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O75582 (KS6A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribosomal protein S6 kinase alpha-5

Short name=S6K-alpha-5
EC=2.7.11.1
Alternative name(s):
90 kDa ribosomal protein S6 kinase 5
Nuclear mitogen- and stress-activated protein kinase 1
RSK-like protein kinase
Short name=RSKL
Gene names
Name:RPS6KA5
Synonyms:MSK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 factors RELA, STAT3 and ETV1/ER81, 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 and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. 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. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2 Ref.7

Cofactor

Magnesium. Ref.1 Ref.2 Ref.7

Enzyme regulation

Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region. Ref.1 Ref.12

Subunit structure

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300. Ref.7 Ref.10

Subcellular location

Nucleus. Cytoplasm. Note: Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid. Ref.1 Ref.14

Tissue specificity

Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver. Ref.1 Ref.2

Post-translational modification

Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain. Ref.12 Ref.13

Ubiquitinated. Ref.18

Miscellaneous

Enzyme activity requires the presence of both kinase domains. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 2 protein kinase domains.

Sequence caution

The sequence AAC69577.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processInflammatory response
Stress response
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement Ref.2. Source: UniProtKB

histone H2A-S1 phosphorylation

Inferred from direct assay Ref.11. Source: UniProtKB

histone H3-S10 phosphorylation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

histone H3-S28 phosphorylation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

histone phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

interleukin-1-mediated signaling pathway

Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

negative regulation of cytokine production

Traceable author statement Ref.15. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.11. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of CREB transcription factor activity

Traceable author statement Ref.15. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.7Ref.14. Source: UniProtKB

positive regulation of histone acetylation

Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL

positive regulation of histone phosphorylation

Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from direct assay Ref.1. Source: UniProtKB

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.14. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.14Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

protein kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MLTKQ9NYL24EBI-73869,EBI-602273

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O75582-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O75582-2)

The sequence of this isoform differs from the canonical sequence as follows:
     549-549: N → V
     550-802: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 802802Ribosomal protein S6 kinase alpha-5
PRO_0000086207

Regions

Domain49 – 318270Protein kinase 1
Domain319 – 38769AGC-kinase C-terminal
Domain426 – 687262Protein kinase 2
Nucleotide binding55 – 639ATP By similarity UniProtKB Q15418
Nucleotide binding432 – 4409ATP By similarity UniProtKB Q15418

Sites

Active site1771Proton acceptor By similarity UniProtKB Q15418
Active site5441Proton acceptor By similarity UniProtKB Q15418
Binding site811ATP By similarity UniProtKB Q15418
Binding site4551ATP By similarity UniProtKB Q15418

Amino acid modifications

Modified residue2121Phosphoserine; by autocatalysis Ref.12 UniProtKB Q15418
Modified residue3601Phosphoserine; by MAPK1, MAPK3 and MAPK14 Ref.12 UniProtKB Q15418
Modified residue3761Phosphoserine; by autocatalysis Ref.12 Ref.16 Ref.19 UniProtKB Q15418
Modified residue3811Phosphoserine; by autocatalysis Ref.12 Ref.19
Modified residue5811Phosphothreonine; by MAPK1, MAPK3 and MAPK14 Ref.12 UniProtKB Q15418
Modified residue6471Phosphoserine Ref.13
Modified residue6571Phosphoserine Ref.13
Modified residue6951Phosphoserine Ref.13
Modified residue7001Phosphothreonine; by MAPK1, MAPK3 and MAPK14 Ref.13
Modified residue7501Phosphoserine; by autocatalysis Ref.12 UniProtKB Q15418
Modified residue7521Phosphoserine; by autocatalysis Ref.12
Modified residue7581Phosphoserine; by autocatalysis Ref.12

Natural variations

Alternative sequence5491N → V in isoform 2.
VSP_041837
Alternative sequence550 – 802253Missing in isoform 2.
VSP_041838
Natural variant1901H → R.
Corresponds to variant rs34699345 [ dbSNP | Ensembl ].
VAR_051634
Natural variant5541D → N. Ref.23
Corresponds to variant rs55911249 [ dbSNP | Ensembl ].
VAR_040634
Natural variant5741P → L. Ref.23
Corresponds to variant rs34604933 [ dbSNP | Ensembl ].
VAR_040635
Natural variant5991Y → C. Ref.23
Corresponds to variant rs55968863 [ dbSNP | Ensembl ].
VAR_040636

