Reviewed, UniProtKB/Swiss-Prot Q15418 (KS6A1_HUMAN)

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
    p90-RSK 1
    pp90RSK1
    p90S6K
    Ribosomal S6 kinase 1
      Short name=RSK-1
    MAP kinase-activated protein kinase 1a
      Short name=MAPKAPK1A

Gene names

Name:	RPS6KA1
Synonyms:	RSK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	735 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of the transcription factor CREB.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by multiple phosphorylations on threonine and serine residues.
Subunit structure	Forms a complex with either ERK1 or ERK2 in quiescent cells. Transiently dissociates following mitogenic stimulation.
Post-translational modification	Autophosphorylated on Ser-380, as part of the activation process.
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
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro protein kinase cascade Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREB1	P16220	1	EBI-963034,EBI-711855

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 735

735

Ribosomal protein S6 kinase alpha-1

PRO_0000086198

Regions

Domain

62 – 321

260

Protein kinase 1

Domain

322 – 391

70

AGC-kinase C-terminal

Domain

418 – 675

258

Protein kinase 2

Nucleotide binding

68 – 76

9

ATP By similarity

Nucleotide binding

424 – 432

9

ATP By similarity

Sites

Active site

187

1

Proton acceptor By similarity

Active site

535

1

Proton acceptor By similarity

Binding site

94

1

ATP By similarity

Binding site

447

1

ATP By similarity

Amino acid modifications

Modified residue

221

1

Phosphoserine

Modified residue

225

1

Phosphothreonine

Modified residue

348

1

Phosphothreonine

Modified residue

359

1

Phosphothreonine

Modified residue

363

1

Phosphoserine

Modified residue

369

1

Phosphoserine

Modified residue

380

1

Phosphoserine; by autocatalysis

Modified residue

573

1

Phosphothreonine

Modified residue

732

1

Phosphoserine

Natural variations

Natural variant

335

1

K → T: dbSNP rs3816540.

VAR_021864

Secondary structure

1

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735

Helix Strand Turn

Details...

Helix

59 – 61

3

Beta strand

62 – 71

10

Beta strand

74 – 81

8

Beta strand

83 – 86

4

Beta strand

90 – 96

7

Beta strand

127 – 133

7

Beta strand

136 – 141

6

Helix

149 – 156

8

Helix

161 – 180

20

Helix

190 – 192

3

Beta strand

193 – 195

3

Beta strand

197 – 199

3

Beta strand

201 – 203

3

Helix

226 – 228

3

Helix

231 – 234

4

Helix

241 – 257

17

Helix

267 – 276

10

Helix

287 – 296

10

Turn

301 – 303

3

Beta strand

307 – 310

4

Helix

312 – 316

5

Helix

319 – 321

3

Helix

326 – 330

5

Sequences

	Sequence		Length	Mass (Da)
	Q15418-1 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 765731A4442A53DF	FASTA	735	82,723
	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

References

	« Hide 'large scale' referencesShow '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: 8141249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-335.
[2]	"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. , 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[4]	"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: 9687510] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"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: 9430688] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT SER-221; THR-359; SER-363; SER-380; THR-573 AND SER-732.
[6]	"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: 12832467] [Abstract] Cited for: INTERACTION WITH MAPK1 OR MAPK3.
[7]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, MASS SPECTROMETRY.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221; THR-225; THR-359; SER-363; SER-369 AND SER-380, MASS SPECTROMETRY.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369; SER-380 AND THR-573, MASS SPECTROMETRY.
[11]	"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. , 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: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-335.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L07597 mRNA. Translation: AAC82497.1.
AL109743 Genomic DNA. Translation: CAC36348.1.
AL627313 Genomic DNA. Translation: CAI14647.1.
AL627313 Genomic DNA. Translation: CAI14648.1.
AL627313 Genomic DNA. Translation: CAI14649.1.
BC014966 mRNA. Translation: AAH14966.1.

PIR

I51901.

RefSeq

NP_001006666.1.
NP_002944.2.

UniGene

Hs.149957

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z7Q	X-ray	2.00	A	33-353	[»]
2Z7R	X-ray	2.00	A	33-353	[»]
2Z7S	X-ray	2.10	A	33-353	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15418.

PTM databases

PhosphoSite

Q15418.

Genome annotation databases

Ensembl

ENSG00000117676. Homo sapiens. [Contig view]

GeneID

6195.