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P51812 (KS6A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length740 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 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 adaptive 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 processCell cycle
Stress response
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Mental retardation
   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

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

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.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-templated 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

signal transduction

Traceable author statement Ref.10. Source: ProtInc

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 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

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

   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 kinase activity

Traceable author statement Ref.10. Source: ProtInc

protein serine/threonine kinase activity

Traceable author statement Ref.6. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 740740Ribosomal protein S6 kinase alpha-3
PRO_0000086203

Regions

Domain68 – 327260Protein kinase 1
Domain328 – 39770AGC-kinase C-terminal
Domain422 – 679258Protein kinase 2
Nucleotide binding74 – 829ATP By similarity
Nucleotide binding428 – 4369ATP By similarity

Sites

Active site1931Proton acceptor By similarity
Active site5391Proton acceptor By similarity
Binding site1001ATP By similarity
Binding site4511ATP By similarity

Amino acid modifications

Modified residue2271Phosphoserine; by PDPK1 Probable
Modified residue3651Phosphothreonine Ref.18 Ref.20 Ref.21 Ref.25
Modified residue3691Phosphoserine Ref.18 Ref.20 Ref.21 Ref.25
Modified residue3751Phosphoserine Ref.18 Ref.20 Ref.21
Modified residue3861Phosphoserine; by autocatalysis and MAPKAPK2 Ref.18 Ref.21
Modified residue4151Phosphoserine Ref.18 Ref.21 Ref.22
Modified residue5291Phosphotyrosine; by FGFR3 By similarity
Modified residue5561Phosphoserine Ref.18
Modified residue7151Phosphoserine Ref.13 Ref.18 Ref.21 Ref.23

Natural variations

Natural variant381I → S. Ref.27 Ref.35
Corresponds to variant rs56218010 [ dbSNP | Ensembl ].
VAR_006188
Natural variant751G → V in CLS. Ref.26
VAR_006189
Natural variant821V → F in CLS. Ref.27
VAR_006190
Natural variant1141R → W in CLS. Ref.28
VAR_006191
Natural variant1151T → S in MRX19. Ref.33
VAR_065892
Natural variant1271H → Q in CLS. Ref.27
VAR_006192
Natural variant1521Missing in MRX19. Ref.33
VAR_065893
Natural variant1541D → Y in CLS. Ref.27
VAR_006193
Natural variant1891I → K in CLS. Ref.29
VAR_065894
Natural variant2021Missing in MRX19. Ref.33
VAR_065895
Natural variant2251A → V in CLS. Ref.27
VAR_006194
Natural variant2271S → A in CLS. Ref.26
VAR_006195
Natural variant2681F → S in CLS. Ref.31
VAR_065896
Natural variant3831R → W in MRX19; kinase activity is decreased but not abolished. Ref.30
VAR_065897
Natural variant4161I → V in a breast cancer sample; somatic mutation. Ref.34
VAR_035627
Natural variant4311G → D in CLS. Ref.27
VAR_006196
Natural variant4771Missing in CLS. Ref.32
VAR_065898
Natural variant4831Y → C in a gastric adenocarcinoma sample; somatic mutation. Ref.35
VAR_040629
Natural variant6081L → F in a glioblastoma multiforme sample; somatic mutation. Ref.35
VAR_040630
Natural variant7231R → C. Ref.35
Corresponds to variant rs35026425 [ dbSNP | Ensembl ].
VAR_040631
Natural variant7291R → Q in CLS. Ref.28
Corresponds to variant rs28935171 [ dbSNP | Ensembl ].
VAR_006197

Experimental info

Sequence conflict891S → L in AAH96303. Ref.5
Sequence conflict4101Missing in BAD92170. Ref.3
Sequence conflict4241V → L in AAC82495. Ref.6
Sequence conflict4801K → N in AAC82495. Ref.6
Sequence conflict4941Missing in AAC82495. Ref.6

Secondary structure

.................................................. 740
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51812 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 486AE8357CEAB6C8

FASTA74083,736
        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 

« Hide

References

« Hide '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. 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].
[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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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. expand/collapse author list , 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. 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: VARIANTS [LARGE SCALE ANALYSIS] SER-38; CYS-483; PHE-608 AND CYS-723.
+Additional computationally mapped references.

Web resources

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.
PIRI38556.
RefSeqNP_004577.1. NM_004586.2.
UniGeneHs.445387.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4D9TX-ray2.40A399-740[»]
4D9UX-ray2.40A399-740[»]
4JG6X-ray2.60A399-740[»]
4JG7X-ray3.00A399-740[»]
4JG8X-ray3.10A399-740[»]
4NUSX-ray2.39A39-359[»]
4NW5X-ray1.94A39-359[»]
4NW6X-ray1.74A39-359[»]
ProteinModelPortalP51812.
SMRP51812. Positions 49-714.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112111. 34 interactions.
DIPDIP-38247N.
IntActP51812. 11 interactions.
MINTMINT-1542962.
STRING9606.ENSP00000368884.

Chemistry

BindingDBP51812.
ChEMBLCHEMBL2345.
GuidetoPHARMACOLOGY1528.

PTM databases

PhosphoSiteP51812.

Polymorphism databases

DMDM1730070.

Proteomic databases

PaxDbP51812.
PeptideAtlasP51812.
PRIDEP51812.

Protocols and materials databases

DNASU6197.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379565; ENSP00000368884; ENSG00000177189.
GeneID6197.
KEGGhsa:6197.
UCSCuc004czu.3. human.

Organism-specific databases

CTD6197.
GeneCardsGC0XM020168.
HGNCHGNC:10432. RPS6KA3.
HPACAB003853.
CAB013520.
HPA003221.
MIM300075. gene.
300844. phenotype.
303600. phenotype.
neXtProtNX_P51812.
Orphanet192. Coffin-Lowry syndrome.
777. X-linked non-syndromic intellectual deficit.
PharmGKBPA34847.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP51812.
KOK04373.
OMAYTLNRQD.
OrthoDBEOG7B8S38.
PhylomeDBP51812.
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.
SignaLinkP51812.

Gene expression databases

ArrayExpressP51812.
BgeeP51812.
CleanExHS_RPS6KA3.
GenevestigatorP51812.

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

ChiTaRSRPS6KA3. human.
GeneWikiRPS6KA3.
GenomeRNAi6197.
NextBio24069.
PROP51812.
SOURCESearch...

Entry information

Entry nameKS6A3_HUMAN
AccessionPrimary (citable) accession number: P51812
Secondary accession number(s): B2R9V4 expand/collapse secondary AC list , Q4VAP3, Q59H26, Q5JPK8, Q7Z3Z7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 149 of the entry and version 1 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 X

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