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P97573

- SHIP1_RAT

UniProt

P97573 - SHIP1_RAT

Protein

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1

Gene

Inpp5d

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    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 By similarity.By similarity

    Catalytic activityi

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

    Enzyme regulationi

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

    GO - Molecular functioni

    1. inositol-4,5-bisphosphate 5-phosphatase activity Source: RGD
    2. protein binding Source: RGD

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. immune system process Source: UniProtKB-KW
    3. phosphatidylinositol dephosphorylation Source: InterPro

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Apoptosis, Immunity

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (EC:3.1.3.86)
    Alternative name(s):
    SH2 domain-containing inositol 5'-phosphatase 1
    Short name:
    SH2 domain-containing inositol phosphatase 1
    Short name:
    SHIP-1
    Gene namesi
    Name:Inpp5d
    Synonyms:Ship, Ship1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2914. Inpp5d.

    Subcellular locationi

    Cytoplasm By similarity. Membrane By similarity; Peripheral membrane protein By similarity
    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 By similarity.By similarity

    GO - Cellular componenti

    1. actin filament Source: RGD
    2. cortical cytoskeleton Source: RGD
    3. cytosol Source: RGD
    4. membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11901190Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1PRO_0000302868Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei917 – 9171PhosphotyrosineBy similarity
    Modified residuei934 – 9341PhosphoserineBy similarity
    Modified residuei944 – 9441PhosphotyrosineBy similarity
    Modified residuei1020 – 10201PhosphotyrosineBy similarity

    Post-translational modificationi

    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.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP97573.
    PRIDEiP97573.

    PTM databases

    PhosphoSiteiP97573.

    Expressioni

    Gene expression databases

    GenevestigatoriP97573.

    Interactioni

    Subunit structurei

    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 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi248482. 6 interactions.
    IntActiP97573. 2 interactions.
    MINTiMINT-2517198.
    STRINGi10116.ENSRNOP00000040111.

    Structurei

    3D structure databases

    ProteinModelPortaliP97573.
    SMRiP97573. Positions 3-115.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini8 – 10497SH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1014 – 102815Interaction with DAB2By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi126 – 1316SH3-binding 1
    Motifi914 – 9174NPXY motif 1
    Motifi969 – 9746SH3-binding 2
    Motifi1017 – 10204NPXY motif 2
    Motifi1038 – 104912SH3-binding 3Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi961 – 1152192Pro-richAdd
    BLAST

    Domaini

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

    Sequence similaritiesi

    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH2 domain, SH3-binding

    Phylogenomic databases

    eggNOGiCOG5411.
    HOGENOMiHOG000004836.
    HOVERGENiHBG106726.
    InParanoidiP97573.
    KOiK03084.
    PhylomeDBiP97573.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    3.60.10.10. 1 hit.
    InterProiIPR005135. Endo/exonuclease/phosphatase.
    IPR000300. IPPc.
    IPR000980. SH2.
    [Graphical view]
    PfamiPF03372. Exo_endo_phos. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00128. IPPc. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    SSF56219. SSF56219. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P97573-1 [UniParc]FASTAAdd to Basket

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    MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR     50
    NCVYTYRILP NEDDKFTVQA SEGVPMRFFT KLDQLIEFYK KENMGLVTHL 100
    QFPVPLEEED AIDEPEEDTE SVMSPPELPP RNIPVSGGPC EAKDLPLPTE 150
    NPRAPEVTRL SLSETLFQRL QSMDTSGLPE EHLKAIQDYL STQLMLDSDF 200
    LKTGSSNLPH LKKLTSLLCK ELHGEVIRTL PSLESLQRLF DQQLSPGLRP 250
    RPQVPGEANP ITMVAKLSQL TSLLSSIEDK VKALLHEGSE STNRRSLIPP 300
    VTFEVKSESL GIPQKMHLKV DVESGKLIIK KSRDGSEDKF YSHKKILQLI 350
    KSQKFLNKLV ILVETEKEKI LRKEYVFSDS KKREGFCQLL QQMKNKHSEQ 400
    SEPDMITIFI GTWNMGNAPP PKKITSWFLS KGQGKTRDDS ADYIPHDIYV 450
    IGTQEDPLGE KEWLEILRHS LQEVTSMTFK TVAIHTLWNI RIVVLAKPEH 500
    ENRISHICTD NVKTGIANTL GNKGAVGVSF MFNGTSLGFV NSHLTSGSEK 550
    KLRRNQNYMN ILRFLALGDK KLSPFNITHR FTHLFWLGDL NYRVELPTWE 600
    AEAIIQKIKQ QQYSDLLAHD QLLLERKEQE VFLHFEEEEI TFAPTYRFER 650
    LTRDKYAYTK QKATGMKYNL PSWCDRVLWK SYPLVHVVCQ SYGSTSDIMT 700
    SDHSPVFATF EAGVTSQFVS KNGPGAVDSQ GQIEFLACYA TLKTKSQTKF 750
    YLELHSSCLE SFVKSQEGEN EEGDEGELVV RFGETLPKLK PIISDPEYLL 800
    DQHILISIKS SDSDESYGEG CIALRLETTE SQLPIYTPLT HHGEMTGHFR 850
    GEIKLQTSEG KMREKLYDFV KTERDESSGM KCLKNLTSHD PMRQWEPAGR 900
    VPACGISSLN EIINPNYIGM GPFGQPLHGK STLSPDQQLT AWSYDQLPKD 950
    SSLGPGRGEG PPTPPSQPPL SPKKFSSSTA NRGSCPRVQE TRPGDLGKVE 1000
    ALPQEDLPLT KPEMFENPLY GSVSPFPKLV PRKEQESPKM MRKEPPPCPD 1050
    PGVSSPSIML PKAQEVENVK GTSKQAPVPV FGPTPRIRSF TCSSSAEGRM 1100
    PSGDKSQGKP KAPASSQAPV PVKRPVKPSR SEMSQQTTPI PAPRPPLPVK 1150
    SPAVLQLQHS KGRDYRDNTE LPHHGKHRQE ESLLGRTAMQ 1190
    Length:1,190
    Mass (Da):133,593
    Last modified:May 1, 1997 - v1
    Checksum:i85DD4F2190F98700
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U55192 mRNA. Translation: AAB40610.1.
    RefSeqiNP_062184.1. NM_019311.1.
    UniGeneiRn.10659.

    Genome annotation databases

    GeneIDi54259.
    KEGGirno:54259.
    UCSCiRGD:2914. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U55192 mRNA. Translation: AAB40610.1 .
    RefSeqi NP_062184.1. NM_019311.1.
    UniGenei Rn.10659.

    3D structure databases

    ProteinModelPortali P97573.
    SMRi P97573. Positions 3-115.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 248482. 6 interactions.
    IntActi P97573. 2 interactions.
    MINTi MINT-2517198.
    STRINGi 10116.ENSRNOP00000040111.

    PTM databases

    PhosphoSitei P97573.

    Proteomic databases

    PaxDbi P97573.
    PRIDEi P97573.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 54259.
    KEGGi rno:54259.
    UCSCi RGD:2914. rat.

    Organism-specific databases

    CTDi 3635.
    RGDi 2914. Inpp5d.

    Phylogenomic databases

    eggNOGi COG5411.
    HOGENOMi HOG000004836.
    HOVERGENi HBG106726.
    InParanoidi P97573.
    KOi K03084.
    PhylomeDBi P97573.

    Miscellaneous databases

    NextBioi 610778.
    PROi P97573.

    Gene expression databases

    Genevestigatori P97573.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    3.60.10.10. 1 hit.
    InterProi IPR005135. Endo/exonuclease/phosphatase.
    IPR000300. IPPc.
    IPR000980. SH2.
    [Graphical view ]
    Pfami PF03372. Exo_endo_phos. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00128. IPPc. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    SSF56219. SSF56219. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation."
      Osborne M.A., Zenner G., Lubinus M., Zhang X., Songyang Z., Cantley L.C., Majerus P., Burn P., Kochan J.P.
      J. Biol. Chem. 271:29271-29278(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, PHOSPHORYLATION, INTERACTION WITH MS4A2; SHC1; GRB2 AND FCER1G.

    Entry informationi

    Entry nameiSHIP1_RAT
    AccessioniPrimary (citable) accession number: P97573
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 11, 2007
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 91 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3