Ribosomal protein S6 kinase alpha-4

Details

Name
Ribosomal protein S6 kinase alpha-4
Synonyms
  • 2.7.11.1
  • 90 kDa ribosomal protein S6 kinase 4
  • MSK2
  • Nuclear mitogen- and stress-activated protein kinase 2
  • Ribosomal protein kinase B
  • RSKB
  • S6K-alpha-4
Gene Name
RPS6KA4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009533|Ribosomal protein S6 kinase alpha-4
MGDEDDDESCAVELRITEANLTGHEEKVSVENFELLKVLGTGAYGKVFLVRKAGGHDAGK
LYAMKVLRKAALVQRAKTQEHTRTERSVLELVRQAPFLVTLHYAFQTDAKLHLILDYVSG
GEMFTHLYQRQYFKEAEVRVYGGEIVLALEHLHKLGIIYRDLKLENVLLDSEGHIVLTDF
GLSKEFLTEEKERTFSFCGTIEYMAPEIIRSKTGHGKAVDWWSLGILLFELLTGASPFTL
EGERNTQAEVSRRILKCSPPFPPRIGPVAQDLLQRLLCKDPKKRLGAGPQGAQEVRNHPF
FQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYS
FVAPSILFDHNNAVMTDGLEAPGAGDRPGRAAVARSAMMQDSPFFQQYELDLREPALGQG
SFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTY
LVLELLRGGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYAD
DTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAAPELLAQQGYDESCDLWSLGVILY
MMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPA
KRLKLEGLRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLK
SVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVASKGAPRRANGPLPPS
Number of residues
772
Molecular Weight
85605.025
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / histone kinase activity (H3-S10 specific) / magnesium ion binding / mitogen-activated protein kinase p38 binding / protein serine/threonine kinase activity / ribosomal protein S6 kinase activity
Processes
axon guidance / histone H3-S10 phosphorylation / histone H3-S28 phosphorylation / histone phosphorylation / inflammatory response / interleukin-1-mediated signaling pathway / intracellular signal transduction / negative regulation of cytokine production / positive regulation of CREB transcription factor activity / positive regulation of histone acetylation / positive regulation of histone phosphorylation / positive regulation of NF-kappaB transcription factor activity / positive regulation of transcription from RNA polymerase II promoter / protein phosphorylation / regulation of transcription, DNA-templated
Components
cytoplasm / nucleoplasm / nucleus
General Function
Ribosomal protein s6 kinase activity
Specific Function
Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0013218|Ribosomal protein S6 kinase alpha-4 (RPS6KA4)
ATGGGGGACGAGGACGACGATGAGAGCTGCGCCGTGGAGCTGCGGATCACAGAAGCCAAC
CTGACCGGGCACGAGGAGAAGGTGAGCGTGGAGAACTTCGAGCTGCTCAAGGTGCTGGGC
ACGGGAGCCTACGGCAAGGTGTTCCTGGTGCGGAAGGCGGGCGGGCACGACGCGGGGAAG
CTGTACGCCATGAAGGTGCTGCGCAAGGCGGCGCTGGTGCAGCGCGCCAAGACGCAAGAG
CACACGCGCACCGAGCGCTCGGTGCTGGAGCTGGTGCGCCAGGCGCCCTTCCTGGTCACG
CTGCACTACGCTTTCCAGACGGATGCCAAGCTGCACCTCATCCTGGACTATGTGAGCGGC
GGGGAGATGTTCACCCACCTCTACCAGCGCCAGTACTTCAAGGAGGCTGAGGTGCGCGTG
TATGGGGGTGAGATCGTGCTGGCCCTGGAACACCTGCACAAGCTCGGCATCATTTACCGA
GACCTGAAACTGGAGAATGTGCTGCTGGACTCCGAGGGCCACATTGTCCTCACGGACTTC
GGGCTGAGCAAGGAGTTCCTGACGGAGGAGAAAGAGCGGACCTTCTCCTTCTGTGGCACC
ATCGAGTACATGGCCCCCGAAATCATCCGTAGCAAGACGGGGCATGGCAAGGCTGTGGAC
TGGTGGAGCCTGGGCATCTTGCTCTTCGAGCTGCTGACGGGGGCCTCGCCCTTCACCCTG
GAGGGCGAGAGGAACACGCAGGCTGAGGTGTCTCGACGGATCCTGAAGTGCTCCCCTCCC
TTCCCCCCTCGGATCGGGCCCGTGGCGCAGGACCTGCTGCAGCGGCTGCTTTGTAAGGAT
CCTAAGAAGCGATTGGGCGCGGGGCCCCAGGGGGCACAAGAAGTCCGGAACCATCCCTTC
TTCCAGGGCCTCGATTGGGTGGCTCTGGCTGCCAGGAAGATTCCAGCCCCATTCCGGCCC
CAAATCCGCTCAGAGCTGGATGTGGGCAACTTTGCGGAGGAATTCACTCGGCTGGAGCCT
GTCTACTCACCCCCTGGCAGCCCCCCACCTGGGGACCCCCGAATCTTTCAGGGATACTCC
TTTGTGGCACCCTCCATTCTCTTTGACCACAACAACGCGGTGATGACCGATGGGCTGGAA
GCGCCTGGTGCTGGAGACCGGCCAGGTCGGGCAGCGGTGGCCAGGAGCGCTATGATGCAG
CAGTACGAGCTGGACCTGCGGGAGCCTGCGCTGGGCCAGGGCAGCTTTTCTGTGTGTCGC
CGCTGCCGCCAGCGCCAGAGCGGCCAGGAGTTCGCAGTCAAGATCCTCAGTCGCAGGCTG
GAGGCGAACACGCAGCGCGAAGTGGCTGCCCTGCGCCTGTGCCAGTCACACCCCAACGTG
GTGAATCTGCACGAGGTGCATCACGACCAGCTGCACACGTACCTGGTCCTGGAGCTGCTG
CGGGGCGGGGAGCTGCTGGAGCACATCCGCAAGAAGCGGCACTTCAGCGAGTCGGAAGCA
AGCCAGATCCTGCGCAGCCTCGTGTCGGCCGTGAGCTTCATGCACGAGGAGGCGGGCGTG
GTGCACCGCGACCTCAAGCCGGAGAACATCCTGTACGCCGACGACACGCCCGGGGCCCCG
GTGAAAATCATCGACTTCGGGTTCGCGCGGTTGCGGCCGCAGAGTCCCGGGGTGCCCATG
CAGACGCCCTGCTTCACGCTGCAGTACGCTGCCCCCGAGCTGCTGGCGCAGCAGGGCTAC
GACGAGTCCTGCGACCTCTGGAGCCTGGGCGTCATTCTGTACATGATGCTGTCGGGGCAG
GTCCCCTTCCAGGGGGCCTCTGGCCAGGGCGGGCAGAGCCAGGCGGCCGAGATCATGTGC
AAAATCCGCGAGGGGCGCTTCTCCCTTGACGGGGAGGCCTGGCAGGGTGTATCCGAGGAA
GCCAAGGAGCTGGTCCGAGGGCTCCTGACCGTGGACCCCGCCAAGCGGCTGAAGCTCGAG
GGACTGCGGGGCAGCTCGTGGCTGCAGGACGGCAGCGCGCGCTCCTCGCCCCCGCTCCGG
ACGCCCGACGTGCTCGAGTCCTCTGGGCCCGCAGTGCGCTCGGGTCTCAACGCCACCTTC
ATGGCATTCAACCGGGGCAAGCGGGAGGGCTTCTTCCTGAAGAGCGTGGAGAATGCACCC
CTGGCCAAGCGGCGGAAGCAGAAGCTGCGGAGCGCCACCGCCTCCCGCCGGGGCTCCCCT
GCACCAGCCAACCCGGGCCGAGCCCCCGTCGCCTCCAAAGGGGCCCCCCGCCGAGCCAAC
GGCCCCCTGCCCCCCTCCTAA
Chromosome Location
11
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO75676
UniProtKB Entry NameKS6A4_HUMAN
HGNC IDHGNC:10433
General References
  1. Pierrat B, Correia JS, Mary JL, Tomas-Zuber M, Lesslauer W: RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK). J Biol Chem. 1998 Nov 6;273(45):29661-71. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Deak M, Clifton AD, Lucocq LM, Alessi DR: Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998 Aug 3;17(15):4426-41. [Article]
  4. Tomas-Zuber M, Mary JL, Lamour F, Bur D, Lesslauer W: C-terminal elements control location, activation threshold, and p38 docking of ribosomal S6 kinase B (RSKB). J Biol Chem. 2001 Feb 23;276(8):5892-9. Epub 2000 Oct 16. [Article]
  5. Soloaga A, Thomson S, Wiggin GR, Rampersaud N, Dyson MH, Hazzalin CA, Mahadevan LC, Arthur JS: MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J. 2003 Jun 2;22(11):2788-97. [Article]
  6. Arthur JS: MSK activation and physiological roles. Front Biosci. 2008 May 1;13:5866-79. [Article]
  7. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  9. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  10. Vermeulen L, Vanden Berghe W, Beck IM, De Bosscher K, Haegeman G: The versatile role of MSKs in transcriptional regulation. Trends Biochem Sci. 2009 Jun;34(6):311-8. doi: 10.1016/j.tibs.2009.02.007. Epub 2009 May 21. [Article]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  12. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  14. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03247Flavin mononucleotideapproved, investigationalunknownDetails