Tchem RPS6KA4 Ribosomal protein S6 kinase alpha-4

Protein Summary

Description

Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Uniprot Accession IDs

• O75676
• A8K7Z8
• O75585
• Q53ES8
• S6K-alpha-4

Gene Name

• RPS6KA4

Ensembl ID

• ENST00000334205
• ENSP00000333896
• ENSG00000162302

Symbol

• MSK2
• MSK2
• RSK-B
• S6K-alpha-4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	1
drug perturbation	0.99
molecular function	0.99
protein domain	0.97
disease perturbation	0.93

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Rsk Family / Msk Subfamily / Ribosomal Protein S6 Kinase Alpha-4

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: 17.39   (req: < 5)

Gene RIFs: 9   (req: <= 3)

Antibodies: 240   (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: 17.39   (req: >= 5)

Gene RIFs: 9   (req: > 3)

Antibodies: 240   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

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

Active Ligands: 6

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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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Approved Drugs (0)

No approved drugs found

Active Ligands (6)

Explore Active Ligands

1 – 6 of 6

staurosporine

RPS6KA4Tchem Kinase

pKd : 7.89

lestaurtinib

RPS6KA4Tchem Kinase

pKd : 7.57

AT-9283

RPS6KA4Tchem Kinase

pKd : 7.92

SID103905167

RPS6KA4Tchem Kinase

pKi : 8.6

BI-2536

RPS6KA4Tchem Kinase

pKd : 7.06

SID103904478

RPS6KA4Tchem Kinase

pKi : 8.2

Protein-Protein Interactions (65)

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1 – 10 of 65

• See Interactions on String-DB

MAPK14

Tchem

Family:  Kinase

Novelty:  0.00045138

p_int:  0.999999903

p_ni:  9.7e-8

Score:  0.965

Data Source:  BioPlex,STRINGDB

HSP90AB3P

Tdark

p_int:  0.999999751

p_ni:  2.49e-7

Data Source:  BioPlex

MYLK2

Tchem

Family:  Kinase

Novelty:  0.0080273

p_int:  0.999999632

p_ni:  3.68e-7

Score:  0.537

Data Source:  BioPlex,STRINGDB

HSP90AA4P

Tdark

p_int:  0.999999338

p_ni:  6.62e-7

Data Source:  BioPlex

HSP90AB4P

Tdark

p_int:  0.99999927

p_ni:  7.3e-7

Data Source:  BioPlex

CSNK2B

Tbio

Family:  Kinase

Novelty:  0.00152367

p_int:  0.999991027

p_ni:  0.000008972

p_wrong:  1e-9

Score:  0.177

Data Source:  BioPlex,STRINGDB

HSP90AA5P

Tdark

p_int:  0.999987399

p_ni:  0.000012601

Data Source:  BioPlex

KLHDC3

Tdark

Novelty:  0.63840156

p_int:  0.999901648

p_ni:  0.000098342

p_wrong:  1e-8

Score:  0.191

Data Source:  BioPlex,STRINGDB

MAPK4

Tbio

Family:  Kinase

Novelty:  0.0223868

p_int:  0.999878617

p_ni:  0.000121189

p_wrong:  1.93e-7

Score:  0.352

Data Source:  BioPlex,STRINGDB

FKBP5

Tchem

Family:  Enzyme

Novelty:  0.00214511

p_int:  0.999676564

p_ni:  0.000323436

Data Source:  BioPlex

Nearest Tclin Targets (1)

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Upstream (1)

1 – 1 of 1

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  2

1: TNF signaling pathway

2: MAPK signaling pathway

Pathways (16)

Reactome (4)

KEGG (2)

PathwayCommons (5)

WikiPathways (5)

Axon guidance (R-HSA-422475)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	L1CAM interactions	100 targets	R-HSA-373760
Reactome	Recycling pathway of L1	28 targets	R-HSA-437239

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
L1CAM interactions	100 targets	R-HSA-373760
Recycling pathway of L1	28 targets	R-HSA-437239

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (22)

Functions (4)

Components (4)

Processes (14)

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GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
ribosomal protein S6 kinase activity	Non-traceable Author Statement (NAS)	UniProtKB
magnesium ion binding	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations ()

No disease associations found

GWAS Traits (38)

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5

1 – 5 of 38

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
urate measurement	EFO_0004531	1	4	4		94.4
waist-hip ratio	EFO_0004343	2	5	5		93.9
BMI-adjusted waist-hip ratio	EFO_0007788	5	5	8		93.8
high density lipoprotein cholesterol measurement	EFO_0004612	3	1	3		79.5
triglyceride measurement	EFO_0004530	1	1	1		78.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
urate measurement	EFO_0004531	4		94.4
waist-hip ratio	EFO_0004343	5		93.9
BMI-adjusted waist-hip ratio	EFO_0007788	8		93.8
high density lipoprotein cholesterol measurement	EFO_0004612	3		79.5
triglyceride measurement	EFO_0004530	1		78.5

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
ATP-binding
Complete proteome
Inflammatory response
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
alopecia areata
apolipoprotein A 1 measurement
apolipoprotein B measurement
basal cell carcinoma
biliary liver cirrhosis
birth weight
BMI-adjusted hip circumference
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body height

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ribosomal protein S6 kinase A4	VGNC:8305	451715
Macaque	ribosomal protein S6 kinase A4		717574
Mouse	ribosomal protein S6 kinase, polypeptide 4	MGI:1930076	56613
Rat	ribosomal protein S6 kinase A4	RGD:1307277	361715
Dog	ribosomal protein S6 kinase A4	VGNC:45741	612105

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ribosomal protein S6 kinase A4
Macaque	ribosomal protein S6 kinase A4
Mouse	ribosomal protein S6 kinase, polypeptide 4
Rat	ribosomal protein S6 kinase A4
Dog	ribosomal protein S6 kinase A4

Publication Statistics

PubMed Score 17.39

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PubTator Score 20.94

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Related Publications

Text Mined References (32)

GeneRif Annotations (9)

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PMID	Year	Title