Experimental info

Mutagenesis1951D → A: Loss of kinase activity. Ref.1
Mutagenesis2121S → A: Inactivates the N-terminal kinase domain. Ref.12
Mutagenesis3601S → A: Decreases kinase activity by 60% in response to PMA and UV-C. Ref.12
Mutagenesis3761S → A: Loss of kinase activity, and decreases the phosphorylation of S-360 and T-581. Ref.12
Mutagenesis5651D → A: Loss of kinase activity. Ref.1
Mutagenesis5811T → A: Loss of kinase activity, and blocks phosphorylation of S-212; S-376 and S-381 in response to PMA and UV-C. Ref.12
Mutagenesis7001T → A or D: Strongly reduces phosphorylation of T-581 in response to PMA and UV-C. Ref.13
Sequence conflict452 – 4532FA → LQ in AAC69577. Ref.3
Sequence conflict5321V → L in AAC69577. Ref.3
Sequence conflict5381V → L in AAC69577. Ref.3
Sequence conflict757 – 7582SS → RG in AAC69577. Ref.3

Secondary structure

............................................................................................ 802
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 76C27D0F6639BFA4

FASTA80289,865
        10         20         30         40         50         60 
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE LLKVLGTGAY 

        70         80         90        100        110        120 
GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT ERQVLEHIRQ SPFLVTLHYA 

       130        140        150        160        170        180 
FQTETKLHLI LDYINGGELF THLSQRERFT EHEVQIYVGE IVLALEHLHK LGIIYRDIKL 

       190        200        210        220        230        240 
ENILLDSNGH VVLTDFGLSK EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS 

       250        260        270        280        290        300 
LGVLMYELLT GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK 

       310        320        330        340        350        360 
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE EFTEMDPTYS 

       370        380        390        400        410        420 
PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV ERPGVTNVAR SAMMKDSPFY 

       430        440        450        460        470        480 
QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ AFAVKIISKR MEANTQKEIT ALKLCEGHPN 

       490        500        510        520        530        540 
IVKLHEVFHD QLHTFLVMEL LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV 

       550        560        570        580        590        600 
VHRDLKPENL LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD 

       610        620        630        640        650        660 
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG EAWKNVSQEA 

       670        680        690        700        710        720 
KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT PDILGSSGAA VHTCVKATFH 

       730        740        750        760        770        780 
AFNKYKREGF CLQNVDKAPL AKRRKMKKTS TSTETRSSSS ESSHSSSSHS HGKTTPTKTL 

       790        800 
QPSNPADSNN PETLFQFSDS VA 

« Hide

Isoform 2 [UniParc].

Checksum: 3CED0A0C50E96C78
Show »

FASTA54961,769

References

« Hide 'large scale' references
[1]"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB."
Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.
EMBO J. 17:4426-4441(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-195 AND ASP-565.
Tissue: Pancreas.
[2]"Cloning and characterization of RLPK, a novel RSK-related protein kinase."
New L., Zhao M., Li Y., Bassett W.W., Feng Y., Ludwig S., Padova F.D., Gram H., Han J.
J. Biol. Chem. 274:1026-1032(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
Tissue: Placenta.
[3]"Assignment of a member of the ribosomal protein S6 kinase family, RPS6KA5, to human chromosome 14q31-q32.1 by radiation hybrid mapping."
Jiang C., Yu L., Tu Q., Zhao Y., Zhang H., Zhao S.
Cytogenet. Cell Genet. 87:261-262(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL LOCATION.
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[6]"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts."
Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S.
Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)."
Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G.
EMBO J. 22:1313-1324(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RELA.
[8]"MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14."
Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H., Hazzalin C.A., Mahadevan L.C., Arthur J.S.
EMBO J. 22:2788-2797(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMGN1/HMG14.
[9]"Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway."
Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E.
Exp. Hematol. 31:398-405(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3.
[10]"Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1)."
Janknecht R.
Oncogene 22:746-755(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, INTERACTION WITH CREBBP AND EP300.
[11]"Phosphorylation of histone H2A inhibits transcription on chromatin templates."
Zhang Y., Griffin K., Mondal N., Parvin J.D.
J. Biol. Chem. 279:21866-21872(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H2A.
[12]"MSK1 activity is controlled by multiple phosphorylation sites."
McCoy C.E., Campbell D.G., Deak M., Bloomberg G.B., Arthur J.S.C.
Biochem. J. 387:507-517(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-212; SER-360; SER-376; SER-381; THR-581; SER-750; SER-752 AND SER-758, MUTAGENESIS OF SER-212; SER-360; SER-376 AND THR-581.
[13]"Identification of novel phosphorylation sites in MSK1 by precursor ion scanning MS."
McCoy C.E., Macdonald A., Morrice N.A., Campbell D.G., Deak M., Toth R., McIlrath J., Arthur J.S.
Biochem. J. 402:491-501(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-647; SER-657; SER-695 AND THR-700, MUTAGENESIS OF THR-700.
[14]"Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition."
Beck I.M., Vanden Berghe W., Vermeulen L., Bougarne N., Vander Cruyssen B., Haegeman G., De Bosscher K.
EMBO J. 27:1682-1693(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]"MSK activation and physiological roles."
Arthur J.S.
Front. Biosci. 13:5866-5879(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[16]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"The versatile role of MSKs in transcriptional regulation."
Vermeulen L., Vanden Berghe W., Beck I.M., De Bosscher K., Haegeman G.
Trends Biochem. Sci. 34:311-318(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[18]"Development and validation of a method for profiling post-translational modification activities using protein microarrays."
Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C.
PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[19]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-381, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein."
Smith K.J., Carter P.S., Bridges A., Horrocks P., Lewis C., Pettman G., Clarke A., Brown M., Hughes J., Wilkinson M., Bax B., Reith A.
Structure 12:1067-1077(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-348.
[22]"The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1."
Malakhova M., D'Angelo I., Kim H.G., Kurinov I., Bode A.M., Dong Z.
J. Mol. Biol. 399:41-52(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 414-738.
[23]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-554; LEU-574 AND CYS-599.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF074393 mRNA. Translation: AAC31171.1.
AF080000 mRNA. Translation: AAD23915.1.
AF090421 mRNA. Translation: AAC69577.1. Frameshift.
AL121784 Genomic DNA. No translation available.
AL133454 Genomic DNA. No translation available.
AL159191 Genomic DNA. No translation available.
BC017187 mRNA. Translation: AAH17187.1.
PIRT13149.
RefSeqNP_004746.2. NM_004755.2.
NP_872198.1. NM_182398.1.
UniGeneHs.510225.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VZOX-ray1.80A2-348[»]
3KN5X-ray2.40A/B414-738[»]
3KN6X-ray2.00A/B414-738[»]
ProteinModelPortalO75582.
SMRO75582. Positions 24-729.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114676. 50 interactions.
IntActO75582. 31 interactions.
MINTMINT-261060.
STRING9606.ENSP00000261991.

Chemistry

BindingDBO75582.
ChEMBLCHEMBL4237.
GuidetoPHARMACOLOGY1523.

PTM databases

PhosphoSiteO75582.

Proteomic databases

PaxDbO75582.
PRIDEO75582.

Protocols and materials databases

DNASU9252.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261991; ENSP00000261991; ENSG00000100784. [O75582-1]
ENST00000418736; ENSP00000402787; ENSG00000100784. [O75582-2]
GeneID9252.
KEGGhsa:9252.
UCSCuc001xys.2. human. [O75582-1]
uc001xyt.3. human. [O75582-2]

Organism-specific databases

CTD9252.
GeneCardsGC14M091337.
HGNCHGNC:10434. RPS6KA5.
HPACAB025458.
HPA001274.
MIM603607. gene.
neXtProtNX_O75582.
PharmGKBPA34849.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidO75582.
KOK04445.
OMAFQSHDKS.
OrthoDBEOG76HQ0Z.
PhylomeDBO75582.
TreeFamTF313438.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkO75582.

Gene expression databases

ArrayExpressO75582.
BgeeO75582.
CleanExHS_RPS6KA5.
GenevestigatorO75582.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016239. Ribosomal_S6_kinase_II.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 2 hits.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00108. PROTEIN_KINASE_ST. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRPS6KA5. human.
EvolutionaryTraceO75582.
GeneWikiRPS6KA5.
GenomeRNAi9252.
NextBio34679.
PROO75582.
SOURCESearch...

Entry information

Entry nameKS6A5_HUMAN
AccessionPrimary (citable) accession number: O75582
Secondary accession number(s): O95316, Q96AF7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM