General Information of Drug Therapeutic Target (DTT) (ID: TTTP2Z1)

DTT Name SH2 domain inositol 5'-phosphatase 1 (INPP5D)
Synonyms
p150Ship; hp51CN; SIP145; SIP-145; SHIP1; SHIP-1; SHIP; SH2 domaincontaining inositol phosphatase 1; SH2 domaincontaining inositol 5'phosphatase 1; SH2 domain-containing inositol phosphatase 1; SH2 domain-containing inositol 5'-phosphatase 1; Phosphatidylinositol 3,4,5trisphosphate 5phosphatase 1; Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; Inositol polyphosphate5phosphatase of 145 kDa; Inositol polyphosphate-5-phosphatase of 145 kDa
Gene Name INPP5D
DTT Type
Clinical trial target
[1]
BioChemical Class
Phosphoric monoester hydrolase
UniProt ID
SHIP1_HUMAN
TTD ID
T46871
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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
Function
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. 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.
KEGG Pathway
Inositol phosphate metabolism (hsa00562 )
Phosphatidylinositol signaling system (hsa04070 )
B cell receptor signaling pathway (hsa04662 )
Fc epsilon RI signaling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
Reactome Pathway
Interleukin receptor SHC signaling (R-HSA-912526 )
PECAM1 interactions (R-HSA-210990 )
BioCyc Pathway
MetaCyc:HS09849-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AQX-1125 DMCH3G5 Chronic obstructive pulmonary disease CA22 Phase 2 [1]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Chronic obstructive pulmonary disease CA23 Lung tissue 9.59E-01 -0.03 -0.1
Chronic obstructive pulmonary disease CA23 Small airway epithelium 5.30E-06 0.24 0.92
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References

1 Characterization 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.