Target Information
| Target General Information | Top | |||||
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| Target ID |
T35063
(Former ID: TTDNC00413)
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| Target Name |
RAS-like protein KIR (GEM)
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| Synonyms |
RASlike protein KIR; GTPbinding protein GEM; GTPbinding mitogeninduced Tcell protein
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| Gene Name |
GEM
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| 2 | Mature B-cell leukaemia [ICD-11: 2A82] | |||||
| 3 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
| 4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Could be a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane. Has guanine nucleotide-binding activity but undetectable intrinsic GTPase activity.
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| BioChemical Class |
Small GTPase superfamily
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| UniProt ID | ||||||
| Sequence |
MTLNNVTMRQGTVGMQPQQQRWSIPADGRHLMVQKEPHQYSHRNRHSATPEDHCRRSWSS
DSTDSVISSESGNTYYRVVLIGEQGVGKSTLANIFAGVHDSMDSDCEVLGEDTYERTLMV DGESATIILLDMWENKGENEWLHDHCMQVGDAYLIVYSITDRASFEKASELRIQLRRARQ TEDIPIILVGNKSDLVRCREVSVSEGRACAVVFDCKFIETSAAVQHNVKELFEGIVRQVR LRRDSKEKNERRLAYQKRKESMPRKARRFWGKIVAKNNKNMAFKLKSKSCHDLSVL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Lirilumab | Drug Info | Phase 2 | Acute myeloid leukaemia | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Lirilumab | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Guanosine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of the small GTPase Gem (GemDNDCaM) in complex to Mg.GDP | PDB:2CJW | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
MTYYRVVLIG 82 EQGVGKSTLA92 NIFAGVHDSE107 VLGEDTYERT117 LMVDGESATI127 ILLDMWENEW 141 LHDHCMQVGD151 AYLIVYSITD161 RASFEKASEL171 RIQLRRARQT181 EDIPIILVGN 191 KSDLVRREVS202 VSEGRAAVVF213 DKFIETSAAV224 QHNVKELFEG234 IVRQVRLRRD 244 SKEKNERRLA254 YQKR> Chain B EFGMTYYRVV 79 LIGEQGVGKS89 TLANIFAGVE111 DTYERTLMVD121 GESATIILLD131 MWENHDHMQV 149 GDAYLIVYSI159 TDRASFEKAS169 ELRIQLRRAR179 QTEDIPIILV189 GNKSDLVRRE 200 VSVSEGRAAV211 VFDCKFIETS221 AAVQHNVKEL231 FEGIVRQVRL241 RRDSKEKNER 251 RLAYQKRKES261
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GLU83[A]
3.890
GLN84[A]
3.694
GLY85[A]
2.708
VAL86[A]
3.327
GLY87[A]
3.089
LYS88[A]
2.731
SER89[A]
3.004
THR90[A]
2.726
ASP131[A]
4.747
GLU134[A]
4.875
ASN191[A]
3.201
LYS192[A]
3.112
SER193[A]
4.818
ASP194[A]
2.770
LEU195[A]
3.403
THR220[A]
4.642
SER221[A]
3.276
ALA222[A]
2.960
ALA223[A]
3.273
GLU83[B]
3.684
GLN84[B]
3.723
GLY85[B]
2.784
VAL86[B]
3.369
GLY87[B]
3.033
LYS88[B]
2.643
SER89[B]
2.994
THR90[B]
2.785
ASP131[B]
4.730
ASN191[B]
3.008
LYS192[B]
3.223
SER193[B]
4.878
ASP194[B]
2.634
LEU195[B]
3.462
THR220[B]
4.415
SER221[B]
3.437
ALA222[B]
2.607
ALA223[B]
3.240
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: S-(Dimethylarsenic)Cysteine | Ligand Info | |||||
| Structure Description | Crystal structure of the small GTPase Gem (GemDNDCaM) in complex to Mg.GDP | PDB:2CJW | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
MTYYRVVLIG 82 EQGVGKSTLA92 NIFAGVHDSE107 VLGEDTYERT117 LMVDGESATI127 ILLDMWENEW 141 LHDHCMQVGD151 AYLIVYSITD161 RASFEKASEL171 RIQLRRARQT181 EDIPIILVGN 191 KSDLVRREVS202 VSEGRAAVVF213 DKFIETSAAV224 QHNVKELFEG234 IVRQVRLRRD 244 SKEKNERRLA254 YQKR> Chain B EFGMTYYRVV 79 LIGEQGVGKS89 TLANIFAGVE111 DTYERTLMVD121 GESATIILLD131 MWENHDHMQV 149 GDAYLIVYSI159 TDRASFEKAS169 ELRIQLRRAR179 QTEDIPIILV189 GNKSDLVRRE 200 VSVSEGRAAV211 VFDCKFIETS221 AAVQHNVKEL231 FEGIVRQVRL241 RRDSKEKNER 251 RLAYQKRKES261
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GLU107[A]
1.336
VAL108[A]
3.260
LEU109[A]
3.303
GLY110[A]
4.371
THR113[A]
4.395
GLU115[A]
2.890
ILE128[A]
4.853
ILE159[A]
4.381
THR160[A]
3.349
PHE165[A]
3.294
GLU166[A]
4.884
ALA168[A]
3.659
SER169[A]
3.592
ARG172[A]
4.340
ARG176[A]
4.363
ILE186[A]
3.295
ILE187[A]
4.923
LEU188[A]
3.683
LEU195[A]
3.115
VAL196[A]
3.256
ARG197[A]
1.332
ARG199[A]
1.332
GLU200[A]
3.349
GLU205[A]
3.062
GLY206[A]
3.302
ARG207[A]
3.295
ALA208[A]
1.341
ALA210[A]
1.337
VAL211[A]
3.333
VAL212[A]
3.461
PHE213[A]
2.849
ASP214[A]
1.329
LYS216[A]
1.327
PHE217[A]
4.178
VAL79[B]
3.648
LEU130[B]
4.938
MET132[B]
3.418
TRP133[B]
3.700
HIS143[B]
3.374
ASP144[B]
3.331
HIS145[B]
1.330
MET147[B]
1.334
GLN148[B]
3.185
VAL149[B]
3.426
GLY150[B]
4.437
TYR153[B]
2.608
ILE159[B]
4.573
THR160[B]
3.593
PHE165[B]
3.575
SER169[B]
4.675
LEU195[B]
3.152
VAL196[B]
3.195
ARG197[B]
1.332
ARG199[B]
1.333
GLU200[B]
3.605
SER204[B]
4.893
GLU205[B]
2.930
GLY206[B]
3.511
ARG207[B]
3.411
ALA208[B]
1.335
ALA210[B]
1.331
VAL211[B]
3.274
VAL212[B]
3.113
PHE213[B]
2.684
ASP214[B]
4.760
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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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 Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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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.
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| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | FSH Signaling Pathway | |||||
| 2 | IL4 Signaling Pathway | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Anti-tumoral efficacy of therapeutic human anti-KIR antibody (Lirilumab/BMS-986015/IPH2102) in a preclinical xenograft tumor model. J Immunother Cancer. 2013; 1(Suppl 1): P40. | |||||
| REF 2 | ClinicalTrials.gov (NCT02481297) Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) Patients. | |||||
| REF 3 | Biochemical and structural characterization of the gem GTPase. J Biol Chem. 2007 Jan 19;282(3):1905-15. | |||||
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