P97573 (SHIP1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 88. History...
Names and origin
|Protein names||Recommended name:|
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
SH2 domain-containing inositol 5'-phosphatase 1
Short name=SH2 domain-containing inositol phosphatase 1
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||1190 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate. Ref.1
Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane By similarity.
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
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.
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.
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
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
Contains 1 SH2 domain.
|Technical term||Complete proteome|
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: UniProtKB-KWimmune system process
Inferred from electronic annotation. Source: UniProtKB-KWphosphatidylinositol dephosphorylation
Inferred from electronic annotation. Source: InterPro
|Cellular_component||actin filamentcortical cytoskeletoncytosolmembrane|
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Molecular_function||inositol-4,5-bisphosphate 5-phosphatase activity|
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1190||1190||Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1||PRO_0000302868|
|Domain||8 – 104||97||SH2|
|Region||1014 – 1028||15||Interaction with DAB2 By similarity|
|Motif||126 – 131||6||SH3-binding 1|
|Motif||914 – 917||4||NPXY motif 1|
|Motif||969 – 974||6||SH3-binding 2|
|Motif||1017 – 1020||4||NPXY motif 2|
|Motif||1038 – 1049||12||SH3-binding 3|
|Compositional bias||961 – 1152||192||Pro-rich|
Amino acid modifications
|Modified residue||917||1||Phosphotyrosine By similarity|
|Modified residue||934||1||Phosphoserine By similarity|
|Modified residue||944||1||Phosphotyrosine By similarity|
|Modified residue||1020||1||Phosphotyrosine By similarity|
|||"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.|
|U55192 mRNA. Translation: AAB40610.1.|
|RefSeq||NP_062184.1. NM_019311.1. |
3D structure databases
|SMR||P97573. Positions 3-115. |
Protein-protein interaction databases
|BioGrid||248482. 6 interactions.|
|IntAct||P97573. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:2914. rat. |
|RGD||2914. Inpp5d. |
Gene expression databases
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
22.214.171.124. 1 hit.
|InterPro||IPR005135. Endo/exonuclease/phosphatase. |
|Pfam||PF03372. Exo_endo_phos. 1 hit. |
PF00017. SH2. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00128. IPPc. 1 hit. |
SM00252. SH2. 1 hit.
|SUPFAM||SSF56219. SSF56219. 1 hit. |
|PROSITE||PS50001. SH2. 1 hit. |
|Accession||Primary (citable) accession number: P97573|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families