Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T66350
(Former ID: TTDR00036)
|
|||||
| Target Name |
Ras-related protein Rab-9A (RAB9A)
|
|||||
| Synonyms |
RAB9A
Click to Show/Hide
|
|||||
| Gene Name |
RAB9A
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Fungal infection [ICD-11: 1F29-1F2F] | |||||
| Function |
Involved in the transport of proteins between the endosomes and the trans Golgi network.
Click to Show/Hide
|
|||||
| BioChemical Class |
Small GTPase superfamily
|
|||||
| UniProt ID | ||||||
| Sequence |
MAGKSSLFKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTMQI
WDTAGQERFRSLRTPFYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFV ILGNKIDISERQVSTEEAQAWCRDNGDYPYFETSAKDATNVAAAFEEAVRRVLATEDRSD HLIQTDTVNLHRKPKPSSSCC Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T05M8H | |||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Guanosine-5'-Triphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of Rab9A-GTP-Nde1 | PDB:7E1T | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | Yes | [4] |
| PDB Sequence |
SLFKVILLGD
15 GGVGKSSLMN25 RYVTNKFDTQ35 LFHTIGVEFL45 NKDLEVDGHF55 VTMQIWDTAG 65 LERFRSLRTP75 FYRGSDCCLL85 TFSVDDSQSF95 QNLSNWKKEF105 IYYADVKEPE 115 SFPFVILGNK125 IDISERQVST135 EEAQAWCRDN145 GDYPYFETSA155 KDATNVAAAF 165 EEAVRRVLAT175
|
|||||
|
|
GLY14
4.475
ASP15
3.598
GLY16
3.152
GLY17
2.419
VAL18
3.191
GLY19
3.033
LYS20
2.456
SER21
3.372
SER22
3.067
PHE32
3.600
ASP33
3.432
THR34
2.600
GLN35
4.361
LEU36
3.907
PHE37
4.367
|
|||||
| Ligand Name: Guanosine-5'-Diphosphate | Ligand Info | |||||
| Structure Description | High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target | PDB:1WMS | ||||
| Method | X-ray diffraction | Resolution | 1.25 Å | Mutation | No | [5] |
| PDB Sequence |
AGKSSLFKVI
11 LLGDGGVGKS21 SLMNRYVTNK31 FDTTIGVEFL45 NKDLEVDGHF55 VTMQIWDTAG 65 QERFRSLRTP75 FYRGSDCCLL85 TFSVDDSQSF95 QNLSNWKKEF105 IYYADVKEPE 115 SFPFVILGNK125 IDISERQVST135 EEAQAWCRDN145 GDYPYFETSA155 KDATNVAAAF 165 EEAVRRVLAT175
|
|||||
|
|
||||||
| 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).
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
Biological Network Descriptors
|
|
|
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.
|
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.27E-07 |
|---|---|---|---|---|---|
| Closeness centrality | 4.48E-04 | Radiality | 1.16E-02 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.75E+00 | Topological coefficient | 7.50E-01 | Eccentricity | 2 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Measles | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4565). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | Nde1 is a Rab9 effector for loading late endosomes to cytoplasmic dynein motor complex. Structure. 2022 Mar 3;30(3):386-395.e5. | |||||
| REF 5 | High resolution crystal structure of human Rab9 GTPase: a novel antiviral drug target. J Biol Chem. 2004 Sep 17;279(38):40204-8. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.