Target Information

Target General Information

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Target ID

T53890 (Former ID: TTDR01136)

Target Name

Gankyrin (PSMD10)

Synonyms

p28(GANK); 26S proteasome regulatory subunit p28; 26S proteasome non-ATPase regulatory subunit 10

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Gene Name

PSMD10

Target Type

Literature-reported target

[1]

Function

In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC).

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UniProt ID

PSD10_HUMAN

Sequence

MEGCVSNLMVCNLAYSGKLEELKESILADKSLATRTDQDSRTALHWACSAGHTEIVEFLL
QLGVPVNDKDDAGWSPLHIAASAGRDEIVKALLGKGAQVNAVNQNGCTPLHYAASKNRHE
IAVMLLEGGANPDAKDHYEATAMHRAAAKGNLKMIHILLYYKASTNIQDTEGNTPLHLAC
DEERVEEAKLLVSQGASIYIENKEEKTPLQVAKGGLGLILKRMVEG

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3D Structure

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PDB

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: Urea

Ligand Info

Structure Description

Snapshots of Human PSMD10(Gankyrin) unfolding by urea: 1 hour incubation

PDB:7VXW

Method

X-ray diffraction

Resolution

2.22 Å

Mutation

[2]

PDB Sequence

GCVSNLMVCN

¹²

LAYSGKLEEL

²²

KESILADKSL

³²

ATRTDQDSRT

⁴²

ALHWACSAGH

⁵²

TEIVEFLLQL

⁶²

GVPVNDKDDA

⁷²

GWSPLHIAAS

⁸²

AGRDEIVKAL

⁹²

LGKGAQVNAV

¹⁰²

NQNGCTPLHY

¹¹²

AASKNRHEIA

¹²²

VMLLEGGANP

¹³²

DAKDHYEATA

¹⁴²

MHRAAAKGNL

¹⁵²

KMIHILLYYK

¹⁶²

ASTNIQDTEG

¹⁷²

NTPLHLACDE

¹⁸²

ERVEEAKLLV

¹⁹²

SQGASIYIEN

²⁰²

KEEKTPLQVA

²¹²

KGGLGLILKR

²²²

MVEG

Residue

Distance (Å)

ASN7

2.635

THR36

4.754

ASP37

4.093

GLN38

3.441

ASN117

2.879

ARG118

3.398

Residue

Distance (Å)

HIS119

2.736

GLU120

2.210

TYR160

2.608

TYR161

3.632

LYS162

3.305

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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). 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
DNA-binding protein RFXANK (RFXANK)	PF13606 ; PF13857	30.114 (53/176)	4.65E-14
Ankyrin repeat domain-containing protein 62 (ANKRD62)	PF13606 ; PF13857 ; PF14915 More >>	29.487 (46/156)	1.61E-12
Krev interaction trapped protein 1 (KRIT1)	PF13857 ; PF00373 ; PF16705 More >>	32.787 (40/122)	3.70E-10
Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3 (ACAP3)	PF13857 ; PF01412 ; PF16746 ; PF00169 More >>	34.831 (31/89)	5.14E-07
Ankyrin and armadillo repeat-containing protein (ANKAR)	PF00514	25.610 (42/164)	1.69E-05
IQ motif and ankyrin repeat domain-containing protein 1 (IQANK1)		32.432 (24/74)	1.56E-04
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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.

Degree	25	Degree centrality	2.69E-03	Betweenness centrality	3.76E-04
Closeness centrality	2.30E-01	Radiality	1.40E+01	Clustering coefficient	6.47E-01
Neighborhood connectivity	4.79E+01	Topological coefficient	1.77E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. J Biol Chem. 2004 Apr 9;279(15):15505-14.

REF 2

Snapshots of urea-induced early structural changes and unfolding of an ankyrin repeat protein at atomic resolution. Protein Sci. 2022 Dec;31(12):e4515.

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