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Q9Z2B9 (KS6A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribosomal protein S6 kinase alpha-4

Short name=S6K-alpha-4
EC=2.7.11.1
Alternative name(s):
90 kDa ribosomal protein S6 kinase 4
Nuclear mitogen- and stress-activated protein kinase 2
RSK-like protein kinase
Short name=RLSK
Gene names
Name:Rps6ka4
Synonyms:Msk2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length773 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 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 By similarity. Ref.4 Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB O75582

Cofactor

Magnesium By similarity. UniProtKB O75582

Enzyme regulation

Activated by phosphorylation at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the activated C-terminal kinase domain By similarity.

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 RPS6KA4 associates with and phosphorylates the NF-kappa-B p65 subunit RELA By similarity.

Subcellular location

Nucleus By similarity UniProtKB O75676.

Post-translational modification

Ser-343 and Thr-568 phosphorylation is required for kinase activity. Ser-343 and Ser-196 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-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain By similarity.

Miscellaneous

Enzyme activity requires the presence of both kinase domains By similarity. UniProtKB O75582

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.

Ontologies

Keywords
   Biological processInflammatory response
Stress response
   Cellular componentNucleus
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processhistone H3-S10 phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-S28 phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

interleukin-1-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of histone acetylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of histone phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

mitogen-activated protein kinase p38 binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Mapk1P630853EBI-412887,EBI-397697

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 773773Ribosomal protein S6 kinase alpha-4
PRO_0000086206

Regions

Domain33 – 301269Protein kinase 1
Domain302 – 37170AGC-kinase C-terminal
Domain417 – 674258Protein kinase 2
Nucleotide binding39 – 479ATP By similarity UniProtKB Q15418
Nucleotide binding417 – 4259ATP By similarity UniProtKB Q15418

Sites

Active site1611Proton acceptor By similarity UniProtKB Q15418
Active site5301Proton acceptor By similarity UniProtKB Q15418
Binding site651ATP By similarity UniProtKB Q15418
Binding site4401ATP By similarity UniProtKB Q15418

Amino acid modifications

Modified residue1961Phosphoserine; by autocatalysis By similarity UniProtKB Q15418
Modified residue3431Phosphoserine; by MAPK1, MAPK3 and MAPK14 Probable UniProtKB Q15418
Modified residue3471Phosphoserine By similarity
Modified residue3601Phosphoserine; by autocatalysis By similarity UniProtKB Q15418
Modified residue3651Phosphoserine; by autocatalysis By similarity
Modified residue5421Phosphothreonine By similarity
Modified residue5681Phosphothreonine; by MAPK1, MAPK3 and MAPK14 By similarity UniProtKB Q15418
Modified residue6341Phosphoserine By similarity
Modified residue6781Phosphoserine By similarity
Modified residue6871Phosphothreonine; by MAPK1, MAPK3 and MAPK14 By similarity
Modified residue7371Phosphoserine; by autocatalysis By similarity UniProtKB Q15418
Modified residue7451Phosphoserine; by autocatalysis Probable

Experimental info

Sequence conflict3071V → W in AAC67394. Ref.1
Sequence conflict3431S → P in AAH12964. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9Z2B9 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 298DA76E00A9937F

FASTA77385,652
        10         20         30         40         50         60 
MGDEDEDEGC AVELQITEAN LTGHEEKVSV ENFALLKVLG TGAYGKVFLV RKTGGHDAGK 

        70         80         90        100        110        120 
LYAMKVLRKA ALVQRAKTQE HTRTERSVLE LVRQAPFLVT LHYAFQTDAK LHLILDYVSG 

       130        140        150        160        170        180 
GEMFTHLYQR QYFKEAEVRV YGGEIVLALE HLHKLGIIYR DLKLENVLLD SEGHIVLTDF 

       190        200        210        220        230        240 
GLSKEFLTEE KERTFSFCGT IEYMAPEIIR SKAGHGKAVD WWSLGILLFE LLTGASPFTL 

       250        260        270        280        290        300 
EGERNTQAEV SRRILKCSPP FPLRIGPVAQ DLLQRLLCKD PKKRLGAGPQ GAQEVKSHPF 

       310        320        330        340        350        360 
FQGLDWVALA ARKIPAPFRP QIRSELDVGN FAEEFTRLEP VYSPAGSPPP GDPRIFQGYS 

       370        380        390        400        410        420 
FVAPSILFDH NNAVMADVLQ APGAGYRPGR AAVARSAMMQ DSPFFQQYEL DLREPALGQG 

       430        440        450        460        470        480 
SFSVCRRCRQ RQSGQEFAVK ILSRRLEENT QREVAALRLC QSHPNVVNLH EVLHDQLHTY 

       490        500        510        520        530        540 
LVLELLRGGE LLEHIRKKRL FSESEASQIL RSLVSAVSFM HEEAGVVHRD LKPENILYAD 

       550        560        570        580        590        600 
DTPGAPVKII DFGFARLRPQ SPAEPMQTPC FTLQYAAPEL LAQQGYDESC DLWSLGVILY 

       610        620        630        640        650        660 
MMLSGQVPFQ GASGQGGQSQ AAEIMCKIRE GRFSLDGEAW QGVSEEAKEL VRGLLTVDPA 

       670        680        690        700        710        720 
KRLKLEGLRS SSWLQDGSAR SSPPLRTPDV LESSGPAVRS GLNATFMAFN RGKREGFFLK 

       730        740        750        760        770 
SVENAPLAKR RKQKLRSAAA SRRGSPVPAS SGRLPASAAK GTTRRANGPL SPS 

« Hide

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].
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
[3]"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].
Tissue: Liver.
[4]"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 IN PHOSPHORYLATION OF CREB1 AND ATF1.
[5]"The kinases MSK1 and MSK2 are required for epidermal growth factor-induced, but not tumor necrosis factor-induced, histone H3 Ser10 phosphorylation."
Duncan E.A., Anest V., Cogswell P., Baldwin A.S.
J. Biol. Chem. 281:12521-12525(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3.
[6]"The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling."
Ananieva O., Darragh J., Johansen C., Carr J.M., McIlrath J., Park J.M., Wingate A., Monk C.E., Toth R., Santos S.G., Iversen L., Arthur J.S.
Nat. Immunol. 9:1028-1036(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1; ATF1 AND HISTONE H3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF074714 mRNA. Translation: AAC67394.1.
AK154674 mRNA. Translation: BAE32757.1.
BC012964 mRNA. Translation: AAH12964.1.
RefSeqNP_064308.2. NM_019924.2.
XP_006527294.1. XM_006527231.1.
UniGeneMm.20914.

3D structure databases

ProteinModelPortalQ9Z2B9.
SMRQ9Z2B9. Positions 12-365, 373-717.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9Z2B9. 1 interaction.

PTM databases

PhosphoSiteQ9Z2B9.

Proteomic databases

PaxDbQ9Z2B9.
PRIDEQ9Z2B9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025903; ENSMUSP00000025903; ENSMUSG00000024952.
ENSMUST00000170516; ENSMUSP00000131581; ENSMUSG00000024952.
GeneID56613.
KEGGmmu:56613.
UCSCuc008gja.1. mouse.

Organism-specific databases

CTD8986.
MGIMGI:1930076. Rps6ka4.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110260.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidQ3U3M8.
KOK16510.
OMATYVNATY.
OrthoDBEOG76HQ0Z.
TreeFamTF313438.

Gene expression databases

BgeeQ9Z2B9.
CleanExMM_RPS6KA4.
GenevestigatorQ9Z2B9.

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

NextBio313035.
PROQ9Z2B9.
SOURCESearch...

Entry information

Entry nameKS6A4_MOUSE
AccessionPrimary (citable) accession number: Q9Z2B9
Secondary accession number(s): Q3U3M8, Q91X18
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot