RPS6KA3 ribosomal protein S6 kinase A3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RPS6KA3provided by HGNC
Official Full Name: ribosomal protein S6 kinase A3provided by HGNC
Primary source: HGNC:HGNC:10432
See related: Ensembl:ENSG00000177189 MIM:300075; AllianceGenome:HGNC:10432
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: CLS; RSK; HU-3; RSK2; MRX19; ISPK-1; XLID19; p90-RSK2; pp90RSK2; MAPKAPK1B; S6K-alpha3
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 members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS). [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in appendix (RPKM 16.2), colon (RPKM 16.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp22.12

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (20149911..20267097, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (19732804..19849803, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (20168029..20285027, complement)

Chromosome X - NC_000023.11 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?

Coffin-Lowry Syndrome Induced by RPS6KA3 Gene Variation in China: A Case Report in Twins.
Title: Coffin-Lowry Syndrome Induced by <i>RPS6KA3</i> Gene Variation in China: A Case Report in Twins.
RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma.
Title: RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma.
A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.
Title: A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.
Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia.
Title: Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia.
The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
Title: The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
VGLL1 phosphorylation and activation promotes gastric cancer malignancy via TGF-beta/ERK/RSK2 signaling.
Title: VGLL1 phosphorylation and activation promotes gastric cancer malignancy via TGF-β/ERK/RSK2 signaling.
RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKalpha2-mediated autophagy.
Title: RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy.
Proteomic Analysis Reveals a Role for RSK in p120-catenin Phosphorylation and Melanoma Cell-Cell Adhesion.
Title: Proteomic Analysis Reveals a Role for RSK in p120-catenin Phosphorylation and Melanoma Cell-Cell Adhesion.
The c.966_967delAA (p.Arg323Thr fs*11) deletional mutation of the RPS6KA3 gene probably underlies Coffin-Lowry syndrome in this Chinese pedigree.
Title: [Analysis of RPS6KA3 gene mutation in a Chinese pedigree affected with Coffin-Lowry syndrome].
In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar.
Title: RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.

Submit: New GeneRIF Correction See all GeneRIFs (88)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Coffin-Lowry syndrome MedGen: C0265252 OMIM: 303600 GeneReviews: Coffin-Lowry Syndrome	Compare labs
Intellectual disability, X-linked 19 MedGen: C0796225 OMIM: 300844 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2022-06-14) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2022-06-14) ClinGen Genome Curation PagePubMed

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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Replication interactions

Interaction	Pubs
Knockdown of ribosomal protein S6 kinase, polypeptide 3 (RPS6KA3) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	RSK2 is selectively involved in LTR stimulation by the HIV-1 Tat protein, but constitutively active RSK2 is unable to stimulate the LTR	PubMed
	tat	Interaction of HIV-1 Tat with p90 ribosomal S6 kinase 2 (RSK2) is observed in vivo and in vitro. The critical interacting residues lie within amino acids 36-39 in Tat and 1-360 in RSK2. RSK2 supports HIV-1 Tat transactivation via binding to F38	PubMed
	tat	Activation of the N-terminal RSK2 kinase activity is enhanced by HIV-1 Tat in a dose-dependent manner.	PubMed
	tat	Phosphorylation of serine 227 in RSK2 is increased by Tat; mutation at position F38 abolishes the Tat-mediated phosphorylation of RSK2.	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RPS6KA3 (e-PCR)
- UniSTS:279040

RPS6KA3 (e-PCR)
- UniSTS:498177

1037J10_T7 (e-PCR)
- UniSTS:259337

D10S275 (e-PCR)
- UniSTS:147992

WI-20350 (e-PCR)
- UniSTS:11559

A010B08 (e-PCR)
- UniSTS:20785

D8S2279 (e-PCR)
- UniSTS:473907

D2S2582 (e-PCR)
- UniSTS:80700

RH36312 (e-PCR)
- UniSTS:17736

G33067 (e-PCR)
- UniSTS:117643

RH69875 (e-PCR)
- UniSTS:28065

DXS6969E (e-PCR)
- UniSTS:57521

DXS1516 (e-PCR)
- UniSTS:99295

Homology

Homologs of the RPS6KA3 gene: The RPS6KA3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 316 organisms have orthologs with human gene RPS6KA3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process	IDA Inferred from Direct Assay 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 kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
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	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables ribosomal protein S6 kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in central nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in peptidyl-serine phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cell growth	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 regulation of DNA-templated transcription in response to stress	TAS Traceable Author Statement more info	PubMed
involved_in regulation of translation in response to stress	TAS Traceable Author Statement more info	PubMed
involved_in response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in skeletal system development	TAS Traceable Author Statement more info	PubMed
involved_in toll-like receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info

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

General protein information

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Preferred Names: ribosomal protein S6 kinase alpha-3

Names: MAP kinase-activated protein kinase 1b; MAPK-activated protein kinase 1b; MAPKAP kinase 1b; MAPKAPK-1b; RSK-2; S6K-alpha-3; epididymis secretory sperm binding protein; insulin-stimulated protein kinase 1; p90-RSK 3; ribosomal S6 kinase 2; ribosomal protein S6 kinase, 90kDa, polypeptide 3

NP_004577.1

EC 2.7.11.1

XP_005274630.1

EC 2.7.11.1

XP_005274634.1

EC 2.7.11.1

XP_011543857.1

EC 2.7.11.1

XP_011543858.1

EC 2.7.11.1

XP_011543859.1

EC 2.7.11.1

XP_011543862.1

EC 2.7.11.1

XP_011543863.1

EC 2.7.11.1

XP_011543864.1

EC 2.7.11.1

XP_016885206.1

EC 2.7.11.1

XP_016885207.1

EC 2.7.11.1

XP_016885208.1

EC 2.7.11.1

XP_047298288.1

EC 2.7.11.1

XP_047298289.1

EC 2.7.11.1

XP_047298290.1

EC 2.7.11.1

XP_047298291.1

EC 2.7.11.1

XP_047298292.1

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.

Genomic

NG_007488.1 RefSeqGene

Range

4724..121722

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004586.3 → NP_004577.1 ribosomal protein S6 kinase alpha-3

See identical proteins and their annotated locations for NP_004577.1

Status: REVIEWED

Source sequence(s)

AA317826, AA858312, AB102662, AK022869, AL732366, AL807772, AV684171, BC015451, BQ427696, BU618685, CA843287, CA843526, CK905714, U08316, W00439

Consensus CDS

CCDS14197.1

UniProtKB/Swiss-Prot

P51812, Q7Z3Z7

UniProtKB/TrEMBL

A0A384MDW3

Related

ENSP00000368884.3, ENST00000379565.9

Conserved Domains (2) summary

cd05582
Location:72 → 388

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:402 → 740

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

20149911..20267097 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011545561.3 → XP_011543863.1 ribosomal protein S6 kinase alpha-3 isoform X6

See identical proteins and their annotated locations for XP_011543863.1

Conserved Domains (4) summary

smart00220
Location:40 → 305

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:44 → 366

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:380 → 718

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:400 → 657

Pkinase; Protein kinase domain
XM_017029719.3 → XP_016885208.1 ribosomal protein S6 kinase alpha-3 isoform X11

UniProtKB/TrEMBL

B4DG22

Related

ENSP00000495974.1, ENST00000644893.1

Conserved Domains (2) summary

cd05582
Location:44 → 360

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:374 → 711

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_047442335.1 → XP_047298291.1 ribosomal protein S6 kinase alpha-3 isoform X9

Conserved Domains (2) summary

cd05582
Location:44 → 360

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:374 → 703

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_017029717.3 → XP_016885206.1 ribosomal protein S6 kinase alpha-3 isoform X8

UniProtKB/TrEMBL

B7ZB17

Related

ENSP00000495462.1, ENST00000646610.1

Conserved Domains (2) summary

cd05582
Location:44 → 360

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:374 → 712

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_047442333.1 → XP_047298289.1 ribosomal protein S6 kinase alpha-3 isoform X5
XM_005274573.3 → XP_005274630.1 ribosomal protein S6 kinase alpha-3 isoform X4

See identical proteins and their annotated locations for XP_005274630.1

Conserved Domains (2) summary

cd05582
Location:72 → 388

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:402 → 739

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_047442332.1 → XP_047298288.1 ribosomal protein S6 kinase alpha-3 isoform X3
XM_011545556.2 → XP_011543858.1 ribosomal protein S6 kinase alpha-3 isoform X2

Conserved Domains (4) summary

smart00220
Location:68 → 333

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:72 → 394

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:408 → 745

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:427 → 684

Pkinase; Protein kinase domain
XM_011545555.2 → XP_011543857.1 ribosomal protein S6 kinase alpha-3 isoform X1

Conserved Domains (4) summary

smart00220
Location:68 → 333

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:72 → 394

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:408 → 737

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:428 → 685

Pkinase; Protein kinase domain
XM_047442336.1 → XP_047298292.1 ribosomal protein S6 kinase alpha-3 isoform X11

UniProtKB/TrEMBL

B4DG22
XM_047442334.1 → XP_047298290.1 ribosomal protein S6 kinase alpha-3 isoform X8

UniProtKB/TrEMBL

B7ZB17

Related

ENSP00000496271.1, ENST00000643085.1
XM_011545560.2 → XP_011543862.1 ribosomal protein S6 kinase alpha-3 isoform X6

See identical proteins and their annotated locations for XP_011543862.1

Conserved Domains (4) summary

smart00220
Location:40 → 305

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:44 → 366

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:380 → 718

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:400 → 657

Pkinase; Protein kinase domain
XM_011545557.3 → XP_011543859.1 ribosomal protein S6 kinase alpha-3 isoform X6

See identical proteins and their annotated locations for XP_011543859.1

Conserved Domains (4) summary

smart00220
Location:40 → 305

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:44 → 366

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:380 → 718

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:400 → 657

Pkinase; Protein kinase domain
XM_005274577.4 → XP_005274634.1 ribosomal protein S6 kinase alpha-3 isoform X12

See identical proteins and their annotated locations for XP_005274634.1

Conserved Domains (2) summary

cd05582
Location:43 → 359

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:373 → 710

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_017029718.3 → XP_016885207.1 ribosomal protein S6 kinase alpha-3 isoform X10

UniProtKB/TrEMBL

B1AXG1

Related

ENSP00000407655.2, ENST00000457145.6

Conserved Domains (2) summary

cd05582
Location:43 → 359

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:373 → 711

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)
XM_011545562.3 → XP_011543864.1 ribosomal protein S6 kinase alpha-3 isoform X7

Conserved Domains (4) summary

smart00220
Location:39 → 304

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:43 → 365

STKc_RSK_N; N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase

cd14176
Location:379 → 717

STKc_RSK2_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3)

pfam00069
Location:399 → 656

Pkinase; Protein kinase domain