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Q9WUT3

- KS6A2_MOUSE

UniProt

Q9WUT3 - KS6A2_MOUSE

Protein

Ribosomal protein S6 kinase alpha-2

Gene

Rps6ka2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei91 – 911ATPPROSITE-ProRule annotation
    Active sitei184 – 1841Proton acceptorBy similarity
    Binding sitei444 – 4441ATPPROSITE-ProRule annotation
    Active sitei532 – 5321Proton acceptorBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi65 – 739ATPPROSITE-ProRule annotation
    Nucleotide bindingi421 – 4299ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. magnesium ion binding Source: InterPro
    3. protein binding Source: MGI
    4. protein kinase activity Source: MGI
    5. protein serine/threonine/tyrosine kinase activity Source: MGI
    6. protein serine/threonine kinase activity Source: MGI
    7. ribosomal protein S6 kinase activity Source: MGI

    GO - Biological processi

    1. brain renin-angiotensin system Source: MGI
    2. cardiac muscle cell apoptotic process Source: MGI
    3. cellular response to carbohydrate stimulus Source: MGI
    4. heart contraction Source: MGI
    5. heart development Source: MGI
    6. intracellular signal transduction Source: InterPro
    7. negative regulation of cell cycle Source: UniProtKB
    8. negative regulation of cell proliferation Source: UniProtKB
    9. negative regulation of meiosis Source: MGI
    10. oocyte maturation Source: MGI
    11. peptidyl-serine phosphorylation Source: MGI
    12. positive regulation of apoptotic process Source: UniProtKB
    13. positive regulation of gene expression Source: MGI
    14. protein phosphorylation Source: MGI
    15. regulation of protein processing Source: MGI

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 3474.
    ReactomeiREACT_188573. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_198245. RSK activation.
    REACT_198246. CREB phosphorylation through the activation of Ras.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
    REACT_215063. ERK/MAPK targets.
    REACT_224314. CREB phosphorylation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ribosomal protein S6 kinase alpha-2 (EC:2.7.11.1)
    Short name:
    S6K-alpha-2
    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 namesi
    Name:Rps6ka2
    Synonyms:Mapkapk1c, Rsk3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:1342290. Rps6ka2.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nucleoplasm Source: Reactome
    3. nucleus Source: UniProtKB
    4. spindle Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 733733Ribosomal protein S6 kinase alpha-2PRO_0000086202Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei218 – 2181Phosphoserine; by PDPK1By similarity
    Modified residuei377 – 3771Phosphoserine; alternate1 Publication
    Modified residuei377 – 3771Phosphoserine; by autocatalysis; alternateBy similarity
    Cross-linki630 – 630Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9WUT3.
    PaxDbiQ9WUT3.
    PRIDEiQ9WUT3.

    PTM databases

    PhosphoSiteiQ9WUT3.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9WUT3.
    BgeeiQ9WUT3.
    CleanExiMM_RPS6KA2.
    GenevestigatoriQ9WUT3.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    IntActiQ9WUT3. 4 interactions.
    MINTiMINT-1486826.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WUT3.
    SMRiQ9WUT3. Positions 20-704.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini59 – 318260Protein kinase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini319 – 38870AGC-kinase C-terminalAdd
    BLAST
    Domaini415 – 672258Protein kinase 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 2 protein kinase domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110260.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    KOiK04373.
    OMAiWIVNREY.
    OrthoDBiEOG7B8S38.
    PhylomeDBiQ9WUT3.
    TreeFamiTF313438.

    Family and domain databases

    InterProiIPR000961. 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]
    PfamiPF00069. Pkinase. 2 hits.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000606. Ribsml_S6_kin_2. 1 hit.
    SMARTiSM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 2 hits.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 2 hits.
    PROSITEiPS51285. 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]

    Sequencei

    Sequence statusi: Complete.

