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Protein

Ribosomal protein S6 kinase alpha-5

Gene

Rps6ka5

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 is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-359, Thr-645 and Thr-764 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-211, Ser-375 and Ser-380 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-814, Ser-816 and Ser-822 in its own C-terminal region.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei80ATPPROSITE-ProRule annotation1
Active sitei176Proton acceptorBy similarity1
Binding sitei454ATPPROSITE-ProRule annotation1
Active sitei608Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi54 – 62ATPPROSITE-ProRule annotation9
Nucleotide bindingi431 – 440ATPPROSITE-ProRule annotation10

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • histone kinase activity (H3-S10 specific) Source: GO_Central
  • magnesium ion binding Source: InterPro
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Inflammatory response, Stress response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-198753. ERK/MAPK targets.
R-MMU-199920. CREB phosphorylation.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-5621575. CD209 (DC-SIGN) signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribosomal protein S6 kinase alpha-5 (EC:2.7.11.1)
Short name:
S6K-alpha-5
Alternative name(s):
90 kDa ribosomal protein S6 kinase 5
Nuclear mitogen- and stress-activated protein kinase 1
RSK-like protein kinase
Short name:
RLSK
Gene namesi
Name:Rps6ka5
Synonyms:Msk1
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1920336. Rps6ka5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862081 – 863Ribosomal protein S6 kinase alpha-5Add BLAST863

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211Phosphoserine; by autocatalysisBy similarity1
Modified residuei359Phosphoserine; by MAPK1, MAPK3 and MAPK14By similarity1
Modified residuei375Phosphoserine; by autocatalysisBy similarity1
Modified residuei380Phosphoserine; by autocatalysisBy similarity1
Modified residuei645Phosphothreonine; by MAPK1, MAPK3 and MAPK14By similarity1
Modified residuei711PhosphoserineBy similarity1
Modified residuei721PhosphoserineBy similarity1
Modified residuei755PhosphoserineCombined sources1
Modified residuei759PhosphoserineBy similarity1
Modified residuei764PhosphothreonineCombined sources1
Modified residuei814Phosphoserine; by autocatalysisBy similarity1
Modified residuei816Phosphoserine; by autocatalysisBy similarity1
Modified residuei822Phosphoserine; by autocatalysisBy similarity1
Modified residuei862PhosphoserineCombined sources1

Post-translational modificationi

Ser-375 and Thr-645 phosphorylation is required for kinase activity. Ser-375 and Ser-211 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-359, Thr-645 and Thr-764 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-814, Ser-816 and Ser-822 by the N-terminal kinase domain (By similarity).By similarity
Ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8C050.
PeptideAtlasiQ8C050.
PRIDEiQ8C050.

PTM databases

iPTMnetiQ8C050.
PhosphoSitePlusiQ8C050.

Expressioni

Gene expression databases

BgeeiENSMUSG00000021180.
CleanExiMM_RPS6KA5.
GenevisibleiQ8C050. MM.

Interactioni

Subunit structurei

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RaraP114162EBI-8391218,EBI-346736

Protein-protein interaction databases

BioGridi215759. 6 interactors.
IntActiQ8C050. 2 interactors.
MINTiMINT-4116279.
STRINGi10090.ENSMUSP00000042987.

Structurei

3D structure databases

ProteinModelPortaliQ8C050.
SMRiQ8C050.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 317Protein kinase 1PROSITE-ProRule annotationAdd BLAST270
Domaini318 – 386AGC-kinase C-terminalAdd BLAST69
Domaini428 – 675Protein kinase 2PROSITE-ProRule annotationAdd BLAST248

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 2 protein kinase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0603. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ8C050.
KOiK04445.
OMAiHDKSLTC.
OrthoDBiEOG091G01KO.
PhylomeDBiQ8C050.
TreeFamiTF313438.

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. 3 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. 3 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2Curated (identifier: Q8C050-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGEGGGSGG AGTSGDSGDG GEQLLTVKHE LRTANLTGHA EKVGIENFEL
60 70 80 90 100
LKVLGTGAYG KVFLVRKISG HDAGKLYAMK VLKKATIVQK AKTTEHTRTE
110 120 130 140 150
RQVLEHIRQS PFLVTLHYAF QTETKLHLIL DYINGGELFT HLSQRERFTE
160 170 180 190 200
HEVQIYVGEI VLALEHLHKL GIIYRDIKLE NILLDSNGHV VLTDFGLSKE
210 220 230 240 250
FVADETERAY SFCGTIEYMA PDIVRGGDSG HDKAVDWWSL GVLMYELLTG
260 270 280 290 300
ASPFTVDGEK NSQAEISRRI LKSEPPYPQE MSTVAKDLLQ RLLMKDPKKR
310 320 330 340 350
LGCGPRDAEE IKEHLFFEKI KWDDLAAKKV PAPFKPVIRD ELDVSNFAEE
360 370 380 390 400
FTEMDPTYSP AALPQSSERL FQGYSFVAPS ILFKRNAAVI DPLQFHMGVD
410 420 430 440 450
RPGVTNVARS AMMKDSPFYQ HYDLDLKDKP LGEGSFSICR KCVHKKTNQA
460 470 480 490 500
FAVKIISKRM EANTQKEITA LKLCEGHPNI VKLHEVFHDQ VAASAQPPGQ
510 520 530 540 550
VVLCSLLLLA LLFNRSLTRK PVTWTWLVHS TSQLPPLPPP MPEIVLFILL
560 570 580 590 600
SDNGQLHTFL VMELLNGGEL FERIKRKKHF SETEASYIMR KLVSAVSHMH
610 620 630 640 650
DVGVVHRDLK PENLLFTDEN DNLEIKVIDF GFARLKPPDN QPLKTPCFTL
660 670 680 690 700
HYAAPELLTH NGYDESCDLW SLGVILYTML SGQVPFQSHD RSLTCTSAVE
710 720 730 740 750
IMKKIKKGDF SFEGEAWKNV SQEAKDLIQG LLTVDPNKRL KMSGLRYNEW
760 770 780 790 800
LQDGSQLSSN PLMTPDILGS SGAAVHTCVK ATFHAFNKYK REGFCLQNVD
810 820 830 840 850
KAPLAKRRKM KRTSTSTETR SSSSESSRSS SSQSHGKTTP TKTLQPSNPT
860
EGSNPDTLFQ FSD
Length:863
Mass (Da):96,583
Last modified:October 24, 2003 - v2
Checksum:i7A3C76D4036EA3EA
GO
Isoform 1Curated (identifier: Q8C050-2) [UniParc]FASTAAdd to basket
Also known as: 5Curated

The sequence of this isoform differs from the canonical sequence as follows:
     490-554: Missing.

Show »
Length:798
Mass (Da):89,515
Checksum:i57AB12399BEF7B0E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2 – 15EGEGG…AGTSG → GGRAAAAAARAPAE in AAQ24165 (Ref. 1) CuratedAdd BLAST14
Sequence conflicti117H → N in BAC27809 (PubMed:16141072).Curated1
Sequence conflicti376F → Y in BAC27809 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_050613490 – 554Missing in isoform 1. 3 PublicationsAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY341873 mRNA. Translation: AAQ24158.1.
AY341881 mRNA. Translation: AAQ24165.1.
AK032316 mRNA. Translation: BAC27809.1.
BC035298 mRNA. Translation: AAH35298.1.
CCDSiCCDS26107.1. [Q8C050-1]
RefSeqiNP_705815.1. NM_153587.3. [Q8C050-1]
UniGeneiMm.220417.
Mm.392855.

Genome annotation databases

EnsembliENSMUST00000043599; ENSMUSP00000042987; ENSMUSG00000021180. [Q8C050-1]
GeneIDi73086.
KEGGimmu:73086.
UCSCiuc007ost.1. mouse. [Q8C050-1]
uc007osu.1. mouse. [Q8C050-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY341873 mRNA. Translation: AAQ24158.1.
AY341881 mRNA. Translation: AAQ24165.1.
AK032316 mRNA. Translation: BAC27809.1.
BC035298 mRNA. Translation: AAH35298.1.
CCDSiCCDS26107.1. [Q8C050-1]
RefSeqiNP_705815.1. NM_153587.3. [Q8C050-1]
UniGeneiMm.220417.
Mm.392855.

3D structure databases

ProteinModelPortaliQ8C050.
SMRiQ8C050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi215759. 6 interactors.
IntActiQ8C050. 2 interactors.
MINTiMINT-4116279.
STRINGi10090.ENSMUSP00000042987.

PTM databases

iPTMnetiQ8C050.
PhosphoSitePlusiQ8C050.

Proteomic databases

PaxDbiQ8C050.
PeptideAtlasiQ8C050.
PRIDEiQ8C050.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000043599; ENSMUSP00000042987; ENSMUSG00000021180. [Q8C050-1]
GeneIDi73086.
KEGGimmu:73086.
UCSCiuc007ost.1. mouse. [Q8C050-1]
uc007osu.1. mouse. [Q8C050-2]

Organism-specific databases

CTDi9252.
MGIiMGI:1920336. Rps6ka5.

Phylogenomic databases

eggNOGiKOG0603. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00860000133668.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ8C050.
KOiK04445.
OMAiHDKSLTC.
OrthoDBiEOG091G01KO.
PhylomeDBiQ8C050.
TreeFamiTF313438.

Enzyme and pathway databases

ReactomeiR-MMU-198753. ERK/MAPK targets.
R-MMU-199920. CREB phosphorylation.
R-MMU-375165. NCAM signaling for neurite out-growth.
R-MMU-5621575. CD209 (DC-SIGN) signaling.

Miscellaneous databases

PROiQ8C050.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021180.
CleanExiMM_RPS6KA5.
GenevisibleiQ8C050. 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. 3 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. 3 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 nameiKS6A5_MOUSE
AccessioniPrimary (citable) accession number: Q8C050
Secondary accession number(s): Q8CI92
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: October 24, 2003
Last modified: November 30, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Enzyme activity requires the presence of both kinase domains.By similarity

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.