Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Ribosomal protein S6 kinase alpha-1  

UniProtKB / Swiss-Prot ID :  KS6A1_HUMAN

Gene Name (Synonyms) : 
RPS6KA1, MAPKAPK1A, RSK1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Nucleus. Cytoplasm. 

Protein 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. 

Protein Sequence MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSKDEGVLKEISITHHVKAGSEKADPSHFELLKVLGQ...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEEEEEEE...
Protein Variant
LocationDescription
335K -> T (in dbSNP:rs2229712). VAR_021864
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
25PhosphothreonineENGQTSGEE
CCCCCCCCC
39.85HPRD
Link-
25Phosphothreonine.ENGQTSGEE
CCCCCCCCC
39.85UniProtKB
Link-
26Phosphoserine.NGQTSGEEA
CCCCCCCCC
36.00UniProtKB
Link-
54PhosphoserineVKAGSEKAD
CCCCCCCCC
40.56Phosphositeplus
Link-
54Phosphoserine.VKAGSEKAD
CCCCCCCCC
40.56UniProtKB
Link-
66Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FELLKVLGQ
EEEEEEEEE
48.30Phosphositeplus
Link-
72Phosphoserine.LGQGSFGKV
EEECCCEEE
23.96UniProtKB
Link-
75Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GSFGKVFLV
CCCEEEEEE
28.01Phosphositeplus
Link-
154PhosphoserineFTRLSKEVM
HHHHHHCCC
24.39HPRD
Link-
204Phosphothreonine.HIKLTDFGL
CEEEEECCE
25.04UniProtKB
Link-
209PhosphoserineDFGLSKEAI
ECCEEEEEC
28.91Phosphositeplus
Link-
209Phosphoserine.DFGLSKEAI
ECCEEEEEC
28.91UniProtKB
Link-
220PhosphotyrosineEKKAYSFCG
CCEEEEECC
15.91HPRD
Link-
220PhosphotyrosineEKKAYSFCG
CCEEEEECC
15.91PhosphoELM
Link-
220PhosphotyrosineEKKAYSFCG
CCEEEEECC
15.91Phosphositeplus
Link-
220Phosphotyrosine.EKKAYSFCG
CCEEEEECC
15.91UniProtKB
Link-
221PhosphoserineKKAYSFCGT
CEEEEECCC
20.94Phosphositeplus
Link-
221PhosphoserineKKAYSFCGT
CEEEEECCC
20.94SysPTM
Link-
221Phosphoserine (PDPK1)KKAYSFCGT
CEEEEECCC
20.94HPRD
Link-
221Phosphoserine (RSK_group;PDK-1)KKAYSFCGT
CEEEEECCC
20.94PhosphoELM
Link-
225PhosphothreonineSFCGTVEYM
EECCCHHHC
16.02HPRD
Link-
225PhosphothreonineSFCGTVEYM
EECCCHHHC
16.02PhosphoELM
Link-
225PhosphothreonineSFCGTVEYM
EECCCHHHC
16.02Phosphositeplus
Link-
225Phosphothreonine (RPS6KA1)SFCGTVEYM
EECCCHHHC
16.02HPRD
Link-
225Phosphothreonine.SFCGTVEYM
EECCCHHHC
16.02UniProtKB
Link-
228PhosphotyrosineGTVEYMAPE
CCHHHCCHH
8.34HPRD
Link-
228PhosphotyrosineGTVEYMAPE
CCHHHCCHH
8.34Phosphositeplus
Link-
278Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ILKAKLGMP
HHCCCCCCC
43.94Phosphositeplus
Link-
307PhosphoserineNRLGSGPDG
HHCCCCCCC
52.31Phosphositeplus
Link-
307Phosphoserine.NRLGSGPDG
HHCCCCCCC
52.31UniProtKB
Link-
316Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)AEEIKRHVF
HHHHHHCCC
39.47Phosphositeplus
Link-
348Phosphothreonine.QPDDTFYFD
CCCCCCCCC