    Q9WUT3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELSMKKFTV RRFFSVYLRK KSRSKSSSLS RLEEEGIVKE IDISNHVKEG    50
    FEKADPSQFE LLKVLGQGSY GKVFLVRKVT GSDAGQLYAM KVLKKATLKV 100
    RDRVRSKMER DILAEVNHPF IVKLHYAFQT EGKLYLILDF LRGGDLFTRL 150
    SKEVMFTEED VKFYLAELAL ALDHLHGLGI IYRDLKPENI LLDEEGHIKI 200
    TDFGLSKEAT DHDKRAYSFC GTIEYMAPEV VNRRGHTQSA DWWSFGVLMF 250
    EMLTGSLPFQ GKDRKETMAL ILKAKLGMPQ FLSAEAQSLL RALFKRNPCN 300
    RLGAGVDGVE EIKRHPFFVT IDWNKLYRKE IKPPFKPAVG RPEDTFHFDP 350
    EFTARTPTDS PGVPPSANAH HLFRGFSFVA SSLVQEPSQQ DVPKAPIHPI 400
    VQQLHGNNIH FTDGYEIKED IGVGSYSVCK RCVHKATDAE YAVKIIDKSK 450
    RDPSEEIEIL LRYGQHPNII TLKDVYDDGK YVYLVMELMR GGELLDRILR 500
    QRCFSEREAS DVLYTIARTM DYLHSQGVVH RDLKPSNILY MDESGNPESI 550
    RICDFGFAKQ LRAENGLLMT PCYTANFVAP EVLKRQGYDA ACDVWSLGIL 600
    LYTMLAGFTP FANGPDDTPE EILARIGSGK YALSGGNWDS ISDAAKDVVS 650
    KMLHVDPQQR LTAVQVLKHP WIVNREYLSQ NQLSRQDVHL VKGAMAATYF 700
    ALNRTPQAPR LEPVLSSSLA QRRGMKRLTS TRL 733
    Length:733
    Mass (Da):83,157
    Last modified:November 1, 1999 - v1
    Checksum:i49C1390316CFCE91
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti72 – 721K → E in BAB31901. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS28376.1.
    RefSeqiNP_035429.1. NM_011299.4.
    UniGeneiMm.268383.

    Genome annotation databases

    EnsembliENSMUST00000024575; ENSMUSP00000024575; ENSMUSG00000023809.
    GeneIDi20112.
    KEGGimmu:20112.
    UCSCiuc008aih.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS28376.1.
    RefSeqi NP_035429.1. NM_011299.4.
    UniGenei Mm.268383.

    3D structure databases

    ProteinModelPortali Q9WUT3.
    SMRi Q9WUT3. Positions 20-704.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9WUT3. 4 interactions.
    MINTi MINT-1486826.

    PTM databases

    PhosphoSitei Q9WUT3.

    Proteomic databases

    MaxQBi Q9WUT3.
    PaxDbi Q9WUT3.
    PRIDEi Q9WUT3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000024575 ; ENSMUSP00000024575 ; ENSMUSG00000023809 .
    GeneIDi 20112.
    KEGGi mmu:20112.
    UCSCi uc008aih.2. mouse.

    Organism-specific databases

    CTDi 6196.
    MGIi MGI:1342290. Rps6ka2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110260.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    KOi K04373.
    OMAi WIVNREY.
    OrthoDBi EOG7B8S38.
    PhylomeDBi Q9WUT3.
    TreeFami TF313438.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 3474.
    Reactomei REACT_188573. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_198245. RSK activation.
    REACT_198246. CREB phosphorylation through the activation of Ras.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
    REACT_215063. ERK/MAPK targets.
    REACT_224314. CREB phosphorylation.

    Miscellaneous databases

    NextBioi 297615.
    PROi Q9WUT3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9WUT3.
    Bgeei Q9WUT3.
    CleanExi MM_RPS6KA2.
    Genevestigatori Q9WUT3.

    Family and domain databases

    InterProi IPR000961. 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 ]
    Pfami PF00069. Pkinase. 2 hits.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000606. Ribsml_S6_kin_2. 1 hit.
    SMARTi SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 2 hits.
    PROSITEi PS51285. 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 ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.

    Entry informationi

    Entry nameiKS6A2_MOUSE
    AccessioniPrimary (citable) accession number: Q9WUT3
    Secondary accession number(s): Q9D2C0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3