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Protein

Ribosomal protein S6 kinase alpha-1

Gene

Rps6ka1

Organism
Mus musculus (Mouse)
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). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:10635333). 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). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+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)DescriptionActionsGraphical viewLength
Binding sitei94ATPPROSITE-ProRule annotation1
Active sitei187Proton acceptorBy similarity1
Binding sitei436ATPPROSITE-ProRule annotation1
Active sitei524Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi68 – 76ATPPROSITE-ProRule annotation9
Nucleotide bindingi413 – 421ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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. 3474.
ReactomeiR-MMU-198753. ERK/MAPK targets.
R-MMU-199920. CREB phosphorylation.
R-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-442742. CREB phosphorylation through the activation of Ras.
R-MMU-444257. RSK activation.
R-MMU-881907. Gastrin-CREB signalling pathway via PKC and MAPK.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104558. Rps6ka1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: MGI
  • spindle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000861991 – 724Ribosomal protein S6 kinase alpha-1Add BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei54PhosphoserineBy similarity1
Modified residuei221Phosphoserine; by PDPK1By similarity1
Modified residuei296PhosphoserineBy similarity1
Modified residuei348PhosphothreonineBy similarity1
Modified residuei352PhosphoserineBy similarity1
Modified residuei358PhosphoserineBy similarity1
Modified residuei369PhosphoserineCombined sources1
Modified residuei562PhosphothreonineBy similarity1
Modified residuei721PhosphoserineBy similarity1

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

EPDiP18653.
MaxQBiP18653.
PaxDbiP18653.
PRIDEiP18653.

PTM databases

iPTMnetiP18653.
PhosphoSitePlusiP18653.
SwissPalmiP18653.

Expressioni

Tissue specificityi

Intestine, thymus, and lung.

Gene expression databases

BgeeiENSMUSG00000003644.
CleanExiMM_RPS6KA1.
ExpressionAtlasiP18653. baseline and differential.
GenevisibleiP18653. MM.

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: UniProtKB

Protein-protein interaction databases

BioGridi203014. 3 interactors.
IntActiP18653. 9 interactors.
MINTiMINT-1486951.
STRINGi10090.ENSMUSP00000101514.

Structurei

3D structure databases

ProteinModelPortaliP18653.
SMRiP18653.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 310Protein kinase 1PROSITE-ProRule annotationAdd BLAST249
Domaini311 – 380AGC-kinase C-terminalAdd BLAST70
Domaini407 – 664Protein kinase 2PROSITE-ProRule annotationAdd BLAST258

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.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP18653.
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.
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

        10         20         30         40         50
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEAI LKEISITHHV
60 70 80 90 100
KAGSEKADPS QFELLKVLGQ GSFGKVFLVR KVTRPDSGHL 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
LMGKDRKETM TLILKAKLGM PQFLSTEAQS LLRALFKRNP ANRLGSGPDG
310 320 330 340 350
AEEIKRHIFY STIDWNKLYR REIKPPFKPA VAQPDDTFYF DTEFTSRTPR
360 370 380 390 400
DSPGIPPSAG AHQLFRGFSF VATGLMEDDG KPRTTQAPLH SVVQQLHGKN
410 420 430 440 450
LVFSDGYVVK ETIGVGSYSV CKRCVHKATN MEYAVKVIDK SKRDPSEEIE
460 470 480 490 500
ILLRYGQHPN IITLKDVYDD GKHVYLVTEL MRGGELLDKI LRQKFFSERE
510 520 530 540 550
ASFVLHTISK TVEYLHSQGV VHRDLKPSNI LYVDESGNPE CLRICDFGFA
560 570 580 590 600
KQLRAENGLL MTPCYTANFV APEVLKRQGY DEGCDIWSLG ILLYTMLAGY
610 620 630 640 650
TPFANGPSDT PEEILTRIGS GKFTLSGGNW NTVSETAKDL VSKMLHVDPH
660 670 680 690 700
QRLTAKQVLQ HPWITQKDKL PQSQLSHQDL QLVKGAMAAT YSALNSSKPT
710 720
PQLKPIESSI LAQRRVRKLP STTL
Length:724
Mass (Da):81,595
Last modified:November 1, 1990 - v1
Checksum:iA5D8E5E5FDBCE4BF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28489 mRNA. Translation: AAA50300.1.
CCDSiCCDS71488.1.
PIRiB32571.
RefSeqiNP_001272434.1. NM_001285505.1.
UniGeneiMm.301827.

3D structure databases

ProteinModelPortaliP18653.
SMRiP18653.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203014. 3 interactors.
IntActiP18653. 9 interactors.
MINTiMINT-1486951.
STRINGi10090.ENSMUSP00000101514.

PTM databases

iPTMnetiP18653.
PhosphoSitePlusiP18653.
SwissPalmiP18653.

Proteomic databases

EPDiP18653.
MaxQBiP18653.
PaxDbiP18653.
PRIDEiP18653.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003741; ENSMUSP00000003741; ENSMUSG00000003644.
GeneIDi20111.
KEGGimmu:20111.
UCSCiuc012dmp.3. mouse.

Organism-specific databases

CTDi6195.
MGIiMGI:104558. Rps6ka1.

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP18653.
KOiK04373.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiR-MMU-198753. ERK/MAPK targets.
R-MMU-199920. CREB phosphorylation.
R-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-442742. CREB phosphorylation through the activation of Ras.
R-MMU-444257. RSK activation.
R-MMU-881907. Gastrin-CREB signalling pathway via PKC and MAPK.

Miscellaneous databases

ChiTaRSiRps6ka1. mouse.
PROiP18653.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003644.
CleanExiMM_RPS6KA1.
ExpressionAtlasiP18653. baseline and differential.
GenevisibleiP18653. MM.

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...

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: November 30, 2016
This is version 154 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

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.