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Protein

Ribosomal protein S6 kinase alpha-1

Gene

Rps6ka1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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 pre-initiation 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) (By similarity). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). 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 similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, 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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei94 – 941ATPPROSITE-ProRule annotation
Active sitei187 – 1871Proton acceptorBy similarity
Binding sitei447 – 4471ATPPROSITE-ProRule annotation
Active sitei535 – 5351Proton acceptorBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi68 – 769ATPPROSITE-ProRule annotation
Nucleotide bindingi424 – 4329ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB
  • magnesium ion binding Source: InterPro
  • protein serine/threonine kinase activity Source: UniProtKB
  • ribosomal protein S6 kinase activity Source: RGD
  • transcription factor binding Source: RGD

GO - Biological processi

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. 5301.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620675. Rps6ka1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: Reactome
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL5528.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 735735Ribosomal protein S6 kinase alpha-1PRO_0000086200Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei54 – 541PhosphoserineBy similarity
Modified residuei221 – 2211Phosphoserine; by PDPK11 Publication
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei359 – 3591PhosphothreonineBy similarity
Modified residuei363 – 3631PhosphoserineBy similarity
Modified residuei369 – 3691Phosphoserine; by autocatalysisBy similarity
Modified residuei380 – 3801Phosphoserine; by autocatalysisBy similarity
Modified residuei573 – 5731PhosphothreonineBy similarity
Modified residuei732 – 7321PhosphoserineBy similarity

Post-translational modificationi

Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-380, as part of the activation process. May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and MAPK3/ERK1.1 Publication
N-terminal myristoylation results in an activated kinase in the absence of added growth factors.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63531.
PRIDEiQ63531.

PTM databases

iPTMnetiQ63531.
PhosphoSiteiQ63531.

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

GO - Molecular functioni

  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi249643. 2 interactions.
IntActiQ63531. 1 interaction.
MINTiMINT-234305.
STRINGi10116.ENSRNOP00000060054.

Structurei

3D structure databases

ProteinModelPortaliQ63531.
SMRiQ63531. Positions 53-340, 414-709.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 321260Protein kinase 1PROSITE-ProRule annotationAdd
BLAST
Domaini322 – 39170AGC-kinase C-terminalAdd
BLAST
Domaini418 – 675258Protein 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

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ63531.
KOiK04373.
PhylomeDBiQ63531.

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.
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.

Q63531-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPLAQLKEPW PLMELVPLDP ENGQASGEEA GLQPSKDEGI LKEISITHHV
60 70 80 90 100
KAGSEKADPS HFELLKVLGQ GSFGKVFLVR KVTRPDNGHL YAMKVLKKAT
110 120 130 140 150
LKVRDRVRTK MERDILADVN HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF
160 170 180 190 200
TRLSKEVMFT EEDVKFYLAE LALGLDHLHS LGIIYRDLKP ENILLDEEGH
210 220 230 240 250
IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHT HSADWWSYGV
260 270 280 290 300
LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN
310 320 330 340 350
PANRLGSGPD GAEEIKRHIF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY
360 370 380 390 400
FDTEFTSRTP RDSPGIPPSA GAHQLFRGFS FVATGLMEDD SKPRATQAPL
410 420 430 440 450
HSVVQQLHGK NLVFSDGYIV KETIGVGSYS VCKRCVHKAT NMEYAVKVID
460 470 480 490 500
KSKRDPSEEI EILLRYGQHP NIITLKDVYD DSKHVYLVTE LMRGGELLDK
510 520 530 540 550
ILRQKFFSER EASFVLYTIS KTVEYLHSQG VVHRDLKPSN ILYVDESGNP
560 570 580 590 600
ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL
610 620 630 640 650
GVLLYTMLAG YTPFANGPSD TPEEILTRIS SGKFTLSGGN WNTVSETAKD
660 670 680 690 700
LVSKMLHVDP HQRLTAKQVL QHPWITQKDK LPQSQLSHQD LQLVKGGMAA
710 720 730
TYSALSSSKP TPQLKPIESS ILAQRRVRKL PSTTL
Length:735
Mass (Da):82,883
Last modified:November 1, 1996 - v1
Checksum:i12DEAD1E07140FDE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99169 mRNA. Translation: AAA02872.1.
PIRiA53300.
RefSeqiNP_112369.1. NM_031107.1.
UniGeneiRn.34915.

Genome annotation databases

GeneIDi81771.
KEGGirno:81771.
UCSCiRGD:620675. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99169 mRNA. Translation: AAA02872.1.
PIRiA53300.
RefSeqiNP_112369.1. NM_031107.1.
UniGeneiRn.34915.

3D structure databases

ProteinModelPortaliQ63531.
SMRiQ63531. Positions 53-340, 414-709.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249643. 2 interactions.
IntActiQ63531. 1 interaction.
MINTiMINT-234305.
STRINGi10116.ENSRNOP00000060054.

Chemistry

ChEMBLiCHEMBL5528.

PTM databases

iPTMnetiQ63531.
PhosphoSiteiQ63531.

Proteomic databases

PaxDbiQ63531.
PRIDEiQ63531.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81771.
KEGGirno:81771.
UCSCiRGD:620675. rat.

Organism-specific databases

CTDi6195.
RGDi620675. Rps6ka1.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
HOVERGENiHBG108317.
InParanoidiQ63531.
KOiK04373.
PhylomeDBiQ63531.

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.

Miscellaneous databases

NextBioi615585.
PROiQ63531.

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.
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]
ProtoNetiSearch...

Publicationsi

  1. "Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase."
    Grove J.R., Price D.J., Banerjee P., Balasubramanyam A., Ahmad M.F., Avruch J.
    Biochemistry 32:7727-7738(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1."
    Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S., Froedin M.
    J. Biol. Chem. 274:27168-27176(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-221.
  3. "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization."
    Fujita N., Sato S., Tsuruo T.
    J. Biol. Chem. 278:49254-49260(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL CYCLE REGULATION, FUNCTION IN PHOSPHORYLATION OF CDKN1B.
  4. "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling."
    Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.
    J. Biol. Chem. 279:29325-29335(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FGFR1, ENZYME REGULATION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiKS6A1_RAT
AccessioniPrimary (citable) accession number: Q63531
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: May 11, 2016
This is version 125 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.