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P97573

- SHIP1_RAT

UniProt

P97573 - SHIP1_RAT

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Protein

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

Gene
Inpp5d, Ship, Ship1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

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
Complete GO annotation...

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; 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.

GO - Cellular componenti

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

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 – 9171Phosphotyrosine By similarity
Modified residuei934 – 9341Phosphoserine By similarity
Modified residuei944 – 9441Phosphotyrosine By similarity
Modified residuei1020 – 10201Phosphotyrosine By 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.1 Publication

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP97573.
SMRiP97573. Positions 3-115.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 10497SH2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1014 – 102815Interaction with DAB2 By 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.
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.

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: June 11, 2014
This is version 90 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

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