Q15418 (KS6A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	735 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. 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 process	Cell cycle Stress response
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing 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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll 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 nerve growth factor 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-dependent 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 stress-activated MAPK cascade Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome toll-like receptor 1 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
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome spindle Inferred from electronic annotation. Source: Compara
Molecular_function	ATP 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
HSP90AB1	P08238	2	EBI-963034,EBI-352572
VASP	P50552	4	EBI-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 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

54

1

Phosphoserine Ref.24

Modified residue

221

1

Phosphoserine; by PDPK1 Probable

Modified residue

307

1

Phosphoserine Ref.24

Modified residue

348

1

Phosphothreonine

Modified residue

359

1

Phosphothreonine Ref.7 Ref.21 Ref.23 Ref.24 Ref.27

Modified residue

363

1

Phosphoserine Ref.7 Ref.21 Ref.23 Ref.24 Ref.27

Modified residue

369

1

Phosphoserine Ref.23 Ref.24

Modified residue

380

1

Phosphoserine; by autocatalysis Ref.7 Ref.21 Ref.23 Ref.24 Ref.25

Modified residue

573

1

Phosphothreonine Ref.7

Modified residue

732

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

1 – 92

92

Missing in isoform 3.

VSP_041580

Alternative sequence

1 – 36

36

MPLAQ…LQPSK → MEQDPKPPRLRLWALIPWLP RKQRPRISQTSLPVPGPGSG PQRDS in isoform 2.

VSP_041380

Natural variant

335

1

K → T. Ref.1 Ref.29
Corresponds to variant rs2229712 [ dbSNP | Ensembl ].

VAR_021864

Experimental info

Sequence conflict

609

1

A → T in BAF85411. Ref.2

Sequence conflict

619

1

S → G in BAF85411. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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

Beta strand

418 – 427

10

Beta strand

430 – 437

8

Turn

438 – 440

3

Beta strand

443 – 450

8

Helix

457 – 466

10

Beta strand

475 – 480

6

Beta strand

482 – 489

8

Helix

497 – 502

6

Beta strand

503 – 505

3

Helix

509 – 528

20

Helix

538 – 540

3

Beta strand

541 – 545

5

Helix

550 – 552

3

Beta strand

553 – 555

3

Turn

574 – 576

3

Helix

588 – 609

22

Helix

622 – 631

10

Helix

639 – 643

5

Helix

646 – 655

10

Helix

660 – 662

3

Helix

666 – 670

5

Helix

673 – 676

4

Helix

678 – 680

3

Helix

691 – 707

17

Helix

717 – 719

3

Helix

721 – 726

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 3121E64369EBDBBF	FASTA	744	83,932
	10 20 30 40 50 60 MEQDPKPPRL RLWALIPWLP RKQRPRISQT SLPVPGPGSG PQRDSDEGVL KEISITHHVK 70 80 90 100 110 120 AGSEKADPSH FELLKVLGQG SFGKVFLVRK VTRPDSGHLY AMKVLKKATL KVRDRVRTKM 130 140 150 160 170 180 ERDILADVNH PFVVKLHYAF QTEGKLYLIL DFLRGGDLFT RLSKEVMFTE EDVKFYLAEL 190 200 210 220 230 240 ALGLDHLHSL GIIYRDLKPE NILLDEEGHI KLTDFGLSKE AIDHEKKAYS FCGTVEYMAP 250 260 270 280 290 300 EVVNRQGHSH SADWWSYGVL MFEMLTGSLP FQGKDRKETM TLILKAKLGM PQFLSTEAQS 310 320 330 340 350 360 LLRALFKRNP ANRLGSGPDG AEEIKRHVFY STIDWNKLYR REIKPPFKPA VAQPDDTFYF 370 380 390 400 410 420 DTEFTSRTPK DSPGIPPSAG AHQLFRGFSF VATGLMEDDG KPRAPQAPLH SVVQQLHGKN 430 440 450 460 470 480 LVFSDGYVVK ETIGVGSYSE CKRCVHKATN MEYAVKVIDK SKRDPSEEIE ILLRYGQHPN 490 500 510 520 530 540 IITLKDVYDD GKHVYLVTEL MRGGELLDKI LRQKFFSERE ASFVLHTIGK TVEYLHSQGV 550 560 570 580 590 600 VHRDLKPSNI LYVDESGNPE CLRICDFGFA KQLRAENGLL MTPCYTANFV APEVLKRQGY 610 620 630 640 650 660 DEGCDIWSLG ILLYTMLAGY TPFANGPSDT PEEILTRIGS GKFTLSGGNW NTVSETAKDL 670 680 690 700 710 720 VSKMLHVDPH QRLTAKQVLQ HPWVTQKDKL PQSQLSHQDL QLVKGAMAAT YSALNSSKPT 730 740 PQLKPIESSI LAQRRVRKLP STTL
	Isoform 3 [UniParc]. Checksum: B8362021FCCC17B5	FASTA	643	72,698
	10 20 30 40 50 60 MKVLKKATLK VRDRVRTKME RDILADVNHP FVVKLHYAFQ TEGKLYLILD FLRGGDLFTR 70 80 90 100 110 120 LSKEVMFTEE DVKFYLAELA LGLDHLHSLG IIYRDLKPEN ILLDEEGHIK LTDFGLSKEA 130 140 150 160 170 180 IDHEKKAYSF CGTVEYMAPE VVNRQGHSHS ADWWSYGVLM FEMLTGSLPF QGKDRKETMT 190 200 210 220 230 240 LILKAKLGMP QFLSTEAQSL LRALFKRNPA NRLGSGPDGA EEIKRHVFYS TIDWNKLYRR 250 260 270 280 290 300 EIKPPFKPAV AQPDDTFYFD TEFTSRTPKD SPGIPPSAGA HQLFRGFSFV ATGLMEDDGK 310 320 330 340 350 360 PRAPQAPLHS VVQQLHGKNL VFSDGYVVKE TIGVGSYSEC KRCVHKATNM EYAVKVIDKS 370 380 390 400 410 420 KRDPSEEIEI LLRYGQHPNI ITLKDVYDDG KHVYLVTELM RGGELLDKIL RQKFFSEREA 430 440 450 460 470 480 SFVLHTIGKT VEYLHSQGVV HRDLKPSNIL YVDESGNPEC LRICDFGFAK QLRAENGLLM 490 500 510 520 530 540 TPCYTANFVA PEVLKRQGYD EGCDIWSLGI LLYTMLAGYT PFANGPSDTP EEILTRIGSG 550 560 570 580 590 600 KFTLSGGNWN TVSETAKDLV SKMLHVDPHQ RLTAKQVLQH PWVTQKDKLP QSQLSHQDLQ 610 620 630 640 LVKGAMAATY SALNSSKPTP QLKPIESSIL AQRRVRKLPS TTL

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] [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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00017305.
IPI00477982.
IPI01011967.

PIR

I51901.

RefSeq

NP_001006666.1. NM_001006665.1.
NP_002944.2. NM_002953.3.

UniGene

Hs.149957.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WNT	X-ray	2.40	A/B	413-719	[»]
2Z7Q	X-ray	2.00	A	33-353	[»]
2Z7R	X-ray	2.00	A	33-353	[»]
2Z7S	X-ray	2.10	A	33-353	[»]
3RNY	X-ray	2.70	A/B	411-735	[»]
3TEI	X-ray	2.40	B	712-735	[»]
4H3P	X-ray	2.30	B/E	712-735	[»]

ProteinModelPortal

Q15418.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29987N.

IntAct

Q15418. 14 interactions.

MINT

MINT-207205.

STRING

9606.ENSP00000363277.

PTM databases

PhosphoSite

Q15418.

Polymorphism databases

DMDM

20178306.

2D gel databases

UCD-2DPAGE

Q15418.

Proteomic databases

PaxDb

Q15418.

PRIDE

Q15418.

Protocols and materials databases

DNASU

6195.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374162; ENSP00000363277; ENSG00000117676.
ENST00000374168; ENSP00000363283; ENSG00000117676.
ENST00000526792; ENSP00000431651; ENSG00000117676.
ENST00000531382; ENSP00000435412; ENSG00000117676.

GeneID

6195.

KEGG

hsa:6195.

UCSC

uc001bmr.1. human.
uc001bms.1. human.

Organism-specific databases

CTD

6195.

GeneCards

GC01P026856.

HGNC

HGNC:10430. RPS6KA1.

HPA

CAB003852.
HPA007981.

MIM

601684. gene.

neXtProt

NX_Q15418.

PharmGKB

PA34845.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG108317.

KO

K04373.

OMA

PWITQKD.

OrthoDB

EOG402WRK.

PhylomeDB

Q15418.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_13685. Neuronal System.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q15418.

Bgee

Q15418.

CleanEx

HS_RPS6KA1.

Genevestigator

Q15418.

GermOnline

ENSG00000117676. Homo sapiens.

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

BindingDB

Q15418.

ChEMBL

CHEMBL2553.

ChiTaRS

RPS6KA1. human.

EvolutionaryTrace

Q15418.

GenomeRNAi

6195.

NextBio

24057.

SOURCE

Search...

Entry information

Entry name

KS6A1_HUMAN

Accession

Primary (citable) accession number: Q15418
Secondary accession number(s): A6NGG4 , 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:	May 1, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.