INPP5D

Inositol polyphosphate-5-phosphatase D
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2YSX​
Identifiers
Symbols	INPP5D ; SHIP; SHIP-1; SHIP1; SIP-145; hp51CN; p150Ship
External IDs	OMIM: 601582 MGI: 107357 HomoloGene: 4046 ChEMBL: 1781870 GeneCards: INPP5D Gene
EC number	3.1.3.86
Gene ontology Molecular function • inositol-polyphosphate 5-phosphatase activity • protein binding • SH3 domain binding • phosphatidylinositol trisphosphate phosphatase activity • PTB domain binding Cellular component • cytosol • membrane Biological process • protein dephosphorylation • phospholipid metabolic process • phosphatidylinositol biosynthetic process • phosphate-containing compound metabolic process • apoptotic process • signal transduction • blood coagulation • determination of adult lifespan • negative regulation of signal transduction • immunoglobulin mediated immune response • negative regulation of B cell proliferation • intracellular signal transduction • positive regulation of apoptotic process • inositol phosphate metabolic process • small molecule metabolic process • negative regulation of interleukin-6 biosynthetic process • positive regulation of B cell differentiation • positive regulation of erythrocyte differentiation • negative regulation of monocyte differentiation • negative regulation of neutrophil differentiation • negative regulation of osteoclast differentiation • negative regulation of bone resorption • phosphatidylinositol dephosphorylation • negative regulation of immune response • T cell receptor signaling pathway • leukocyte migration Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3635	16331
Ensembl	ENSG00000168918	ENSMUSG00000026288
UniProt	Q92835	Q9ES52
RefSeq (mRNA)	NM_001017915	NM_001110192
RefSeq (protein)	NP_001017915	NP_001103662
Location (UCSC)	Chr 2: 233.06 – 233.21 Mb	Chr 1: 87.62 – 87.72 Mb
PubMed search

Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 is an enzyme that in humans is encoded by the INPP5D gene.^[1][2][3] INPP5D also called SHIP1 was also shown to be a negative regulator of BCR signalling in B cells.^[4]

This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[3]

Interactions

INPP5D has been shown to interact with DOK2,^[5] LYN,^[6] CD22,^[7] Grb2,^[8] CRKL,^[9] CD31,^[10] DOK1^[5][11] and SHC1.^{[1][5][12][13][14]}

References

1. Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW, Krystal G (July 1996). "The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase". Proc Natl Acad Sci U S A 93 (4): 1689–93. doi:10.1073/pnas.93.4.1689. PMC 40003. PMID 8643691.
2. Ware MD, Rosten P, Damen JE, Liu L, Humphries RK, Krystal G (December 1996). "Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation". Blood 88 (8): 2833–40. PMID 8874179.
3. "Entrez Gene: INPP5D inositol polyphosphate-5-phosphatase, 145kDa".
4. . PMID 24914134. Missing or empty |title= (help)
5. Dunant, N M; Wisniewski D; Strife A; Clarkson B; Resh M D (May 2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cell. Signal. (ENGLAND) 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. ISSN 0898-6568. PMID 10822173.
6. Baran, Christopher P; Tridandapani Susheela; Helgason Cheryl D; Humphries R Keith; Krystal Gerald; Marsh Clay B (October 2003). "The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity". J. Biol. Chem. (United States) 278 (40): 38628–36. doi:10.1074/jbc.M305021200. ISSN 0021-9258. PMID 12882960.
7. Poe, J C; Fujimoto M; Jansen P J; Miller A S; Tedder T F (June 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". J. Biol. Chem. (UNITED STATES) 275 (23): 17420–7. doi:10.1074/jbc.M001892200. ISSN 0021-9258. PMID 10748054.
8. Kavanaugh, W M; Pot D A; Chin S M; Deuter-Reinhard M; Jefferson A B; Norris F A; Masiarz F R; Cousens L S; Majerus P W; Williams L T (April 1996). "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Curr. Biol. (ENGLAND) 6 (4): 438–45. doi:10.1016/S0960-9822(02)00511-0. ISSN 0960-9822. PMID 8723348.
9. Arai, A; Kanda E; Nosaka Y; Miyasaka N; Miura O (August 2001). "CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling". J. Biol. Chem. (United States) 276 (35): 33282–90. doi:10.1074/jbc.M102924200. ISSN 0021-9258. PMID 11443118.
10. Pumphrey, N J; Taylor V; Freeman S; Douglas M R; Bradfield P F; Young S P; Lord J M; Wakelam M J; Bird I N; Salmon M; Buckley C D (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Lett. (NETHERLANDS) 450 (1–2): 77–83. doi:10.1016/S0014-5793(99)00446-9. ISSN 0014-5793. PMID 10350061.
11. van Dijk, T B; van Den Akker E; Amelsvoort M P; Mano H; Löwenberg B; von Lindern M (November 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood (UNITED STATES) 96 (10): 3406–13. ISSN 0006-4971. PMID 11071635.
12. Wisniewski, D; Strife A; Swendeman S; Erdjument-Bromage H; Geromanos S; Kavanaugh W M; Tempst P; Clarkson B (April 1999). "A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells". Blood (UNITED STATES) 93 (8): 2707–20. ISSN 0006-4971. PMID 10194451.
13. Leitges, Michael; Gimborn Kerstin; Elis Winfried; Kalesnikoff Janet; Hughes Michael R; Krystal Gerald; Huber Michael (June 2002). "Protein Kinase C-δ Is a Negative Regulator of Antigen-Induced Mast Cell Degranulation". Mol. Cell. Biol. (United States) 22 (12): 3970–80. doi:10.1128/MCB.22.12.3970-3980.2002. ISSN 0270-7306. PMC 133855. PMID 12024011.
14. March, M E; Lucas D M; Aman M J; Ravichandran K S (September 2000). "p135 src homology 2 domain-containing inositol 5'-phosphatase (SHIPbeta ) isoform can substitute for p145 SHIP in fcgamma RIIB1-mediated inhibitory signaling in B cells". J. Biol. Chem. (UNITED STATES) 275 (39): 29960–7. doi:10.1074/jbc.M003714200. ISSN 0021-9258. PMID 10900203.

Further reading

• MacDonald SM, Vonakis BM (2003). "Association of the Src homology 2 domain-containing inositol 5' phosphatase (SHIP) to releasability in human basophils". Mol. Immunol. 38 (16–18): 1323–7. doi:10.1016/S0161-5890(02)00082-2. PMID 12217402.
• Lioubin MN, Algate PA, Tsai S, et al. (1996). "p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity". Genes Dev. 10 (9): 1084–95. doi:10.1101/gad.10.9.1084. PMID 8654924.
• Kavanaugh WM, Pot DA, Chin SM, et al. (1997). "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Curr. Biol. 6 (4): 438–45. doi:10.1016/S0960-9822(02)00511-0. PMID 8723348.
• Drayer AL, Pesesse X, De Smedt F, et al. (1996). "Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase". Biochem. Biophys. Res. Commun. 225 (1): 243–9. doi:10.1006/bbrc.1996.1161. PMID 8769125.
• Geier SJ, Algate PA, Carlberg K, et al. (1997). "The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood". Blood 89 (6): 1876–85. PMID 9058707.
• Odai H, Sasaki K, Iwamatsu A, et al. (1997). "Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl". Blood 89 (8): 2745–56. PMID 9108392.
• Liu L, Damen JE, Ware MD, Krystal G (1997). "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2". J. Biol. Chem. 272 (17): 10998–1001. doi:10.1074/jbc.272.17.10998. PMID 9110989.
• Giuriato S, Payrastre B, Drayer AL, et al. (1997). "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets". J. Biol. Chem. 272 (43): 26857–63. doi:10.1074/jbc.272.43.26857. PMID 9341117.
• Kuroiwa A, Yamashita Y, Inui M, et al. (1998). "Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene". J. Biol. Chem. 273 (2): 1070–4. doi:10.1074/jbc.273.2.1070. PMID 9422771.
• Liu Q, Shalaby F, Jones J, et al. (1998). "The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed during hematopoiesis and spermatogenesis". Blood 91 (8): 2753–9. PMID 9531585.
• Zhang S, Broxmeyer HE (1999). "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells". Biochem. Biophys. Res. Commun. 254 (2): 440–5. doi:10.1006/bbrc.1998.9959. PMID 9918857.
• Mikhalap SV, Shlapatska LM, Berdova AG, et al. (1999). "CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis". J. Immunol. 162 (10): 5719–27. PMID 10229804.
• Pumphrey NJ, Taylor V, Freeman S, et al. (1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Lett. 450 (1–2): 77–83. doi:10.1016/S0014-5793(99)00446-9. PMID 10350061.
• Mason JM, Beattie BK, Liu Q, et al. (2000). "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor". J. Biol. Chem. 275 (6): 4398–406. doi:10.1074/jbc.275.6.4398. PMID 10660611.
• Bone H, Welham MJ (2000). "Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains". Cell. Signal. 12 (3): 183–94. doi:10.1016/S0898-6568(99)00088-1. PMID 10704825.
• Lemay S, Davidson D, Latour S, Veillette A (2000). "Dok-3, a Novel Adapter Molecule Involved in the Negative Regulation of Immunoreceptor Signaling". Mol. Cell. Biol. 20 (8): 2743–54. doi:10.1128/MCB.20.8.2743-2754.2000. PMC 85490. PMID 10733577.
• Poe JC, Fujimoto M, Jansen PJ, et al. (2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". J. Biol. Chem. 275 (23): 17420–7. doi:10.1074/jbc.M001892200. PMID 10748054.
• Dunant NM, Wisniewski D, Strife A, et al. (2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cell. Signal. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.