P51812 (KS6A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribosomal protein S6 kinase alpha-3
Short name=S6K-alpha-3
EC=2.7.11.1

Alternative name(s):
90 kDa ribosomal protein S6 kinase 3
Short name=p90-RSK 3
Short name=p90RSK3
Insulin-stimulated protein kinase 1
Short name=ISPK-1
MAP kinase-activated protein kinase 1b
Short name=MAPK-activated protein kinase 1b
Short name=MAPKAP kinase 1b
Short name=MAPKAPK-1b
Ribosomal S6 kinase 2
Short name=RSK-2
pp90RSK2

Gene names

Name:	RPS6KA3
Synonyms:	ISPK1, MAPKAPK1B, RSK2

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	740 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 and histone H3 at 'Ser-10', 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. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.16
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-227 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD.
Subunit structure	Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation By similarity. Interacts with NFATC4, ETV1/ER81 and FGFR1. Ref.14
Subcellular location	Nucleus By similarity. Cytoplasm By similarity.
Tissue specificity	Expressed in many tissues, highest levels in skeletal muscle.
Post-translational modification	Activated by phosphorylation at Ser-227 by PDPK1. Autophosphorylated on Ser-386, as part of the activation process. May be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1. Can also be activated via phosphorylation at Ser-386 by MAPKAPK2. N-terminal myristoylation results in an activated kinase in the absence of added growth factors.
Involvement in disease	Coffin-Lowry syndrome (CLS) [MIM:303600]: A X-linked mental retardation associated with facial and digital dysmorphisms, progressive skeletal malformations, growth retardation, hearing deficit and paroxysmal movement disorders. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Mental retardation, X-linked 19 (MRX19) [MIM:300844]: A non-syndromic form of mild to moderate mental retardation. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.33
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 caution	The sequence BAD92170.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Cell cycle Stress response
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mental retardation
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 central nervous system development Traceable author statement Ref.30. Source: ProtInc innate immune response Traceable author statement. Source: Reactome negative regulation of apoptotic process Traceable author statement Ref.19. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of cell differentiation Traceable author statement Ref.19. Source: UniProtKB positive regulation of cell growth Traceable author statement Ref.19. 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.19. Source: UniProtKB regulation of translation in response to stress Traceable author statement Ref.19. Source: UniProtKB response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB skeletal system development Traceable author statement Ref.26. Source: ProtInc 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
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 Traceable author statement Ref.6. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 740

740

Ribosomal protein S6 kinase alpha-3

PRO_0000086203

Regions

Domain

68 – 327

260

Protein kinase 1

Domain

328 – 397

70

AGC-kinase C-terminal

Domain

422 – 679

258

Protein kinase 2

Nucleotide binding

74 – 82

9

ATP By similarity

Nucleotide binding

428 – 436

9

ATP By similarity

Sites

Active site

193

1

Proton acceptor By similarity

Active site

539

1

Proton acceptor By similarity

Binding site

100

1

ATP By similarity

Binding site

451

1

ATP By similarity

Amino acid modifications

Modified residue

227

1

Phosphoserine; by PDPK1 Probable

Modified residue

365

1

Phosphothreonine Ref.18 Ref.20 Ref.21 Ref.25

Modified residue

369

1

Phosphoserine Ref.18 Ref.20 Ref.21 Ref.25

Modified residue

375

1

Phosphoserine Ref.18 Ref.20 Ref.21

Modified residue

386

1

Phosphoserine; by autocatalysis and MAPKAPK2 Ref.18 Ref.21

Modified residue

415

1

Phosphoserine Ref.18 Ref.21 Ref.22

Modified residue

529

1

Phosphotyrosine; by FGFR3 By similarity

Modified residue

556

1

Phosphoserine Ref.18

Modified residue

715

1

Phosphoserine Ref.13 Ref.18 Ref.21 Ref.23

Natural variations

Natural variant

38

1

I → S. Ref.27 Ref.35
Corresponds to variant rs56218010 [ dbSNP | Ensembl ].

VAR_006188

Natural variant

75

1

G → V in CLS. Ref.26

VAR_006189

Natural variant

82

1

V → F in CLS. Ref.27

VAR_006190

Natural variant

114

1

R → W in CLS. Ref.28

VAR_006191

Natural variant

115

1

T → S in MRX19. Ref.33

VAR_065892

Natural variant

127

1

H → Q in CLS. Ref.27

VAR_006192

Natural variant

152

1

Missing in MRX19. Ref.33

VAR_065893

Natural variant

154

1

D → Y in CLS. Ref.27

VAR_006193

Natural variant

189

1

I → K in CLS. Ref.29

VAR_065894

Natural variant

202

1

Missing in MRX19. Ref.33

VAR_065895

Natural variant

225

1

A → V in CLS. Ref.27

VAR_006194

Natural variant

227

1

S → A in CLS. Ref.26

VAR_006195

Natural variant

268

1

F → S in CLS. Ref.31

VAR_065896

Natural variant

383

1

R → W in MRX19; kinase activity is decreased but not abolished. Ref.30

VAR_065897

Natural variant

416

1

I → V in a breast cancer sample; somatic mutation. Ref.34

VAR_035627

Natural variant

431

1

G → D in CLS. Ref.27

VAR_006196

Natural variant

477

1

Missing in CLS. Ref.32

VAR_065898

Natural variant

483

1

Y → C in a gastric adenocarcinoma sample; somatic mutation. Ref.35

VAR_040629

Natural variant

608

1

L → F in a glioblastoma multiforme sample; somatic mutation. Ref.35

VAR_040630

Natural variant

723

1

R → C. Ref.35
Corresponds to variant rs35026425 [ dbSNP | Ensembl ].

VAR_040631

Natural variant

729

1

R → Q in CLS. Ref.28
Corresponds to variant rs28935171 [ dbSNP | Ensembl ].

VAR_006197

Experimental info

Sequence conflict

89

1

S → L in AAH96303. Ref.5

Sequence conflict

410

1

Missing in BAD92170. Ref.3

Sequence conflict

424

1

V → L in AAC82495. Ref.6

Sequence conflict

480

1

K → N in AAC82495. Ref.6

Sequence conflict

494

1

Missing in AAC82495. Ref.6

Secondary structure

1

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740

Helix Strand Turn

Details...

Helix

412 – 414

3

Turn

419 – 421

3

Beta strand

422 – 430

9

Beta strand

432 – 441

10

Turn

442 – 445

4

Beta strand

446 – 454

9

Turn

455 – 457

3

Helix

461 – 470

10

Beta strand

479 – 484

6

Beta strand

486 – 494

9

Helix

501 – 506

6

Helix

513 – 532

20

Helix

542 – 544

3

Beta strand

545 – 551

7

Helix

554 – 556

3

Beta strand

557 – 559

3

Helix

587 – 613

27

Helix

626 – 635

10

Helix

643 – 645

3

Helix

650 – 659

10

Turn

664 – 666

3

Helix

670 – 673

4

Helix

677 – 680

4

Helix

682 – 684

3

Helix

696 – 710

15

Sequences

	Sequence		Length	Mass (Da)
	P51812 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 486AE8357CEAB6C8	FASTA	740	83,736
	10 20 30 40 50 60 MPLAQLADPW QKMAVESPSD SAENGQQIMD EPMGEEEINP QTEEVSIKEI AITHHVKEGH 70 80 90 100 110 120 EKADPSQFEL LKVLGQGSFG KVFLVKKISG SDARQLYAMK VLKKATLKVR DRVRTKMERD 130 140 150 160 170 180 ILVEVNHPFI VKLHYAFQTE GKLYLILDFL RGGDLFTRLS KEVMFTEEDV KFYLAELALA 190 200 210 220 230 240 LDHLHSLGII YRDLKPENIL LDEEGHIKLT DFGLSKESID HEKKAYSFCG TVEYMAPEVV 250 260 270 280 290 300 NRRGHTQSAD WWSFGVLMFE MLTGTLPFQG KDRKETMTMI LKAKLGMPQF LSPEAQSLLR 310 320 330 340 350 360 MLFKRNPANR LGAGPDGVEE IKRHSFFSTI DWNKLYRREI HPPFKPATGR PEDTFYFDPE 370 380 390 400 410 420 FTAKTPKDSP GIPPSANAHQ LFRGFSFVAI TSDDESQAMQ TVGVHSIVQQ LHRNSIQFTD 430 440 450 460 470 480 GYEVKEDIGV GSYSVCKRCI HKATNMEFAV KIIDKSKRDP TEEIEILLRY GQHPNIITLK 490 500 510 520 530 540 DVYDDGKYVY VVTELMKGGE LLDKILRQKF FSEREASAVL FTITKTVEYL HAQGVVHRDL 550 560 570 580 590 600 KPSNILYVDE SGNPESIRIC DFGFAKQLRA ENGLLMTPCY TANFVAPEVL KRQGYDAACD 610 620 630 640 650 660 IWSLGVLLYT MLTGYTPFAN GPDDTPEEIL ARIGSGKFSL SGGYWNSVSD TAKDLVSKML 670 680 690 700 710 720 HVDPHQRLTA ALVLRHPWIV HWDQLPQYQL NRQDAPHLVK GAMAATYSAL NRNQSPVLEP 730 740 VGRSTLAQRR GIKKITSTAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients." Bjoerbaek C., Vik T.A., Echwald S.M., Webb G.C., Wang J.P., Yang P.-Y., Vestergaard H., Richmond K., Hansen T., Erikson R.L., Miklos G.L.G., Cohen P.T.W., Pedersen O. Diabetes 44:90-97(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta and T-cell.
[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].
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] 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].
[6]	"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] OF 2-582. Tissue: Skeletal muscle.
[7]	"Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees." Kitano T., Schwarz C., Nickel B., Paeaebo S. Mol. Biol. Evol. 20:1281-1289(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-735.
[8]	"Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling." Sutherland C., Leighton I.A., Cohen P. Biochem. J. 296:15-19(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF GSK3B.
[9]	"Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene." De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P. Proc. Natl. Acad. Sci. U.S.A. 95:12202-12207(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1.
[10]	"Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3." Sassone-Corsi P., Mizzen C.A., Cheung P., Crosio C., Monaco L., Jacquot S., Hanauer A., Allis C.D. Science 285:886-891(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3.
[11]	"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.
[12]	"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.
[13]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-715, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"RSK2 mediates muscle cell differentiation through regulation of NFAT3." Cho Y.-Y., Yao K., Bode A.M., Bergen H.R. III, Madden B.J., Oh S.-M., Ermakova S., Kang B.S., Choi H.S., Shim J.-H., Dong Z. J. Biol. Chem. 282:8380-8392(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFATC4.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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-365; SER-369; SER-375; SER-386; SER-415; SER-556 AND SER-715, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"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.
[20]	"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-365; SER-369 AND SER-375, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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 THR-365; SER-369; SER-375; SER-386; SER-415 AND SER-715, MASS SPECTROMETRY.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[23]	"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-715, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[24]	"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].
[25]	"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-365 AND SER-369, MASS SPECTROMETRY.
[26]	"Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome." Trivier E., de Cesare D., Jacquot S., Pannetier S., Zackai E., Young I., Mandel J.-L., Sassone-Corsi P., Hanauer A. Nature 384:567-570(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLS VAL-75 AND ALA-227.
[27]	"Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of De novo mutations." Jacquot S., Merienne K., de Cesare D., Pannetier S., Mandel J.-L., Sassone-Corsi P., Hanauer A. Am. J. Hum. Genet. 63:1631-1640(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLS PHE-82; GLN-127; TYR-154; VAL-225 AND ASP-431, VARIANT SER-38.
[28]	"Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS)." Abidi F., Jacquot S., Lassiter C., Trivier E., Hanauer A., Schwartz C.E. Eur. J. Hum. Genet. 7:20-26(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CLS TRP-114 AND GLN-729.
[29]	"Unreported RSK2 missense mutation in two male sibs with an unusually mild form of Coffin-Lowry syndrome." Manouvrier-Hanu S., Amiel J., Jacquot S., Merienne K., Moerman A., Coeslier A., Labarriere F., Vallee L., Croquette M.F., Hanauer A. J. Med. Genet. 36:775-778(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLS LYS-189.
[30]	"A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental retardation." Merienne K., Jacquot S., Pannetier S., Zeniou M., Bankier A., Gecz J., Mandel J.L., Mulley J., Sassone-Corsi P., Hanauer A. Nat. Genet. 22:13-14(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MRX19 TRP-383, CHARACTERIZATION OF VARIANT MRX19 TRP-383.
[31]	"Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome." Martinez-Garay I., Ballesta M.J., Oltra S., Orellana C., Palomeque A., Molto M.D., Prieto F., Martinez F. Clin. Genet. 64:491-496(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLS SER-268.
[32]	"Cardiomyopathy in Coffin-Lowry syndrome." Facher J.J., Regier E.J., Jacobs G.H., Siwik E., Delaunoy J.P., Robin N.H. Am. J. Med. Genet. A 128:176-178(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CLS ILE-477 DEL.
[33]	"Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation." Field M., Tarpey P., Boyle J., Edkins S., Goodship J., Luo Y., Moon J., Teague J., Stratton M.R., Futreal P.A., Wooster R., Raymond F.L., Turner G. Clin. Genet. 70:509-515(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MRX19 SER-115; GLY-152 DEL AND ASP-202 DEL.
[34]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-416.
[35]	"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: VARIANTS [LARGE SCALE ANALYSIS] SER-38; CYS-483; PHE-608 AND CYS-723.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U08316 mRNA. Translation: AAA81952.1.
AK313932 mRNA. Translation: BAG36651.1.
AB208933 mRNA. Translation: BAD92170.1. Different initiation.
AL732366, AL807772 Genomic DNA. Translation: CAI40548.1.
AL807772, AL732366 Genomic DNA. Translation: CAI39687.1.
BC096301 mRNA. Translation: AAH96301.1.
BC096302 mRNA. Translation: AAH96302.1.
BC096303 mRNA. Translation: AAH96303.1.
L07599 mRNA. Translation: AAC82495.1.
AB102662 mRNA. Translation: BAC81131.1.

IPI

IPI00020898.

PIR

I38556.

RefSeq

NP_004577.1. NM_004586.2.

UniGene

Hs.445387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4D9T	X-ray	2.40	A	399-740	[»]
4D9U	X-ray	2.40	A	399-740	[»]

ProteinModelPortal

P51812.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38247N.

IntAct

P51812. 4 interactions.

MINT

MINT-1542962.

STRING

9606.ENSP00000368884.

PTM databases

PhosphoSite

P51812.

Polymorphism databases

DMDM

1730070.

Proteomic databases

PaxDb

P51812.

PeptideAtlas

P51812.

PRIDE

P51812.

Protocols and materials databases

DNASU

6197.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379565; ENSP00000368884; ENSG00000177189.

GeneID

6197.

KEGG

hsa:6197.

UCSC

uc004czu.3. human.

Organism-specific databases

CTD

6197.

GeneCards

GC0XM020168.

HGNC

HGNC:10432. RPS6KA3.

HPA

CAB003853.
CAB013520.
HPA003221.

MIM

300075. gene.
300844. phenotype.
303600. phenotype.

neXtProt

NX_P51812.

Orphanet

192. Coffin-Lowry syndrome.
777. X-linked nonsyndromic intellectual deficit.

PharmGKB

PA34847.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

InParanoid

P51812.

KO

K04373.

OMA

EYLHVQG.

OrthoDB

EOG402WRK.

PhylomeDB

P51812.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

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

P51812.

Bgee

P51812.

CleanEx

HS_RPS6KA3.

Genevestigator

P51812.

GermOnline

ENSG00000177189. 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

P51812.

ChEMBL

CHEMBL2345.

ChiTaRS

RPS6KA3. human.

GenomeRNAi

6197.

NextBio

24069.

SOURCE

Search...

Entry information

Entry name

KS6A3_HUMAN

Accession

Primary (citable) accession number: P51812
Secondary accession number(s): B2R9V4 , Q4VAP3, Q59H26, Q5JPK8, Q7Z3Z7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 138 of the entry and version 1 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.