27.84UniProtKB
Link-
359PhosphothreonineFTSRTPKDS
HHHCCCCCC
34.16Phosphositeplus
Link-
359PhosphothreonineFTSRTPKDS
HHHCCCCCC
34.16SysPTM
Link-
359Phosphothreonine (MAPK1)FTSRTPKDS
HHHCCCCCC
34.16HPRD
Link-
359Phosphothreonine (MAPK_group)FTSRTPKDS
HHHCCCCCC
34.16PhosphoELM
Link-
359Phosphothreonine.FTSRTPKDS
HHHCCCCCC
34.16UniProtKB
Link-
363PhosphoserineTPKDSPGIP
CCCCCCCCC
31.02Phosphositeplus
Link-
363PhosphoserineTPKDSPGIP
CCCCCCCCC
31.02SysPTM
Link-
363Phosphoserine (MAPK1)TPKDSPGIP
CCCCCCCCC
31.02HPRD
Link-
363Phosphoserine (MAPK_group)TPKDSPGIP
CCCCCCCCC
31.02PhosphoELM
Link-
363Phosphoserine.TPKDSPGIP
CCCCCCCCC
31.02UniProtKB
Link-
369PhosphoserineGIPPSAGAH
CCCCCCCHH
33.70HPRD
Link-
369PhosphoserineGIPPSAGAH
CCCCCCCHH
33.70PhosphoELM
Link-
369PhosphoserineGIPPSAGAH
CCCCCCCHH
33.70Phosphositeplus
Link-
369PhosphoserineGIPPSAGAH
CCCCCCCHH
33.70SysPTM
Link-
369Phosphoserine.GIPPSAGAH
CCCCCCCHH
33.70UniProtKB
Link-
380PhosphoserineFRGFSFVAT
HHHHHHHHH
22.95PhosphoELM
Link-
380PhosphoserineFRGFSFVAT
HHHHHHHHH
22.95Phosphositeplus
Link-
380PhosphoserineFRGFSFVAT
HHHHHHHHH
22.95SysPTM
Link-
380Phosphoserine (RPS6KA1)FRGFSFVAT
HHHHHHHHH
22.95HPRD
Link-
380Phosphoserine; by autocatalysis.FRGFSFVAT
HHHHHHHHH
22.95UniProtKB
Link-
573PhosphothreonineGLLMTPCYT
CEEEEECCC
15.35HPRD
Link
573PhosphothreonineGLLMTPCYT
CEEEEECCC
15.35PhosphoELM
Link
573PhosphothreonineGLLMTPCYT
CEEEEECCC
15.35Phosphositeplus
Link
573PhosphothreonineGLLMTPCYT
CEEEEECCC
15.35SysPTM
Link
573Phosphothreonine.GLLMTPCYT
CEEEEECCC
15.35UniProtKB
Link
576PhosphotyrosineMTPCYTANF
EEECCCHHH
15.30HPRD
Link
576PhosphotyrosineMTPCYTANF
EEECCCHHH
15.30Phosphositeplus
Link
576Phosphotyrosine.MTPCYTANF
EEECCCHHH
15.30UniProtKB
Link
577PhosphothreonineTPCYTANFV
EECCCHHHC
23.11HPRD
Link-
577PhosphothreonineTPCYTANFV
EECCCHHHC
23.11PhosphoELM
Link-
577PhosphothreonineTPCYTANFV
EECCCHHHC
23.11Phosphositeplus
Link-
577Phosphothreonine (RPS6KA1)TPCYTANFV
EECCCHHHC
23.11HPRD
Link-
635Phosphothreonine.SGKFTLSGG
CCCCCCCCC
24.41UniProtKB
Link
637PhosphoserineKFTLSGGNW
CCCCCCCCC
41.41Phosphositeplus
Link
637Phosphoserine.KFTLSGGNW
CCCCCCCCC
41.41UniProtKB
Link
684PhosphoserineKLPQSQLSH
CCCCCCCCC
31.02Phosphositeplus
Link
684Phosphoserine.KLPQSQLSH
CCCCCCCCC
31.02UniProtKB
Link
732PhosphoserineRKLPSTTL
CCCCCCCC
44.45HPRD
Link-
732PhosphoserineRKLPSTTL
CCCCCCCC
44.45PhosphoELM
Link-
732PhosphoserineRKLPSTTL
CCCCCCCC
44.45Phosphositeplus
Link-
732Phosphoserine.RKLPSTTL
CCCCCCCC
44.45UniProtKB
Link-
733PhosphothreonineKLPSTTL
CCCCCCC
30.12HPRD
Link-
733PhosphothreonineKLPSTTL
CCCCCCC
30.12PhosphoELM
Link-
733PhosphothreonineKLPSTTL
CCCCCCC
30.12Phosphositeplus
Link-
733PhosphothreonineKLPSTTL
CCCCCCC
30.12SysPTM
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
IF4B_HUMANphosphorylation reactionMINT-2793474MINT16763566
MK03_HUMANphysical interactionMINT-14472MINT9915826
CREB1_HUMANphosphorylationEBI-963054
intact16282323
CREB1_HUMANin vitroHPRD:03402HPRD9687510
11175347
9829964
8688081
12235136
EF1D_HUMANin vitroHPRD:03402HPRD9353277
ESR1_HUMANin vitro
in vivo
HPRD:03402HPRD12093745
9528769
11507039
11139588
11432835
FOS_HUMANin vitroHPRD:03402HPRD8248197
1545828
IKBA_HUMANin vitro
in vivo
HPRD:03402HPRD9214631
8601309
9721103
10723127
CEBPB_HUMANin vitro
in vivo
HPRD:03402HPRD10635333
L1CAM_HUMANin vitro
in vivo
HPRD:03402HPRD8663493
1433B_HUMANin vitro
in vivo
HPRD:03402HPRD12618428
PPR3A_HUMANin vitro
in vivo
HPRD:03402HPRD10648825
ETV1_HUMANin vitro
in vivo
HPRD:03402HPRD12213813
12569367
12917345
11551945
CBP_HUMANin vitro
in vivo
HPRD:03402HPRD8756728
SRF_HUMANin vitro
in vivo
HPRD:03402HPRD10753652
8413226
10318869
KS6A1_HUMANin vitro
in vivo
HPRD:03402HPRD9430688
12618428
10648825
GMFB_HUMANin vitro
in vivo
HPRD:03402HPRD9030586
BAD_HUMANin vitro
in vivo
HPRD:03402HPRD10949026
10837486
10880354
9381178
10521512
12897128
TRMB_HUMANin vitroHPRD:03402HPRD15861136
EF2K_HUMANin vitro
in vivo
HPRD:03402HPRD11500364
14709557
15024086
11171059
NR4A3_HUMANin vivoHPRD:03402HPRD16223362
NR4A2_HUMANin vivoHPRD:03402HPRD16223362
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Global phosphoproteome of HT-29 human colon adenocarcinoma cells.";
Kim J.-E., Tannenbaum S.R., White F.M.;
J. Proteome Res. 4:1339-1346(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, AND MASSSPECTROMETRY.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, ANDMASS SPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221; THR-225; THR-359;SER-363; SER-369 AND SER-380, AND MASS SPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369;SER-380 AND THR-573, AND MASS SPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369;SER-380 AND THR-573, AND MASS SPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-25; SER-26; SER-54;SER-72; THR-204; SER-209; TYR-220; SER-221; SER-307; THR-359; SER-363;SER-369; SER-380; THR-573; TYR-576; THR-635; SER-637; SER-684 ANDSER-732, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28 AND SER-31(ISOFORM 2), AND MASS SPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, AND MASSSPECTROMETRY.
"Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rskthat are inducible by MAPK.";
Dalby K.N., Morrice N., Caudwell F.B., Avruch J., Cohen P.;
J. Biol. Chem. 273:1496-1505(1998).
Cited for: FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT SER-221; THR-359;SER-363; SER-380; THR-573 AND SER-732.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures