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Q9ES52 (SHIP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1

EC=3.1.3.86
Alternative name(s):
Inositol polyphosphate-5-phosphatase of 145 kDa
Short name=SIP-145
SH2 domain-containing inositol 5'-phosphatase 1
Short name=SH2 domain-containing inositol phosphatase 1
Short name=SHIP-1
p150Ship
Gene names
Name:Inpp5d
Synonyms:7a33, Ship, Ship1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1191 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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. Ref.1 Ref.11 Ref.13 Ref.25 Ref.26 Ref.27 Ref.28 Ref.34 Ref.36 Ref.37 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.47 Ref.50 Ref.52

Catalytic activity

1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate. Ref.1 Ref.2 Ref.21

Enzyme regulation

Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.

Subunit structure

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. Interacts with MILR1 (tyrosine-phosphorylated). Isoform 5 interacts with IL6ST/gp130. Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Ref.1 Ref.2 Ref.4 Ref.14 Ref.15 Ref.16 Ref.17 Ref.20 Ref.22 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.35 Ref.38 Ref.39 Ref.42 Ref.45 Ref.46 Ref.47 Ref.48 Ref.51

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 in membrane localization. Ref.23 Ref.38 Ref.49

Isoform 5: Cell membrane; Peripheral membrane protein. Note: Constitutively present at the cell membrane. Ref.23 Ref.38 Ref.49

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 coexpressed with other isoforms in hematopoietic stem cells, and disappears with differentiation. Ref.1 Ref.2 Ref.4 Ref.24

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. Ref.4 Ref.24

Induction

By activin/TGF-beta (at protein level). Regulated by the Smad pathway. Isoform 3 is expressed during myeloid development. Ref.40

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. Ref.14

The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. Ref.14

Post-translational modification

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. Ref.1 Ref.4 Ref.12 Ref.15 Ref.29 Ref.31 Ref.39

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. Ref.25 Ref.28 Ref.41

Sequence similarities

Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processApoptosis
Immunity
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
SH2 domain
SH3-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

dephosphorylation

Inferred from direct assay Ref.2PubMed 8890215. Source: GOC

determination of adult lifespan

Inferred from mutant phenotype Ref.28. Source: MGI

immune system process

Inferred from electronic annotation. Source: UniProtKB-KW

immunoglobulin mediated immune response

Inferred from mutant phenotype PubMed 10704460. Source: MGI

intracellular signal transduction

Inferred from mutant phenotype PubMed 10704460. Source: MGI

negative regulation of B cell activation

Inferred from mutant phenotype PubMed 10704460. Source: MGI

negative regulation of B cell proliferation

Inferred from mutant phenotype PubMed 10704460. Source: MGI

negative regulation of bone resorption

Inferred from mutant phenotype Ref.41. Source: MGI

negative regulation of cell proliferation

Inferred from direct assay PubMed 8890215. Source: MGI

negative regulation of granulocyte differentiation

Inferred from mutant phenotype Ref.28. Source: MGI

negative regulation of immune response

Inferred from mutant phenotype PubMed 10704460. Source: MGI

negative regulation of interleukin-6 biosynthetic process

Inferred from mutant phenotype Ref.41. Source: MGI

negative regulation of monocyte differentiation

Inferred from mutant phenotype Ref.28. Source: MGI

negative regulation of neutrophil differentiation

Inferred from mutant phenotype Ref.28. Source: MGI

negative regulation of osteoclast differentiation

Inferred from mutant phenotype Ref.41. Source: MGI

negative regulation of signal transduction

Inferred from mutant phenotype PubMed 10704460Ref.41Ref.28. Source: MGI

phosphatidylinositol dephosphorylation

Inferred from electronic annotation. Source: InterPro

positive regulation of B cell differentiation

Inferred from mutant phenotype PubMed 10704460Ref.28. Source: MGI

positive regulation of apoptotic process

Inferred from mutant phenotype Ref.41. Source: MGI

positive regulation of erythrocyte differentiation

Inferred from mutant phenotype Ref.28. Source: MGI

positive regulation of lymphocyte differentiation

Inferred from mutant phenotype Ref.28. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionPTB domain binding

Inferred from direct assay Ref.1. Source: MGI

SH3 domain binding

Inferred from direct assay Ref.2. Source: MGI

hydrolase activity

Inferred from electronic annotation. Source: UniProtKB-KW

inositol-polyphosphate 5-phosphatase activity

Inferred from direct assay Ref.2. Source: MGI

phosphatidylinositol trisphosphate phosphatase activity

Inferred from direct assay PubMed 8890215. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PIK3R1P237272EBI-1452545,EBI-520244From a different organism.
Plcg2Q8CIH53EBI-300210,EBI-617954

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9ES52-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9ES52-2)

The sequence of this isoform differs from the canonical sequence as follows:
     120-120: Missing.
Isoform 3 (identifier: Q9ES52-3)

Also known as: 135 kDa SHIP;

The sequence of this isoform differs from the canonical sequence as follows:
     920-980: Missing.
Isoform 4 (identifier: Q9ES52-4)

Also known as: SHIPdelta;

The sequence of this isoform differs from the canonical sequence as follows:
     120-120: Missing.
     920-960: GMGPFGQPLH...DSSLGPGRGE → VFIFHSQPRS...GPAADEARDV
     961-1191: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 5 (identifier: Q9ES52-5)

Also known as: s-SHIP;

The sequence of this isoform differs from the canonical sequence as follows:
     1-263: Missing.
Isoform 6 (identifier: Q9ES52-6)

Also known as: s-SHIPD183;

The sequence of this isoform differs from the canonical sequence as follows:
     1-263: Missing.
     920-980: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11911191Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
PRO_0000302867

Regions

Domain8 – 10497SH2
Region1015 – 102915Interaction with DAB2
Motif127 – 1326SH3-binding 1
Motif915 – 9184NPXY motif 1
Motif970 – 9756SH3-binding 2
Motif1018 – 10214NPXY motif 2
Motif1039 – 105012SH3-binding 3
Compositional bias962 – 1153192Pro-rich

Amino acid modifications

Modified residue9181Phosphotyrosine Ref.15
Modified residue9351Phosphoserine Ref.18
Modified residue9451Phosphotyrosine Ref.18
Modified residue10211Phosphotyrosine Ref.15

Natural variations

Alternative sequence1 – 263263Missing in isoform 5 and isoform 6.
VSP_027980
Alternative sequence1201Missing in isoform 2 and isoform 4.
VSP_027981
Alternative sequence920 – 98061Missing in isoform 3 and isoform 6.
VSP_027982
Alternative sequence920 – 96041GMGPF…PGRGE → VFIFHSQPRSLPQGARGKTW GSGKGGSSAPGGPAADEARD V in isoform 4.
VSP_027983
Alternative sequence961 – 1191231Missing in isoform 4.
VSP_027984

Experimental info

Mutagenesis6761D → G: Loss of function. Ref.34
Mutagenesis9181Y → F: Strongly impairs function, tyrosine phosphorylation, subcellular location and interaction with DOK1; when associated with F-1021. Ref.15 Ref.34 Ref.35
Mutagenesis10211Y → F: Strongly impairs function, tyrosine phosphorylation, subcellular location and interaction with DOK1; when associated with F-918. Ref.15 Ref.34 Ref.35
Sequence conflict431Y → C in AAB18937. Ref.2
Sequence conflict5271V → A in AAC53023. Ref.3
Sequence conflict5341N → I in AAC53023. Ref.3
Sequence conflict9051C → E AA sequence Ref.2
Sequence conflict9811A → T in AAB18937. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 11, 2007. Version 2.
Checksum: AF9F21326A59EC7A

FASTA1,191133,542
        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 

« Hide

Isoform 2 [UniParc].

Checksum: DF81F3046F33A07F
Show »

FASTA1,190133,443
Isoform 3 (135 kDa SHIP) [UniParc].

Checksum: C3E2F1EB206034BF
Show »

FASTA1,130127,199
Isoform 4 (SHIPdelta) [UniParc].

Checksum: B95D49476957345E
Show »

FASTA959108,345
Isoform 5 (s-SHIP) [UniParc].

Checksum: 7390D08E57505B82
Show »

FASTA928104,101
Isoform 6 (s-SHIPD183) [UniParc].

Checksum: F848515DE853AD65
Show »

FASTA86797,758

References

« Hide 'large scale' references
[1]"p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity."
Lioubin M.N., Algate P.A., Tsai S., Carlberg K., Aebersold A., Rohrschneider L.R.
Genes Dev. 10:1084-1095(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 2-9 AND 1163-1173, FUNCTION, ENZYME ACTIVITY, PHOSPHORYLATION, TISSUE SPECIFICITY, INTERACTION WITH SHC1.
Strain: DBA/2.
[2]"The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase."
Damen J.E., Liu L., Rosten P., Humphries R.K., Jefferson A.B., Majerus P.W., Krystal G.
Proc. Natl. Acad. Sci. U.S.A. 93:1689-1693(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 902-916, ENZYME ACTIVITY, TISSUE SPECIFICITY, INTERACTION WITH GRB2 AND SHC1.
[3]"Molecular cloning and chromosomal localization in human and mouse of the SH2-containing inositol phosphatase, INPP5D (SHIP)."
Liu Q., Dumont D.J.
Genomics 39:109-112(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"A novel spliced form of SH2-containing inositol phosphatase is expressed during myeloid development."
Lucas D.M., Rohrschneider L.R.
Blood 93:1922-1933(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PHOSPHORYLATION, INTERACTION WITH SHC1 AND GRB2, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: BALB/c.
[5]"Cloning of the genomic locus of mouse SH2 containing inositol 5-phosphatase (SHIP) and a novel 110-kDa splice isoform, SHIPdelta."
Wolf I., Lucas D.M., Algate P.A., Rohrschneider L.R.
Genomics 69:104-112(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 4).
Strain: 129/Sv.
[6]"Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5'-phosphatase isoform that partners with the Grb2 adapter protein."
Tu Z., Ninos J.M., Ma Z., Wang J.-W., Lemos M.P., Desponts C., Ghansah T., Howson J.M., Kerr W.G.
Blood 98:2028-2038(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[7]"The transcriptional landscape of the mammalian genome."
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. expand/collapse author list , 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.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Spleen.
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Thyroid.
[9]"Analysis of lipopolysaccharide-response genes in B-lineage cells demonstrates that they can have differentiation stage-restricted expression and contain SH2 domains."
Kerr W.G., Heller M., Herzenberg L.A.
Proc. Natl. Acad. Sci. U.S.A. 93:3947-3952(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-106.
[10]"Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2."
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.
Curr. Biol. 6:438-445(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[11]"Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB."
Ono M., Bolland S., Tempst P., Ravetch J.V.
Nature 383:263-266(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145-kDa inositol polyphosphate 5-phosphatase, SHIP."
Chacko G.W., Tridandapani S., Damen J.E., Liu L., Krystal G., Coggeshall K.M.
J. Immunol. 157:2234-2238(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[13]"Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling."
Ono M., Okada H., Bolland S., Yanagi S., Kurosaki T., Ravetch J.V.
Cell 90:293-301(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"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."
Liu L., Damen J.E., Hughes M.R., Babic I., Jirik F.R., Krystal G.
J. Biol. Chem. 272:8983-8988(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN SH2, INTERACTION WITH SHC1.
[15]"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."
Lamkin T.D., Walk S.F., Liu L., Damen J.E., Krystal G., Ravichandran K.S.
J. Biol. Chem. 272:10396-10401(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-918 AND TYR-1021, INTERACTION WITH SHC1, MUTAGENESIS OF TYR-918 AND TYR-1021.
[16]"Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2."
Liu L., Damen J.E., Ware M.D., Krystal G.
J. Biol. Chem. 272:10998-11001(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN11.
[17]"Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2."
Morris S.M., Cooper J.A.
Traffic 2:111-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2.
[18]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-935 AND TYR-945, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[19]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions."
Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T., Shibayama S., Shibuya K., Shibuya A.
Nat. Immunol. 11:601-607(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MILR1.
[21]"Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets."
Giuriato S., Payrastre B., Drayer A.L., Plantavid M., Woscholski R., Parker P., Erneux C., Chap H.
J. Biol. Chem. 272:26857-26863(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY.
[22]"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."
Sattler M., Salgia R., Shrikhande G., Verma S., Choi J.-L., Rohrschneider L.R., Griffin J.D.
Oncogene 15:2379-2384(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN11.
[23]"Multiple forms of the SH2-containing inositol phosphatase, SHIP, are generated by C-terminal truncation."
Damen J.E., Liu L., Ware M.D., Ermolaeva M., Majerus P.W., Krystal G.
Blood 92:1199-1205(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[24]"The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed during hematopoiesis and spermatogenesis."
Liu Q., Shalaby F., Jones J., Bouchard D., Dumont D.J.
Blood 91:2753-2759(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[25]"Targeted disruption of SHIP leads to Steel factor-induced degranulation of mast cells."
Huber M., Helgason C.D., Scheid M.P., Duronio V., Humphries R.K., Krystal G.
EMBO J. 17:7311-7319(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[26]"The inositol polyphosphate 5-phosphatase ship is a crucial negative regulator of B cell antigen receptor signaling."
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.
J. Exp. Med. 188:1333-1342(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[27]"The src homology 2-containing inositol phosphatase (SHIP) is the gatekeeper of mast cell degranulation."
Huber M., Helgason C.D., Damen J.E., Liu L., Humphries R.K., Krystal G.
Proc. Natl. Acad. Sci. U.S.A. 95:11330-11335(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[28]"Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span."
Helgason C.D., Damen J.E., Rosten P., Grewal R., Sorensen P., Chappel S.M., Borowski A., Jirik F., Krystal G., Humphries R.K.
Genes Dev. 12:1610-1620(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[29]"Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells."
Tridandapani S., Phee H., Shivakumar L., Kelley T.W., Coggeshall K.M.
Mol. Immunol. 35:1135-1146(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHC1 AND FCGR2B, PHOSPHORYLATION.
[30]"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."
Giuriato S., Bodin S., Erneux C., Woscholski R., Plantavid M., Chap H., Payrastre B.
Biochem. J. 348:107-112(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SRC.
[31]"The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor."
Mason J.M., Beattie B.K., Liu Q., Dumont D.J., Barber D.L.
J. Biol. Chem. 275:4398-4406(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPOR, PHOSPHORYLATION.
[32]"Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by fcgamma RIIB."
Bruhns P., Vely F., Malbec O., Fridman W.H., Vivier E., Daeeron M.
J. Biol. Chem. 275:37357-37364(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCGR2B.
[33]"Essential role for the C-terminal noncatalytic region of SHIP in FcgammaRIIB1-mediated inhibitory signaling."
Aman M.J., Walk S.F., March M.E., Su H.-P., Carver D.J., Ravichandran K.S.
Mol. Cell. Biol. 20:3576-3589(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCGR2B.
[34]"SHIP's C-terminus is essential for its hydrolysis of PIP3 and inhibition of mast cell degranulation."
Damen J.E., Ware M.D., Kalesnikoff J., Hughes M.R., Krystal G.
Blood 97:1343-1351(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-676; TYR-918 AND TYR-1021.
[35]"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."
Sattler M., Verma S., Pride Y.B., Salgia R., Rohrschneider L.R., Griffin J.D.
J. Biol. Chem. 276:2451-2458(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DOK1 AND CRKL, MUTAGENESIS OF TYR-918 AND TYR-1021.
[36]"Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB."
Malbec O., Schmitt C., Bruhns P., Krystal G., Fridman W.H., Daeeron M.
J. Biol. Chem. 276:30381-30391(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[37]"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)."
Cox D., Dale B.M., Kashiwada M., Helgason C.D., Greenberg S.
J. Exp. Med. 193:61-71(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[38]"SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells."
Galandrini R., Tassi I., Mattia G., Lenti L., Piccoli M., Frati L., Santoni A.
Blood 100:4581-4589(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH FCGR3.
[39]"Src homology 2 domain-containing inositol polyphosphate phosphatase regulates NF-kappa B-mediated gene transcription by phagocytic Fc gamma Rs in human myeloid cells."
Tridandapani S., Wang Y., Marsh C.B., Anderson C.L.
J. Immunol. 169:4370-4378(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FCGR2A, PHOSPHORYLATION.
[40]"Activin/TGF-beta induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP."
Valderrama-Carvajal H., Cocolakis E., Lacerte A., Lee E.-H., Krystal G., Ali S., Lebrun J.-J.
Nat. Cell Biol. 4:963-969(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[41]"SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts."
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.
Nat. Med. 8:943-949(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[42]"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."
Mancini A., Koch A., Wilms R., Tamura T.
Oncogene 21:1477-1484(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MET.
[43]"The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity."
Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., Krystal G., Marsh C.B.
J. Biol. Chem. 278:38628-38636(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[44]"SHIP1 and Lyn kinase negatively regulate integrin alpha IIb beta 3 signaling in platelets."
Maxwell M.J., Yuan Y., Anderson K.E., Hibbs M.L., Salem H.H., Jackson S.P.
J. Biol. Chem. 279:32196-32204(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[45]"Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap."
Isnardi I., Lesourne R., Bruhns P., Fridman W.H., Cambier J.C., Daeeron M.
J. Biol. Chem. 279:51931-51938(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCGR2B.
[46]"SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase."
Tomlinson M.G., Heath V.L., Turck C.W., Watson S.P., Weiss A.
J. Biol. Chem. 279:55089-55096(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TEC.
[47]"Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid phosphatase that interacts with the adaptor molecule Dok-3."
Robson J.D., Davidson D., Veillette A.
Mol. Cell. Biol. 24:2332-2343(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DOK3.
[48]"Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and modulates EGF-induced PLC activity."
Song M., Kim M.J., Ha S., Park J.B., Ryu S.H., Suh P.-G.
Exp. Mol. Med. 37:161-168(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLCG1.
[49]"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."
Isnardi I., Bruhns P., Bismuth G., Fridman W.H., Daeeron M.
Immunol. Lett. 104:156-165(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[50]"SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-dependent alterations in D-type cyclins and p27."
Zhou P., Kitaura H., Teitelbaum S.L., Krystal G., Ross F.P., Takeshita S.
J. Immunol. 177:8777-8784(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[51]"s-SHIP associates with receptor complexes essential for pluripotent stem cell growth and survival."
Desponts C., Ninos J.M., Kerr W.G.
Stem Cells Dev. 15:641-646(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL6ST.
[52]"Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1."
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.
Nat. Cell Biol. 9:36-44(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U51742 mRNA. Translation: AAC52606.1.
U39203 mRNA. Translation: AAB18937.1.
U52044 mRNA. Translation: AAC53023.1.
AF125996 mRNA. Translation: AAD37118.1.
AF235502 expand/collapse EMBL AC list , AF235496, AF235498, AF235499, AF235500, AF235501 Genomic DNA. Translation: AAG23922.1.
AF228679 mRNA. Translation: AAF69143.1.
AF184912 mRNA. Translation: AAF25823.1.
AF184913 mRNA. Translation: AAF25824.1.
AK143560 mRNA. Translation: BAE25436.1.
BC108328 mRNA. Translation: AAI08329.1.
PIRJC6118.
RefSeqNP_001103662.1. NM_001110192.1.
NP_001103663.1. NM_001110193.1.
NP_034696.2. NM_010566.2.
UniGeneMm.15105.

3D structure databases

ProteinModelPortalQ9ES52.
SMRQ9ES52. Positions 3-152, 405-717, 730-817.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200769. 24 interactions.
IntActQ9ES52. 11 interactions.
MINTMINT-205819.

PTM databases

PhosphoSiteQ9ES52.

Proteomic databases

PaxDbQ9ES52.
PRIDEQ9ES52.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000042275; ENSMUSP00000044647; ENSMUSG00000026288. [Q9ES52-2]
ENSMUST00000072999; ENSMUSP00000072763; ENSMUSG00000026288. [Q9ES52-4]
ENSMUST00000167032; ENSMUSP00000126569; ENSMUSG00000026288. [Q9ES52-5]
ENSMUST00000168783; ENSMUSP00000131244; ENSMUSG00000026288. [Q9ES52-3]
ENSMUST00000169754; ENSMUSP00000127941; ENSMUSG00000026288. [Q9ES52-1]
ENSMUST00000170300; ENSMUSP00000132384; ENSMUSG00000026288. [Q9ES52-6]
GeneID16331.
KEGGmmu:16331.
UCSCuc007bxc.2. mouse. [Q9ES52-1]
uc007bxd.2. mouse. [Q9ES52-3]
uc007bxf.2. mouse. [Q9ES52-2]
uc007bxg.2. mouse. [Q9ES52-6]

Organism-specific databases

CTD3635.
MGIMGI:107357. Inpp5d.

Phylogenomic databases

eggNOGCOG5411.
GeneTreeENSGT00750000117420.
HOVERGENHBG106726.
InParanoidQ9ES52.
KOK03084.
OMARKEPPPC.
OrthoDBEOG75F4CD.
PhylomeDBQ9ES52.
TreeFamTF323475.

Gene expression databases

ArrayExpressQ9ES52.
BgeeQ9ES52.
CleanExMM_INPP5D.
GenevestigatorQ9ES52.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
3.60.10.10. 1 hit.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR000980. SH2.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00128. IPPc. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
SSF56219. SSF56219. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio289418.
PROQ9ES52.
SOURCESearch...

Entry information

Entry nameSHIP1_MOUSE
AccessionPrimary (citable) accession number: Q9ES52
Secondary accession number(s): Q3UPF9 expand/collapse secondary AC list , Q4U212, Q61034, Q61173, Q61181, Q9JKR7, Q9JLF9, Q9JLG0, Q9QVN8, Q9WUC2
Entry history
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: September 11, 2007
Last modified: April 16, 2014
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot