Tchem MAP3K20 Mitogen-activated protein kinase kinase kinase 20

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Mitogen-activated Protein Kinase Kinase Kinase 20

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Mlk Family / Mlk Subfamily / Mitogen-activated Protein Kinase Kinase Kinase Mlt

Protein Summary

Description

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2 (PubMed:10924358, PubMed:11836244, PubMed:15342622, PubMed:21224381). Involved in limb development (PubMed:26755636). Isoform 1: Phosphorylates histone H3 at 'Ser-28' (PubMed:15684425). May have role in neoplastic cell transformation and cancer development (PubMed:15172994). Causes cell shrinkage and disruption of actin stress fibers (PubMed:11042189). This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9NYL2
• B3KPG2
• Q53SX1
• Q580W8
• Q59GY5
• Q86YW8
• Q9HCC4
• Q9HCC5
• Q9HDD2
• Q9NYE9

Gene Name

• MAP3K20

Ensembl ID

• ENST00000338983
• ENSP00000340257
• ENSG00000091436
• ENST00000375213
• ENSP00000364361
• ENST00000409176
• ENSP00000387259
• ENST00000539448
• ENSP00000439414

Symbol

• MLTK
• ZAK
• pk
• AZK
• MLT
• MRK
• ZAK
• CNM6
• MLK7
• MLTK
• SFMMP
• mlklak
• MLTKbeta
• MLTKalpha

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0
biological term	0
cell line	0
cell type or tissue	0
cellular component	0

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 16.1   (req: < 5)

Gene RIFs: 19   (req: <= 3)

Antibodies: 270   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 16.1   (req: >= 5)

Gene RIFs: 19   (req: > 3)

Antibodies: 270   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 29

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3

Approved Drugs (3)

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1 – 3 of 3

sorafenib

MAP3K20Tchem Kinase

Kd : 8.2

nilotinib

MAP3K20Tchem Kinase

Kd : 7.96

vemurafenib

MAP3K20Tchem Kinase

IC50 : 7.64

Active Ligands (29)

Explore Active Ligands

1 – 10 of 29

AST-487

MAP3K20Tchem Kinase

Kd : 8.64

motesanib

MAP3K20Tchem Kinase

Kd : 8.1

compound 15b [PMID: 16539403]

MAP3K20Tchem Kinase

IC50 : 6.1500001

CHEMBL4450810

MAP3K20Tchem Kinase

Kd : 8.1

CHEMBL4098896

MAP3K20Tchem Kinase

Kd : 8.57

CHEMBL4524151

MAP3K20Tchem Kinase

IC50 : 8.72

CHEMBL4542865

MAP3K20Tchem Kinase

IC50 : 8.68

CHEMBL4526537

MAP3K20Tchem Kinase

IC50 : 8.64

CHEMBL4574656

MAP3K20Tchem Kinase

IC50 : 8.52

CHEMBL4579609

MAP3K20Tchem Kinase

IC50 : 8.48

GWAS Traits (24)

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5

1 – 5 of 24

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1	2	2		83.8
mathematical ability	EFO_0004875	4	3	5		78.4
age at first sexual intercourse measurement	EFO_0009749	1	1	1		64.4
self reported educational attainment	EFO_0004784	1	2	2		62.5
cognitive function measurement	EFO_0008354	1	1	1		53.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	2		83.8
mathematical ability	EFO_0004875	5		78.4
age at first sexual intercourse measurement	EFO_0009749	1		64.4
self reported educational attainment	EFO_0004784	2		62.5
cognitive function measurement	EFO_0008354	1		53.7

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Orthologs (6)

1 – 5 of 6

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase kinase kinase 20		698274
Mouse	mitogen-activated protein kinase kinase kinase 20	MGI:2443258	65964
Dog	mitogen-activated protein kinase kinase kinase 20	VGNC:53099	478802
Platypus	mitogen-activated protein kinase kinase kinase 20		100084257
Zebrafish	sterile alpha motif and leucine zipper containing kinase AZK	ZDB-GENE-070912-386	405768

Species	Name	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase kinase kinase 20
Mouse	mitogen-activated protein kinase kinase kinase 20
Dog	mitogen-activated protein kinase kinase kinase 20
Platypus	mitogen-activated protein kinase kinase kinase 20
Zebrafish	sterile alpha motif and leucine zipper containing kinase AZK

Protein Structure (2 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9NYL2-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (12)

KEGG (1)

PathwayCommons (1)

WikiPathways (10)

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5

1 – 1 of 1

Data Source	Name	Explore in Pharos	Explore in Source
KEGG	MAPK signaling pathway	295 targets	path:hsa04010

Name	Explore in Pharos	Explore in Source
MAPK signaling pathway	295 targets	path:hsa04010

Gene Ontology Terms (23)

Functions (5)

Components (3)

Processes (15)

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10

1 – 5 of 5

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
magnesium ion binding	Inferred from Direct Assay (IDA)	UniProtKB
MAP kinase kinase kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB

Protein-Protein Interactions (20)

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1 – 10 of 20

• See Interactions on String-DB

ZNF544

Tdark

Family:  TF

Novelty:  0.99233516

p_int:  0.999999953

p_ni:  4.7e-8

Score:  0.642

Data Source:  BioPlex,STRINGDB

ZNF227

Tdark

Family:  TF

Novelty:  2.78882514

p_int:  0.999998116

p_ni:  0.000001883

Score:  0.513

Data Source:  BioPlex,STRINGDB

ZNF71

Tbio

Family:  TF

Novelty:  0.24703192

p_int:  0.884231373

p_ni:  0.010571824

p_wrong:  0.105196804

Score:  0.234

Data Source:  BioPlex,STRINGDB

PKN1

Tchem

Family:  Kinase

Novelty:  0.00780975

Score:  0.951

Data Source:  STRINGDB

MAP2K6

Tchem

Family:  Kinase

Novelty:  0.00569655

Score:  0.947

Data Source:  STRINGDB

MAP2K7

Tchem

Family:  Kinase

Novelty:  0.00916401

Score:  0.897

Data Source:  STRINGDB

ZNF33A

Tbio

Family:  TF

Novelty:  0.14568295

Score:  0.823

Data Source:  STRINGDB

ZNF567

Tdark

Family:  TF

Novelty:  1.90648197

Score:  0.703

Data Source:  STRINGDB

MAP2K4

Tchem

Family:  Kinase

Novelty:  0.00252847

Score:  0.595

Data Source:  STRINGDB

SLC25A20

Tbio

Family:  Transporter

Novelty:  0.00503518

Score:  0.531

Data Source:  STRINGDB

Publication Statistics

PubMed Score  16.10

PubMed score by year

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PubTator Score  229.94

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

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PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
ATP-binding
Cell cycle
Complete proteome
Cytoplasm
Disease mutation
Kinase
Magnesium

GWAS Trait Find Similar Targets

No Header	No Header
age at first sexual intercourse measurement
apolipoprotein A 1 measurement
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
breast carcinoma
chin morphology measurement
chronotype measurement
cognitive function measurement
diastolic blood pressure
gut microbiome measurement

MGI Phenotype Find Similar Targets

No Header	No Header
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
limbs/digits/tail phenotype
mortality/aging
skeleton phenotype