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P18653

- KS6A1_MOUSE

UniProt

P18653 - KS6A1_MOUSE

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Protein

Ribosomal protein S6 kinase alpha-1

Gene
Rps6ka1, Mapkapk1a, Rsk1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei94 – 941ATP By similarity
Active sitei187 – 1871Proton acceptor By similarity
Binding sitei436 – 4361ATP By similarity
Active sitei524 – 5241Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi68 – 769ATP By similarity
Nucleotide bindingi413 – 4219ATP By similarity

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
Complete GO annotation...

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
Complete GO annotation...

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 – 541Phosphoserine By similarity
Modified residuei221 – 2211Phosphoserine; by PDPK1 By similarity
Modified residuei296 – 2961Phosphoserine By similarity
Modified residuei337 – 3371Phosphothreonine By similarity
Modified residuei348 – 3481Phosphothreonine By similarity
Modified residuei352 – 3521Phosphoserine By similarity
Modified residuei358 – 3581Phosphoserine By similarity
Modified residuei369 – 3691Phosphoserine; alternate2 Publications
Modified residuei369 – 3691Phosphoserine; by autocatalysis; alternate By similarity
Modified residuei562 – 5621Phosphothreonine By similarity
Modified residuei721 – 7211Phosphoserine By 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.
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.

Protein-protein interaction databases

IntActiP18653. 4 interactions.
MINTiMINT-1486951.

Structurei

3D structure databases

ProteinModelPortaliP18653.
SMRiP18653. Positions 10-698.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 310249Protein kinase 1Add
BLAST
Domaini311 – 38070AGC-kinase C-terminalAdd
BLAST
Domaini407 – 664258Protein kinase 2Add
BLAST

Sequence similaritiesi

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

« Hide

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 129 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

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