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

UniProt Q92835 Organism Homo sapiens Gene INPP5D, SHIP, SHIP1 EC 3.1.3.86, 3.1.3.56, 3.1.3.36

Also known as: INPP5D, SHIP, SHIP1

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. Also, is able to hydrolyze the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3), 1D-myo-inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. 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.

Classification

Family (Pfam): PF24147 C2_SHIP1-2_2nd, PF24150 C2_SHIP1-2_first, PF22669 Exo_endo_phos2, PF00017 SH2
InterPro: C2_SHIP1-2_2nd, C2_SHIP1-2_first, Endo/exonu/phosph_ase_sf, IPPc, SH2, SH2_dom_sf
Functional cluster: Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 99

2YSX NMR
5RW2 X-ray 1.22A
5RW3 X-ray 1.37A
5RW4 X-ray 1.31A
5RW5 X-ray 1.38A
5RW6 X-ray 1.32A
5RW7 X-ray 1.23A
5RW8 X-ray 1.27A
5RW9 X-ray 1.45A
5RWA X-ray 1.29A
5RWB X-ray 1.25A
5RWC X-ray 1.40A
… and 87 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

Drugs targeting this protein · 1

ROSIPTOR activator

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Inositol polyphosphate-5-phosphatase A 2 shared papers
Docking protein 1 1 shared papers
Phosphatidylinositol polyphosphate 5-phosphatase type IV 2 shared papers
Signaling lymphocytic activation molecule 1 shared papers
Growth factor receptor-bound protein 2 3 shared papers
Inositol polyphosphate 5-phosphatase OCRL 2 shared papers
Fc receptor-like protein 6 1 shared papers
SHC-transforming protein 1 1 shared papers
Thrombopoietin receptor 1 shared papers
Polyphosphatidylinositol phosphatase SYNJ2 1 shared papers
Tyrosine-protein kinase SYK 2 shared papers
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 1 shared papers

Literature · 19 cited papers

Discovery and Characterization of a Selective Inhibitor of Synaptojanin1 5-Phosphatase Activity. ACS Pharmacol. Transl. Sci. · 2025
Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling. Exp. Hematol. · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
FCRL6 receptor: expression and associated proteins. Immunol. Lett. · 2011
FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling. J. Immunol. · 2009
The Src homology 2-containing inositol 5-phosphatase 1 (SHIP1) is involved in CD32a signaling in human neutrophils. Cell. Signal. · 2006
Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia. Leukemia · 2003
Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors. J. Immunol. · 2002
The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells. Cell. Signal. · 2000
… and 7 more in the literature graph

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