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P97573 (SHIP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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 names
Name:Inpp5d
Synonyms:Ship, Ship1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1190 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 By similarity.

Catalytic activity

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

Enzyme regulation

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

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 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. Ref.1

Subcellular location

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.

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 By similarity.

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

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

Sequence similarities

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

Contains 1 SH2 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11901190Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
PRO_0000302868

Regions

Domain8 – 10497SH2
Region1014 – 102815Interaction with DAB2 By similarity
Motif126 – 1316SH3-binding 1
Motif914 – 9174NPXY motif 1
Motif969 – 9746SH3-binding 2
Motif1017 – 10204NPXY motif 2
Motif1038 – 104912SH3-binding 3
Compositional bias961 – 1152192Pro-rich

Amino acid modifications

Modified residue9171Phosphotyrosine By similarity
Modified residue9341Phosphoserine By similarity
Modified residue9441Phosphotyrosine By similarity
Modified residue10201Phosphotyrosine By similarity

Sequences

Sequence LengthMass (Da)Tools
P97573 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 85DD4F2190F98700

FASTA1,190133,593
        10         20         30         40         50         60 
MPAMVPGWNH GNITRSKAEE LLSRAGKDGS FLVRASESIP RAYALCVLFR NCVYTYRILP 

        70         80         90        100        110        120 
NEDDKFTVQA SEGVPMRFFT KLDQLIEFYK KENMGLVTHL QFPVPLEEED AIDEPEEDTE 

       130        140        150        160        170        180 
SVMSPPELPP RNIPVSGGPC EAKDLPLPTE NPRAPEVTRL SLSETLFQRL QSMDTSGLPE 

       190        200        210        220        230        240 
EHLKAIQDYL STQLMLDSDF LKTGSSNLPH LKKLTSLLCK ELHGEVIRTL PSLESLQRLF 

       250        260        270        280        290        300 
DQQLSPGLRP RPQVPGEANP ITMVAKLSQL TSLLSSIEDK VKALLHEGSE STNRRSLIPP 

       310        320        330        340        350        360 
VTFEVKSESL GIPQKMHLKV DVESGKLIIK KSRDGSEDKF YSHKKILQLI KSQKFLNKLV 

       370        380        390        400        410        420 
ILVETEKEKI LRKEYVFSDS KKREGFCQLL QQMKNKHSEQ SEPDMITIFI GTWNMGNAPP 

       430        440        450        460        470        480 
PKKITSWFLS KGQGKTRDDS ADYIPHDIYV IGTQEDPLGE KEWLEILRHS LQEVTSMTFK 

       490        500        510        520        530        540 
TVAIHTLWNI RIVVLAKPEH ENRISHICTD NVKTGIANTL GNKGAVGVSF MFNGTSLGFV 

       550        560        570        580        590        600 
NSHLTSGSEK KLRRNQNYMN ILRFLALGDK KLSPFNITHR FTHLFWLGDL NYRVELPTWE 

       610        620        630        640        650        660 
AEAIIQKIKQ QQYSDLLAHD QLLLERKEQE VFLHFEEEEI TFAPTYRFER LTRDKYAYTK 

       670        680        690        700        710        720 
QKATGMKYNL PSWCDRVLWK SYPLVHVVCQ SYGSTSDIMT SDHSPVFATF EAGVTSQFVS 

       730        740        750        760        770        780 
KNGPGAVDSQ GQIEFLACYA TLKTKSQTKF YLELHSSCLE SFVKSQEGEN EEGDEGELVV 

       790        800        810        820        830        840 
RFGETLPKLK PIISDPEYLL DQHILISIKS SDSDESYGEG CIALRLETTE SQLPIYTPLT 

       850        860        870        880        890        900 
HHGEMTGHFR GEIKLQTSEG KMREKLYDFV KTERDESSGM KCLKNLTSHD PMRQWEPAGR 

       910        920        930        940        950        960 
VPACGISSLN EIINPNYIGM GPFGQPLHGK STLSPDQQLT AWSYDQLPKD SSLGPGRGEG 

       970        980        990       1000       1010       1020 
PPTPPSQPPL SPKKFSSSTA NRGSCPRVQE TRPGDLGKVE ALPQEDLPLT KPEMFENPLY 

      1030       1040       1050       1060       1070       1080 
GSVSPFPKLV PRKEQESPKM MRKEPPPCPD PGVSSPSIML PKAQEVENVK GTSKQAPVPV 

      1090       1100       1110       1120       1130       1140 
FGPTPRIRSF TCSSSAEGRM PSGDKSQGKP KAPASSQAPV PVKRPVKPSR SEMSQQTTPI 

      1150       1160       1170       1180       1190 
PAPRPPLPVK SPAVLQLQHS KGRDYRDNTE LPHHGKHRQE ESLLGRTAMQ 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U55192 mRNA. Translation: AAB40610.1.
RefSeqNP_062184.1. NM_019311.1.
UniGeneRn.10659.

3D structure databases

ProteinModelPortalP97573.
SMRP97573. Positions 3-115.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248482. 6 interactions.
IntActP97573. 2 interactions.
MINTMINT-2517198.
STRING10116.ENSRNOP00000040111.

PTM databases

PhosphoSiteP97573.

Proteomic databases

PaxDbP97573.
PRIDEP97573.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID54259.
KEGGrno:54259.
UCSCRGD:2914. rat.

Organism-specific databases

CTD3635.
RGD2914. Inpp5d.

Phylogenomic databases

eggNOGCOG5411.
HOGENOMHOG000004836.
HOVERGENHBG106726.
InParanoidP97573.
KOK03084.
PhylomeDBP97573.

Gene expression databases

GenevestigatorP97573.

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

NextBio610778.
PROP97573.

Entry information

Entry nameSHIP1_RAT
AccessionPrimary (citable) accession number: P97573
Entry history
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 89 of the entry and version 1 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