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Protein

Ribosomal protein S6 kinase alpha-1

Gene

Rps6ka1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104558 Rps6ka1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3309057

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 Expressed in 242 organ(s), highest expression level in intestinal villus
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

Protein-protein interaction databases

BioGridi203014, 4 interactors
IntActiP18653, 9 interactors
MINTiP18653
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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0598 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00920000148962
HOGENOMiHOG000233033
HOVERGENiHBG108317
InParanoidiP18653
KOiK04373

Family and domain databases

InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR011009 Kinase-like_dom_sf
IPR017892 Pkinase_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR016239 Ribosomal_S6_kinase_II
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 2 hits
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000606 Ribsml_S6_kin_2, 1 hit
SMARTiView protein in SMART
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 2 hits
SUPFAMiSSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 1 hit
PS00107 PROTEIN_KINASE_ATP, 2 hits
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00108 PROTEIN_KINASE_ST, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q505N6Q505N6_MOUSE
Ribosomal protein S6 kinase
Rps6ka1
735Annotation score:
E9PWV3E9PWV3_MOUSE
Ribosomal protein S6 kinase
Rps6ka1
719Annotation score:
F6RQA2F6RQA2_MOUSE
Ribosomal protein S6 kinase
Rps6ka1
736Annotation score:
G3UZI3G3UZI3_MOUSE
Non-specific serine/threonine prote...
Rps6ka1
625Annotation score:
F6Q8A4F6Q8A4_MOUSE
Ribosomal protein S6 kinase alpha-1
Rps6ka1
741Annotation score:

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

Similar proteinsi

Entry informationi

Entry nameiKS6A1_MOUSE
AccessioniPrimary (citable) accession number: P18653
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: September 12, 2018
This is version 166 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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