Target Information

Target General Information

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Target ID

T17339 (Former ID: TTDNR00662)

Target Name

Dual specificity protein phosphatase 10 (DUSP10)

Synonyms

Mitogen-activated protein kinase phosphatase 5; MKP5; MKP-5; MAP kinase phosphatase 5

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Gene Name

DUSP10

Target Type

Literature-reported target

[1]

Function

Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38. Protein phosphatase involved in the inactivation of MAP kinases.

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BioChemical Class

Phosphoric monoester hydrolase

UniProt ID

DUS10_HUMAN

EC Number

EC 3.1.3.16

Sequence

MPPSPLDDRVVVALSRPVRPQDLNLCLDSSYLGSANPGSNSHPPVIATTVVSLKAANLTY
MPSSSGSARSLNCGCSSASCCTVATYDKDNQAQTQAIAAGTTTTAIGTSTTCPANQMVNN
NENTGSLSPSSGVGSPVSGTPKQLASIKIIYPNDLAKKMTKCSKSHLPSQGPVIIDCRPF
MEYNKSHIQGAVHINCADKISRRRLQQGKITVLDLISCREGKDSFKRIFSKEIIVYDENT
NEPSRVMPSQPLHIVLESLKREGKEPLVLKGGLSSFKQNHENLCDNSLQLQECREVGGGA
SAASSLLPQPIPTTPDIENAELTPILPFLFLGNEQDAQDLDTMQRLNIGYVINVTTHLPL
YHYEKGLFNYKRLPATDSNKQNLRQYFEEAFEFIEEAHQCGKGLLIHCQAGVSRSATIVI
AYLMKHTRMTMTDAYKFVKGKRPIISPNLNFMGQLLEFEEDLNNGVTPRILTPKLMGVET
VV

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3D Structure

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AlphaFold

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: 1-{[(10aP)-5,6-dihydropyrido[2,3-h]quinazolin-2-yl]sulfanyl}-3,3-dimethylbutan-2-one

Ligand Info

Structure Description

Structure of MAP kinase phosphatase 5 in complex with 3,3-dimethyl-1-((5,6-dihydropyrido[2,3-h]quinazolin-2-yl)thio)butan-2-one, an allosteric inhibitor

PDB:7UMV

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[2]

PDB Sequence

HMAELTPILP

³²⁷

FLFLGNEQDA

³³⁷

QDLDTMQRLN

³⁴⁷

IGYVINVTTH

³⁵⁷

LPLYHYEKGL

³⁶⁷

FNYKRLPATD

³⁷⁷

SNKQNLRQYF

³⁸⁷

EEAFEFIEEA

³⁹⁷

HQCGKGLLIH

⁴⁰⁷

CQAGVSRSAT

⁴¹⁷

IVIAYLMKHT

⁴²⁷

RMTMTDAYKF

⁴³⁷

VKGKRPIISP

⁴⁴⁷

NLNFMGQLLE

⁴⁵⁷

FEEDLNNGVT

⁴⁶⁷

Residue

Distance (Å)

SER413

3.465

ALA416

4.620

THR417

3.546

ILE420

3.633

MET431

3.748

THR432

4.579

TYR435

3.252

Residue

Distance (Å)

ILE445

3.424

SER446

3.481

PRO447

3.313

ASN448

3.064

PHE451

3.737

MET452

3.180

LEU455

4.143

Ligand Name: 3,3-Dimethyl-1-[(9-propyl-5,6-dihydrothieno[3,4-h]quinazolin-2-yl)sulfanyl]butan-2-one

Ligand Info

Structure Description

Structure of MAP kinase phosphatase 5 in complex with 3,3-dimethyl-1-((9-propyl-5,6-dihydrothieno[3,4-h]quinazolin-2-yl)thio)butan-2-one, an allosteric inhibitor

PDB:7U4O

Method

X-ray diffraction

Resolution

2.30 Å

Mutation

[2]

PDB Sequence

SHMAELTPIL

³²⁶

PFLFLGNEQD

³³⁶

AQDLDTMQRL

³⁴⁶

NIGYVINVTT

³⁵⁶

HLPLYHYEKG

³⁶⁶

LFNYKRLPAT

³⁷⁶

DSNKQNLRQY

³⁸⁶

FEEAFEFIEE

³⁹⁶

AHQCGKGLLI

⁴⁰⁶

HCQAGVSRSA

⁴¹⁶

TIVIAYLMKH

⁴²⁶

TRMTMTDAYK

⁴³⁶

FVKGKRPIIS

⁴⁴⁶

PNLNFMGQLL

⁴⁵⁶

EFEEDLNNGV

⁴⁶⁶

Residue

Distance (Å)

SER413

3.481

ALA416

4.133

THR417

3.431

ILE420

3.710

MET431

4.211

THR432

4.797

TYR435

3.227

Residue

Distance (Å)

ILE445

3.927

SER446

3.493

PRO447

3.435

ASN448

3.145

PHE451

3.724

MET452

3.122

LEU455

3.877

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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 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 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 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 Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	1.43E-06
Closeness centrality	2.23E-01	Radiality	1.39E+01	Clustering coefficient	3.00E-01
Neighborhood connectivity	5.88E+01	Topological coefficient	3.50E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target