Details of the Target

General Information of Target

Target ID LDTP09895
Target Name Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (INPP5D)
Gene Name INPP5D
Gene ID 3635
Synonyms
SHIP; SHIP1; Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; EC 3.1.3.86; Inositol polyphosphate-5-phosphatase D; EC 3.1.3.56; Inositol polyphosphate-5-phosphatase of 145 kDa; SIP-145; Phosphatidylinositol 4,5-bisphosphate 5-phosphatase; EC 3.1.3.36; SH2 domain-containing inositol 5'-phosphatase 1; SH2 domain-containing inositol phosphatase 1; SHIP-1; p150Ship; hp51CN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MREPEELMPDSGAVFTFGKSKFAENNPGKFWFKNDVPVHLSCGDEHSAVVTGNNKLYMFG
SNNWGQLGLGSKSAISKPTCVKALKPEKVKLAACGRNHTLVSTEGGNVYATGGNNEGQLG
LGDTEERNTFHVISFFTSEHKIKQLSAGSNTSAALTEDGRLFMWGDNSEGQIGLKNVSNV
CVPQQVTIGKPVSWISCGYYHSAFVTTDGELYVFGEPENGKLGLPNQLLGNHRTPQLVSE
IPEKVIQVACGGEHTVVLTENAVYTFGLGQFGQLGLGTFLFETSEPKVIENIRDQTISYI
SCGENHTALITDIGLMYTFGDGRHGKLGLGLENFTNHFIPTLCSNFLRFIVKLVACGGCH
MVVFAAPHRGVAKEIEFDEINDTCLSVATFLPYSSLTSGNVLQRTLSARMRRRERERSPD
SFSMRRTLPPIEGTLGLSACFLPNSVFPRCSERNLQESVLSEQDLMQPEEPDYLLDEMTK
EAEIDNSSTVESLGETTDILNMTHIMSLNSNEKSLKLSPVQKQKKQQTIGELTQDTALTE
NDDSDEYEEMSEMKEGKACKQHVSQGIFMTQPATTIEAFSDEEVGNDTGQVGPQADTDGE
GLQKEVYRHENNNGVDQLDAKEIEKESDGGHSQKESEAEEIDSEKETKLAEIAGMKDLRE
REKSTKKMSPFFGNLPDRGMNTESEENKDFVKKRESCKQDVIFDSERESVEKPDSYMEGA
SESQQGIADGFQQPEAIEFSSGEKEDDEVETDQNIRYGRKLIEQGNEKETKPIISKSMAK
YDFKCDRLSEIPEEKEGAEDSKGNGIEEQEVEANEENVKVHGGRKEKTEILSDDLTDKAE
DHEFSKTEELKLEDVDEEINAENVESKKKTVGDDESVPTGYHSKTEGAERTNDDSSAETI
EKKEKANLEERAICEYNENPKGYMLDDADSSSLEILENSETTPSKDMKKTKKIFLFKRVP
SINQKIVKNNNEPLPEIKSIGDQIILKSDNKDADQNHMSQNHQNIPPTNTERRSKSCTIL
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Inositol 1,4,5-trisphosphate 5-phosphatase family
Subcellular location
Cytoplasm
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. Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. 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.
TTD ID
T46871
Uniprot ID
Q92835
DrugMap ID
TTTP2Z1
Ensemble ID
ENST00000359570.9
HGNC ID
HGNC:6079
ChEMBL ID
CHEMBL1781870

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
786O SNV: p.G922R .
A101D SNV: p.H753Y .
AGS SNV: p.K337T DBIA    Probe Info 
DU145 SNV: p.D239E; p.G1171V .
FTC133 SNV: p.T1136P .
HCC15 SNV: p.E751D .
HEC1 SNV: p.R1140W .
JHH7 SNV: p.R1162H .
KPNYN SNV: p.T1136P .
NB1 SNV: p.D436E .
NCIH23 SNV: p.P1058S DBIA    Probe Info 
OPM2 Deletion: p.P1180_P1182del DBIA    Probe Info 
SNU1 Deletion: p.E775SfsTer4 .
TOV21G SNV: p.E139Ter; p.G919W .
U937 SNV: p.A1080T DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info  		C1088(0.00); C506(0.00)  LDD0241  [1]
DBIA
 Probe Info  		C506(1.36)  LDD3314  [2]
Alkyne-RA190
 Probe Info  		3.35  LDD0300  [3]
W1
 Probe Info  		C1088(0.86)  LDD0239  [1]
IA-alkyne
 Probe Info  		C506(0.00); C385(0.00); C672(0.00)  LDD0167  [4]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
VE-P
 Probe Info  		N.A.  LDD0396  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0198  Dimethyl Fumarate(DMF) T cell C1088(5.11)  LDD0513  [6]
 LDCM0625  F8 Ramos C506(1.44); C1088(1.03); C138(1.47); C217(0.75)  LDD2187  [7]
 LDCM0572  Fragment10 Ramos C506(0.70); C1088(0.75); C138(1.21); C217(1.46)  LDD2189  [7]
 LDCM0573  Fragment11 Ramos C506(5.92); C1088(3.25); C138(0.31); C217(16.72)  LDD2190  [7]
 LDCM0574  Fragment12 Ramos C506(0.65); C1088(0.31); C138(0.93); C217(2.02)  LDD2191  [7]
 LDCM0575  Fragment13 Ramos C506(1.09); C1088(0.79); C138(0.99); C217(0.38)  LDD2192  [7]
 LDCM0576  Fragment14 Ramos C506(1.31); C1088(1.28); C138(0.80); C217(0.86)  LDD2193  [7]
 LDCM0579  Fragment20 Ramos C506(0.52); C1088(0.34); C138(0.90); C217(1.48)  LDD2194  [7]
 LDCM0580  Fragment21 Ramos C506(0.86); C1088(1.05); C138(1.02); C217(0.68)  LDD2195  [7]
 LDCM0582  Fragment23 Ramos C506(0.66); C1088(0.51); C138(0.96); C217(2.84)  LDD2196  [7]
 LDCM0578  Fragment27 Ramos C506(0.88); C1088(0.91); C138(1.09); C217(0.89)  LDD2197  [7]
 LDCM0586  Fragment28 Ramos C506(0.93); C1088(0.59); C138(1.18); C217(0.50)  LDD2198  [7]
 LDCM0588  Fragment30 Ramos C506(0.99); C1088(0.61); C138(1.55); C217(1.34)  LDD2199  [7]
 LDCM0589  Fragment31 Ramos C506(0.79); C1088(0.44); C138(1.11); C217(2.34)  LDD2200  [7]
 LDCM0590  Fragment32 Ramos C506(0.67); C1088(0.81); C138(1.36); C217(2.99)  LDD2201  [7]
 LDCM0468  Fragment33 Ramos C506(1.07); C1088(0.63); C138(1.23); C217(1.79)  LDD2202  [7]
 LDCM0596  Fragment38 Ramos C506(1.00); C1088(0.69); C138(0.95); C217(0.48)  LDD2203  [7]
 LDCM0566  Fragment4 Ramos C506(1.22); C1088(0.96); C138(0.96); C217(0.84)  LDD2184  [7]
 LDCM0610  Fragment52 Ramos C506(1.39); C1088(0.90); C138(1.28); C217(0.60)  LDD2204  [7]
 LDCM0614  Fragment56 Ramos C506(1.19); C1088(0.50); C138(1.37); C217(0.48)  LDD2205  [7]
 LDCM0569  Fragment7 Ramos C506(0.87); C1088(0.83); C138(1.19); C217(0.74)  LDD2186  [7]
 LDCM0571  Fragment9 Ramos C506(0.79); C1088(0.44); C138(0.99); C217(2.37)  LDD2188  [7]
 LDCM0022  KB02 Ramos C506(1.30); C1088(1.66); C138(1.35); C217(0.87)  LDD2182  [7]
 LDCM0023  KB03 Ramos C506(1.15); C1088(1.55); C138(1.03); C217(2.29)  LDD2183  [7]
 LDCM0024  KB05 IGR37 C506(1.36)  LDD3314  [2]
 LDCM0131  RA190 MM1.R 3.35  LDD0300  [3]
 LDCM0170  Structure8 Ramos 5.13  LDD0433  [8]
 LDCM0112  W16 Hep-G2 C1088(0.86)  LDD0239  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Immunoglobulin
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B) . P31994
Natural killer cell receptor 2B4 (CD244) . Q9BZW8
Other
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cysteine-rich tail protein 1 (CYSRT1) CYSRT1 family A8MQ03
Keratin, type I cuticular Ha1 (KRT31) Intermediate filament family Q15323
Keratin, type I cytoskeletal 40 (KRT40) Intermediate filament family Q6A162
KH domain-containing, RNA-binding, signal transduction-associated protein 3 (KHDRBS3) KHDRBS family O75525
Keratin-associated protein 1-3 (KRTAP1-3) KRTAP type 1 family Q8IUG1
Keratin-associated protein 10-7 (KRTAP10-7) KRTAP type 10 family P60409
Keratin-associated protein 10-9 (KRTAP10-9) KRTAP type 10 family P60411
Notch homolog 2 N-terminal-like protein A (NOTCH2NLA) NOTCH family Q7Z3S9
SH3 domain-containing kinase-binding protein 1 (SH3KBP1) . Q96B97

The Drug(s) Related To This Target

Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Aqx-1125 Small molecular drug D02HDG

References

1 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.
4 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
5 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
6 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
7 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
8 2-Sulfonylpyridines as Tunable, Cysteine-Reactive Electrophiles. J Am Chem Soc. 2020 May 13;142(19):8972-8979. doi: 10.1021/jacs.0c02721. Epub 2020 Apr 29.