RPS6KA5 ribosomal protein S6 kinase A5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RPS6KA5provided by HGNC
Official Full Name: ribosomal protein S6 kinase A5provided by HGNC
Primary source: HGNC:HGNC:10434
See related: Ensembl:ENSG00000100784 MIM:603607; AllianceGenome:HGNC:10434
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MSK1; RLPK; MSPK1
Summary: Enables ATP binding activity and protein kinase activity. Involved in several processes, including interleukin-1-mediated signaling pathway; protein phosphorylation; and regulation of DNA-templated transcription. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in brain (RPKM 2.4), endometrium (RPKM 2.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q32.11

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (90847861..91060641, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (85073446..85286084, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (91314205..91526985, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study.
Title: Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study.
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.
Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction.
Title: Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction.
14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients.
Title: 14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients.
Overexpression of the MSK1 Kinase in Patients With Chronic Lung Allograft Dysfunction and Its Confirmed Role in a Murine Model.
Title: Overexpression of the MSK1 Kinase in Patients With Chronic Lung Allograft Dysfunction and Its Confirmed Role in a Murine Model.
MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjogren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1.
Title: MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1.
show that expression of nuclear PKCdelta activates ERK and MSK1, that ERK activation is required for MSK1 activation, and that both ERK and MSK1 activation are required for apoptosis
Title: EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases.
These studies suggest that MSK1 acts through a direct interaction with p53 to function as a transcriptional coactivator and that MSK1 activation by upstream MAPK signaling is important for efficient p21 gene expression.
Title: MSK1 functions as a transcriptional coactivator of p53 in the regulation of p21 gene expression.
We show that MSK1 downregulation impairs the differentiation of breast cancer cells, increasing their bone homing and growth capacities. MSK1 controls the expression of genes required for luminal cell differentiation, including the GATA3 and FOXA1 transcription factors, by modulating their promoter chromatin status.
Title: MSK1 regulates luminal cell differentiation and metastatic dormancy in ER(+) breast cancer.
MSK1 was overexpressed in 148 out of 329 colorectal cancer (CRC) patients. CRC patients with high MSK1 expression had shorter overall survival than those with low MSK1, especially among patients with stage III tumors. Overexpression of MSK1 is associated with poor prognosis in CRC and is connected to tumor aggressiveness.
Title: Overexpression of MSK1 is associated with tumor aggressiveness and poor prognosis in colorectal cancer.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat-peptide(48-60) inhibits AGC-family kinases (PKB, SGK1, S6K1, MSK1), CAMK-family kinases (CAMK1 and MELK) and a STE family kinase (MKK1)	PubMed
Vpu	vpu	In vitro protein-protein interaction analysis identifies a Vpu-binding host protein ribosomal protein S6 kinase, 90kDa, polypeptide 5 (RPS6KA5, MSK1)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH101942 (e-PCR)
- UniSTS:96277

RH66186 (e-PCR)
- UniSTS:26697

G35701 (e-PCR)
- UniSTS:10335

G35828 (e-PCR)
- UniSTS:26242

G35963 (e-PCR)
- UniSTS:73350

RH93294 (e-PCR)
- UniSTS:85397

G35600 (e-PCR)
- UniSTS:5531

G63724 (e-PCR)
- UniSTS:140755

SHGC-81746 (e-PCR)
- UniSTS:103913

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 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 histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
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 protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	TAS Traceable Author Statement 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 DNA-templated transcription	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	IMP Inferred from Mutant Phenotype 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	IDA Inferred from Direct Assay 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
involved_in regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynapse organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
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 nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: ribosomal protein S6 kinase alpha-5

Names: 90 kDa ribosomal protein S6 kinase 5; RSK-like protein kinase; RSKL; S6K-alpha-5; nuclear mitogen- and stress-activated protein kinase 1; ribosomal protein S6 kinase, 90kDa, polypeptide 5

NP_001309156.1

EC 2.7.11.1

NP_001309157.1

EC 2.7.11.1

NP_001309158.1

EC 2.7.11.1

NP_001309159.1

EC 2.7.11.1

NP_001309160.1

EC 2.7.11.1

NP_001309161.1

EC 2.7.11.1

NP_001309162.1

EC 2.7.11.1

NP_001309163.1

EC 2.7.11.1

NP_001309164.1

EC 2.7.11.1

NP_001309165.1

EC 2.7.11.1

NP_001309166.1

EC 2.7.11.1

NP_001309167.1

EC 2.7.11.1

NP_004746.2

EC 2.7.11.1

NP_872198.1

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_001322227.2 → NP_001309156.1 ribosomal protein S6 kinase alpha-5 isoform c

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00220
Location:149 → 406

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14179
Location:137 → 446

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:1 → 99

PKc_like; Protein Kinases, catalytic domain
NM_001322228.2 → NP_001309157.1 ribosomal protein S6 kinase alpha-5 isoform d

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00133
Location:284 → 343

S_TK_X; Extension to Ser/Thr-type protein kinases

cd14179
Location:382 → 691

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:48 → 301

PKc_like; Protein Kinases, catalytic domain
NM_001322229.2 → NP_001309158.1 ribosomal protein S6 kinase alpha-5 isoform e

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00133
Location:320 → 379

S_TK_X; Extension to Ser/Thr-type protein kinases

cd05613
Location:48 → 337

STKc_MSK1_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cd14179
Location:418 → 720

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1
NM_001322230.2 → NP_001309159.1 ribosomal protein S6 kinase alpha-5 isoform f

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (2) summary

cd14179
Location:151 → 460

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:2 → 113

PKc_like; Protein Kinases, catalytic domain
NM_001322231.2 → NP_001309160.1 ribosomal protein S6 kinase alpha-5 isoform g

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00220
Location:191 → 448

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14179
Location:179 → 488

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:7 → 141

PKc_like; Protein Kinases, catalytic domain
NM_001322232.2 → NP_001309161.1 ribosomal protein S6 kinase alpha-5 isoform h

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (4) summary

smart00133
Location:247 → 306

S_TK_X; Extension to Ser/Thr-type protein kinases

smart00220
Location:357 → 614

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14179
Location:345 → 654

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:59 → 264

PKc_like; Protein Kinases, catalytic domain
NM_001322233.2 → NP_001309162.1 ribosomal protein S6 kinase alpha-5 isoform i

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (2) summary

cd05583
Location:54 → 320

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

cd14179
Location:364 → 673

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1
NM_001322234.2 → NP_001309163.1 ribosomal protein S6 kinase alpha-5 isoform j

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00220
Location:238 → 495

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14179
Location:226 → 535

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:16 → 188

PKc_like; Protein Kinases, catalytic domain
NM_001322235.2 → NP_001309164.1 ribosomal protein S6 kinase alpha-5 isoform k

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Consensus CDS

CCDS81839.1

UniProtKB/Swiss-Prot

O75582

Conserved Domains (3) summary

smart00133
Location:241 → 300

S_TK_X; Extension to Ser/Thr-type protein kinases

cd14179
Location:339 → 648

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:1 → 258

PKc_like; Protein Kinases, catalytic domain
NM_001322236.2 → NP_001309165.1 ribosomal protein S6 kinase alpha-5 isoform l

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (3) summary

smart00220
Location:402 → 659

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14179
Location:390 → 699

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:48 → 352

PKc_like; Protein Kinases, catalytic domain
NM_001322237.2 → NP_001309166.1 ribosomal protein S6 kinase alpha-5 isoform k

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Consensus CDS

CCDS81839.1

UniProtKB/Swiss-Prot

O75582

Related

ENSP00000442803.2, ENST00000536315.6

Conserved Domains (3) summary

smart00133
Location:241 → 300

S_TK_X; Extension to Ser/Thr-type protein kinases

cd14179
Location:339 → 648

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:1 → 258

PKc_like; Protein Kinases, catalytic domain
NM_001322238.2 → NP_001309167.1 ribosomal protein S6 kinase alpha-5 isoform m

Status: VALIDATED

Source sequence(s)

AL121784, AL133454, AL159191

Conserved Domains (2) summary

cd14179
Location:199 → 508

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:1 → 161

PKc_like; Protein Kinases, catalytic domain
NM_004755.4 → NP_004746.2 ribosomal protein S6 kinase alpha-5 isoform a

See identical proteins and their annotated locations for NP_004746.2

Status: VALIDATED

Description

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

Source sequence(s)

AL121784, AL133454, AL159191

Consensus CDS

CCDS9893.1

UniProtKB/Swiss-Prot

B7Z2Y5, O75582, O95316, Q96AF7

Related

ENSP00000479667.1, ENST00000614987.5

Conserved Domains (3) summary

smart00133
Location:320 → 379

S_TK_X; Extension to Ser/Thr-type protein kinases

cd05613
Location:48 → 337

STKc_MSK1_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cd14179
Location:418 → 727

STKc_MSK1_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1
NM_182398.3 → NP_872198.1 ribosomal protein S6 kinase alpha-5 isoform b

See identical proteins and their annotated locations for NP_872198.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate in-frame segment in the 3' coding region, compared to variant 1. Isoform b has a shorter C-terminus, compared to isoform a.

Source sequence(s)

AL121784, AL133454

Consensus CDS

CCDS45149.1

UniProtKB/Swiss-Prot

O75582

Related

ENSP00000402787.2, ENST00000418736.6

Conserved Domains (3) summary

smart00133
Location:320 → 379

S_TK_X; Extension to Ser/Thr-type protein kinases

cd05613
Location:48 → 337

STKc_MSK1_N; N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1

cl21453
Location:418 → 548

PKc_like; Protein Kinases, catalytic domain