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Protein

Ribosomal protein S6 kinase alpha-2

Gene

Rps6ka2

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 transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-218 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei91ATPPROSITE-ProRule annotation1
Active sitei184Proton acceptorBy similarity1
Binding sitei444ATPPROSITE-ProRule annotation1
Active sitei532Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi65 – 73ATPPROSITE-ProRule annotation9
Nucleotide bindingi421 – 429ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • protein kinase activity Source: MGI
  • protein serine/threonine/tyrosine kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: MGI
  • ribosomal protein S6 kinase activity Source: MGI

GO - Biological processi

  • brain renin-angiotensin system Source: MGI
  • cardiac muscle cell apoptotic process Source: MGI
  • cellular response to carbohydrate stimulus Source: MGI
  • heart contraction Source: MGI
  • heart development Source: MGI
  • intracellular signal transduction Source: GO_Central
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of meiotic nuclear division Source: MGI
  • oocyte maturation Source: MGI
  • peptidyl-serine phosphorylation Source: MGI
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of gene expression Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of protein processing Source: MGI

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-2 (EC:2.7.11.1)
Short name:
S6K-alpha-2
Alternative name(s):
90 kDa ribosomal protein S6 kinase 2
Short name:
p90-RSK 2
Short name:
p90RSK2
MAP kinase-activated protein kinase 1c
Short name:
MAPK-activated protein kinase 1c
Short name:
MAPKAP kinase 1c
Short name:
MAPKAPK-1c
Protein-tyrosine kinase Mpk-9
Ribosomal S6 kinase 3
Short name:
RSK-3
pp90RSK3
Gene namesi
Name:Rps6ka2
Synonyms:Mapkapk1c, Rsk3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1342290. Rps6ka2.

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

Keywords - Diseasei

Tumor suppressor

Chemistry databases

ChEMBLiCHEMBL3351220.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862021 – 733Ribosomal protein S6 kinase alpha-2Add BLAST733

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei218Phosphoserine; by PDPK1By similarity1
Modified residuei377PhosphoserineCombined sources1

Post-translational modificationi

Activated by phosphorylation at Ser-218 by PDPK1. Autophosphorylated on Ser-377, as part of the activation process. May be phosphorylated at Thr-356 and Ser-360 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

MaxQBiQ9WUT3.
PaxDbiQ9WUT3.
PRIDEiQ9WUT3.

PTM databases

iPTMnetiQ9WUT3.
PhosphoSitePlusiQ9WUT3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000023809.
CleanExiMM_RPS6KA2.
GenevisibleiQ9WUT3. MM.

Interactioni

Subunit structurei

Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation (By similarity).By similarity

Protein-protein interaction databases

BioGridi203015. 1 interactor.
IntActiQ9WUT3. 4 interactors.
MINTiMINT-1486826.
STRINGi10090.ENSMUSP00000024575.

Structurei

3D structure databases

ProteinModelPortaliQ9WUT3.
SMRiQ9WUT3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini59 – 318Protein kinase 1PROSITE-ProRule annotationAdd BLAST260
Domaini319 – 388AGC-kinase C-terminalAdd BLAST70
Domaini415 – 672Protein kinase 2PROSITE-ProRule annotationAdd BLAST258

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00890000139324.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ9WUT3.
KOiK04373.
OMAiTMDYLHS.
OrthoDBiEOG091G05Z7.
PhylomeDBiQ9WUT3.
TreeFamiTF313438.

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.

Sequencei

Sequence statusi: Complete.

Q9WUT3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELSMKKFTV RRFFSVYLRK KSRSKSSSLS RLEEEGIVKE IDISNHVKEG
60 70 80 90 100
FEKADPSQFE LLKVLGQGSY GKVFLVRKVT GSDAGQLYAM KVLKKATLKV
110 120 130 140 150
RDRVRSKMER DILAEVNHPF IVKLHYAFQT EGKLYLILDF LRGGDLFTRL
160 170 180 190 200
SKEVMFTEED VKFYLAELAL ALDHLHGLGI IYRDLKPENI LLDEEGHIKI
210 220 230 240 250
TDFGLSKEAT DHDKRAYSFC GTIEYMAPEV VNRRGHTQSA DWWSFGVLMF
260 270 280 290 300
EMLTGSLPFQ GKDRKETMAL ILKAKLGMPQ FLSAEAQSLL RALFKRNPCN
310 320 330 340 350
RLGAGVDGVE EIKRHPFFVT IDWNKLYRKE IKPPFKPAVG RPEDTFHFDP
360 370 380 390 400
EFTARTPTDS PGVPPSANAH HLFRGFSFVA SSLVQEPSQQ DVPKAPIHPI
410 420 430 440 450
VQQLHGNNIH FTDGYEIKED IGVGSYSVCK RCVHKATDAE YAVKIIDKSK
460 470 480 490 500
RDPSEEIEIL LRYGQHPNII TLKDVYDDGK YVYLVMELMR GGELLDRILR
510 520 530 540 550
QRCFSEREAS DVLYTIARTM DYLHSQGVVH RDLKPSNILY MDESGNPESI
560 570 580 590 600
RICDFGFAKQ LRAENGLLMT PCYTANFVAP EVLKRQGYDA ACDVWSLGIL
610 620 630 640 650
LYTMLAGFTP FANGPDDTPE EILARIGSGK YALSGGNWDS ISDAAKDVVS
660 670 680 690 700
KMLHVDPQQR LTAVQVLKHP WIVNREYLSQ NQLSRQDVHL VKGAMAATYF
710 720 730
ALNRTPQAPR LEPVLSSSLA QRRGMKRLTS TRL
Length:733
Mass (Da):83,157
Last modified:November 1, 1999 - v1
Checksum:i49C1390316CFCE91
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti72K → E in BAB31901 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ131021 mRNA. Translation: CAB44492.1.
AK019881 mRNA. Translation: BAB31901.1.
BC043064 mRNA. Translation: AAH43064.1.
BC051079 mRNA. Translation: AAH51079.1.
BC056946 mRNA. Translation: AAH56946.1.
X57237 mRNA. Translation: CAA40513.1.
CCDSiCCDS28376.1.
RefSeqiNP_035429.1. NM_011299.4.
UniGeneiMm.268383.

Genome annotation databases

EnsembliENSMUST00000024575; ENSMUSP00000024575; ENSMUSG00000023809.
GeneIDi20112.
KEGGimmu:20112.
UCSCiuc008aih.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiKS6A2_MOUSE
AccessioniPrimary (citable) accession number: Q9WUT3
Secondary accession number(s): Q9D2C0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: November 22, 2017
This is version 167 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

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