Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T46871
(Former ID: TTDI02174)
|
|||||
| Target 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
Click to Show/Hide
|
|||||
| Gene Name |
INPP5D
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
Phosphoric monoester hydrolase
|
|||||
| 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 Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | AQX-1125 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | AQX-1125 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 1-Benzyl-4-pyrrol-1-yl-piperidine | Ligand Info | |||||
| Structure Description | INPP5D PanDDA analysis group deposition -- Crystal Structure of the phosphatase and C2 domains of SHIP1 in complex with Z2856434898 | PDB:5RWO | ||||
| Method | X-ray diffraction | Resolution | 1.29 Å | Mutation | No | [3] |
| PDB Sequence |
QPEPDMITIF
406 IGTWNMGNAP416 PPKKITSWFL426 SKGQGKTRDD436 SADYIPHDIY446 VIGTQEDPLS 456 EKEWLEILKH466 SLQEITSVTF476 KTVAIHTLWN486 IRIVVLAKPE496 HENRISHICT 506 DNVKTGIANT516 LGNKGAVGVS526 FMFNGTSLGF536 VNSHLTSGSE546 KKLRRNQNYM 556 NILRFLALGD566 KKLSPFNITH576 RFTHLFWFGD586 LNYRVDLPTW596 EAETIIQKIK 606 QQQYADLLSH616 DQLLTERREQ626 KVFLHFEEEE636 ITFAPTYRFE646 RLTRDKYAYT 656 KQKATGMKYN666 LPSWCDRVLW676 KSYPLVHVVC686 QSYGSTSDIM696 TSDHSPVFAT 706 FEAGVTSQFV716 SKNGPGTVDS726 QGQIEFLRCY736 ATLKTKSQTK746 FYLEFHSSCL 756 ESFVKSQEGE766 NEEGSEGELV776 VKFGETLPKL786 KPIISDPEYL796 LDQHILISIK 806 SSDSDESYGE816 GCIALRLEAT826 ETQLPIYTPL836 THHGELTGHF846 QGEIKLQTSQ 856
|
|||||
|
|
||||||
| Ligand Name: 1-[(Furan-2-yl)methyl]-4-(methylsulfonyl)piperazine | Ligand Info | |||||
| Structure Description | INPP5D PanDDA analysis group deposition -- Crystal Structure of the phosphatase and C2 domains of SHIP1 in complex with Z2241115980 | PDB:5RWW | ||||
| Method | X-ray diffraction | Resolution | 1.16 Å | Mutation | No | [4] |
| PDB Sequence |
QPEPDMITIF
406 IGTWNMGNAP416 PPKKITSWFL426 SKGQGKTRDD436 SADYIPHDIY446 VIGTQEDPLS 456 EKEWLEILKH466 SLQEITSVTF476 KTVAIHTLWN486 IRIVVLAKPE496 HENRISHICT 506 DNVKTGIANT516 LGNKGAVGVS526 FMFNGTSLGF536 VNSHLTSGSE546 KKLRRNQNYM 556 NILRFLALGD566 KKLSPFNITH576 RFTHLFWFGD586 LNYRVDLPTW596 EAETIIQKIK 606 QQQYADLLSH616 DQLLTERREQ626 KVFLHFEEEE636 ITFAPTYRFE646 RLTRDKYAYT 656 KQKATGMKYN666 LPSWCDRVLW676 KSYPLVHVVC686 QSYGSTSDIM696 TSDHSPVFAT 706 FEAGVTSQFV716 SKNGPGTVDS726 QGQIEFLRCY736 ATLKTKSQTK746 FYLEFHSSCL 756 ESFVKSQEGE766 NEEGSEGELV776 VKFGETLPKL786 KPIISDPEYL796 LDQHILISIK 806 SSDSDESYGE816 GCIALRLEAT826 ETQLPIYTPL836 THHGELTGHF846 QGEIKLQTSQ 856
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Inositol phosphate metabolism | hsa00562 | Affiliated Target |
|
| Class: Metabolism => Carbohydrate metabolism | Pathway Hierarchy | ||
| Phosphatidylinositol signaling system | hsa04070 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| B cell receptor signaling pathway | hsa04662 | Affiliated Target |
|
| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Fc epsilon RI signaling pathway | hsa04664 | Affiliated Target |
|
| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Fc gamma R-mediated phagocytosis | hsa04666 | Affiliated Target |
|
| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 15 | Degree centrality | 1.61E-03 | Betweenness centrality | 1.20E-03 |
|---|---|---|---|---|---|
| Closeness centrality | 2.31E-01 | Radiality | 1.41E+01 | Clustering coefficient | 2.00E-01 |
| Neighborhood connectivity | 3.80E+01 | Topological coefficient | 1.29E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 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. | |||||
| REF 2 | ClinicalTrials.gov (NCT02324972) Pilot Efficacy and Safety Study of AQX-1125 in Atopic Dermatitis. U.S. National Institutes of Health. | |||||
| REF 3 | INPP5D PanDDA analysis group deposition | |||||
| REF 4 | INPP5D PanDDA analysis group deposition | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.