RPS6KA3

Ribosomal protein S6 kinase, 90kDa, polypeptide 3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4D9T​, 4D9U​, 4JG6​, 4JG7​, 4JG8​, 4NUS​, 4NW5​, 4NW6​
Identifiers
Symbols	RPS6KA3 ; CLS; HU-3; ISPK-1; MAPKAPK1B; MRX19; RSK; RSK2; S6K-alpha3; p90-RSK2; pp90RSK2
External IDs	OMIM: 300075 MGI: 104557 HomoloGene: 37940 ChEMBL: 2345 GeneCards: RPS6KA3 Gene
EC number	2.7.11.1
Gene ontology Molecular function • magnesium ion binding • protein kinase activity • protein serine/threonine kinase activity • ribosomal protein S6 kinase activity • protein binding • ATP binding • protein kinase binding • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Cellular component • nucleoplasm • cytoplasm • cytosol Biological process • skeletal system development • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • protein phosphorylation • cell cycle • signal transduction • synaptic transmission • axon guidance • central nervous system development • positive regulation of cell growth • response to lipopolysaccharide • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • intracellular signal transduction • TRIF-dependent toll-like receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • negative regulation of apoptotic process • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • regulation of translation in response to stress • regulation of DNA-templated transcription in response to stress • innate immune response • positive regulation of cell differentiation • positive regulation of transcription from RNA polymerase II promoter • neurotrophin TRK receptor signaling pathway • stress-activated MAPK cascade Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6197	110651
Ensembl	ENSG00000177189	ENSMUSG00000031309
UniProt	P51812	P18654
RefSeq (mRNA)	NM_004586	NM_148945
RefSeq (protein)	NP_004577	NP_683747
Location (UCSC)	Chr X: 20.15 – 20.27 Mb	Chr X: 159.21 – 159.37 Mb
PubMed search

Ribosomal protein S6 kinase, 90kDa, polypeptide 3, also known as RPS6KA3, is an enzyme that in humans is encoded by the RPS6KA3 gene.^[1][2]

Function

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.^[1]

Clinical significance

Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS).^[3]

Interactions

RPS6KA3 has been shown to interact with CREB-binding protein,^[4] MAPK1^[5][6] and PEA15.^[7]

References

1. "Entrez Gene: RPS6KA3 ribosomal protein S6 kinase, 90kDa, polypeptide 3".
2. Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M (February 1994). "Human rsk isoforms: cloning and characterization of tissue-specific expression". Am. J. Physiol. 266 (2 Pt 1): C351–9. PMID 8141249.
3. Jacquot S, Zeniou M, Touraine R, Hanauer A (January 2002). "X-linked Coffin-Lowry syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90(rsk2), RSK2, ISPK, MAPKAP1)". Eur. J. Hum. Genet. 10 (1): 2–5. doi:10.1038/sj.ejhg.5200738. PMID 11896450.
4. Merienne, K; Pannetier S; Harel-Bellan A; Sassone-Corsi P (October 2001). "Mitogen-Regulated RSK2-CBP Interaction Controls Their Kinase and Acetylase Activities". Mol. Cell. Biol. (United States) 21 (20): 7089–96. doi:10.1128/MCB.21.20.7089-7096.2001. ISSN 0270-7306. PMC 99884. PMID 11564891.
5. Zhao, Y; Bjorbaek C; Moller D E (November 1996). "Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases". J. Biol. Chem. (UNITED STATES) 271 (47): 29773–9. doi:10.1074/jbc.271.47.29773. ISSN 0021-9258. PMID 8939914.
6. Smith, J A; Poteet-Smith C E; Malarkey K; Sturgill T W (January 1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". J. Biol. Chem. (UNITED STATES) 274 (5): 2893–8. doi:10.1074/jbc.274.5.2893. ISSN 0021-9258. PMID 9915826.
7. Vaidyanathan, Hema; Ramos Joe W (August 2003). "RSK2 activity is regulated by its interaction with PEA-15". J. Biol. Chem. (United States) 278 (34): 32367–72. doi:10.1074/jbc.M303988200. ISSN 0021-9258. PMID 12796492.

Further reading

• Omary MB, Baxter GT, Chou CF, et al. (1992). "PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and 18". J. Cell Biol. 117 (3): 583–93. doi:10.1083/jcb.117.3.583. PMC 2289443. PMID 1374067.
• Ku NO, Omary MB (1994). "Identification of the major physiologic phosphorylation site of human keratin 18: potential kinases and a role in filament reorganization". J. Cell Biol. 127 (1): 161–71. doi:10.1083/jcb.127.1.161. PMC 2120194. PMID 7523419.
• Adams MD, Kerlavage AR, Fleischmann RD, et al. (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature 377 (6547 Suppl): 3–174. PMID 7566098.
• Zhao Y, Bjørbaek C, Weremowicz S, et al. (1995). "RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation". Mol. Cell. Biol. 15 (8): 4353–63. PMC 230675. PMID 7623830.
• Bjørbaek C, Vik TA, Echwald SM, et al. (1995). "Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients". Diabetes 44 (1): 90–7. doi:10.2337/diabetes.44.1.90. PMID 7813820.
• Donnelly AJ, Choo KH, Kozman HM, et al. (1994). "Regional localisation of a non-specific X-linked mental retardation gene (MRX19) to Xp22". Am. J. Med. Genet. 51 (4): 581–5. doi:10.1002/ajmg.1320510457. PMID 7943043.
• Moller DE, Xia CH, Tang W, et al. (1994). "Human rsk isoforms: cloning and characterization of tissue-specific expression". Am. J. Physiol. 266 (2 Pt 1): C351–9. PMID 8141249.
• Xing J, Ginty DD, Greenberg ME (1996). "Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase". Science 273 (5277): 959–63. doi:10.1126/science.273.5277.959. PMID 8688081.
• Trivier E, De Cesare D, Jacquot S, et al. (1997). "Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome". Nature 384 (6609): 567–70. doi:10.1038/384567a0. PMID 8955270.
• Paudel HK (1997). "Phosphorylation by neuronal cdc2-like protein kinase promotes dimerization of Tau protein in vitro". J. Biol. Chem. 272 (45): 28328–34. doi:10.1074/jbc.272.45.28328. PMID 9353289.
• Joel PB, Smith J, Sturgill TW, et al. (1998). "pp90rsk1 Regulates Estrogen Receptor-Mediated Transcription through Phosphorylation of Ser-167". Mol. Cell. Biol. 18 (4): 1978–84. PMC 121427. PMID 9528769.
• Zheng-Fischhöfer Q, Biernat J, Mandelkow EM, et al. (1998). "Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation". Eur. J. Biochem. 252 (3): 542–52. doi:10.1046/j.1432-1327.1998.2520542.x. PMID 9546672.
• Deak M, Clifton AD, Lucocq LM, Alessi DR (1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB". EMBO J. 17 (15): 4426–41. doi:10.1093/emboj/17.15.4426. PMC 1170775. PMID 9687510.
• Du K, Montminy M (1999). "CREB is a regulatory target for the protein kinase Akt/PKB". J. Biol. Chem. 273 (49): 32377–9. doi:10.1074/jbc.273.49.32377. PMID 9829964.
• Hanger DP, Betts JC, Loviny TL, et al. (1998). "New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry". J. Neurochem. 71 (6): 2465–76. doi:10.1046/j.1471-4159.1998.71062465.x. PMID 9832145.
• Jacquot S, Merienne K, De Cesare D, et al. (1999). "Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations". Am. J. Hum. Genet. 63 (6): 1631–40. doi:10.1086/302153. PMC 1377634. PMID 9837815.
• Jacquot S, Merienne K, Pannetier S, et al. (1999). "Germline mosaicism in Coffin-Lowry syndrome". Eur. J. Hum. Genet. 6 (6): 578–82. doi:10.1038/sj.ejhg.5200230. PMID 9887375.
• Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". J. Biol. Chem. 274 (5): 2893–8. doi:10.1074/jbc.274.5.2893. PMID 9915826.
• Abidi F, Jacquot S, Lassiter C, et al. (1999). "Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS)". Eur. J. Hum. Genet. 7 (1): 20–6. doi:10.1038/sj.ejhg.5200231. PMID 10094187.
• Merienne K, Jacquot S, Pannetier S, et al. (1999). "A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation". Nat. Genet. 22 (1): 13–4. doi:10.1038/8719. PMID 10319851.

External links

• GeneReviews/NCBI/NIH/UW entry on Coffin-Lowry syndrome