RPS6KA3

RPS6KA3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4D9T, 4D9U, 4JG6, 4JG7, 4JG8, 4NUS, 4NW5, 4NW6, 5D9K, 5D9L
Identifiers
Aliases	RPS6KA3 , CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK, RSK2, S6K-alpha3, p90-RSK2, pp90RSK2, ribosomal protein S6 kinase A3, XLID19
External IDs	OMIM: 300075 MGI: 104557 HomoloGene: 37940 GeneCards: RPS6KA3
Gene location (Human) Chr. X chromosome (human) [1] Band Xp22.12 Start 20,149,911 bp [1] End 20,267,519 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X F4|X 73.27 cM Start 157,993,303 bp [2] End 158,151,240 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in biceps brachii triceps brachii muscle islet of Langerhans deltoid muscle gastrocnemius muscle quadriceps femoris muscle Achilles tendon vastus lateralis muscle jejunal mucosa tibialis anterior muscle Top expressed in trigeminal ganglion body of femur left colon white adipose tissue Paneth cell left lung lobe fossa dermis triceps brachii muscle subcutaneous adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding metal ion binding cysteine-type endopeptidase inhibitor activity involved in apoptotic process protein binding ATP binding protein kinase binding magnesium ion binding kinase activity protein serine/threonine kinase activity ribosomal protein S6 kinase activity Cellular component cytoplasm cytosol nucleoplasm nucleus Biological process skeletal system development negative regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of translation in response to stress intracellular signal transduction phosphorylation negative regulation of apoptotic process protein phosphorylation central nervous system development positive regulation of cell growth response to lipopolysaccharide positive regulation of cell differentiation cell cycle regulation of DNA-templated transcription in response to stress signal transduction positive regulation of transcription by RNA polymerase II toll-like receptor signaling pathway apoptotic process peptidyl-serine phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6197 110651 Ensembl ENSG00000177189 ENSMUSG00000031309 UniProt P51812 P18654 RefSeq (mRNA) NM_004586 NM_148945 NM_001346675 RefSeq (protein) NP_004577 NP_001333604 NP_683747 Location (UCSC) Chr X: 20.15 – 20.27 Mb Chr X: 157.99 – 158.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

protein S6 kinase, 90kDa, polypeptide 3, also s RPS6KA3, is an enzyme that in humans is encoded by the RPS6KA3 gene. ^{[5] [6]}

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. ^[5]

Clinical significance

Mutations in this gene have been associated with Coffin–Lowry syndrome (CLS). ^[7]

Interactions

RPS6KA3 has been shown to interact with CREB-binding protein, ^[8] MAPK1 ^{[9] [10]} and PEA15. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000177189 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031309 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: RPS6KA3 ribosomal protein S6 kinase, 90kDa, polypeptide 3".
6. Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M (February 1994). "Human rsk isoforms: cloning and characterization of tissue-specific expression". The American Journal of Physiology. 266 (2 Pt 1): C351–9. doi:10.1152/ajpcell.1994.266.2.C351. PMID   8141249.
7. 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)". European Journal of Human Genetics. 10 (1): 2–5. doi: 10.1038/sj.ejhg.5200738 . PMID   11896450.
8. Merienne K, Pannetier S, Harel-Bellan A, Sassone-Corsi P (October 2001). "Mitogen-regulated RSK2-CBP interaction controls their kinase and acetylase activities". Molecular and Cellular Biology. 21 (20): 7089–96. doi:10.1128/MCB.21.20.7089-7096.2001. PMC   99884 . PMID   11564891.
9. Zhao Y, Bjorbaek C, Moller DE (November 1996). "Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases". The Journal of Biological Chemistry. 271 (47): 29773–9. doi: 10.1074/jbc.271.47.29773 . PMID   8939914.
10. Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (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". The Journal of Biological Chemistry. 274 (5): 2893–8. doi: 10.1074/jbc.274.5.2893 . PMID   9915826.
11. Vaidyanathan H, Ramos JW (August 2003). "RSK2 activity is regulated by its interaction with PEA-15". The Journal of Biological Chemistry. 278 (34): 32367–72. doi: 10.1074/jbc.M303988200 . PMID   12796492.

Further reading

• Omary MB, Baxter GT, Chou CF, Riopel CL, Lin WY, Strulovici B (May 1992). "PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and 18". The Journal of Cell Biology. 117 (3): 583–93. doi:10.1083/jcb.117.3.583. PMC   2289443 . PMID   1374067.
• Ku NO, Omary MB (October 1994). "Identification of the major physiologic phosphorylation site of human keratin 18: potential kinases and a role in filament reorganization". The Journal of Cell Biology. 127 (1): 161–71. doi:10.1083/jcb.127.1.161. PMC   2120194 . PMID   7523419.
• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 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, Morton CC, Moller DE (August 1995). "RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation". Molecular and Cellular Biology. 15 (8): 4353–63. doi:10.1128/MCB.15.8.4353. PMC   230675 . PMID   7623830.
• Bjørbaek C, Vik TA, Echwald SM, Yang PY, Vestergaard H, Wang JP, Webb GC, Richmond K, Hansen T, Erikson RL (January 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, Gedeon AK, Danks DM, Mulley JC (July 1994). "Regional localisation of a non-specific X-linked mental retardation gene (MRX19) to Xp22". American Journal of Medical Genetics. 51 (4): 581–5. doi:10.1002/ajmg.1320510457. PMID   7943043.
• Moller DE, Xia CH, Tang W, Zhu AX, Jakubowski M (February 1994). "Human rsk isoforms: cloning and characterization of tissue-specific expression". The American Journal of Physiology. 266 (2 Pt 1): C351–9. doi:10.1152/ajpcell.1994.266.2.C351. PMID   8141249.
• Xing J, Ginty DD, Greenberg ME (August 1996). "Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase". Science. 273 (5277): 959–63. Bibcode:1996Sci...273..959X. doi:10.1126/science.273.5277.959. PMID   8688081. S2CID   22226803.
• Trivier E, De Cesare D, Jacquot S, Pannetier S, Zackai E, Young I, Mandel JL, Sassone-Corsi P, Hanauer A (December 1996). "Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome". Nature. 384 (6609): 567–70. Bibcode:1996Natur.384..567T. doi:10.1038/384567a0. PMID   8955270. S2CID   4242547.
• Paudel HK (November 1997). "Phosphorylation by neuronal cdc2-like protein kinase promotes dimerization of Tau protein in vitro". The Journal of Biological Chemistry. 272 (45): 28328–34. doi: 10.1074/jbc.272.45.28328 . PMID   9353289.
• Joel PB, Smith J, Sturgill TW, Fisher TL, Blenis J, Lannigan DA (April 1998). "pp90rsk1 regulates estrogen receptor-mediated transcription through phosphorylation of Ser-167". Molecular and Cellular Biology. 18 (4): 1978–84. doi:10.1128/mcb.18.4.1978. PMC   121427 . PMID   9528769.
• Zheng-Fischhöfer Q, Biernat J, Mandelkow EM, Illenberger S, Godemann R, Mandelkow E (March 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". European Journal of Biochemistry. 252 (3): 542–52. doi: 10.1046/j.1432-1327.1998.2520542.x . PMID   9546672.
• Deak M, Clifton AD, Lucocq LM, Alessi DR (August 1998). "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB". The EMBO Journal. 17 (15): 4426–41. doi:10.1093/emboj/17.15.4426. PMC   1170775 . PMID   9687510.
• Du K, Montminy M (December 1998). "CREB is a regulatory target for the protein kinase Akt/PKB". The Journal of Biological Chemistry. 273 (49): 32377–9. doi: 10.1074/jbc.273.49.32377 . PMID   9829964.
• Hanger DP, Betts JC, Loviny TL, Blackstock WP, Anderton BH (December 1998). "New phosphorylation sites identified in hyperphosphorylated tau (paired helical filament-tau) from Alzheimer's disease brain using nanoelectrospray mass spectrometry". Journal of Neurochemistry. 71 (6): 2465–76. doi: 10.1046/j.1471-4159.1998.71062465.x . PMID   9832145.
• Jacquot S, Merienne K, De Cesare D, Pannetier S, Mandel JL, Sassone-Corsi P, Hanauer A (December 1998). "Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations". American Journal of Human Genetics. 63 (6): 1631–40. doi:10.1086/302153. PMC   1377634 . PMID   9837815.
• Jacquot S, Merienne K, Pannetier S, Blumenfeld S, Schinzel A, Hanauer A (1999). "Germline mosaicism in Coffin-Lowry syndrome". European Journal of Human Genetics. 6 (6): 578–82. doi: 10.1038/sj.ejhg.5200230 . PMID   9887375.
• Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (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". The Journal of Biological Chemistry. 274 (5): 2893–8. doi: 10.1074/jbc.274.5.2893 . PMID   9915826.
• Abidi F, Jacquot S, Lassiter C, Trivier E, Hanauer A, Schwartz CE (January 1999). "Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS)". European Journal of Human Genetics. 7 (1): 20–6. doi: 10.1038/sj.ejhg.5200231 . PMID   10094187.
• Merienne K, Jacquot S, Pannetier S, Zeniou M, Bankier A, Gecz J, Mandel JL, Mulley J, Sassone-Corsi P, Hanauer A (May 1999). "A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation". Nature Genetics. 22 (1): 13–4. doi:10.1038/8719. PMID   10319851. S2CID   30949315.

External links

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