates with receptor complexes essential for pluripotent stem
RT cell growth and survival.";
RL Stem Cells Dev. 15:641-646(2006).
RN [55]
RP FUNCTION.
RX PubMed=17173042; DOI=10.1038/ncb1515;
RA Nishio M., Watanabe K., Sasaki J., Taya C., Takasuga S., Iizuka R.,
RA Balla T., Yamazaki M., Watanabe H., Itoh R., Kuroda S., Horie Y.,
RA Foerster I., Mak T.W., Yonekawa H., Penninger J.M., Kanaho Y., Suzuki A.,
RA Sasaki T.;
RT "Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase
RT SHIP1.";
RL Nat. Cell Biol. 9:36-44(2007).
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 (By
CC similarity). Also able to hydrolyze the 5-phosphate of
CC phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol
CC 1,3,4,5-tetrakisphosphate (PubMed:9367159). Acts as a negative
CC regulator of B-cell antigen receptor signaling. Mediates signaling from
CC the FC-gamma-RIIB receptor (FCGR2B), playing a central role in
CC terminating signal transduction from activating immune/hematopoietic
CC cell receptor systems. Acts as a negative regulator of myeloid cell
CC proliferation/survival and chemotaxis, mast cell degranulation, immune
CC cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and
CC JNK signaling in B-cells. Regulates proliferation of osteoclast
CC precursors, macrophage programming, phagocytosis and activation and is
CC required for endotoxin tolerance. Involved in the control of cell-cell
CC junctions, CD32a signaling in neutrophils and modulation of EGF-induced
CC phospholipase C activity. Key regulator of neutrophil migration, by
CC governing the formation of the leading edge and polarization required
CC for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells.
CC Mediates the activin/TGF-beta-induced apoptosis through its Smad-
CC dependent expression. {ECO:0000250|UniProtKB:Q92835,
CC ECO:0000269|PubMed:11136821, ECO:0000269|PubMed:11222379,
CC ECO:0000269|PubMed:11359765, ECO:0000269|PubMed:11896575,
CC ECO:0000269|PubMed:12161749, ECO:0000269|PubMed:12370370,
CC ECO:0000269|PubMed:12447389, ECO:0000269|PubMed:12882960,
CC ECO:0000269|PubMed:14993273, ECO:0000269|PubMed:15166241,
CC ECO:0000269|PubMed:17142780, ECO:0000269|PubMed:17173042,
CC ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:8805703,
CC ECO:0000269|PubMed:9244303, ECO:0000269|PubMed:9367159,
CC ECO:0000269|PubMed:9620849, ECO:0000269|PubMed:9736736,
CC ECO:0000269|PubMed:9763612, ECO:0000269|PubMed:9857188}.
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; Evidence={ECO:0000269|PubMed:8643691,
CC ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9341117};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456; EC=3.1.3.36;
CC Evidence={ECO:0000269|PubMed:9367159};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,3,4-trisphosphate + phosphate; Xref=Rhea:RHEA:11392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414; EC=3.1.3.56;
CC Evidence={ECO:0000250|UniProtKB:Q92835};
CC -!- ACTIVITY REGULATION: Activated upon translocation to the sites of
CC synthesis of PtdIns(3,4,5)P3 in the membrane.
CC -!- SUBUNIT: Interacts with tyrosine phosphorylated form of SHC1
CC (PubMed:8654924, PubMed:8643691, PubMed:10068665, PubMed:9083021,
CC PubMed:9099679, PubMed:10395202). Interacts with tyrosine
CC phosphorylated form of DOK1 (PubMed:11031258). Interacts with tyrosine
CC phosphorylated form of DOK3 (PubMed:14993273). Interacts with tyrosine
CC phosphorylated form of SLAMF1/CD150 (By similarity). Interacts with
CC PTPN11/SHP-2 in response to IL-3 (PubMed:9110989, PubMed:9393882).
CC Interacts with receptor EPOR (PubMed:10660611). Interacts with
CC receptors MS4A2/FCER1B and FCER1G (By similarity). Interacts with
CC receptors FCGR2B and FCGR3 (PubMed:10395202, PubMed:11016922,
CC PubMed:10779347, PubMed:15456754, PubMed:12393695). Interacts with
CC receptor FCGR2A, leading to regulate gene expression during the
CC phagocytic process (PubMed:12370370). Interacts with GRB2
CC (PubMed:8643691, PubMed:10068665). Interacts with PLCG1
CC (PubMed:16000869). Interacts with tyrosine kinases SRC and TEC
CC (PubMed:10794720, PubMed:15492005). Interacts with CRKL
CC (PubMed:11031258). Interacts with c-Met/MET (PubMed:11896575).
CC Interacts with MILR1 (tyrosine-phosphorylated) (PubMed:20526344).
CC Isoform 5 interacts with IL6ST/gp130 (PubMed:17105399). Can weakly
CC interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction
CC is impaired by tyrosine phosphorylation of the NPXY motif
CC (PubMed:11247302). Interacts (via SH2 domain) with tyrosine
CC phosphorylated KLRC1 (via ITIM). {ECO:0000250|UniProtKB:P97573,
CC ECO:0000250|UniProtKB:Q92835, ECO:0000269|PubMed:10068665,
CC ECO:0000269|PubMed:10395202, ECO:0000269|PubMed:10660611,
CC ECO:0000269|PubMed:10779347, ECO:0000269|PubMed:10794720,
CC ECO:0000269|PubMed:11016922, ECO:0000269|PubMed:11031258,
CC ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11896575,
CC ECO:0000269|PubMed:12370370, ECO:0000269|PubMed:12393695,
CC ECO:0000269|PubMed:14993273, ECO:0000269|PubMed:15456754,
CC ECO:0000269|PubMed:15492005, ECO:0000269|PubMed:16000869,
CC ECO:0000269|PubMed:17105399, ECO:0000269|PubMed:20526344,
CC ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924,
CC ECO:0000269|PubMed:9083021, ECO:0000269|PubMed:9099679,
CC ECO:0000269|PubMed:9110989, ECO:0000269|PubMed:9393882,
CC ECO:0000269|PubMed:9485206}.
CC -!- INTERACTION:
CC Q9ES52; Q8CIH5: Plcg2; NbExp=3; IntAct=EBI-300210, EBI-617954;
CC Q9ES52-1; P23727: PIK3R1; Xeno; NbExp=2; IntAct=EBI-1452545, EBI-520244;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16406061}. Cell
CC membrane {ECO:0000269|PubMed:12393695}; Peripheral membrane protein
CC {ECO:0000305|PubMed:12393695}. Membrane raft
CC {ECO:0000269|PubMed:12393695}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9694708}. Note=Translocates to the plasma membrane
CC when activated, translocation is probably due to different mechanisms
CC depending on the stimulus and cell type (PubMed:12393695). Translocates
CC from the cytoplasm to membrane ruffles in a FCGR3/CD16-dependent manner
CC (PubMed:12393695). Colocalizes with FC-gamma-RIIB receptor (FCGR2B) or
CC FCGR3/CD16 at membrane ruffles (PubMed:12393695). Tyrosine
CC phosphorylation may also participate in membrane localization
CC (PubMed:12393695). {ECO:0000269|PubMed:12393695}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane
CC {ECO:0000269|PubMed:11567986}; Peripheral membrane protein
CC {ECO:0000305|PubMed:11567986}. Note=Constitutively present at the cell
CC membrane (PubMed:11567986). {ECO:0000269|PubMed:11567986}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q9ES52-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ES52-2; Sequence=VSP_027981;
CC Name=3; Synonyms=135 kDa SHIP;
CC IsoId=Q9ES52-3; Sequence=VSP_027982;
CC Name=4; Synonyms=SHIPdelta;
CC IsoId=Q9ES52-4; Sequence=VSP_027981, VSP_027983, VSP_027984;
CC Name=5; Synonyms=s-SHIP;
CC IsoId=Q9ES52-5; Sequence=VSP_027980;
CC Name=6; Synonyms=s-SHIPD183;
CC IsoId=Q9ES52-6; Sequence=VSP_027980, VSP_027982;
CC -!- TISSUE SPECIFICITY: Specifically expressed in immune and hematopoietic
CC cells. Levels vary considerably within this compartment. Lost during
CC erythropoiesis when erythroid cells become Ter119+. Increases
CC substantially with T-cell maturation and when resting B-cells are
CC activated. Also present in mature granulocytes, monocyte/macrophages,
CC mast cells and platelets. Isoform 5 is the only form expressed in
CC embryonic stem (ES) cells and is coexpressed with other isoforms in
CC hematopoietic stem cells, and disappears with differentiation.
CC {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:8643691,
CC ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:9531585}.
CC -!- DEVELOPMENTAL STAGE: Expressed in late primitive-streak stage embryos
CC (7.5 dpc), when hematopoiesis is thought to begin, and the expression
CC is restricted to the hematopoietic lineage in embryo. In adults
CC expression continues to be in the majority of cells from hematopoietic
CC origin, including granulocytes, monocytes and lymphocytes, and is also
CC found in the spermatids of the testis. {ECO:0000269|PubMed:10068665,
CC ECO:0000269|PubMed:9531585}.
CC -!- INDUCTION: By activin/TGF-beta (at protein level). Regulated by the
CC Smad pathway. Isoform 3 is expressed during myeloid development.
CC {ECO:0000269|PubMed:12447389}.
CC -!- DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of
CC proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2
CC for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is
CC also required for tyrosine phosphorylation.
CC {ECO:0000269|PubMed:9083021}.
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:0000269|PubMed:9083021}.
CC -!- PTM: Tyrosine phosphorylated by the members of the SRC family after
CC exposure to a diverse array of extracellular stimuli such as cytokines,
CC growth factors, antibodies, chemokines, integrin ligands and hypertonic
CC and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.
CC {ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:10395202,
CC ECO:0000269|PubMed:10660611, ECO:0000269|PubMed:12370370,
CC ECO:0000269|PubMed:8654924, ECO:0000269|PubMed:8805618,
CC ECO:0000269|PubMed:9099679}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile. They however fail to
CC thrive and only 40% survive by 14 weeks of age. Mortality is associated
CC with extensive consolidation of the lungs resulting from infiltration
CC by myeloid cells. Increased numbers of granulocyte-macrophage
CC progenitors are observed in both the bone marrow and spleen. Absence of
CC Inpp5d leads to steel factor-induced degranulation of mast cells. They
CC also display increased numbers of osteoclast precursors leading to a
CC severe osteoporosis. {ECO:0000269|PubMed:12161749,
CC ECO:0000269|PubMed:9620849, ECO:0000269|PubMed:9857188}.
CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; U51742; AAC52606.1; -; mRNA.
DR EMBL; U39203; AAB18937.1; -; mRNA.
DR EMBL; U52044; AAC53023.1; -; mRNA.
DR EMBL; AF125996; AAD37118.1; -; mRNA.
DR EMBL; AF235502; AAG23922.1; -; Genomic_DNA.
DR EMBL; AF235496; AAG23922.1; JOINED; Genomic_DNA.
DR EMBL; AF235498; AAG23922.1; JOINED; Genomic_DNA.
DR EMBL; AF235499; AAG23922.1; JOINED; Genomic_DNA.
DR EMBL; AF235500; AAG23922.1; JOINED; Genomic_DNA.
DR EMBL; AF235501; AAG23922.1; JOINED; Genomic_DNA.
DR EMBL; AF228679; AAF69143.1; -; mRNA.
DR EMBL; AF184912; AAF25823.1; -; mRNA.
DR EMBL; AF184913; AAF25824.1; -; mRNA.
DR EMBL; AK143560; BAE25436.1; -; mRNA.
DR EMBL; BC108328; AAI08329.1; -; mRNA.
DR CCDS; CCDS35655.1; -. [Q9ES52-1]
DR CCDS; CCDS48310.1; -. [Q9ES52-3]
DR CCDS; CCDS48311.1; -. [Q9ES52-2]
DR PIR; JC6118; JC6118.
DR RefSeq; NP_001103662.1; NM_001110192.2. [Q9ES52-2]
DR RefSeq; NP_001103663.1; NM_001110193.2. [Q9ES52-3]
DR RefSeq; NP_034696.2; NM_010566.3. [Q9ES52-1]
DR PDB; 6DLG; X-ray; 1.50 A; A=402-861.
DR PDBsum; 6DLG; -.
DR AlphaFoldDB; Q9ES52; -.
DR SMR; Q9ES52; -.
DR BioGRID; 200769; 29.
DR CORUM; Q9ES52; -.
DR IntAct; Q9ES52; 16.
DR MINT; Q9ES52; -.
DR STRING; 10090.ENSMUSP00000127941; -.
DR SwissLipids; SLP:000000873; -.
DR iPTMnet; Q9ES52; -.
DR PhosphoSitePlus; Q9ES52; -.
DR SwissPalm; Q9ES52; -.
DR EPD; Q9ES52; -.
DR jPOST; Q9ES52; -.
DR MaxQB; Q9ES52; -.
DR PaxDb; Q9ES52; -.
DR PeptideAtlas; Q9ES52; -.
DR PRIDE; Q9ES52; -.
DR ProteomicsDB; 255405; -. [Q9ES52-1]
DR ProteomicsDB; 255406; -. [Q9ES52-2]
DR ProteomicsDB; 255407; -. [Q9ES52-3]
DR ProteomicsDB; 255408; -. [Q9ES52-4]
DR ProteomicsDB; 255409; -. [Q9ES52-5]
DR ProteomicsDB; 255410; -. [Q9ES52-6]
DR Antibodypedia; 4272; 578 antibodies from 44 providers.
DR DNASU; 16331; -.
DR Ensembl; ENSMUST00000042275; ENSMUSP00000044647; ENSMUSG00000026288. [Q9ES52-2]
DR Ensembl; ENSMUST00000072999; ENSMUSP00000072763; ENSMUSG00000026288. [Q9ES52-4]
DR Ensembl; ENSMUST00000167032; ENSMUSP00000126569; ENSMUSG00000026288. [Q9ES52-5]
DR Ensembl; ENSMUST00000168783; ENSMUSP00000131244; ENSMUSG00000026288. [Q9ES52-3]
DR Ensembl; ENSMUST00000169754; ENSMUSP00000127941; ENSMUSG00000026288. [Q9ES52-1]
DR Ensembl; ENSMUST00000170300; ENSMUSP00000132384; ENSMUSG00000026288. [Q9ES52-6]
DR GeneID; 16331; -.
DR KEGG; mmu:16331; -.
DR UCSC; uc007bxc.3; mouse. [Q9ES52-1]
DR UCSC; uc007bxd.3; mouse. [Q9ES52-3]
DR UCSC; uc007bxf.3; mouse. [Q9ES52-2]
DR UCSC; uc007bxg.3; mouse. [Q9ES52-6]
DR CTD; 3635; -.
DR MGI; MGI:107357; Inpp5d.
DR VEuPathDB; HostDB:ENSMUSG00000026288; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000156202; -.
DR HOGENOM; CLU_007493_1_0_1; -.
DR InParanoid; Q9ES52; -.
DR OMA; DSWFQCK; -.
DR OrthoDB; 311217at2759; -.
DR PhylomeDB; Q9ES52; -.
DR TreeFam; TF323475; -.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR BioGRID-ORCS; 16331; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Inpp5d; mouse.
DR PRO; PR:Q9ES52; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9ES52; protein.
DR Bgee; ENSMUSG00000026288; Expressed in stroma of bone marrow and 187 other tissues.
DR ExpressionAtlas; Q9ES52; baseline and differential.
DR Genevisible; Q9ES52; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0030863; C:cortical cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0052659; F:inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0030487; F:inositol-4,5-bisphosphate 5-phosphatase activity; ISO:MGI.
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; IEA:RHEA.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:MGI.
DR GO; GO:0050869; P:negative regulation of B cell activation; IMP:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:MGI.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IMP:MGI.
DR GO; GO:0050777; P:negative regulation of immune response; IMP:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:MGI.
DR GO; GO:0045656; P:negative regulation of monocyte differentiation; IMP:MGI.
DR GO; GO:0045659; P:negative regulation of neutrophil differentiation; IMP:MGI.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IMP:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; IMP:MGI.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:MGI.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:MGI.
DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; IMP:MGI.
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 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; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell membrane; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Hydrolase; Immunity;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW SH2 domain; SH3-binding.
FT CHAIN 1..1191
FT /note="Phosphatidylinositol 3,4,5-trisphosphate 5-
FT phosphatase 1"
FT /id="PRO_0000302867"
FT DOMAIN 8..104
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 122..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 947..994
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1015..1029
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000269|PubMed:11247302"
FT REGION 1021..1191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 127..132
FT /note="SH3-binding 1"
FT MOTIF 915..918
FT /note="NPXY motif 1"
FT MOTIF 970..975
FT /note="SH3-binding 2"
FT MOTIF 1018..1021
FT /note="NPXY motif 2"
FT MOTIF 1039..1050
FT /note="SH3-binding 3"
FT COMPBIAS 1088..1115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1161..1184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 918
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9099679"
FT MOD_RES 935
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 945
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 964
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 972
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1021
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9099679"
FT VAR_SEQ 1..263
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11567986"
FT /id="VSP_027980"
FT VAR_SEQ 120
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11013080,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8643691,
FT ECO:0000303|PubMed:8654924"
FT /id="VSP_027981"
FT VAR_SEQ 920..980
FT /note="Missing (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:10068665"
FT /id="VSP_027982"
FT VAR_SEQ 920..960
FT /note="GMGPFGQPLHGKSTLSPDQQLTAWSYDQLPKDSSLGPGRGE -> VFIFHSQ
FT PRSLPQGARGKTWGSGKGGSSAPGGPAADEARDV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11013080"
FT /id="VSP_027983"
FT VAR_SEQ 961..1191
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11013080"
FT /id="VSP_027984"
FT MUTAGEN 676
FT /note="D->G: Loss of function."
FT /evidence="ECO:0000269|PubMed:11222379"
FT MUTAGEN 918
FT /note="Y->F: Strongly impairs function, tyrosine
FT phosphorylation, subcellular location and interaction with
FT DOK1; when associated with F-1021."
FT /evidence="ECO:0000269|PubMed:11031258,
FT ECO:0000269|PubMed:11222379, ECO:0000269|PubMed:9099679"
FT MUTAGEN 1021
FT /note="Y->F: Strongly impairs function, tyrosine
FT phosphorylation, subcellular location and interaction with
FT DOK1; when associated with F-918."
FT /evidence="ECO:0000269|PubMed:11031258,
FT ECO:0000269|PubMed:11222379, ECO:0000269|PubMed:9099679"
FT CONFLICT 43
FT /note="Y -> C (in Ref. 2; AAB18937)"
FT /evidence="ECO:0000305"
FT CONFLICT 527
FT /note="V -> A (in Ref. 3; AAC53023)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="N -> I (in Ref. 3; AAC53023)"
FT /evidence="ECO:0000305"
FT CONFLICT 905
FT /note="C -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 981
FT /note="A -> T (in Ref. 2; AAB18937)"
FT /evidence="ECO:0000305"
FT STRAND 405..415
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 426..429
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 448..456
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 461..476
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 481..488
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 491..497
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 499..504
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 505..514
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 525..533
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 536..544
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 552..565
FT /evidence="ECO:0007829|PDB:6DLG"
FT TURN 578..580
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 583..590
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 599..601
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 602..610
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 614..618
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 622..628
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 631..633
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 676..682
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 688..695
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 701..704
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 707..714
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 734..744
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 751..756
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 760..762
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 770..773
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 778..783
FT /evidence="ECO:0007829|PDB:6DLG"
FT HELIX 797..800
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 804..811
FT /evidence="ECO:0007829|PDB:6DLG"
FT TURN 812..814
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 817..824
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 835..842
FT /evidence="ECO:0007829|PDB:6DLG"
FT STRAND 845..855
FT /evidence="ECO:0007829|PDB:6DLG"
SQ SEQUENCE 1191 AA; 133542 MW; AF9F21326A59EC7A CRC64;
MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR NCVYTYRILP
NEDDKFTVQA SEGVPMRFFT KLDQLIDFYK KENMGLVTHL QYPVPLEEED AIDEAEEDTV
ESVMSPPELP PRNIPMSAGP SEAKDLPLAT ENPRAPEVTR LSLSETLFQR LQSMDTSGLP
EEHLKAIQDY LSTQLLLDSD FLKTGSSNLP HLKKLMSLLC KELHGEVIRT LPSLESLQRL
FDQQLSPGLR PRPQVPGEAS PITMVAKLSQ LTSLLSSIED KVKSLLHEGS ESTNRRSLIP
PVTFEVKSES LGIPQKMHLK VDVESGKLIV KKSKDGSEDK FYSHKKILQL IKSQKFLNKL
VILVETEKEK ILRKEYVFAD SKKREGFCQL LQQMKNKHSE QPEPDMITIF IGTWNMGNAP
PPKKITSWFL SKGQGKTRDD SADYIPHDIY VIGTQEDPLG EKEWLELLRH SLQEVTSMTF
KTVAIHTLWN IRIVVLAKPE HENRISHICT DNVKTGIANT LGNKGAVGVS FMFNGTSLGF
VNSHLTSGSE KKLRRNQNYM NILRFLALGD KKLSPFNITH RFTHLFWLGD LNYRVELPTW
EAEAIIQKIK QQQYSDLLAH DQLLLERKDQ KVFLHFEEEE ITFAPTYRFE RLTRDKYAYT
KQKATGMKYN LPSWCDRVLW KSYPLVHVVC QSYGSTSDIM TSDHSPVFAT FEAGVTSQFV
SKNGPGTVDS QGQIEFLACY ATLKTKSQTK FYLEFHSSCL ESFVKSQEGE NEEGSEGELV
VRFGETLPKL KPIISDPEYL LDQHILISIK SSDSDESYGE GCIALRLETT EAQHPIYTPL
THHGEMTGHF RGEIKLQTSQ GKMREKLYDF VKTERDESSG MKCLKNLTSH DPMRQWEPSG
RVPACGVSSL NEMINPNYIG MGPFGQPLHG KSTLSPDQQL TAWSYDQLPK DSSLGPGRGE
GPPTPPSQPP LSPKKFSSST ANRGPCPRVQ EARPGDLGKV EALLQEDLLL TKPEMFENPL
YGSVSSFPKL VPRKEQESPK MLRKEPPPCP DPGISSPSIV LPKAQEVESV KGTSKQAPVP
VLGPTPRIRS FTCSSSAEGR MTSGDKSQGK PKASASSQAP VPVKRPVKPS RSEMSQQTTP
IPAPRPPLPV KSPAVLQLQH SKGRDYRDNT ELPHHGKHRQ EEGLLGRTAM Q
