Target Information

Target General Information

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Target ID

T01283 (Former ID: TTDI02200)

Target Name

Tumor susceptibility gene protein 101 (TSG101)

Synonyms

Tumor susceptibility gene 101 protein; ESCRT-I complex subunit TSG101

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Gene Name

TSG101

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Influenza [ICD-11: 1E30-1E32]

Function

Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan. It may also play a role in the extracellular release of microvesicles that differ from the exosomes. Component of the ESCRT-I complex, a regulator of vesicular trafficking process.

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BioChemical Class

Ubiquitin-conjugating enzyme

UniProt ID

TS101_HUMAN

Sequence

MAVSESQLKKMVSKYKYRDLTVRETVNVITLYKDLKPVLDSYVFNDGSSRELMNLTGTIP
VPYRGNTYNIPICLWLLDTYPYNPPICFVKPTSSMTIKTGKHVDANGKIYLPYLHEWKHP
QSDLLGLIQVMIVVFGDEPPVFSRPISASYPPYQATGPPNTSYMPGMPGGISPYPSGYPP
NPSGYPGCPYPPGGPYPATTSSQYPSQPPVTTVGPSRDGTISEDTIRASLISAVSDKLRW
RMKEEMDRAQAELNALKRTEEDLKKGHQKLEEMVTRLDQEVAEVDKNIELLKKKDEELSS
ALEKMENQSENNDIDEVIIPTAPLYKQILNLYAEENAIEDTIFYLGEALRRGVIDLDVFL
KHVRLLSRKQFQLRALMQKARKTAGLSDLY

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

FGI-101-1A6

Drug Info

Phase 1

Influenza virus infection

[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: 4-methoxy-1-(5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)-3,5-dimethyl-2-(sulfanylmethyl)pyridin-1-ium

Ligand Info

Structure Description

Solution-state NMR structural ensemble of human Tsg101 UEV in complex with tenatoprazole

PDB:5VKG

Method

Solution NMR

Resolution

N.A.

Mutation

Yes

[2]

PDB Sequence

AVSESQLKKM

¹¹

VSKYKYRDLT

²¹

VRETVNVITL

³¹

YKDLKPVLDS

⁴¹

YVFNDGSSRE

⁵¹

LMNLTGTIPV

⁶¹

PYRGNTYNIP

⁷¹

ICLWLLDTYP

⁸¹

YNPPICFVKP

⁹¹

TSSMTIKTGK

¹⁰¹

HVDANGKIYL

¹¹¹

PYLHEWKHPQ

¹²¹

SDLLGLIQVM

¹³¹

IVVFGDEPPV

¹⁴¹

FSRP

Residue

Distance (Å)

ASP40

2.295

SER41

2.453

TYR42

3.767

VAL43

3.810

THR56

1.918

Residue

Distance (Å)

GLY57

4.851

PRO71

4.883

CYS73

2.028

TRP75

3.136

LYS90

1.760

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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

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).

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Centriolin (CNTRL)	PF14580	28.421 (27/95)	3.00E-03


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
Viral life cycle - HIV-1	hsa03250	Affiliated Target
Class: Genetic Information Processing => Information processing in viruses	Pathway Hierarchy
Endocytosis	hsa04144	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy

Degree	34	Degree centrality	3.65E-03	Betweenness centrality	5.08E-03
Closeness centrality	2.47E-01	Radiality	1.43E+01	Clustering coefficient	2.87E-01
Neighborhood connectivity	4.12E+01	Topological coefficient	6.39E-02	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target