EC 3.1.3.n1
SH2 domain-containing inositol-5'-phosphatase 1
SH2 domain-containing inositol phosphatase 1
SHIP-1
Inositol polyphosphate-5-phosphatase of 145 kDa
SIP-145
p150Ship

Gene name

	Name:	Inpp5d
	Synonyms:	7a33, Ship, Ship1

From

Mus musculus (Mouse)

[TaxID: 10090]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 2-9 AND 1163-1173, FUNCTION, ENZYME ACTIVITY, PHOSPHORYLATION, TISSUE SPECIFICITY, AND INTERACTION WITH SHC1. STRAIN=DBA/2; PubMed=8654924 [NCBI, ExPASy, EBI, Israel, Japan] Lioubin M.N., Algate P.A., Tsai S., Carlberg K., Aebersold A., Rohrschneider L.R.; "p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity."; Genes Dev. 10:1084-1095(1996).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 902-916, ENZYME ACTIVITY, TISSUE SPECIFICITY, AND INTERACTION WITH GRB2 AND SHC1. DOI=10.1073/pnas.93.4.1689; PubMed=8643691 [NCBI, ExPASy, EBI, Israel, Japan] Damen J.E., Liu L., Rosten P., Humphries R.K., Jefferson A.B., Majerus P.W., Krystal G.; "The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase."; Proc. Natl. Acad. Sci. U.S.A. 93:1689-1693(1996).
[3]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1006/geno.1996.4374; PubMed=9027494 [NCBI, ExPASy, EBI, Israel, Japan] Liu Q., Dumont D.J.; "Molecular cloning and chromosomal localization in human and mouse of the SH2-containing inositol phosphatase, INPP5D (SHIP)."; Genomics 39:109-112(1997).
[4]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PHOSPHORYLATION, INTERACTION WITH SHC1 AND GRB2, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. STRAIN=BALB/c; PubMed=10068665 [NCBI, ExPASy, EBI, Israel, Japan] Lucas D.M., Rohrschneider L.R.; "A novel spliced form of SH2-containing inositol phosphatase is expressed during myeloid development."; Blood 93:1922-1933(1999).
[5]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 4). STRAIN=129/Sv; DOI=10.1006/geno.2000.6324; PubMed=11013080 [NCBI, ExPASy, EBI, Israel, Japan] Wolf I., Lucas D.M., Algate P.A., Rohrschneider L.R.; "Cloning of the genomic locus of mouse SH2 containing inositol 5-phosphatase (SHIP) and a novel 110-kDa splice isoform, SHIPdelta."; Genomics 69:104-112(2000).
[6]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). DOI=10.1182/blood.V98.7.2028; PubMed=11567986 [NCBI, ExPASy, EBI, Israel, Japan] Tu Z., Ninos J.M., Ma Z., Wang J.-W., Lemos M.P., Desponts C., Ghansah T., Howson J.M., Kerr W.G.; "Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5'-phosphatase isoform that partners with the Grb2 adapter protein."; Blood 98:2028-2038(2001).
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). STRAIN=C57BL/6J; TISSUE=Spleen; DOI=10.1126/science.1112014; PubMed=16141072 [NCBI, ExPASy, EBI, Israel, Japan] Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; "The transcriptional landscape of the mammalian genome."; Science 309:1559-1563(2005).
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). TISSUE=Thyroid; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[9]	NUCLEOTIDE SEQUENCE [MRNA] OF 1-106. DOI=10.1073/pnas.93.9.3947; PubMed=8632995 [NCBI, ExPASy, EBI, Israel, Japan] Kerr W.G., Heller M., Herzenberg L.A.; "Analysis of lipopolysaccharide-response genes in B-lineage cells demonstrates that they can have differentiation stage-restricted expression and contain SH2 domains."; Proc. Natl. Acad. Sci. U.S.A. 93:3947-3952(1996).
[10]	PARTIAL PROTEIN SEQUENCE. DOI=10.1016/S0960-9822(02)00511-0; PubMed=8723348 [NCBI, ExPASy, EBI, Israel, Japan] Kavanaugh W.M., Pot D.A., Chin S.M., Deuter-Reinhard M., Jefferson A.B., Norris F.A., Masiarz F.R., Cousens L.S., Majerus P.W., Williams L.T.; "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2."; Curr. Biol. 6:438-445(1996).
[11]	FUNCTION. DOI=10.1038/383263a0; PubMed=8805703 [NCBI, ExPASy, EBI, Israel, Japan] Ono M., Bolland S., Tempst P., Ravetch J.V.; "Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB."; Nature 383:263-266(1996).
[12]	PHOSPHORYLATION. PubMed=8805618 [NCBI, ExPASy, EBI, Israel, Japan] Chacko G.W., Tridandapani S., Damen J.E., Liu L., Krystal G., Coggeshall K.M.; "Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5-phosphatase, SHIP."; J. Immunol. 157:2234-2238(1996).
[13]	FUNCTION. DOI=10.1016/S0092-8674(00)80337-2; PubMed=9244303 [NCBI, ExPASy, EBI, Israel, Japan] Ono M., Okada H., Bolland S., Yanagi S., Kurosaki T., Ravetch J.V.; "Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling."; Cell 90:293-301(1997).
[14]	DOMAIN SH2, AND INTERACTION WITH SHC1. DOI=10.1074/jbc.272.14.8983; PubMed=9083021 [NCBI, ExPASy, EBI, Israel, Japan] Liu L., Damen J.E., Hughes M.R., Babic I., Jirik F.R., Krystal G.; "The Src homology 2 (SH2) domain of SH2-containing inositol phosphatase (SHIP) is essential for tyrosine phosphorylation of SHIP, its association with Shc, and its induction of apoptosis."; J. Biol. Chem. 272:8983-8988(1997).
[15]	PHOSPHORYLATION AT TYR-918 AND TYR-1021, INTERACTION WITH SHC1, AND MUTAGENESIS OF TYR-918 AND TYR-1021. DOI=10.1074/jbc.272.16.10396; PubMed=9099679 [NCBI, ExPASy, EBI, Israel, Japan] Lamkin T.D., Walk S.F., Liu L., Damen J.E., Krystal G., Ravichandran K.S.; "Shc interaction with Src homology 2 domain containing inositol phosphatase (SHIP) in vivo requires the Shc-phosphotyrosine binding domain and two specific phosphotyrosines on SHIP."; J. Biol. Chem. 272:10396-10401(1997).
[16]	INTERACTION WITH PTPN11. DOI=10.1074/jbc.272.17.10998; PubMed=9110989 [NCBI, ExPASy, EBI, Israel, Japan] Liu L., Damen J.E., Ware M.D., Krystal G.; "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2."; J. Biol. Chem. 272:10998-11001(1997).
[17]	ENZYME ACTIVITY. DOI=10.1074/jbc.272.43.26857; PubMed=9341117 [NCBI, ExPASy, EBI, Israel, Japan] Giuriato S., Payrastre B., Drayer A.L., Plantavid M., Woscholski R., Parker P., Erneux C., Chap H.; "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets."; J. Biol. Chem. 272:26857-26863(1997).
[18]	INTERACTION WITH PTPN11. DOI=10.1038/sj.onc.1201422; PubMed=9393882 [NCBI, ExPASy, EBI, Israel, Japan] Sattler M., Salgia R., Shrikhande G., Verma S., Choi J.-L., Rohrschneider L.R., Griffin J.D.; "The phosphatidylinositol polyphosphate 5-phosphatase SHIP and the protein tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can be regulated by BCR/ABL and growth factors."; Oncogene 15:2379-2384(1997).
[19]	SUBCELLULAR LOCATION. PubMed=9694708 [NCBI, ExPASy, EBI, Israel, Japan] Damen J.E., Liu L., Ware M.D., Ermolaeva M., Majerus P.W., Krystal G.; "Multiple forms of the SH2-containing inositol phosphatase, SHIP, are generated by C-terminal truncation."; Blood 92:1199-1205(1998).
[20]	TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. PubMed=9531585 [NCBI, ExPASy, EBI, Israel, Japan] Liu Q., Shalaby F., Jones J., Bouchard D., Dumont D.J.; "The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed during hematopoiesis and spermatogenesis."; Blood 91:2753-2759(1998).
[21]	FUNCTION, AND DISRUPTION PHENOTYPE. DOI=10.1093/emboj/17.24.7311; PubMed=9857188 [NCBI, ExPASy, EBI, Israel, Japan] Huber M., Helgason C.D., Scheid M.P., Duronio V., Humphries R.K., Krystal G.; "Targeted disruption of SHIP leads to Steel factor-induced degranulation of mast cells."; EMBO J. 17:7311-7319(1998).
[22]	FUNCTION. DOI=10.1084/jem.188.7.1333; PubMed=9763612 [NCBI, ExPASy, EBI, Israel, Japan] Liu Q., Oliveira-Dos-Santos A.J., Mariathasan S., Bouchard D., Jones J., Sarao R., Kozieradzki I., Ohashi P.S., Penninger J.M., Dumont D.J.; "The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling."; J. Exp. Med. 188:1333-1342(1998).
[23]	FUNCTION. DOI=10.1073/pnas.95.19.11330; PubMed=9736736 [NCBI, ExPASy, EBI, Israel, Japan] Huber M., Helgason C.D., Damen J.E., Liu L., Humphries R.K., Krystal G.; "The src homology 2-containing inositol phosphatase (SHIP) is the gatekeeper of mast cell degranulation."; Proc. Natl. Acad. Sci. U.S.A. 95:11330-11335(1998).
[24]	FUNCTION, AND DISRUPTION PHENOTYPE. PubMed=9620849 [NCBI, ExPASy, EBI, Israel, Japan] Helgason C.D., Damen J.E., Rosten P., Grewal R., Sorensen P., Chappel S.M., Borowski A., Jirik F., Krystal G., Humphries R.K.; "Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span."; Genes Dev. 12:1610-1620(1998).
[25]	INTERACTION WITH SHC1 AND FCGR2B, AND PHOSPHORYLATION. DOI=10.1016/S0161-5890(98)00097-2; PubMed=10395202 [NCBI, ExPASy, EBI, Israel, Japan] Tridandapani S., Phee H., Shivakumar L., Kelley T.W., Coggeshall K.M.; "Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells."; Mol. Immunol. 35:1135-1146(1998).
[26]	INTERACTION WITH SRC. DOI=10.1042/0264-6021:3480107; PubMed=10794720 [NCBI, ExPASy, EBI, Israel, Japan] Giuriato S., Bodin S., Erneux C., Woscholski R., Plantavid M., Chap H., Payrastre B.; "pp60c-src associates with the SH2-containing inositol-5-phosphatase SHIP1 and is involved in its tyrosine phosphorylation downstream of alphaIIbbeta3 integrin in human platelets."; Biochem. J. 348:107-112(2000).
[27]	INTERACTION WITH EPOR, AND PHOSPHORYLATION. DOI=10.1074/jbc.275.6.4398; PubMed=10660611 [NCBI, ExPASy, EBI, Israel, Japan] Mason J.M., Beattie B.K., Liu Q., Dumont D.J., Barber D.L.; "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor."; J. Biol. Chem. 275:4398-4406(2000).
[28]	INTERACTION WITH FCGR2B. DOI=10.1074/jbc.M003518200; PubMed=11016922 [NCBI, ExPASy, EBI, Israel, Japan] Bruhns P., Vely F., Malbec O., Fridman W.H., Vivier E., Daeeron M.; "Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by fcgamma RIIB."; J. Biol. Chem. 275:37357-37364(2000).
[29]	INTERACTION WITH FCGR2B. DOI=10.1128/MCB.20.10.3576-3589.2000; PubMed=10779347 [NCBI, ExPASy, EBI, Israel, Japan] Aman M.J., Walk S.F., March M.E., Su H.-P., Carver D.J., Ravichandran K.S.; "Essential role for the C-terminal noncatalytic region of SHIP in FcgammaRIIB1-mediated inhibitory signaling."; Mol. Cell. Biol. 20:3576-3589(2000).
[30]	FUNCTION, AND MUTAGENESIS OF ASP-676; TYR-918 AND TYR-1021. DOI=10.1182/blood.V97.5.1343; PubMed=11222379 [NCBI, ExPASy, EBI, Israel, Japan] Damen J.E., Ware M.D., Kalesnikoff J., Hughes M.R., Krystal G.; "SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation."; Blood 97:1343-1351(2001).
[31]	INTERACTION WITH DOK1 AND CRKL, AND MUTAGENESIS OF TYR-918 AND TYR-1021. DOI=10.1074/jbc.M006250200; PubMed=11031258 [NCBI, ExPASy, EBI, Israel, Japan] Sattler M., Verma S., Pride Y.B., Salgia R., Rohrschneider L.R., Griffin J.D.; "SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL."; J. Biol. Chem. 276:2451-2458(2001).
[32]	FUNCTION. DOI=10.1074/jbc.M011094200; PubMed=11359765 [NCBI, ExPASy, EBI, Israel, Japan] Malbec O., Schmitt C., Bruhns P., Krystal G., Fridman W.H., Daeeron M.; "Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB."; J. Biol. Chem. 276:30381-30391(2001).
[33]	FUNCTION. DOI=10.1084/jem.193.1.61; PubMed=11136821 [NCBI, ExPASy, EBI, Israel, Japan] Cox D., Dale B.M., Kashiwada M., Helgason C.D., Greenberg S.; "A regulatory role for Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) in phagocytosis mediated by Fc gamma receptors and complement receptor 3 (alpha(M)beta(2); CD11b/CD18)."; J. Exp. Med. 193:61-71(2001).
[34]	SUBCELLULAR LOCATION, AND INTERACTION WITH FCGR3. DOI=10.1182/blood-2002-04-1058; PubMed=12393695 [NCBI, ExPASy, EBI, Israel, Japan] Galandrini R., Tassi I., Mattia G., Lenti L., Piccoli M., Frati L., Santoni A.; "SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells."; Blood 100:4581-4589(2002).
[35]	FUNCTION, INTERACTION WITH FCGR2A, AND PHOSPHORYLATION. PubMed=12370370 [NCBI, ExPASy, EBI, Israel, Japan] Tridandapani S., Wang Y., Marsh C.B., Anderson C.L.; "Src homology 2 domain-containing inositol polyphosphate phosphatase regulates NF-kappa B-mediated gene transcription by phagocytic Fc gamma Rs in human myeloid cells."; J. Immunol. 169:4370-4378(2002).
[36]	FUNCTION, AND INDUCTION. DOI=10.1038/ncb885; PubMed=12447389 [NCBI, ExPASy, EBI, Israel, Japan] Valderrama-Carvajal H., Cocolakis E., Lacerte A., Lee E.-H., Krystal G., Ali S., Lebrun J.-J.; "Activin/TGF-beta induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP."; Nat. Cell Biol. 4:963-969(2002).
[37]	FUNCTION, AND DISRUPTION PHENOTYPE. DOI=10.1038/nm752; PubMed=12161749 [NCBI, ExPASy, EBI, Israel, Japan] Takeshita S., Namba N., Zhao J.J., Jiang Y., Genant H.K., Silva M.J., Brodt M.D., Helgason C.D., Kalesnikoff J., Rauh M.J., Humphries R.K., Krystal G., Teitelbaum S.L., Ross F.P.; "SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts."; Nat. Med. 8:943-949(2002).
[38]	FUNCTION, AND INTERACTION WITH MET. DOI=10.1038/sj.onc.1205224; PubMed=11896575 [NCBI, ExPASy, EBI, Israel, Japan] Mancini A., Koch A., Wilms R., Tamura T.; "The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the control of cell-cell junction and induces dissociation and dispersion of MDCK cells."; Oncogene 21:1477-1484(2002).
[39]	FUNCTION. DOI=10.1074/jbc.M305021200; PubMed=12882960 [NCBI, ExPASy, EBI, Israel, Japan] Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., Krystal G., Marsh C.B.; "The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity."; J. Biol. Chem. 278:38628-38636(2003).
[40]	FUNCTION. DOI=10.1074/jbc.M400746200; PubMed=15166241 [NCBI, ExPASy, EBI, Israel, Japan] Maxwell M.J., Yuan Y., Anderson K.E., Hibbs M.L., Salem H.H., Jackson S.P.; "SHIP1 and Lyn kinase negatively regulate integrin alpha IIb beta 3 signaling in platelets."; J. Biol. Chem. 279:32196-32204(2004).
[41]	INTERACTION WITH FCGR2B. DOI=10.1074/jbc.M410261200; PubMed=15456754 [NCBI, ExPASy, EBI, Israel, Japan] Isnardi I., Lesourne R., Bruhns P., Fridman W.H., Cambier J.C., Daeeron M.; "Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap."; J. Biol. Chem. 279:51931-51938(2004).
[42]	INTERACTION WITH TEC. DOI=10.1074/jbc.M408141200; PubMed=15492005 [NCBI, ExPASy, EBI, Israel, Japan] Tomlinson M.G., Heath V.L., Turck C.W., Watson S.P., Weiss A.; "SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase."; J. Biol. Chem. 279:55089-55096(2004).
[43]	FUNCTION, AND INTERACTION WITH DOK3. DOI=10.1128/MCB.24.6.2332-2343.2004; PubMed=14993273 [NCBI, ExPASy, EBI, Israel, Japan] Robson J.D., Davidson D., Veillette A.; "Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid phosphatase that interacts with the adaptor molecule Dok-3."; Mol. Cell. Biol. 24:2332-2343(2004).
[44]	INTERACTION WITH PLCG1. PubMed=16000869 [NCBI, ExPASy, EBI, Israel, Japan] Song M., Kim M.J., Ha S., Park J.B., Ryu S.H., Suh P.-G.; "Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and modulates EGF-induced PLC activity."; Exp. Mol. Med. 37:161-168(2005).
[45]	SUBCELLULAR LOCATION. DOI=10.1016/j.imlet.2005.11.027; PubMed=16406061 [NCBI, ExPASy, EBI, Israel, Japan] Isnardi I., Bruhns P., Bismuth G., Fridman W.H., Daeeron M.; "The SH2 domain-containing inositol 5-phosphatase SHIP1 is recruited to the intracytoplasmic domain of human FcgammaRIIB and is mandatory for negative regulation of B cell activation."; Immunol. Lett. 104:156-165(2006).
[46]	FUNCTION. PubMed=17142780 [NCBI, ExPASy, EBI, Israel, Japan] Zhou P., Kitaura H., Teitelbaum S.L., Krystal G., Ross F.P., Takeshita S.; "SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-dependent alterations in D-type cyclins and p27."; J. Immunol. 177:8777-8784(2006).
[47]	INTERACTION WITH IL6ST. DOI=10.1089/scd.2006.15.641; PubMed=17105399 [NCBI, ExPASy, EBI, Israel, Japan] Desponts C., Ninos J.M., Kerr W.G.; "s-SHIP associates with receptor complexes essential for pluripotent stem cell growth and survival."; Stem Cells Dev. 15:641-646(2006).
[48]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-868; SER-935 AND TYR-945, AND MASS SPECTROMETRY. TISSUE=Mast cell; PubMed=17947660 [NCBI, ExPASy, EBI, Israel, Japan] Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.; "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."; J. Immunol. 179:5864-5876(2007).
[49]	FUNCTION. DOI=10.1038/ncb1515; PubMed=17173042 [NCBI, ExPASy, EBI, Israel, Japan] Nishio M., Watanabe K., Sasaki J., Taya C., Takasuga S., Iizuka R., Balla T., Yamazaki M., Watanabe H., Itoh R., Kuroda S., Horie Y., Foerster I., Mak T.W., Yonekawa H., Penninger J.M., Kanaho Y., Suzuki A., Sasaki T.; "Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1."; Nat. Cell Biol. 9:36-44(2007).
[50]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-868 AND SER-972, AND MASS SPECTROMETRY. TISSUE=Macrophage; DOI=10.1016/j.immuni.2008.11.006; PubMed=19144319 [NCBI, ExPASy, EBI, Israel, Japan] Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.; "The phagosomal proteome in interferon-gamma-activated macrophages."; Immunity 30:143-154(2009).

Comments

FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.
CATALYTIC ACTIVITY: Phosphatidylinositol 3,4,5-trisphosphate + H₂O = phosphatidylinositol 3,4-bisphosphate + phosphate.
ENZYME REGULATION: Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.
SUBUNIT: Interacts with tyrosine phosphorylated forms of SHC1, DOK1, DOK3, PTPN11/SHP-2, SLAMF1/CD150. Interacts with PTPN11 in response to IL-3. Interacts with receptors EPOR, MS4A2/FCER1B and FCER1G, FCGR2A, FCGR2B and FCGR3. Interacts with GRB2 and PLCG1. Interacts with tyrosine kinases SRC and TEC. Interacts with FCGR2A, leading to regulate gene expression during the phagocytic process. Interacts with c-Met/MET. Isoform 5 interacts with IL6ST/gp130.
INTERACTION:
P35329:Cd22; NbExp=1; IntAct=EBI-300210, EBI-300059;
Q60631:Grb2; NbExp=1; IntAct=EBI-1452545, EBI-1688;
Q60631:Grb2; NbExp=1; IntAct=EBI-1452551, EBI-1688;
P23727:PIK3R1 (xeno); NbExp=1; IntAct=EBI-1452545, EBI-520244;
P23727:PIK3R1 (xeno); NbExp=1; IntAct=EBI-1452551, EBI-520244;
Q62077:Plcg1; NbExp=1; IntAct=EBI-300210, EBI-300133;
P98083:Shc1; NbExp=1; IntAct=EBI-1452545, EBI-300201;
P98083:Shc1; NbExp=1; IntAct=EBI-1452551, EBI-300201;
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein. Note=Translocates to the plasma membrane when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B) or CD16/FCGR3. Tyrosine phosphorylation may also participate to membrane localization.
SUBCELLULAR LOCATION: Isoform 5: Cell membrane; Peripheral membrane protein. Note=Constitutively present at the cell membrane.

ALTERNATIVE PRODUCTS: 6 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	Q9ES52-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	Q9ES52-2
Features which should be applied to build the isoform sequence: VSP_027981.

Name	3
Synonyms	135 kDa SHIP
Isoform ID	Q9ES52-3
Features which should be applied to build the isoform sequence: VSP_027982.

Name	4
Synonyms	SHIPdelta
Isoform ID	Q9ES52-4
Features which should be applied to build the isoform sequence: VSP_027981, VSP_027983, VSP_027984.

Name	5
Synonyms	s-SHIP
Isoform ID	Q9ES52-5
Features which should be applied to build the isoform sequence: VSP_027980.

Name	6
Synonyms	s-SHIPD183
Isoform ID	Q9ES52-6
Features which should be applied to build the isoform sequence: VSP_027980, VSP_027982.

TISSUE SPECIFICITY: Specifically expressed in immune and hematopoietic cells. Levels vary considerably within this compartment. Lost during erythropoiesis when erythroid cells become Ter119+. Increases substantially with T-cell maturation and when resting B-cells are activated. Also present in mature granulocytes, monocyte/macrophages, mast cells and platelets. Isoform 5 is the only form expressed in embryonic stem (ES) cells and is co-expressed with other isoforms in hematopoietic stem cells, and disapears with differentiation.
DEVELOPMENTAL STAGE: Expressed in late primitive-streak stage embryos (7.5 dpc), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in embryo. In adults expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes and lymphocytes, and is also found in the spermatids of the testis.
INDUCTION: By activin/TGF-beta (at protein level). Regulated by the Smad pathway. Isoform 3 is expressed during myeloid development.
DOMAIN: The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation.
DOMAIN: The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.
PTM: Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.
DISRUPTION PHENOTYPE: Mice are viable and fertile. They however fail to thrive and only 40% survive by 14 weeks of age. Mortality is associated with extensive consolidation of the lungs resulting from infiltration by myeloid cells. Increased numbers of granulocyte-macrophage progenitors are observed in both the bone marrow and spleen. Absence of Inpp5d leads to steel factor-induced degranulation of mast cells. They also display increased numbers of osteoclast precursors leading to a severe osteoporosis.
SIMILARITY: Belongs to the inositol-1,4,5-trisphosphate 5-phosphatase family.
SIMILARITY: Contains 1 SH2 domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U51742; AAC52606.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U39203; AAB18937.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U52044; AAC53023.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF125996; AAD37118.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235502; AAG23922.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235496; AAG23922.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235498; AAG23922.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235499; AAG23922.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235500; AAG23922.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF235501; AAG23922.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF228679; AAF69143.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF184912; AAF25823.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF184913; AAF25824.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AK143560; BAE25436.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC108328; AAI08329.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00120516; -.
IPI00124504; -.
IPI00856529; -.
IPI00857008; -.
IPI00857200; -.
IPI00857938; -.

PIR

JC6118; JC6118.

RefSeq

NP_001103662.1; -.
NP_001103663.1; -.
NP_034696.2; -.

UniGene

Mm.15105

3D structure databases

HSSP

P23727; 1QAD. [HSSP ENTRY / PDB]

ModBase

Q9ES52.

Protein-protein interaction databases

IntAct

Q9ES52; 10.

PTM databases

PhosphoSite

Q9ES52; -.

Organism-specific databases

MGI

MGI:107357; Inpp5d.

Gene expression databases

ArrayExpress

Q9ES52; -.

Bgee

Q9ES52; -.

CleanEx

MM_INPP5D; -.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005886;	Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0004437;	Molecular function: inositol or phosphatidylinositol phosphatase activity (inferred from electronic annotation from InterPro).
GO:0017124;	Molecular function: SH3 domain binding (inferred from electronic annotation from UniProtKB-KW).
GO:0006915;	Biological process: apoptosis (inferred from electronic annotation from UniProtKB-KW).
GO:0008340;	Biological process: determination of adult life span (inferred from mutant phenotype from MGI).
GO:0016064;	Biological process: immunoglobulin mediated immune response (inferred from mutant phenotype from MGI).
GO:0007242;	Biological process: intracellular signaling cascade (inferred from mutant phenotype from MGI).
GO:0030889;	Biological process: negative regulation of B cell proliferation (inferred from mutant phenotype from MGI).
GO:0045779;	Biological process: negative regulation of bone resorption (inferred from mutant phenotype from MGI).
GO:0050777;	Biological process: negative regulation of immune response (inferred from mutant phenotype from MGI).
GO:0045409;	Biological process: negative regulation of interleukin-6 biosynthetic process (inferred from mutant phenotype from MGI).
GO:0045656;	Biological process: negative regulation of monocyte differentiation (inferred from mutant phenotype from MGI).
GO:0045659;	Biological process: negative regulation of neutrophil differentiation (inferred from mutant phenotype from MGI).
GO:0045671;	Biological process: negative regulation of osteoclast differentiation (inferred from mutant phenotype from MGI).
GO:0009968;	Biological process: negative regulation of signal transduction (inferred from mutant phenotype from MGI).
GO:0043065;	Biological process: positive regulation of apoptosis (inferred from mutant phenotype from MGI).
GO:0045579;	Biological process: positive regulation of B cell differentiation (inferred from mutant phenotype from MGI).
GO:0045648;	Biological process: positive regulation of erythrocyte differentiation (inferred from mutant phenotype from MGI).
QuickGo view.

Family and domain databases

InterPro

IPR005135; Endo/exonuclease/phosphatase.
IPR000300; IPPc.
IPR000980; SH2.
Graphical view of domain structure.

Pfam

PF03372; Exo_endo_phos; 1.
PF00017; SH2; 1.
Pfam graphical view of domain structure.

PRINTS

PR00401; SH2DOMAIN.

ProDom

PD000093; SH2; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00128; IPPc; 1.
SM00252; SH2; 1.
SMART graphical view of domain structure.

PROSITE

PS50001; SH2; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSMUSG00000026288; Mus musculus. [Contig view]

GeneID

16331; -.

KEGG

mmu:16331; -.

NMPDR

fig|10090.3.peg.725; -.

Phylogenomic databases

HOVERGEN

Q9ES52; -.

OMA

Q9ES52; QKVFLHF.

Other

NextBio

289418; -.

SOURCE

Inpp5d; Mus musculus.

ProtoNet

Q9ES52.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Apoptosis; Cell membrane; Cytoplasm; Direct protein sequencing; Hydrolase; Immune response; Membrane; Phosphoprotein; Repeat; SH2 domain; SH3-binding.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1191`	`1191`	`Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1.`	`PRO_0000302867`
`DOMAIN`	`8 104`	`97`	`SH2.`
`MOTIF`	`127 132`	`6`	`SH3-binding 1.`
`MOTIF`	`915 918`	`4`	`NPXY motif 1.`
`MOTIF`	`970 975`	`6`	`SH3-binding 2.`
`MOTIF`	`1018 1021`	`4`	`NPXY motif 2.`
`MOTIF`	`1039 1050`	`12`	`SH3-binding 3.`
`COMPBIAS`	`962 1153`	`192`	`Pro-rich.`
`MOD_RES`	`868 868`		`Phosphotyrosine.`
`MOD_RES`	`918 918`		`Phosphotyrosine.`
`MOD_RES`	`935 935`		`Phosphoserine.`
`MOD_RES`	`945 945`		`Phosphotyrosine.`
`MOD_RES`	`972 972`		`Phosphoserine.`
`MOD_RES`	`1021 1021`		`Phosphotyrosine.`
`VAR_SEQ`	`1 263`		`Missing (in isoform 5 and isoform 6).`	`VSP_027980`
`VAR_SEQ`	`120 120`		`Missing (in isoform 2 and isoform 4).`	`VSP_027981`
`VAR_SEQ`	`920 980`		`Missing (in isoform 3 and isoform 6).`	`VSP_027982`
`VAR_SEQ`	`920 960`		`GMGPFGQPLHGKSTLSPDQQLTAWSYDQLPKDSSLG` `PGRGE -> VFIFHSQPRSLPQGARGKTWGSGKGGSSAPGGPAAD` `EARDV (in isoform 4).`	`VSP_027983`
`VAR_SEQ`	`961 1191`		`Missing (in isoform 4).`	`VSP_027984`
`MUTAGEN`	`676 676`		`D->G: Loss of function.`
`MUTAGEN`	`918 918`		`Y->F: Strongly impairs function, tyrosine phosphorylation, subcellular location and interaction with DOK1; when associated with F-1021.`
`MUTAGEN`	`1021 1021`		`Y->F: Strongly impairs function, tyrosine phosphorylation, subcellular location and interaction with DOK1; when associated with F-918.`
`CONFLICT`	`43 43`		`Y -> C (in Ref. 2; AAB18937).`
`CONFLICT`	`527 527`		`V -> A (in Ref. 3; AAC53023).`
`CONFLICT`	`534 534`		`N -> I (in Ref. 3; AAC53023).`
`CONFLICT`	`905 905`		`C -> E (in Ref. 2; AA sequence).`
`CONFLICT`	`981 981`		`A -> T (in Ref. 2; AAB18937).`

Sequence information

Length: 1191 AA [This is the length of the unprocessed precursor]

Molecular weight: 133542 Da [This is the MW of the unprocessed precursor]

CRC64: AF9F21326A59EC7A [This is a checksum on the sequence]

        10         20         30         40         50         60 
MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR NCVYTYRILP 

        70         80         90        100        110        120 
NEDDKFTVQA SEGVPMRFFT KLDQLIDFYK KENMGLVTHL QYPVPLEEED AIDEAEEDTV 

       130        140        150        160        170        180 
ESVMSPPELP PRNIPMSAGP SEAKDLPLAT ENPRAPEVTR LSLSETLFQR LQSMDTSGLP 

       190        200        210        220        230        240 
EEHLKAIQDY LSTQLLLDSD FLKTGSSNLP HLKKLMSLLC KELHGEVIRT LPSLESLQRL 

       250        260        270        280        290        300 
FDQQLSPGLR PRPQVPGEAS PITMVAKLSQ LTSLLSSIED KVKSLLHEGS ESTNRRSLIP 

       310        320        330        340        350        360 
PVTFEVKSES LGIPQKMHLK VDVESGKLIV KKSKDGSEDK FYSHKKILQL IKSQKFLNKL 

       370        380        390        400        410        420 
VILVETEKEK ILRKEYVFAD SKKREGFCQL LQQMKNKHSE QPEPDMITIF IGTWNMGNAP 

       430        440        450        460        470        480 
PPKKITSWFL SKGQGKTRDD SADYIPHDIY VIGTQEDPLG EKEWLELLRH SLQEVTSMTF 

       490        500        510        520        530        540 
KTVAIHTLWN IRIVVLAKPE HENRISHICT DNVKTGIANT LGNKGAVGVS FMFNGTSLGF 

       550        560        570        580        590        600 
VNSHLTSGSE KKLRRNQNYM NILRFLALGD KKLSPFNITH RFTHLFWLGD LNYRVELPTW 

       610        620        630        640        650        660 
EAEAIIQKIK QQQYSDLLAH DQLLLERKDQ KVFLHFEEEE ITFAPTYRFE RLTRDKYAYT 

       670        680        690        700        710        720 
KQKATGMKYN LPSWCDRVLW KSYPLVHVVC QSYGSTSDIM TSDHSPVFAT FEAGVTSQFV 

       730        740        750        760        770        780 
SKNGPGTVDS QGQIEFLACY ATLKTKSQTK FYLEFHSSCL ESFVKSQEGE NEEGSEGELV 

       790        800        810        820        830        840 
VRFGETLPKL KPIISDPEYL LDQHILISIK SSDSDESYGE GCIALRLETT EAQHPIYTPL 

       850        860        870        880        890        900 
THHGEMTGHF RGEIKLQTSQ GKMREKLYDF VKTERDESSG MKCLKNLTSH DPMRQWEPSG 

       910        920        930        940        950        960 
RVPACGVSSL NEMINPNYIG MGPFGQPLHG KSTLSPDQQL TAWSYDQLPK DSSLGPGRGE 

       970        980        990       1000       1010       1020 
GPPTPPSQPP LSPKKFSSST ANRGPCPRVQ EARPGDLGKV EALLQEDLLL TKPEMFENPL 

      1030       1040       1050       1060       1070       1080 
YGSVSSFPKL VPRKEQESPK MLRKEPPPCP DPGISSPSIV LPKAQEVESV KGTSKQAPVP 

      1090       1100       1110       1120       1130       1140 
VLGPTPRIRS FTCSSSAEGR MTSGDKSQGK PKASASSQAP VPVKRPVKPS RSEMSQQTTP 

      1150       1160       1170       1180       1190 
IPAPRPPLPV KSPAVLQLQH SKGRDYRDNT ELPHHGKHRQ EEGLLGRTAM Q

Q9ES52 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools