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Q15418 (KS6A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length735 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, 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. Ref.7 Ref.12

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. Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus. Cytoplasm Ref.6 Ref.12.

Post-translational modification

Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-380, as part of the activation process. May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and MAPK3/ERK1. Ref.7

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

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
   Biological processCell cycle
Stress response
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 18402937. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of cell differentiation

Traceable author statement Ref.22. Source: UniProtKB

positive regulation of cell growth

Traceable author statement Ref.22. Source: UniProtKB

positive regulation of hepatic stellate cell activation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 22065586. Source: BHF-UCL

regulation of DNA-templated transcription in response to stress

Traceable author statement Ref.22. Source: UniProtKB

regulation of translation in response to stress

Traceable author statement Ref.22. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

spindle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from direct assay PubMed 18402937. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

protein serine/threonine kinase activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSP90AB1P082382EBI-963034,EBI-352572
VASPP505524EBI-963034,EBI-748201

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15418-1)

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.
Isoform 2 (identifier: Q15418-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MPLAQLKEPW...GEEAGLQPSK → MEQDPKPPRL...GPGSGPQRDS
Isoform 3 (identifier: Q15418-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 735735Ribosomal protein S6 kinase alpha-1
PRO_0000086198

Regions

Domain62 – 321260Protein kinase 1
Domain322 – 39170AGC-kinase C-terminal
Domain418 – 675258Protein kinase 2
Nucleotide binding68 – 769ATP By similarity
Nucleotide binding424 – 4329ATP By similarity

Sites

Active site1871Proton acceptor By similarity
Active site5351Proton acceptor By similarity
Binding site941ATP By similarity
Binding site4471ATP By similarity

Amino acid modifications

Modified residue541Phosphoserine Ref.24
Modified residue2211Phosphoserine; by PDPK1 Probable
Modified residue3071Phosphoserine Ref.24
Modified residue3481Phosphothreonine
Modified residue3591Phosphothreonine Ref.7 Ref.21 Ref.23 Ref.24 Ref.27
Modified residue3631Phosphoserine Ref.7 Ref.21 Ref.23 Ref.24 Ref.27
Modified residue3691Phosphoserine Ref.23 Ref.24
Modified residue3801Phosphoserine; by autocatalysis Ref.7 Ref.21 Ref.23 Ref.24 Ref.25
Modified residue5731Phosphothreonine Ref.7
Modified residue7321Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 9292Missing in isoform 3.
VSP_041580
Alternative sequence1 – 3636MPLAQ…LQPSK → MEQDPKPPRLRLWALIPWLP RKQRPRISQTSLPVPGPGSG PQRDS in isoform 2.
VSP_041380
Natural variant3351K → T. Ref.1 Ref.29
Corresponds to variant rs2229712 [ dbSNP | Ensembl ].
VAR_021864

Experimental info

Sequence conflict6091A → T in BAF85411. Ref.2
Sequence conflict6191S → G in BAF85411. Ref.2

Secondary structure

............................................................................................. 735
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: 765731A4442A53DF

FASTA73582,723
        10         20         30         40         50         60 
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEGV LKEISITHHV KAGSEKADPS 

        70         80         90        100        110        120 
HFELLKVLGQ 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 PEVVNRQGHS 

       250        260        270        280        290        300 
HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN 

       310        320        330        340        350        360 
PANRLGSGPD GAEEIKRHVF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY FDTEFTSRTP 

       370        380        390        400        410        420 
KDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRAPQAPL HSVVQQLHGK NLVFSDGYVV 

       430        440        450        460        470        480 
KETIGVGSYS ECKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP NIITLKDVYD 

       490        500        510        520        530        540 
DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIG KTVEYLHSQG VVHRDLKPSN 

       550        560        570        580        590        600 
ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL 

       610        620        630        640        650        660 
GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD LVSKMLHVDP 

       670        680        690        700        710        720 
HQRLTAKQVL QHPWVTQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP TPQLKPIESS 

       730 
ILAQRRVRKL PSTTL 

« Hide

Isoform 2 [UniParc].

Checksum: 3121E64369EBDBBF
Show »

FASTA74483,932
Isoform 3 [UniParc].

Checksum: B8362021FCCC17B5
Show »

FASTA64372,698

References

« Hide 'large scale' references
[1]"Human rsk isoforms: cloning and characterization of tissue-specific expression."
Moller D.E., Xia C.-H., Tang W., Zhu A.X., Jakubowski M.
Am. J. Physiol. 266:C351-C359(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-335.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Testis and Thyroid.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[6]"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB."
Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.
EMBO J. 17:4426-4441(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK."
Dalby K.N., Morrice N., Caudwell F.B., Avruch J., Cohen P.
J. Biol. Chem. 273:1496-1505(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT SER-221; THR-359; SER-363; SER-380; THR-573 AND SER-732.
[8]"Rsk1 mediates a MEK-MAP kinase cell survival signal."
Shimamura A., Ballif B.A., Richards S.A., Blenis J.
Curr. Biol. 10:127-135(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[9]"C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival."
Buck M., Poli V., Hunter T., Chojkier M.
Mol. Cell 8:807-816(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CEBPB.
[10]"Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 kinase 1 and protein kinase A."
Wu J., Janknecht R.
J. Biol. Chem. 277:42669-42679(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, INTERACTION WITH ETV1/ER81.
[11]"Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity."
Roux P.P., Richards S.A., Blenis J.
Mol. Cell. Biol. 23:4796-4804(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK1 OR MAPK3.
[12]"90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling."
Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.
J. Biol. Chem. 279:29325-29335(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FGFR1, ENZYME REGULATION, SUBCELLULAR LOCATION.
[13]"Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase."
Roux P.P., Ballif B.A., Anjum R., Gygi S.P., Blenis J.
Proc. Natl. Acad. Sci. U.S.A. 101:13489-13494(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTOR SIGNALING, INTERACTION WITH TSC2.
[14]"The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling."
Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.
Curr. Biol. 15:1762-1767(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF DAPK1.
[15]"Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation."
Wingate A.D., Campbell D.G., Peggie M., Arthur J.S.
Biochem. J. 393:715-724(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NR4A1/NUR77.
[16]"The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity."
Shahbazian D., Roux P.P., Mieulet V., Cohen M.S., Raught B., Taunton J., Hershey J.W., Blenis J., Pende M., Sonenberg N.
EMBO J. 25:2781-2791(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRANSLATION REGULATION, FUNCTION IN PHOSPHORYLATION OF EIF4B.
[17]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation."
Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J., Sonenberg N., Blenis J.
J. Biol. Chem. 282:14056-14064(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RPS6.
[19]"Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation."
Carriere A., Cargnello M., Julien L.A., Gao H., Bonneil E., Thibault P., Roux P.P.
Curr. Biol. 18:1269-1277(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTOR SIGNALING.
[20]"The RSK factors of activating the Ras/MAPK signaling cascade."
Carriere A., Ray H., Blenis J., Roux P.P.
Front. Biosci. 13:4258-4275(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[21]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363 AND SER-380, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"The RSK family of kinases: emerging roles in cellular signalling."
Anjum R., Blenis J.
Nat. Rev. Mol. Cell Biol. 9:747-758(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[23]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369 AND SER-380, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-307; THR-359; SER-363; SER-369 AND SER-380, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors."
Ikuta M., Kornienko M., Byrne N., Reid J.C., Mizuarai S., Kotani H., Munshi S.K.
Protein Sci. 16:2626-2635(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 33-353 IN COMPLEX WITH INHIBITOR.
[29]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-335.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L07597 mRNA. Translation: AAC82497.1.
AK292722 mRNA. Translation: BAF85411.1.
AK299007 mRNA. Translation: BAH12926.1.
AK315730 mRNA. Translation: BAG38085.1.
AL109743 Genomic DNA. Translation: CAC36348.1.
AL627313 Genomic DNA. Translation: CAI14647.1.
AL627313 Genomic DNA. Translation: CAI14648.1.
AL627313 Genomic DNA. Translation: CAI14649.1.
CH471059 Genomic DNA. Translation: EAX07799.1.
BC014966 mRNA. Translation: AAH14966.1.
PIRI51901.
RefSeqNP_001006666.1. NM_001006665.1.
NP_002944.2. NM_002953.3.
XP_005246024.1. XM_005245967.2.
UniGeneHs.149957.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WNTX-ray2.40A/B413-719[»]
2Z7QX-ray2.00A33-353[»]
2Z7RX-ray2.00A33-353[»]
2Z7SX-ray2.10A33-353[»]
3RNYX-ray2.70A/B411-735[»]
3TEIX-ray2.40B712-735[»]
4H3PX-ray2.30B/E712-735[»]
ProteinModelPortalQ15418.
SMRQ15418. Positions 10-709.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112109. 203 interactions.
DIPDIP-29987N.
IntActQ15418. 28 interactions.
MINTMINT-207205.
STRING9606.ENSP00000363277.

Chemistry

BindingDBQ15418.
ChEMBLCHEMBL2553.
GuidetoPHARMACOLOGY1527.

PTM databases

PhosphoSiteQ15418.

Polymorphism databases

DMDM20178306.

2D gel databases

UCD-2DPAGEQ15418.

Proteomic databases

PaxDbQ15418.
PRIDEQ15418.

Protocols and materials databases

DNASU6195.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374162; ENSP00000363277; ENSG00000117676. [Q15418-3]
ENST00000374168; ENSP00000363283; ENSG00000117676. [Q15418-1]
ENST00000526792; ENSP00000431651; ENSG00000117676. [Q15418-3]
ENST00000531382; ENSP00000435412; ENSG00000117676. [Q15418-2]
GeneID6195.
KEGGhsa:6195.
UCSCuc001bmr.1. human. [Q15418-1]
uc001bms.1. human. [Q15418-2]

Organism-specific databases

CTD6195.
GeneCardsGC01P026856.
HGNCHGNC:10430. RPS6KA1.
HPACAB003852.
HPA007981.
MIM601684. gene.
neXtProtNX_Q15418.
PharmGKBPA34845.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108317.
KOK04373.
OMAPWITQKD.
OrthoDBEOG7B8S38.
PhylomeDBQ15418.
TreeFamTF313438.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_120956. Cellular responses to stress.
REACT_13685. Neuronal System.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkQ15418.

Gene expression databases

ArrayExpressQ15418.
BgeeQ15418.
CleanExHS_RPS6KA1.
GenevestigatorQ15418.

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

ChiTaRSRPS6KA1. human.
EvolutionaryTraceQ15418.
GeneWikiRPS6KA1.
GenomeRNAi6195.
NextBio24057.
PROQ15418.
SOURCESearch...

Entry information

Entry nameKS6A1_HUMAN
AccessionPrimary (citable) accession number: Q15418
Secondary accession number(s): A6NGG4 expand/collapse secondary AC list , A8K9K7, B2RDY8, B7Z5J0, Q5SVM5, Q5SVM8, Q5SVM9, Q96C05, Q9BQK2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 16, 2002
Last modified: April 16, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM