RPS6KA4 ribosomal protein S6 kinase A4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RPS6KA4provided by HGNC
Official Full Name: ribosomal protein S6 kinase A4provided by HGNC
Primary source: HGNC:HGNC:10433
See related: Ensembl:ENSG00000162302 MIM:603606; AllianceGenome:HGNC:10433
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MSK2; RSK-B; S6K-alpha-4
Summary: 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]
Expression: Ubiquitous expression in spleen (RPKM 12.2), colon (RPKM 9.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (64359162..64372215)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (64349167..64362217)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (64126634..64139687)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mitogen- and stress-activated protein kinase (MSK1/2) regulated gene expression in normal and disease states.
Title: Mitogen- and stress-activated protein kinase (MSK1/2) regulated gene expression in normal and disease states.
Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.
Title: Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.
Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses.
Title: Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses.
Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction.
Title: Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction.
Two novel DMRs, located in RPS6KA4/MIR1237 and the AURKC promoter, were found to be hypermethylated in WT
Title: RPS6KA4/MIR1237 and AURKC promoter regions are differentially methylated in Wilms' tumor.
KSHV activates the MSK1/2-CREB1 pathway during primary infection and that it depends on this pathway for viral lytic replication. I
Title: Screening of the Human Kinome Identifies MSK1/2-CREB1 as an Essential Pathway Mediating Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication during Primary Infection.
Data suggest that MSK1 and MSK2 are the major CREB kinases in fibroblast-like synoviocytes from rheumatoid arthritis patients stimulated with lysophosphatidic acid and that phosphorylation of CREB1 at Ser-133 plays a significant role in IL-8 production.
Title: Lysophosphatidic acid-induced IL-8 secretion involves MSK1 and MSK2 mediated activation of CREB1 in human fibroblast-like synoviocytes.
MSK1 and MSK2 are required for maximal TFF 1 induction.
Title: Mitogen- and stress-activated protein kinases 1 and 2 are required for maximal trefoil factor 1 induction.
MSK2 functions as an adaptor in mediating PKR activation, apparently independent of its catalytic activity.
Title: HCV-induced PKR activation is stimulated by the mitogen- and stress-activated protein kinase MSK2.
MSK1- and MSK2-mediated H3K27me3S28 phosphorylation serves as a mechanism to activate a subset of PcG target genes determined by the biological stimuli and thereby modulate the gene expression program determining cell fate.
Title: Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3S28 kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in interleukin-1-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cytokine production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of CREB transcription factor activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in post-translational protein modification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: ribosomal protein S6 kinase alpha-4

Names: 90 kDa ribosomal protein S6 kinase 4; mitogen- and stress-activated protein kinase 2; nuclear mitogen- and stress-activated protein kinase 2; ribosomal protein S6 kinase, 90kDa, polypeptide 4; ribosomal protein kinase B

NP_001006945.1

EC 2.7.11.1

NP_001287731.1

EC 2.7.11.1

NP_001305290.1

EC 2.7.11.1

NP_003933.1

EC 2.7.11.1

XP_005274437.1

EC 2.7.11.1

XP_047283799.1

EC 2.7.11.1

XP_047283800.1

EC 2.7.11.1

XP_054226401.1

EC 2.7.11.1

XP_054226402.1

EC 2.7.11.1

XP_054226403.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001006944.2 → NP_001006945.1 ribosomal protein S6 kinase alpha-4 isoform b

See identical proteins and their annotated locations for NP_001006945.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform b).

Source sequence(s)

AF074715, AJ010119, BI523588

UniProtKB/TrEMBL

A0A0A6YYC0

Related

ENSP00000432945.1, ENST00000530504.1

Conserved Domains (3) summary

smart00220
Location:33 → 301

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05614
Location:32 → 364

STKc_MSK2_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2

cl21453
Location:400 → 708

PKc_like; Protein Kinases, catalytic domain
NM_001300802.2 → NP_001287731.1 ribosomal protein S6 kinase alpha-4 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform c).

Source sequence(s)

AJ010119, AK223561, AK313567, AP003774

Consensus CDS

CCDS73313.1

UniProtKB/TrEMBL

A0A0A6YYC0, E9PJN1

Related

ENSP00000435580.1, ENST00000528057.5

Conserved Domains (3) summary

smart00220
Location:33 → 301

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05614
Location:32 → 364

STKc_MSK2_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2

cl21453
Location:400 → 707

PKc_like; Protein Kinases, catalytic domain
NM_001318361.2 → NP_001305290.1 ribosomal protein S6 kinase alpha-4 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice junction in the 5' end compared to variant 1. The resulting isoform (d) is shorter at the N-terminus compared to isoform a.

Source sequence(s)

AJ010119, AK298507, AP003774, BI253655

UniProtKB/TrEMBL

B4DPV1

Conserved Domains (2) summary

smart00220
Location:354 → 611

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:1 → 301

PKc_like; Protein Kinases, catalytic domain
NM_003942.3 → NP_003933.1 ribosomal protein S6 kinase alpha-4 isoform a

See identical proteins and their annotated locations for NP_003933.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AJ010119, BC028079, BI523588

Consensus CDS

CCDS8073.1

UniProtKB/Swiss-Prot

A8K7Z8, O75585, O75676, Q53ES8

UniProtKB/TrEMBL

B4DPV1

Related

ENSP00000333896.4, ENST00000334205.9

Conserved Domains (3) summary

smart00220
Location:33 → 301

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05614
Location:32 → 364

STKc_MSK2_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2

cl21453
Location:404 → 714

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

64359162..64372215

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005274380.2 → XP_005274437.1 ribosomal protein S6 kinase alpha-4 isoform X1

UniProtKB/TrEMBL

B4DPV1

Conserved Domains (1) summary

cl21453
Location:32 → 308

PKc_like; Protein Kinases, catalytic domain
XM_047427843.1 → XP_047283799.1 ribosomal protein S6 kinase alpha-4 isoform X2
XM_047427844.1 → XP_047283800.1 ribosomal protein S6 kinase alpha-4 isoform X3