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Identification
HMDB Protein ID HMDBP03787
Secondary Accession Numbers
  • 9375
Name Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
Synonyms
  1. Inositol polyphosphate-5-phosphatase of 145 kDa
  2. SH2 domain-containing inositol phosphatase 1
  3. SH2 domain-containing inositol-5'-phosphatase 1
  4. SHIP-1
  5. SIP-145
  6. hp51CN
  7. p150Ship
  8. SH2 domain-containing inositol 5'-phosphatase 1
Gene Name INPP5D
Protein Type Enzyme
Biological Properties
General Function Involved in inositol or phosphatidylinositol phosphatase activity
Specific 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.
Pathways
  • B cell receptor signaling pathway
  • Fc Epsilon Receptor I Signaling in Mast Cells
  • Fc epsilon RI signaling pathway
  • Fc gamma R-mediated phagocytosis
  • Inositol phosphate metabolism
  • Joubert syndrome
  • Phosphatidylinositol Phosphate Metabolism
  • Phosphatidylinositol signaling system
Reactions
1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + Water → 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + Phosphoric acid details
Phosphatidylinositol-3,4,5-trisphosphate + Water → 1-Phosphatidyl-1D-myo-inositol 3,4-bisphosphate + Phosphoric acid details
GO Classification
Biological Process
small molecule metabolic process
determination of adult lifespan
positive regulation of apoptotic process
negative regulation of bone resorption
phosphatidylinositol biosynthetic process
apoptotic process
leukocyte migration
T cell receptor signaling pathway
blood coagulation
phosphatidylinositol phosphorylation
immunoglobulin mediated immune response
negative regulation of B cell proliferation
negative regulation of immune response
negative regulation of interleukin-6 biosynthetic process
negative regulation of monocyte differentiation
negative regulation of neutrophil differentiation
negative regulation of osteoclast differentiation
negative regulation of signal transduction
positive regulation of B cell differentiation
positive regulation of erythrocyte differentiation
intracellular signal transduction
Cellular Component
cytosol
actin filament
plasma membrane
cortical cytoskeleton
Function
hydrolase activity, acting on ester bonds
binding
catalytic activity
hydrolase activity
phosphoric ester hydrolase activity
phosphatase activity
protein binding
inositol or phosphatidylinositol phosphatase activity
Molecular Function
inositol-polyphosphate 5-phosphatase activity
inositol-4,5-bisphosphate 5-phosphatase activity
phosphatidylinositol trisphosphate phosphatase activity
Cellular Location
  1. Cytoplasm
  2. Peripheral membrane protein
  3. Membrane
Gene Properties
Chromosome Location 2
Locus 2q37.1
SNPs INPP5D
Gene Sequence
>3570 bp
ATGGTCCCCTGCTGGAACCATGGCAACATCACCCGCTCCAAGGCGGAGGAGCTGCTTTCC
AGGACAGGCAAGGACGGGAGCTTCCTCGTGCGTGCCAGCGAGTCCATCTCCCGGGCATAC
GCGCTCTGCGTGCTGTATCGGAATTGCGTTTACACTTACAGAATTCTGCCCAATGAAGAT
GATAAATTCACTGTTCAGGCATCCGAAGGCGTCTCCATGAGGTTCTTCACCAAGCTGGAC
CAGCTCATCGAGTTTTACAAGAAGGAAAACATGGGGCTGGTGACCCATCTGCAATACCCT
GTGCCGCTGGAGGAAGAGGACACAGGCGACGACCCTGAGGAGGACACAGTAGAAAGTGTC
GTGTCTCCACCCGAGCTGCCCCCAAGAAACATCCCGCTGACTGCCAGCTCCTGTGAGGCC
AAGGAGGTTCCTTTTTCAAACGAGAATCCCCGAGCGACCGAGACCAGCCGGCCGAGCCTC
TCCGAGACATTGTTCCAGCGACTGCAAAGCATGGACACCAGTGGGCTTCCAGAAGAGCAT
CTTAAGGCCATCCAAGATTATTTAAGCACTCAGCTCGCCCAGGACTCTGAATTTGTGAAG
ACAGGGTCCAGCAGTCTTCCTCACCTGAAGAAACTGACCACACTGCTCTGCAAGGAGCTC
TATGGAGAAGTCATCCGGACCCTCCCATCCCTGGAGTCTCTGCAGAGGTTATTTGACCAG
CAGCTCTCCCCGGGCCTCCGTCCACGTCCTCAGGTTCCTGGTGAGGCCAATCCCATCAAC
ATGGTGTCCAAGCTCAGCCAACTGACAAGCCTGTTGTCATCCATTGAAGACAAGGTCAAG
GCCTTGCTGCACGAGGGTCCTGAGTCTCCGCACCGGCCCTCCCTTATCCCTCCAGTCACC
TTTGAGGTGAAGGCAGAGTCTCTGGGGATTCCTCAGAAAATGCAGCTCAAAGTCGACGTT
GAGTCTGGGAAACTGATCATTAAGAAGTCCAAGGATGGTTCTGAGGACAAGTTCTACAGC
CACAAGAAAATCCTGCAGCTCATTAAGTCACAGAAATTTCTGAATAAGTTGGTGATCTTG
GTGGAAACAGAGAAGGAGAAGATCCTGCGGAAGGAATATGTTTTTGCTGACTCCAAAAAG
AGAGAAGGCTTCTGCCAGCTCCTGCAGCAGATGAAGAACAAGCACTCAGAGCAGCCGGAG
CCCGACATGATCACCATCTTCATCGGCACCTGGAACATGGGTAACGCCCCCCCTCCCAAG
AAGATCACGTCCTGGTTTCTCTCCAAGGGGCAGGGAAAGACGCGGGACGACTCTGCGGAC
TACATCCCCCATGACATTTACGTGATCGGCACCCAAGAGGACCCCCTGAGTGAGAAGGAG
TGGCTGGAGATCCTCAAACACTCCCTGCAAGAAATCACCAGTGTGACTTTTAAAACAGTC
GCCATCCACACGCTCTGGAACATCCGCATCGTGGTGCTGGCCAAGCCTGAGCACGAGAAC
CGGATCAGCCACATCTGTACTGACAACGTGAAGACAGGCATTGCAAACACACTGGGGAAC
AAGGGAGCCGTGGGGGTGTCGTTCATGTTCAATGGAACCTCCTTAGGGTTCGTCAACAGC
CACTTGACTTCAGGAAGTGAAAAGAAACTCAGGCGAAACCAAAACTATATGAACATTCTC
CGGTTCCTGGCCCTGGGCGACAAGAAGCTGAGTCCCTTTAACATCACTCACCGCTTCACG
CACCTCTTCTGGTTTGGGGATCTTAACTACCGTGTGGATCTGCCTACCTGGGAGGCAGAA
ACCATCATCCAGAAAATCAAGCAGCAGCAGTACGCAGACCTCCTGTCCCACGACCAGCTG
CTCACAGAGAGGAGGGAGCAGAAGGTCTTCCTACACTTCGAGGAGGAAGAAATCACGTTT
GCCCCAACCTACCGTTTTGAGAGACTGACTCGGGACAAATACGCCTACACCAAGCAGAAA
GCGACAGGGATGAAGTACAACTTGCCTTCCTGGTGTGACCGAGTCCTCTGGAAGTCTTAT
CCCCTGGTGCACGTGGTGTGTCAGTCTTATGGCAGTACCAGCGACATCATGACGAGTGAC
CACAGCCCTGTCTTTGCCACATTTGAGGCAGGAGTCACTTCCCAGTTTGTCTCCAAGAAC
GGTCCCGGGACTGTTGACAGCCAAGGACAGATTGAGTTTCTCAGGTGCTATGCCACATTG
AAGACCAAGTCCCAGACCAAATTCTACCTGGAGTTCCACTCGAGCTGCTTGGAGAGTTTT
GTCAAGAGTCAGGAAGGAGAAAATGAAGAAGGAAGTGAGGGGGAGCTGGTGGTGAAGTTT
GGTGAGACTCTTCCAAAGCTGAAGCCCATTATCTCTGACCCTGAGTACCTGCTAGACCAG
CACATCCTCATCAGCATCAAGTCCTCTGACAGCGACGAATCCTATGGCGAGGGCTGCATT
GCCCTTCGGTTAGAGGCCACAGAAACGCAGCTGCCCATCTACACGCCTCTCACCCACCAT
GGGGAGTTGACAGGCCACTTCCAGGGGGAGATCAAGCTGCAGACCTCTCAGGGCAAGACG
AGGGAGAAGCTCTATGACTTTGTGAAGACGGAGCGTGATGAATCCAGTGGGCCAAAGACC
CTGAAGAGCCTCACCAGCCACGACCCCATGAAGCAGTGGGAAGTCACTAGCAGGGCCCCT
CCGTGCAGTGGCTCCAGCATCACTGAAATCATCAACCCCAACTACATGGGAGTGGGGCCC
TTTGGGCCACCAATGCCCCTGCACGTGAAGCAGACCTTGTCCCCTGACCAGCAGCCCACA
GCCTGGAGCTACGACCAGCCGCCCAAGGACTCCCCGCTGGGGCCCTGCAGGGGAGAAAGT
CCTCCGACACCTCCCGGCCAGCCGCCCATATCACCCAAGAAGTTTTTACCCTCAACAGCA
AACCGGGGTCTCCCTCCCAGGACACAGGAGTCAAGGCCCAGTGACCTGGGGAAGAACGCA
GGGGACACGCTGCCTCAGGAGGACCTGCCGCTGACGAAGCCCGAGATGTTTGAGAACCCC
CTGTATGGGTCCCTGAGTTCCTTCCCTAAGCCTGCTCCCAGGAAGGACCAGGAATCCCCC
AAAATGCCGCGGAAGGAACCCCCGCCCTGCCCGGAACCCGGCATCTTGTCGCCCAGCATC
GTGCTCACCAAAGCCCAGGAGGCTGATCGCGGCGAGGGGCCCGGCAAGCAGGTGCCCGCG
CCCCGGCTGCGCTCCTTCACGTGCTCATCCTCTGCCGAGGGCAGGGCGGCCGGCGGGGAC
AAGAGCCAAGGGAAGCCCAAGACCCCGGTCAGCTCCCAGGCCCCGGTGCCGGCCAAGAGG
CCCATCAAGCCTTCCAGATCGGAAATCAACCAGCAGACCCCGCCCACCCCGACGCCGCGG
CCGCCGCTGCCAGTCAAGAGCCCGGCGGTGCTGCACCTCCAGCACTCCAAGGGCCGCGAC
TACCGCGACAACACCGAGCTCCCGCATCACGGCAAGCACCGGCCGGAGGAGGGGCCACCA
GGGCCTCTAGGCAGGACTGCCATGCAGTGA
Protein Properties
Number of Residues 1189
Molecular Weight 133291.4
Theoretical pI 7.589
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1
MVPCWNHGNITRSKAEELLSRTGKDGSFLVRASESISRAYALCVLYRNCVYTYRILPNED
DKFTVQASEGVSMRFFTKLDQLIEFYKKENMGLVTHLQYPVPLEEEDTGDDPEEDTVESV
VSPPELPPRNIPLTASSCEAKEVPFSNENPRATETSRPSLSETLFQRLQSMDTSGLPEEH
LKAIQDYLSTQLAQDSEFVKTGSSSLPHLKKLTTLLCKELYGEVIRTLPSLESLQRLFDQ
QLSPGLRPRPQVPGEANPINMVSKLSQLTSLLSSIEDKVKALLHEGPESPHRPSLIPPVT
FEVKAESLGIPQKMQLKVDVESGKLIIKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVIL
VETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPK
KITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLSEKEWLEILKHSLQEITSVTFKTV
AIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNS
HLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWFGDLNYRVDLPTWEAE
TIIQKIKQQQYADLLSHDQLLTERREQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQK
ATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKN
GPGTVDSQGQIEFLRCYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVKF
GETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLEATETQLPIYTPLTHH
GELTGHFQGEIKLQTSQGKTREKLYDFVKTERDESSGPKTLKSLTSHDPMKQWEVTSRAP
PCSGSSITEIINPNYMGVGPFGPPMPLHVKQTLSPDQQPTAWSYDQPPKDSPLGPCRGES
PPTPPGQPPISPKKFLPSTANRGLPPRTQESRPSDLGKNAGDTLPQEDLPLTKPEMFENP
LYGSLSSFPKPAPRKDQESPKMPRKEPPPCPEPGILSPSIVLTKAQEADRGEGPGKQVPA
PRLRSFTCSSSAEGRAAGGDKSQGKPKTPVSSQAPVPAKRPIKPSRSEINQQTPPTPTPR
PPLPVKSPAVLHLQHSKGRDYRDNTELPHHGKHRPEEGPPGPLGRTAMQ
GenBank ID Protein 64085167
UniProtKB/Swiss-Prot ID Q92835
UniProtKB/Swiss-Prot Entry Name SHIP1_HUMAN
PDB IDs
GenBank Gene ID NM_001017915.1
GeneCard ID INPP5D
GenAtlas ID INPP5D
HGNC ID HGNC:6079
References
General References
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  2. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [PubMed:15592455 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  5. Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C: 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. 1996 Aug 5;225(1):243-9. [PubMed:8769125 ]
  6. Ware MD, Rosten P, Damen JE, Liu L, Humphries RK, Krystal G: Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation. Blood. 1996 Oct 15;88(8):2833-40. [PubMed:8874179 ]
  7. Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT: Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2. Curr Biol. 1996 Apr 1;6(4):438-45. [PubMed:8723348 ]
  8. Geier SJ, Algate PA, Carlberg K, Flowers D, Friedman C, Trask B, Rohrschneider LR: The human SHIP gene is differentially expressed in cell lineages of the bone marrow and blood. Blood. 1997 Mar 15;89(6):1876-85. [PubMed:9058707 ]
  9. Odai H, Sasaki K, Iwamatsu A, Nakamoto T, Ueno H, Yamagata T, Mitani K, Yazaki Y, Hirai H: 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. 1997 Apr 15;89(8):2745-56. [PubMed:9108392 ]
  10. Mikhalap SV, Shlapatska LM, Berdova AG, Law CL, Clark EA, Sidorenko SP: CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis. J Immunol. 1999 May 15;162(10):5719-27. [PubMed:10229804 ]
  11. Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD: The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells. Cell Signal. 2000 May;12(5):317-26. [PubMed:10822173 ]
  12. Freeburn RW, Wright KL, Burgess SJ, Astoul E, Cantrell DA, Ward SG: 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 Nov 15;169(10):5441-50. [PubMed:12421919 ]
  13. Vaillancourt M, Levasseur S, Tremblay ML, Marois L, Rollet-Labelle E, Naccache PH: The Src homology 2-containing inositol 5-phosphatase 1 (SHIP1) is involved in CD32a signaling in human neutrophils. Cell Signal. 2006 Nov;18(11):2022-32. Epub 2006 Apr 3. [PubMed:16682172 ]
  14. Luo JM, Yoshida H, Komura S, Ohishi N, Pan L, Shigeno K, Hanamura I, Miura K, Iida S, Ueda R, Naoe T, Akao Y, Ohno R, Ohnishi K: Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia. Leukemia. 2003 Jan;17(1):1-8. [PubMed:12529653 ]