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P18653

- KS6A1_MOUSE

UniProt

P18653 - KS6A1_MOUSE

Protein

Ribosomal protein S6 kinase alpha-1

Gene

Rps6ka1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Nov 1990)
      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 the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression 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-562 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-369, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei94 – 941ATPPROSITE-ProRule annotation
    Active sitei187 – 1871Proton acceptorBy similarity
    Binding sitei436 – 4361ATPPROSITE-ProRule annotation
    Active sitei524 – 5241Proton acceptorBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi68 – 769ATPPROSITE-ProRule annotation
    Nucleotide bindingi413 – 4219ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. intracellular signal transduction Source: InterPro
    2. negative regulation of apoptotic process Source: UniProtKB
    3. positive regulation of hepatic stellate cell activation Source: UniProtKB

    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-1 (EC:2.7.11.1)
    Short name:
    S6K-alpha-1
    Alternative name(s):
    90 kDa ribosomal protein S6 kinase 1
    Short name:
    p90-RSK 1
    Short name:
    p90RSK1
    Short name:
    p90S6K
    MAP kinase-activated protein kinase 1a
    Short name:
    MAPK-activated protein kinase 1a
    Short name:
    MAPKAP kinase 1a
    Short name:
    MAPKAPK-1a
    Ribosomal S6 kinase 1
    Short name:
    RSK-1
    Gene namesi
    Name:Rps6ka1
    Synonyms:Mapkapk1a, Rsk1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:104558. Rps6ka1.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. spindle Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 724724Ribosomal protein S6 kinase alpha-1PRO_0000086199Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei54 – 541PhosphoserineBy similarity
    Modified residuei221 – 2211Phosphoserine; by PDPK1By similarity
    Modified residuei296 – 2961PhosphoserineBy similarity
    Modified residuei337 – 3371PhosphothreonineBy similarity
    Modified residuei348 – 3481PhosphothreonineBy similarity
    Modified residuei352 – 3521PhosphoserineBy similarity
    Modified residuei358 – 3581PhosphoserineBy similarity
    Modified residuei369 – 3691Phosphoserine; alternate2 Publications
    Modified residuei369 – 3691Phosphoserine; by autocatalysis; alternateBy similarity
    Modified residuei562 – 5621PhosphothreonineBy similarity
    Modified residuei721 – 7211PhosphoserineBy similarity

    Post-translational modificationi

    Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-369, as part of the activation process. May be phosphorylated at Thr-348 and Ser-352 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

    Phosphoprotein

    Proteomic databases

    MaxQBiP18653.
    PaxDbiP18653.
    PRIDEiP18653.

    PTM databases

    PhosphoSiteiP18653.

    Expressioni

    Tissue specificityi

    Intestine, thymus, and lung.

    Gene expression databases

    ArrayExpressiP18653.
    BgeeiP18653.
    CleanExiMM_RPS6KA1.
    GenevestigatoriP18653.

    Interactioni

    Subunit structurei

    Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation. Interacts with ETV1/ER81 and FGFR1 By similarity.By similarity

    Protein-protein interaction databases

    IntActiP18653. 4 interactions.
    MINTiMINT-1486951.

    Structurei

    3D structure databases

    ProteinModelPortaliP18653.
    SMRiP18653. Positions 10-698.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini62 – 310249Protein kinase 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini311 – 38070AGC-kinase C-terminalAdd
    BLAST
    Domaini407 – 664258Protein 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.

    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.

    P18653-1 [UniParc]FASTAAdd to Basket

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    MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEAI LKEISITHHV    50
    KAGSEKADPS QFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT 100
    LKVRDRVRTK MERDILADVN HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF 150
    TRLSKEVMFT EEDVKFYLAE LALGLDHLHS LGIIYRDLKP ENILLDEEGH 200
    IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHT HSADWWSYGV 250
    LMGKDRKETM TLILKAKLGM PQFLSTEAQS LLRALFKRNP ANRLGSGPDG 300
    AEEIKRHIFY STIDWNKLYR REIKPPFKPA VAQPDDTFYF DTEFTSRTPR 350
    DSPGIPPSAG AHQLFRGFSF VATGLMEDDG KPRTTQAPLH SVVQQLHGKN 400
    LVFSDGYVVK ETIGVGSYSV CKRCVHKATN MEYAVKVIDK SKRDPSEEIE 450
    ILLRYGQHPN IITLKDVYDD GKHVYLVTEL MRGGELLDKI LRQKFFSERE 500
    ASFVLHTISK TVEYLHSQGV VHRDLKPSNI LYVDESGNPE CLRICDFGFA 550
    KQLRAENGLL MTPCYTANFV APEVLKRQGY DEGCDIWSLG ILLYTMLAGY 600
    TPFANGPSDT PEEILTRIGS GKFTLSGGNW NTVSETAKDL VSKMLHVDPH 650
    QRLTAKQVLQ HPWITQKDKL PQSQLSHQDL QLVKGAMAAT YSALNSSKPT 700
    PQLKPIESSI LAQRRVRKLP STTL 724
    Length:724
    Mass (Da):81,595
    Last modified:November 1, 1990 - v1
    Checksum:iA5D8E5E5FDBCE4BF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M28489 mRNA. Translation: AAA50300.1.
    CCDSiCCDS71488.1.
    PIRiB32571.
    RefSeqiNP_001272434.1. NM_001285505.1.
    UniGeneiMm.301827.

    Genome annotation databases

    EnsembliENSMUST00000003741; ENSMUSP00000003741; ENSMUSG00000003644.
    GeneIDi20111.
    KEGGimmu:20111.
    UCSCiuc012dmp.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M28489 mRNA. Translation: AAA50300.1 .
    CCDSi CCDS71488.1.
    PIRi B32571.
    RefSeqi NP_001272434.1. NM_001285505.1.
    UniGenei Mm.301827.

    3D structure databases

    ProteinModelPortali P18653.
    SMRi P18653. Positions 10-698.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P18653. 4 interactions.
    MINTi MINT-1486951.

    PTM databases

    PhosphoSitei P18653.

    Proteomic databases

    MaxQBi P18653.
    PaxDbi P18653.
    PRIDEi P18653.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000003741 ; ENSMUSP00000003741 ; ENSMUSG00000003644 .
    GeneIDi 20111.
    KEGGi mmu:20111.
    UCSCi uc012dmp.2. mouse.

    Organism-specific databases

    CTDi 6195.
    MGIi MGI:104558. Rps6ka1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110260.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    KOi K04373.

    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

    PROi P18653.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P18653.
    Bgeei P18653.
    CleanExi MM_RPS6KA1.
    Genevestigatori P18653.

    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. "Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase."
      Alcorta D.A., Crews C.M., Sweet L.J., Bankston L., Jones S.W., Erikson R.L.
      Mol. Cell. Biol. 9:3850-3859(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    3. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiKS6A1_MOUSE
    AccessioniPrimary (citable) accession number: P18653
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: November 1, 1990
    Last modified: October 1, 2014
    This is version 130 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