INPP5D

INPP5D
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YSX
Identifiers
Aliases	INPP5D, SHIP, SHIP-1, SHIP1, SIP-145, hp51CN, p150Ship, inositol polyphosphate-5-phosphatase D
External IDs	MGI: 107357 HomoloGene: 4046 GeneCards: INPP5D
Genetically Related Diseases
Alzheimer's disease[1]
Gene ontology Molecular function • SH3 domain binding • inositol-polyphosphate 5-phosphatase activity • PTB domain binding • phosphatidylinositol trisphosphate phosphatase activity • protein binding • hydrolase activity • phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity • inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity • phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity Cellular component • cytoplasm • cytosol • membrane • plasma membrane • membrane raft • cytoskeleton Biological process • negative regulation of interleukin-6 biosynthetic process • negative regulation of monocyte differentiation • intracellular signal transduction • determination of adult lifespan • positive regulation of erythrocyte differentiation • negative regulation of osteoclast differentiation • negative regulation of granulocyte differentiation • immune system process • positive regulation of B cell differentiation • negative regulation of B cell activation • inositol phosphate metabolic process • negative regulation of neutrophil differentiation • negative regulation of immune response • phosphatidylinositol dephosphorylation • positive regulation of lymphocyte differentiation • immunoglobulin mediated immune response • positive regulation of apoptotic process • phosphate-containing compound metabolic process • phosphatidylinositol biosynthetic process • negative regulation of signal transduction • negative regulation of B cell proliferation • T cell receptor signaling pathway • leukocyte migration • signal transduction • negative regulation of bone resorption • negative regulation of cell proliferation • apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3635	16331
Ensembl	n/a	ENSMUSG00000026288
UniProt	Q92835	Q9ES52
RefSeq (mRNA)	NM_001017915 NM_005541	NM_001110192 NM_001110193 NM_010566
RefSeq (protein)	NP_001017915.1 NP_005532.2	NP_001103662.1 NP_001103663.1 NP_034696.2
Location (UCSC)	Chr 2: 233.06 – 233.21 Mb	Chr 1: 87.62 – 87.72 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 is an enzyme that in humans is encoded by the INPP5D gene.^[4][5][6] INPP5D also called SHIP1 was also shown to be a negative regulator of BCR signalling in B cells.^[7]

Function

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.^[6]

Interactions

INPP5D has been shown to interact with DOK2,^[8] LYN,^[9] CD22,^[10] Grb2,^[11] CRKL,^[12] CD31,^[13] DOK1^[8][14] and SHC1.^{[4][8][15][16][17]}

Medicines

Rosiptor (AQX-1125) is an INPP5D activator that is under development as an anti-inflammatory drug.^[18][19]

References

1. "Diseases that are genetically associated with INPP5D view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW, Krystal G (February 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". Proceedings of the National Academy of Sciences of the United States of America. 93 (4): 1689–93. doi:10.1073/pnas.93.4.1689. PMC 40003. PMID 8643691.
5. Ware MD, Rosten P, Damen JE, Liu L, Humphries RK, Krystal G (October 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.
6. "Entrez Gene: INPP5D inositol polyphosphate-5-phosphatase, 145kDa".
7. Cui B, Chen L, Zhang S, Mraz M, Fecteau JF, Yu J, Ghia EM, Zhang L, Bao L, Rassenti LZ, Messer K, Calin GA, Croce CM, Kipps TJ (July 2014). "MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia". Blood. 124 (4): 546–54. doi:10.1182/blood-2014-03-559690. PMC 4110661. PMID 24914134.
8. Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (May 2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cellular Signalling. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.
9. Baran CP, Tridandapani S, Helgason CD, Humphries RK, Krystal G, Marsh CB (October 2003). "The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity". The Journal of Biological Chemistry. 278 (40): 38628–36. doi:10.1074/jbc.M305021200. PMID 12882960.
10. Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (June 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry. 275 (23): 17420–7. doi:10.1074/jbc.M001892200. PMID 10748054.
11. Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT (April 1996). "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Current Biology. 6 (4): 438–45. doi:10.1016/S0960-9822(02)00511-0. PMID 8723348.
12. 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". The Journal of Biological Chemistry. 276 (35): 33282–90. doi:10.1074/jbc.M102924200. PMID 11443118.
13. Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Letters. 450 (1-2): 77–83. doi:10.1016/S0014-5793(99)00446-9. PMID 10350061.
14. van Dijk TB, van Den Akker E, Amelsvoort MP, 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. 96 (10): 3406–13. PMID 11071635.
15. Wisniewski D, Strife A, Swendeman S, Erdjument-Bromage H, Geromanos S, Kavanaugh WM, 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. 93 (8): 2707–20. PMID 10194451.
16. Leitges M, Gimborn K, Elis W, Kalesnikoff J, Hughes MR, Krystal G, Huber M (June 2002). "Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Molecular and Cellular Biology. 22 (12): 3970–80. doi:10.1128/MCB.22.12.3970-3980.2002. PMC 133855. PMID 12024011.
17. March ME, Lucas DM, Aman MJ, Ravichandran KS (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". The Journal of Biological Chemistry. 275 (39): 29960–7. doi:10.1074/jbc.M003714200. PMID 10900203.
18. AdisInsight. "AQX-1125". Springer. Retrieved 20 July 2016.
19. World Health Organization, International Nonproprietary Names for Pharmaceutical Substances (INN): Proposed INN: List 115 (PDF)

Further reading

• MacDonald SM, Vonakis BM (September 2002). "Association of the Src homology 2 domain-containing inositol 5' phosphatase (SHIP) to releasability in human basophils". Molecular Immunology. 38 (16-18): 1323–7. doi:10.1016/S0161-5890(02)00082-2. PMID 12217402.
• Lioubin MN, Algate PA, Tsai S, Carlberg K, Aebersold A, Rohrschneider LR (May 1996). "p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity". Genes & Development. 10 (9): 1084–95. doi:10.1101/gad.10.9.1084. PMID 8654924.
• Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT (April 1996). "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2". Current Biology. 6 (4): 438–45. doi:10.1016/S0960-9822(02)00511-0. PMID 8723348.
• Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C (August 1996). "Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase". Biochemical and Biophysical Research Communications. 225 (1): 243–9. doi:10.1006/bbrc.1996.1161. PMID 8769125.
• Geier SJ, Algate PA, Carlberg K, Flowers D, Friedman C, Trask B, Rohrschneider LR (March 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, Nakamoto T, Ueno H, Yamagata T, Mitani K, Yazaki Y, Hirai H (April 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 (April 1997). "Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2". The Journal of Biological Chemistry. 272 (17): 10998–1001. doi:10.1074/jbc.272.17.10998. PMID 9110989.
• Giuriato S, Payrastre B, Drayer AL, Plantavid M, Woscholski R, Parker P, Erneux C, Chap H (October 1997). "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets". The Journal of Biological Chemistry. 272 (43): 26857–63. doi:10.1074/jbc.272.43.26857. PMID 9341117.
• Kuroiwa A, Yamashita Y, Inui M, Yuasa T, Ono M, Nagabukuro A, Matsuda Y, Takai T (January 1998). "Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene". The Journal of Biological Chemistry. 273 (2): 1070–4. doi:10.1074/jbc.273.2.1070. PMID 9422771.
• Liu Q, Shalaby F, Jones J, Bouchard D, Dumont DJ (April 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 (January 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". Biochemical and Biophysical Research Communications. 254 (2): 440–5. doi:10.1006/bbrc.1998.9959. PMID 9918857.
• Mikhalap SV, Shlapatska LM, Berdova AG, Law CL, Clark EA, Sidorenko SP (May 1999). "CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis". Journal of Immunology. 162 (10): 5719–27. PMID 10229804.
• Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Letters. 450 (1-2): 77–83. doi:10.1016/S0014-5793(99)00446-9. PMID 10350061.
• Mason JM, Beattie BK, Liu Q, Dumont DJ, Barber DL (February 2000). "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor". The Journal of Biological Chemistry. 275 (6): 4398–406. doi:10.1074/jbc.275.6.4398. PMID 10660611.
• Bone H, Welham MJ (March 2000). "Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains". Cellular Signalling. 12 (3): 183–94. doi:10.1016/S0898-6568(99)00088-1. PMID 10704825.
• Lemay S, Davidson D, Latour S, Veillette A (April 2000). "Dok-3, a novel adapter molecule involved in the negative regulation of immunoreceptor signaling". Molecular and Cellular Biology. 20 (8): 2743–54. doi:10.1128/MCB.20.8.2743-2754.2000. PMC 85490. PMID 10733577.
• Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (June 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry. 275 (23): 17420–7. doi:10.1074/jbc.M001892200. PMID 10748054.
• Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (May 2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cellular Signalling. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.