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P18653 (KS6A1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ribosomal protein S6 kinase alpha-1

Short name=S6K-alpha-1
EC=2.7.11.1
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 names
Name:Rps6ka1
Synonyms:Mapkapk1a, Rsk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length724 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 preinitiation 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). 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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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.

Subunit structure

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.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity.

Tissue specificity

Intestine, thymus, and lung.

Post-translational modification

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.

N-terminal myristoylation results in an activated kinase in the absence of added growth factors By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 2 protein kinase domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 724724Ribosomal protein S6 kinase alpha-1
PRO_0000086199

Regions

Domain62 – 310249Protein kinase 1
Domain311 – 38070AGC-kinase C-terminal
Domain407 – 664258Protein kinase 2
Nucleotide binding68 – 769ATP By similarity
Nucleotide binding413 – 4219ATP By similarity

Sites

Active site1871Proton acceptor By similarity
Active site5241Proton acceptor By similarity
Binding site941ATP By similarity
Binding site4361ATP By similarity

Amino acid modifications

Modified residue541Phosphoserine By similarity
Modified residue2211Phosphoserine; by PDPK1 By similarity
Modified residue2961Phosphoserine By similarity
Modified residue3371Phosphothreonine By similarity
Modified residue3481Phosphothreonine By similarity
Modified residue3521Phosphoserine By similarity
Modified residue3581Phosphoserine By similarity
Modified residue3691Phosphoserine; alternate Ref.2 Ref.3
Modified residue3691Phosphoserine; by autocatalysis; alternate By similarity
Modified residue5621Phosphothreonine By similarity
Modified residue7211Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P18653 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: A5D8E5E5FDBCE4BF

FASTA72481,595
        10         20         30         40         50         60 
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEAI LKEISITHHV KAGSEKADPS 

        70         80         90        100        110        120 
QFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN 

       130        140        150        160        170        180 
HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS 

       190        200        210        220        230        240 
LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHT 

       250        260        270        280        290        300 
HSADWWSYGV LMGKDRKETM TLILKAKLGM PQFLSTEAQS LLRALFKRNP ANRLGSGPDG 

       310        320        330        340        350        360 
AEEIKRHIFY STIDWNKLYR REIKPPFKPA VAQPDDTFYF DTEFTSRTPR DSPGIPPSAG 

       370        380        390        400        410        420 
AHQLFRGFSF VATGLMEDDG KPRTTQAPLH SVVQQLHGKN LVFSDGYVVK ETIGVGSYSV 

       430        440        450        460        470        480 
CKRCVHKATN MEYAVKVIDK SKRDPSEEIE ILLRYGQHPN IITLKDVYDD GKHVYLVTEL 

       490        500        510        520        530        540 
MRGGELLDKI LRQKFFSERE ASFVLHTISK TVEYLHSQGV VHRDLKPSNI LYVDESGNPE 

       550        560        570        580        590        600 
CLRICDFGFA KQLRAENGLL MTPCYTANFV APEVLKRQGY DEGCDIWSLG ILLYTMLAGY 

       610        620        630        640        650        660 
TPFANGPSDT PEEILTRIGS GKFTLSGGNW NTVSETAKDL VSKMLHVDPH QRLTAKQVLQ 

       670        680        690        700        710        720 
HPWITQKDKL PQSQLSHQDL QLVKGAMAAT YSALNSSKPT PQLKPIESSI LAQRRVRKLP 


STTL 

« Hide

References

« Hide 'large scale' references
[1]"Sequence and expression of chicken and mouse rsk: homologs of Xenopus laevis ribosomal S6 kinase."
Alcorta D.A., Crews C.M., Sweet L.J., Bankston L., Jones S.W., Erikson R.L.
Mol. Cell. Biol. 9:3850-3859(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[3]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M28489 mRNA. Translation: AAA50300.1.
CCDSCCDS71488.1.
PIRB32571.
RefSeqNP_001272434.1. NM_001285505.1.
UniGeneMm.301827.

3D structure databases

ProteinModelPortalP18653.
SMRP18653. Positions 10-698.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP18653. 4 interactions.
MINTMINT-1486951.

PTM databases

PhosphoSiteP18653.

Proteomic databases

MaxQBP18653.
PaxDbP18653.
PRIDEP18653.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003741; ENSMUSP00000003741; ENSMUSG00000003644.
GeneID20111.
KEGGmmu:20111.
UCSCuc012dmp.2. mouse.

Organism-specific databases

CTD6195.
MGIMGI:104558. Rps6ka1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110260.
HOGENOMHOG000233033.
HOVERGENHBG108317.
KOK04373.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressP18653.
BgeeP18653.
CleanExMM_RPS6KA1.
GenevestigatorP18653.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016239. Ribosomal_S6_kinase_II.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 2 hits.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 2 hits.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

PROP18653.
SOURCESearch...

Entry information

Entry nameKS6A1_MOUSE
AccessionPrimary (citable) accession number: P18653
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot