RPS6KA2 ribosomal protein S6 kinase A2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RPS6KA2provided by HGNC
Official Full Name: ribosomal protein S6 kinase A2provided by HGNC
Primary source: HGNC:HGNC:10431
See related: Ensembl:ENSG00000071242 MIM:601685; AllianceGenome:HGNC:10431
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: RSK; HU-2; RSK3; p90RSK2; p90-RSK3; pp90RSK3; MAPKAPK1C; S6K-alpha; S6K-alpha2
Summary: This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains two 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. Alternative splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2016]
Expression: Ubiquitous expression in thyroid (RPKM 23.1), lung (RPKM 22.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q27

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (166409364..166862773, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (167786324..168245548, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (166822852..167276013, complement)

Chromosome 6 - NC_000006.12 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3beta dependent manner.
Title: TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner.
RSK3 switches cell fate: from stress-induced senescence to malignant progression.
Title: RSK3 switches cell fate: from stress-induced senescence to malignant progression.
mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer.
Title: mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer.
Multiomics analysis identifies key genes and pathways related to N6-methyladenosine RNA modification in ovarian cancer.
Title: Multiomics analysis identifies key genes and pathways related to N6-methyladenosine RNA modification in ovarian cancer.
Genome-wide association study of cafe-au-lait macule number in neurofibromatosis type 1.
Title: Genome-wide association study of café-au-lait macule number in neurofibromatosis type 1.
Elevated ribosomal protein S6 kinase A2 (RSK3) expression is responsible for BET bromodomain inhibitors (BETi) resistance. Proto-Oncogene Proteins c-jun (JunD)-dependent RSK3 transcription mediates BETi resistance. JunD/RSK3 signalling correlates to BET inhibition sensitivity. Loss of BRD4/FOXD3/miR-548d-3p axis enhances JunD/RSK3 signalling and determines BET inhibition resistance.
Title: Enhanced JunD/RSK3 signalling due to loss of BRD4/FOXD3/miR-548d-3p axis determines BET inhibition resistance.
Data suggest that millisecond dynamic changes in PDZ1 domain conformation are responsible for higher affinity of scribble PDZ1 for phosphorylated ligands; oligopeptide fragments of RPS6KA2 and MCC were used as ligands in these nuclear magnetic resonance chemical shift experiments. (RPS6KA2 = ribosomal protein S6 kinase 2; MCC = mutated in colorectal cancer protein)
Title: The Sign of Nuclear Magnetic Resonance Chemical Shift Difference as a Determinant of the Origin of Binding Selectivity: Elucidation of the Position Dependence of Phosphorylation in Ligands Binding to Scribble PDZ1.
RSK1 and 3 but not RSK2 are down-regulated in breast tumour and are associated with disease progression. RSK may be a key component in the progression and metastasis of breast cancer.
Title: The Clinical Implications of RSK1-3 in Human Breast Cancer.
Data indicate that S6 kinase 2 (S6K2) can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation.
Title: S6 kinase 2 is bound to chromatin-nuclear matrix cellular fractions and is able to phosphorylate histone H3 at threonine 45 in vitro and in vivo.
Kinome screening revealed RPS6KA2 expression, in human pancreatic cancer cells, protects against erlotinib induced apoptosis.
Title: Synthetic lethality screen identifies RPS6KA2 as modifier of epidermal growth factor receptor activity in pancreatic cancer.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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

EBI GWAS Catalog

Description
Gene-Smoking Interactions Identify Several Novel Blood Pressure Loci in the Framingham Heart Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan of dental caries in the permanent dentition. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. 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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Markers

RPS6KA2__5527 (e-PCR)
- UniSTS:463876

RH65049 (e-PCR)
- UniSTS:86795

WI-17352 (e-PCR)
- UniSTS:65038

AL022447 (e-PCR)
- UniSTS:66839

SHGC-107446 (e-PCR)
- UniSTS:170355

RH121975 (e-PCR)
- UniSTS:94854

A002B12 (e-PCR)
- UniSTS:8332

D6S1169E (e-PCR)
- UniSTS:44185

D6S1585 (e-PCR), detects polymorphism
- UniSTS:41372

SHGC-57104 (e-PCR)
- UniSTS:63905

D6S297 (e-PCR), detects polymorphism
- UniSTS:22946

AL023486 (e-PCR)
- UniSTS:54709

STS-W96228 (e-PCR)
- UniSTS:36280

RH121484 (e-PCR)
- UniSTS:134612

AL023487 (e-PCR)
- UniSTS:26589

RH123785 (e-PCR)
- UniSTS:136162

RH45609 (e-PCR)
- UniSTS:70391

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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
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	TAS Traceable Author Statement more info
enables protein serine/threonine/tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

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
located_in cytosol	TAS Traceable Author Statement 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 nucleoplasm	TAS Traceable Author Statement 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-2

Names: MAP kinase-activated protein kinase 1c; MAPK-activated protein kinase 1c; mitogen-activated protein kinase-activated protein kinase 1C; ribosomal S6 kinase 3; ribosomal protein S6 kinase, 90kDa, polypeptide 2

NP_001006933.3

EC 2.7.11.1

NP_001305865.2

EC 2.7.11.1

NP_001305866.1

EC 2.7.11.1

NP_001305867.1

EC 2.7.11.1

NP_066958.2

EC 2.7.11.1

XP_006715612.1

EC 2.7.11.1

XP_047275189.1

EC 2.7.11.1

XP_047275190.1

EC 2.7.11.1

XP_047275191.1

EC 2.7.11.1

XP_054212163.1

EC 2.7.11.1

XP_054212164.1

EC 2.7.11.1

XP_054212165.1

EC 2.7.11.1

XP_054212166.1

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_001006932.3 → NP_001006933.3 ribosomal protein S6 kinase alpha-2 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region compared to variant 1, and initiates translation at an alternate start codon. The encoded isoform (b) has a distinct N-terminus and is longer than isoform a.

Source sequence(s)

AL022069, AL159163, Z98049

Consensus CDS

CCDS34570.1

UniProtKB/TrEMBL

A0AAQ5BI00

Related

ENSP00000427015.1, ENST00000503859.5

Conserved Domains (2) summary

cd05582
Location:71 → 387

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

cd14178
Location:419 → 711

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)
NM_001318936.2 → NP_001305865.2 ribosomal protein S6 kinase alpha-2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region compared to variant 1, and initiates translation at an alternate start codon. The encoded isoform (c) has a distinct N-terminus and is longer than isoform a.

Source sequence(s)

AL022069, AL023775, AL159163, Z98049

Consensus CDS

CCDS83148.1

UniProtKB/TrEMBL

A0AAQ5BI00, F2Z2J1

Related

ENSP00000422435.1, ENST00000510118.5

Conserved Domains (2) summary

cd05582
Location:88 → 404

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

cd14178
Location:436 → 728

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)
NM_001318937.2 → NP_001305866.1 ribosomal protein S6 kinase alpha-2 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region compared to variant 1, and initiates translation at an alternate start codon. The encoded isoform (d) has a distinct N-terminus and is shorter than isoform a.

Source sequence(s)

AB209116, AL022069, BQ029058, DA320139, KJ535080

UniProtKB/TrEMBL

A0AAQ5BI00

Conserved Domains (2) summary

cd14178
Location:313 → 605

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)

cl21453
Location:3 → 281

PKc_like; Protein Kinases, catalytic domain
NM_001318938.1 → NP_001305867.1 ribosomal protein S6 kinase alpha-2 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and lacks a portion of the 5' coding region compared to variant 1, and initiates translation at a downstream start codon. The encoded isoform (e) has a shorter N-terminus than isoform a.

Source sequence(s)

AB209116, AK295674, AL022069, BQ029058, DC402728, Z98049

Consensus CDS

CCDS83147.1

UniProtKB/TrEMBL

A0AAQ5BI00, B7Z3B5

Related

ENSP00000422484.1, ENST00000481261.6

Conserved Domains (4) summary

smart00220
Location:1 → 229

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:1 → 290

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

cd14178
Location:322 → 614

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)

pfam00069
Location:326 → 583

Pkinase; Protein kinase domain
NM_021135.6 → NP_066958.2 ribosomal protein S6 kinase alpha-2 isoform a

See identical proteins and their annotated locations for NP_066958.2

Status: REVIEWED

Description

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

Source sequence(s)

AB209116, AL022069, BC002363, BQ029058, HY150133

Consensus CDS

CCDS5294.1

UniProtKB/Swiss-Prot

B3KTK9, Q15349, Q15419, Q59GJ3, Q5TI68, Q96J38, Q9UJN5

UniProtKB/TrEMBL

A0AAQ5BI00

Related

ENSP00000265678.4, ENST00000265678.9

Conserved Domains (4) summary

smart00220
Location:59 → 318

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:63 → 379

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

cd14178
Location:411 → 703

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)

pfam00069
Location:415 → 672

Pkinase; Protein kinase 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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

166409364..166862773 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419235.1 → XP_047275191.1 ribosomal protein S6 kinase alpha-2 isoform X4

UniProtKB/TrEMBL

A0AAQ5BI00, B7Z3B5
XM_047419233.1 → XP_047275189.1 ribosomal protein S6 kinase alpha-2 isoform X2

UniProtKB/TrEMBL

A0AAQ5BI00
XM_047419234.1 → XP_047275190.1 ribosomal protein S6 kinase alpha-2 isoform X3

UniProtKB/TrEMBL

A0AAQ5BI00

Related

ENSP00000519662.1, ENST00000714395.1
XM_006715549.4 → XP_006715612.1 ribosomal protein S6 kinase alpha-2 isoform X1

UniProtKB/TrEMBL

A0AAQ5BI00

Conserved Domains (4) summary

smart00220
Location:87 → 346

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd05582
Location:91 → 407

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

cd14178
Location:439 → 731

STKc_RSK3_C; C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2)

pfam00069
Location:443 → 700

Pkinase; Protein kinase domain

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

167786324..168245548 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054356191.1 → XP_054212166.1 ribosomal protein S6 kinase alpha-2 isoform X4

UniProtKB/TrEMBL

A0AAQ5BI00, B7Z3B5
XM_054356189.1 → XP_054212164.1 ribosomal protein S6 kinase alpha-2 isoform X2

UniProtKB/TrEMBL

A0AAQ5BI00
XM_054356190.1 → XP_054212165.1 ribosomal protein S6 kinase alpha-2 isoform X3

UniProtKB/TrEMBL

A0AAQ5BI00
XM_054356188.1 → XP_054212163.1 ribosomal protein S6 kinase alpha-2 isoform X1

UniProtKB/TrEMBL

A0AAQ5BI00