Ribosomal protein S6 kinase alpha-1

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P18653 (KS6A1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 117. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from electronic annotation. Source: InterPro negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of hepatic stellate cell activation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle Inferred from direct assay PubMed 15509711. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 724

724

Ribosomal protein S6 kinase alpha-1

PRO_0000086199

Regions

Domain

62 – 310

249

Protein kinase 1

Domain

311 – 380

AGC-kinase C-terminal

Domain

407 – 664

258

Protein kinase 2

Nucleotide binding

68 – 76

ATP By similarity

Nucleotide binding

413 – 421

ATP By similarity

Sites

Active site

187

Proton acceptor By similarity

Active site

524

Proton acceptor By similarity

Binding site

ATP By similarity

Binding site

436

ATP By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

221

Phosphoserine; by PDPK1 By similarity

Modified residue

296

Phosphoserine By similarity

Modified residue

337

Phosphothreonine By similarity

Modified residue

348

Phosphothreonine By similarity

Modified residue

352

Phosphoserine By similarity

Modified residue

358

Phosphoserine By similarity

Modified residue

369

Phosphoserine; by autocatalysis By similarity

Modified residue

562

Phosphothreonine By similarity

Modified residue

721

Phosphoserine Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

P18653 [UniParc].

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

724

81,595

        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

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References

	« Hide 'large scale' referencesShow '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-721, MASS SPECTROMETRY. Tissue: Liver.
[3]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, MASS SPECTROMETRY. Tissue: Melanoma.
[4]	"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, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M28489 mRNA. Translation: AAA50300.1.
IPI	IPI00114332.
PIR	B32571.
UniGene	Mm.301827.
3D structure databases
ProteinModelPortal	P18653.
SMR	P18653. Positions 53-698.
ModBase	Search...
Protein-protein interaction databases
IntAct	P18653. 1 interaction.
MINT	MINT-1486951.
PTM databases
PhosphoSite	P18653.
Proteomic databases
PaxDb	P18653.
PRIDE	P18653.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000003741; ENSMUSP00000003741; ENSMUSG00000003644.
Organism-specific databases
MGI	MGI:104558. Rps6ka1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099806.
HOGENOM	HOG000233033.
HOVERGEN	HBG108317.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
ArrayExpress	P18653.
Bgee	P18653.
CleanEx	MM_RPS6KA1.
Genevestigator	P18653.
GermOnline	ENSMUSG00000003644. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR000719. Prot_kinase_cat_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]
Pfam	PF00069. Pkinase. 2 hits. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000606. Ribsml_S6_kin_2. 1 hit.
SMART	SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 2 hits. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 2 hits.
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. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

KS6A1_MOUSE

Accession

Primary (citable) accession number: P18653

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents