Target Information

Target General Information

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Target ID

T66350 (Former ID: TTDR00036)

Target Name

Ras-related protein Rab-9A (RAB9A)

Synonyms

RAB9A

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Gene Name

RAB9A

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Fungal infection [ICD-11: 1F29-1F2F]

Function

Involved in the transport of proteins between the endosomes and the trans Golgi network.

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BioChemical Class

Small GTPase superfamily

UniProt ID

RAB9A_HUMAN

Sequence

MAGKSSLFKVILLGDGGVGKSSLMNRYVTNKFDTQLFHTIGVEFLNKDLEVDGHFVTMQI
WDTAGQERFRSLRTPFYRGSDCCLLTFSVDDSQSFQNLSNWKKEFIYYADVKEPESFPFV
ILGNKIDISERQVSTEEAQAWCRDNGDYPYFETSAKDATNVAAAFEEAVRRVLATEDRSD
HLIQTDTVNLHRKPKPSSSCC

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3D Structure

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PDB

HIT2.0 ID

T05M8H

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Benzoic Acid

Drug Info

Approved

Fungal infection

[2], [3]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

Benzoic Acid

Drug Info

[1]

Guanosine-5'-Diphosphate

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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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

GGVGKSSLMN

²⁵

RYVTNKFDTQ

³⁵

LFHTIGVEFL

⁴⁵

NKDLEVDGHF

⁵⁵

VTMQIWDTAG

⁶⁵

LERFRSLRTP

⁷⁵

FYRGSDCCLL

⁸⁵

TFSVDDSQSF

⁹⁵

QNLSNWKKEF

¹⁰⁵

IYYADVKEPE

¹¹⁵

SFPFVILGNK

¹²⁵

IDISERQVST

¹³⁵

EEAQAWCRDN

¹⁴⁵

GDYPYFETSA

¹⁵⁵

KDATNVAAAF

¹⁶⁵

EEAVRRVLAT

¹⁷⁵

Residue

Distance (Å)

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

Residue

Distance (Å)

HIS38

2.551

THR39

2.977

THR63

4.029

ALA64

3.933

GLY65

2.921

LEU66

3.973

ASN124

3.297

LYS125

2.833

ASP127

2.223

ILE128

3.602

THR153

4.742

SER154

3.493

ALA155

2.827

LYS156

3.162

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

[5]

PDB Sequence

AGKSSLFKVI

¹¹

LLGDGGVGKS

²¹

SLMNRYVTNK

³¹

FDTTIGVEFL

⁴⁵

NKDLEVDGHF

⁵⁵

VTMQIWDTAG

⁶⁵

QERFRSLRTP

⁷⁵

FYRGSDCCLL

⁸⁵

TFSVDDSQSF

⁹⁵

QNLSNWKKEF

¹⁰⁵

IYYADVKEPE

¹¹⁵

SFPFVILGNK

¹²⁵

IDISERQVST

¹³⁵

EEAQAWCRDN

¹⁴⁵

GDYPYFETSA

¹⁵⁵

KDATNVAAAF

¹⁶⁵

EEAVRRVLAT

¹⁷⁵

Residue

Distance (Å)

ASP15

3.829

GLY16

3.847

GLY17

2.828

VAL18

3.325

GLY19

2.954

LYS20

2.805

SER21

2.909

SER22

2.676

PHE32

3.233

THR34

3.024

Residue

Distance (Å)

ASP62

4.159

ASN124

3.246

LYS125

3.044

ASP127

2.825

ILE128

3.740

THR153

4.707

SER154

3.354

ALA155

2.860

LYS156

3.279

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

Different Human System Profiles of Target

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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).

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
ADP-ribosylation factor-like protein 8B (ARL8B)	PF00025	26.446 (32/121)	1.21E-08
ADP-ribosylation factor-like protein 8A (ARL8A)	PF00025	24.793 (30/121)	4.06E-08
ADP-ribosylation factor-like protein 14 (ARL14)	PF00025	28.333 (34/120)	1.40E-06
ADP-ribosylation factor-like protein 4A (ARL4A)	PF00025	26.400 (33/125)	2.11E-06
ADP-ribosylation factor-like protein 1 (ARL1)	PF00025	25.595 (43/168)	9.32E-06
ADP-ribosylation factor-like protein 4C (ARL4C)	PF00025	25.781 (33/128)	4.17E-05
ADP-ribosylation factor-like protein 4D (ARL4D)	PF00025	28.099 (34/121)	5.70E-05
Rab-like protein 3 (RABL3)	PF08477	23.973 (35/146)	7.12E-05
ADP-ribosylation factor-like protein 11 (ARL11)	PF00025	25.203 (31/123)	9.95E-05
ADP-ribosylation factor-like protein 6 (ARL6)	PF00025	22.561 (37/164)	1.20E-04
ADP-ribosylation factor-like protein 2 (ARL2)	PF00025	26.804 (26/97)	3.00E-03
Click to Show/Hide the Information of Human Similarity Proteins


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

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Co-Targets

Co-Targets Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Measles

References

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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.

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