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Q9WUT3 (KS6A2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribosomal protein S6 kinase alpha-2

Short name=S6K-alpha-2
EC=2.7.11.1
Alternative name(s):
90 kDa ribosomal protein S6 kinase 2
Short name=p90-RSK 2
Short name=p90RSK2
MAP kinase-activated protein kinase 1c
Short name=MAPK-activated protein kinase 1c
Short name=MAPKAP kinase 1c
Short name=MAPKAPK-1c
Protein-tyrosine kinase Mpk-9
Ribosomal S6 kinase 3
Short name=RSK-3
pp90RSK3
Gene names
Name:Rps6ka2
Synonyms:Mapkapk1c, Rsk3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length733 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-218 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD.

Subunit structure

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity.

Post-translational modification

Activated by phosphorylation at Ser-218 by PDPK1. Autophosphorylated on Ser-377, as part of the activation process. May be phosphorylated at Thr-356 and Ser-360 by MAPK1/ERK2 and MAPK3/ERK1 By similarity.

N-terminal myristoylation results in an activated kinase in the absence of added growth factors By similarity.

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
   Cellular componentCytoplasm
Nucleus
   DiseaseTumor suppressor
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain renin-angiotensin system

Inferred from direct assay PubMed 16585392. Source: MGI

cardiac muscle cell apoptotic process

Inferred from direct assay PubMed 16585392. Source: MGI

cellular response to carbohydrate stimulus

Inferred from direct assay PubMed 16585392. Source: MGI

heart contraction

Inferred from direct assay PubMed 16585392. Source: MGI

heart development

Inferred from direct assay PubMed 16585392. Source: MGI

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of meiosis

Inferred from direct assay PubMed 15526037. Source: MGI

oocyte maturation

Inferred from direct assay PubMed 15526037. Source: MGI

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 7508917. Source: MGI

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 16585392. Source: MGI

protein phosphorylation

Inferred from direct assay PubMed 15526037. Source: MGI

regulation of protein processing

Inferred from direct assay PubMed 16585392. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15526037. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

spindle

Inferred from direct assay PubMed 15509711. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 15526037. Source: MGI

protein kinase activity

Inferred from direct assay PubMed 15526037. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay PubMed 7508917. Source: MGI

protein serine/threonine/tyrosine kinase activity

Inferred from sequence orthology PubMed 22797923. Source: MGI

ribosomal protein S6 kinase activity

Inferred from direct assay PubMed 16585392. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 733733Ribosomal protein S6 kinase alpha-2
PRO_0000086202

Regions

Domain59 – 318260Protein kinase 1
Domain319 – 38870AGC-kinase C-terminal
Domain415 – 672258Protein kinase 2
Nucleotide binding65 – 739ATP By similarity
Nucleotide binding421 – 4299ATP By similarity

Sites

Active site1841Proton acceptor By similarity
Active site5321Proton acceptor By similarity
Binding site911ATP By similarity
Binding site4441ATP By similarity

Amino acid modifications

Modified residue2181Phosphoserine; by PDPK1 By similarity
Modified residue3771Phosphoserine; alternate Ref.5
Modified residue3771Phosphoserine; by autocatalysis; alternate By similarity
Cross-link630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict721K → E in BAB31901. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9WUT3 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 49C1390316CFCE91

FASTA73383,157
        10         20         30         40         50         60 
MELSMKKFTV RRFFSVYLRK KSRSKSSSLS RLEEEGIVKE IDISNHVKEG FEKADPSQFE 

        70         80         90        100        110        120 
LLKVLGQGSY GKVFLVRKVT GSDAGQLYAM KVLKKATLKV RDRVRSKMER DILAEVNHPF 

       130        140        150        160        170        180 
IVKLHYAFQT EGKLYLILDF LRGGDLFTRL SKEVMFTEED VKFYLAELAL ALDHLHGLGI 

       190        200        210        220        230        240 
IYRDLKPENI LLDEEGHIKI TDFGLSKEAT DHDKRAYSFC GTIEYMAPEV VNRRGHTQSA 

       250        260        270        280        290        300 
DWWSFGVLMF EMLTGSLPFQ GKDRKETMAL ILKAKLGMPQ FLSAEAQSLL RALFKRNPCN 

       310        320        330        340        350        360 
RLGAGVDGVE EIKRHPFFVT IDWNKLYRKE IKPPFKPAVG RPEDTFHFDP EFTARTPTDS 

       370        380        390        400        410        420 
PGVPPSANAH HLFRGFSFVA SSLVQEPSQQ DVPKAPIHPI VQQLHGNNIH FTDGYEIKED 

       430        440        450        460        470        480 
IGVGSYSVCK RCVHKATDAE YAVKIIDKSK RDPSEEIEIL LRYGQHPNII TLKDVYDDGK 

       490        500        510        520        530        540 
YVYLVMELMR GGELLDRILR QRCFSEREAS DVLYTIARTM DYLHSQGVVH RDLKPSNILY 

       550        560        570        580        590        600 
MDESGNPESI RICDFGFAKQ LRAENGLLMT PCYTANFVAP EVLKRQGYDA ACDVWSLGIL 

       610        620        630        640        650        660 
LYTMLAGFTP FANGPDDTPE EILARIGSGK YALSGGNWDS ISDAAKDVVS KMLHVDPQQR 

       670        680        690        700        710        720 
LTAVQVLKHP WIVNREYLSQ NQLSRQDVHL VKGAMAATYF ALNRTPQAPR LEPVLSSSLA 

       730 
QRRGMKRLTS TRL 

« Hide

References

« Hide 'large scale' references
[1]"The mouse Rsk3 gene maps to the Leh66 elements carrying the T-complex responder Tcr."
Kispert A., Stoeger R.J., Caparros M., Herrmann B.G.
Mamm. Genome 10:794-802(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[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: C57BL/6J.
Tissue: Ovary and Uterus.
[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].
Strain: C57BL/6.
Tissue: Brain and Retina.
[4]"An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain."
Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P.
Oncogene 7:2499-2506(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 534-592.
Strain: C57BL/6.
Tissue: Embryonic brain.
[5]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ131021 mRNA. Translation: CAB44492.1.
AK019881 mRNA. Translation: BAB31901.1.
BC043064 mRNA. Translation: AAH43064.1.
BC051079 mRNA. Translation: AAH51079.1.
BC056946 mRNA. Translation: AAH56946.1.
X57237 mRNA. Translation: CAA40513.1.
CCDSCCDS28376.1.
RefSeqNP_035429.1. NM_011299.4.
UniGeneMm.268383.

3D structure databases

ProteinModelPortalQ9WUT3.
SMRQ9WUT3. Positions 20-704.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9WUT3. 4 interactions.
MINTMINT-1486826.

PTM databases

PhosphoSiteQ9WUT3.

Proteomic databases

MaxQBQ9WUT3.
PaxDbQ9WUT3.
PRIDEQ9WUT3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000024575; ENSMUSP00000024575; ENSMUSG00000023809.
GeneID20112.
KEGGmmu:20112.
UCSCuc008aih.2. mouse.

Organism-specific databases

CTD6196.
MGIMGI:1342290. Rps6ka2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110260.
HOGENOMHOG000233033.
HOVERGENHBG108317.
KOK04373.
OMAWIVNREY.
OrthoDBEOG7B8S38.
PhylomeDBQ9WUT3.
TreeFamTF313438.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressQ9WUT3.
BgeeQ9WUT3.
CleanExMM_RPS6KA2.
GenevestigatorQ9WUT3.

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

NextBio297615.
PROQ9WUT3.
SOURCESearch...

Entry information

Entry nameKS6A2_MOUSE
AccessionPrimary (citable) accession number: Q9WUT3
Secondary accession number(s): Q9D2C0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 132 of the entry and version 1 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