Tchem MAPKAPK5 MAP kinase-activated protein kinase 5

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Map Kinase-activated Protein Kinase 5

Protein / Cytoskeletal Protein / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Map Kinase-activated Protein Kinase 5

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Mapkapk Family / Mapkapk Subfamily / Map Kinase-activated Protein Kinase 5

Protein Summary

Description

Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family. In response to cellular stress and proinflammatory cytokines, this kinase is activated through its phosphorylation by MAP kinases including MAPK1/ERK, MAPK14/p38-alpha, and MAPK11/p38-beta. The encoded protein is found in the nucleus but translocates to the cytoplasm upon phosphorylation and activation. This kinase phosphorylates heat shock protein HSP27 at its physiologically relevant sites. Two alternately spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2012]

Uniprot Accession IDs

• Q8IW41
• B3KVA5
• O60491
• Q86X46
• Q9BVX9
• Q9UG86
• MAPK-activated protein kinase 5

Gene Name

• MAPKAPK5

Ensembl ID

• ENST00000550735
• ENSP00000449667
• ENSG00000089022
• ENST00000551404
• ENSP00000449381

Symbol

• PRAK
• MK5
• MK-5
• PRAK
• MAPKAP-K5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.99
histone modification site profile	0.9
transcription factor binding site profile	0.83
kinase perturbation	0.81
kinase	0.8

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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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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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: 83.08   (req: < 5)

Gene RIFs: 15   (req: <= 3)

Antibodies: 547   (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: 83.08   (req: >= 5)

Gene RIFs: 15   (req: > 3)

Antibodies: 547   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

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

Active Ligands: 5

Tclin

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

Active Drug: 0

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

CHEMBL259084

MAPKAPK5Tchem Kinase

Kd : 8.1

CHEMBL461139

MAPKAPK5Tchem Kinase

IC50 : 7.62

CHEMBL226403

MAPKAPK5Tchem Kinase

IC50 : 6.09000015

CHEMBL461140

MAPKAPK5Tchem Kinase

IC50 : 7.55

Galapagos MAPKAPK5 inhibitor D

MAPKAPK5Tchem Kinase

IC50 : 7.42999983

GWAS Traits (1)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1	1	1		25.4

• 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	1		25.4

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase-activated protein kinase 5		713521
Mouse	MAP kinase-activated protein kinase 5	MGI:1333110	17165
Rat	mitogen-activated protein kinase-activated protein kinase 5	RGD:1564113	498183
Dog	mitogen-activated protein kinase-activated protein kinase 5	VGNC:43008	477480
Horse	mitogen-activated protein kinase-activated protein kinase 5	VGNC:19968	100057579

Species	Name	OMA	EggNOG	Inparanoid
Macaque	mitogen-activated protein kinase-activated protein kinase 5
Mouse	MAP kinase-activated protein kinase 5
Rat	mitogen-activated protein kinase-activated protein kinase 5
Dog	mitogen-activated protein kinase-activated protein kinase 5
Horse	mitogen-activated protein kinase-activated protein kinase 5

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-Q8IW41-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (93)

Reactome (13)

KEGG (1)

PathwayCommons (6)

WikiPathways (73)

Cellular Senescence (R-HSA-2559583)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cellular Senescence	164 targets	R-HSA-2559583
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Cellular responses to stress	392 targets	R-HSA-2262752
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Cellular Senescence	164 targets	R-HSA-2559583
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Cellular responses to stress	392 targets	R-HSA-2262752
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Gene Ontology Terms (23)

Functions (7)

Components (4)

Processes (12)

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1 – 7 of 7

GO Term	Evidence	Assigned by
p53 binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
calcium-dependent protein serine/threonine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
calmodulin-dependent protein kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
mitogen-activated protein kinase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
MAP kinase kinase activity	Traceable Author Statement (TAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (71)

Explore Interacting Targets

1 – 10 of 71

• See Interactions on String-DB

MAPK6

Tbio

Family: Kinase

Novelty: 0.01012514

p_int: 0.999999998

p_ni: 1e-9

p_wrong: 2e-9

Score: 0.978

Data Source: BioPlex,Reactome,STRINGDB

MAPK4

Tbio

Family: Kinase

Novelty: 0.0223868

p_int: 0.999999428

p_ni: 5.69e-7

p_wrong: 4e-9

Score: 0.967

Data Source: BioPlex,Reactome,STRINGDB

ZNF577

Tdark

Family: TF

Novelty: 0.29636548

p_int: 0.999611145

p_ni: 0.000388854

p_wrong: 1e-9

Data Source: BioPlex

TP53

Tchem

Family: TF

Novelty: 0.00001907

Score: 0.99

Data Source: Reactome,STRINGDB

HSPB1

Tchem

Novelty: 0.00081373

Score: 0.984

Data Source: Reactome,STRINGDB

MAPK11

Tchem

Family: Kinase

Novelty: 0.00545217

Score: 0.968

Data Source: Reactome,STRINGDB

MAPK14

Tchem

Family: Kinase

Novelty: 0.00045138

Score: 0.968

Data Source: Reactome,STRINGDB

MYC

Tbio

Family: TF

Novelty: 0.00005734

Score: 0.952

Data Source: STRINGDB

MAPK12

Tchem

Family: Kinase

Novelty: 0.00835017

Score: 0.938

Data Source: STRINGDB

MAPK13

Tchem

Family: Kinase

Novelty: 0.01071621

Score: 0.927

Data Source: STRINGDB

Publication Statistics

PubMed Score  83.08

PubMed score by year

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PubTator Score  48.08

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

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

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Structural Annotations

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UniProt Keyword Find Similar Targets

Alternative splicing
ATP-binding
Coiled coil
Complete proteome
Cytoplasm
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

mean corpuscular volume

MGI Phenotype Find Similar Targets

cellular phenotype
integument phenotype
mortality/aging
neoplasm