Target General Infomation
Target ID
T46871
Former ID
TTDI02174
Target Name
SH2 domain inositol phosphatase
Gene Name
INPP5D
Synonyms
Inositol polyphosphate5phosphatase of 145 kDa; Phosphatidylinositol 3,4,5trisphosphate 5phosphatase 1; SH2 domaincontaining inositol 5'phosphatase 1; SH2 domaincontaining inositol phosphatase 1; SHIP1; SIP145; hp51CN; p150Ship; INPP5D
Target Type
Clinical Trial
Disease Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
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, immunecells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activationand 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.
BioChemical Class
Phosphoric monoester hydrolases
UniProt ID
EC Number
EC 3.1.3.86
Sequence
MVPCWNHGNITRSKAEELLSRTGKDGSFLVRASESISRAYALCVLYRNCVYTYRILPNED
DKFTVQASEGVSMRFFTKLDQLIEFYKKENMGLVTHLQYPVPLEEEDTGDDPEEDTVESV
VSPPELPPRNIPLTASSCEAKEVPFSNENPRATETSRPSLSETLFQRLQSMDTSGLPEEH
LKAIQDYLSTQLAQDSEFVKTGSSSLPHLKKLTTLLCKELYGEVIRTLPSLESLQRLFDQ
QLSPGLRPRPQVPGEANPINMVSKLSQLTSLLSSIEDKVKALLHEGPESPHRPSLIPPVT
FEVKAESLGIPQKMQLKVDVESGKLIIKKSKDGSEDKFYSHKKILQLIKSQKFLNKLVIL
VETEKEKILRKEYVFADSKKREGFCQLLQQMKNKHSEQPEPDMITIFIGTWNMGNAPPPK
KITSWFLSKGQGKTRDDSADYIPHDIYVIGTQEDPLSEKEWLEILKHSLQEITSVTFKTV
AIHTLWNIRIVVLAKPEHENRISHICTDNVKTGIANTLGNKGAVGVSFMFNGTSLGFVNS
HLTSGSEKKLRRNQNYMNILRFLALGDKKLSPFNITHRFTHLFWFGDLNYRVDLPTWEAE
TIIQKIKQQQYADLLSHDQLLTERREQKVFLHFEEEEITFAPTYRFERLTRDKYAYTKQK
ATGMKYNLPSWCDRVLWKSYPLVHVVCQSYGSTSDIMTSDHSPVFATFEAGVTSQFVSKN
GPGTVDSQGQIEFLRCYATLKTKSQTKFYLEFHSSCLESFVKSQEGENEEGSEGELVVKF
GETLPKLKPIISDPEYLLDQHILISIKSSDSDESYGEGCIALRLEATETQLPIYTPLTHH
GELTGHFQGEIKLQTSQGKTREKLYDFVKTERDESSGPKTLKSLTSHDPMKQWEVTSRAP
PCSGSSITEIINPNYMGVGPFGPPMPLHVKQTLSPDQQPTAWSYDQPPKDSPLGPCRGES
PPTPPGQPPISPKKFLPSTANRGLPPRTQESRPSDLGKNAGDTLPQEDLPLTKPEMFENP
LYGSLSSFPKPAPRKDQESPKMPRKEPPPCPEPGILSPSIVLTKAQEADRGEGPGKQVPA
PRLRSFTCSSSAEGRAAGGDKSQGKPKTPVSSQAPVPAKRPIKPSRSEINQQTPPTPTPR
PPLPVKSPAVLHLQHSKGRDYRDNTELPHHGKHRPEEGPPGPLGRTAMQ
Drugs and Mode of Action
Drug(s) AQX-1125 Drug Info Phase 2 Chronic obstructive pulmonary disease [525040]
Agonist AQX-1125 Drug Info [532100]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway 3-phosphoinositide degradation
1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)
Superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism
Superpathway of inositol phosphate compounds
D-myo-inositol (1,3,4)-trisphosphate biosynthesis
KEGG Pathway Inositol phosphate metabolism
Phosphatidylinositol signaling system
B cell receptor signaling pathway
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
PathWhiz Pathway Phosphatidylinositol Phosphate Metabolism
Fc Epsilon Receptor I Signaling in Mast Cells
Reactome PECAM1 interactions
Interleukin receptor SHC signaling
WikiPathways EGF/EGFR Signaling Pathway
IL-4 Signaling Pathway
Kit receptor signaling pathway
IL-3 Signaling Pathway
Interleukin-2 signaling
B Cell Receptor Signaling Pathway
TCR signaling
Interleukin-3, 5 and GM-CSF signaling
Cell surface interactions at the vascular wall
References
Ref 525040ClinicalTrials.gov (NCT02324972) Pilot Efficacy and Safety Study of AQX-1125 in Atopic Dermatitis. U.S. National Institutes of Health.
Ref 532100Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 2. Efficacy studies in allergic and pulmonary inflammation models in vivo. Br J Pharmacol. 2013 Mar;168(6):1519-29.

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