[1]	NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-195 AND ASP-565. TISSUE=Pancreas; DOI=10.1093/emboj/17.15.4426; PubMed=9687510 [NCBI, ExPASy, EBI, Israel, Japan] Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.; "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB."; EMBO J. 17:4426-4441(1998).
[2]	NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. TISSUE=Placenta; DOI=10.1074/jbc.274.2.1026; PubMed=9873047 [NCBI, ExPASy, EBI, Israel, Japan] New L., Zhao M., Li Y., Bassett W.W., Feng Y., Ludwig S., Padova F.D., Gram H., Han J.; "Cloning and characterization of RLPK, a novel RSK-related protein kinase."; J. Biol. Chem. 274:1026-1032(1999).
[3]	NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL LOCATION. PubMed=10702687 [NCBI, ExPASy, EBI, Israel, Japan] Jiang C., Yu L., Tu Q., Zhao Y., Zhang H., Zhao S.; "Assignment of a member of the ribosomal protein S6 kinase family, RPS6KA5, to human chromosome 14q31-q32.1 by radiation hybrid mapping."; Cytogenet. Cell Genet. 87:261-262(1999).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-549. TISSUE=Placenta; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	FUNCTION. DOI=10.1128/MCB.22.8.2871-2881.2002; PubMed=11909979 [NCBI, ExPASy, EBI, Israel, Japan] Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S.; "MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts."; Mol. Cell. Biol. 22:2871-2881(2002).
[6]	FUNCTION, AND INTERACTION WITH RELA. DOI=10.1093/emboj/cdg139; PubMed=12628924 [NCBI, ExPASy, EBI, Israel, Japan] Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G.; "Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)."; EMBO J. 22:1313-1324(2003).
[7]	FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMG14. DOI=10.1093/emboj/cdg273; PubMed=12773393 [NCBI, ExPASy, EBI, Israel, Japan] Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H., Hazzalin C.A., Mahadevan L.C., Arthur J.S.; "MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14."; EMBO J. 22:2788-2797(2003).
[8]	FUNCTION IN PHOSPHORYLATION OF HISTONE H2A. DOI=10.1074/jbc.M400099200; PubMed=15010469 [NCBI, ExPASy, EBI, Israel, Japan] Zhang Y., Griffin K., Mondal N., Parvin J.D.; "Phosphorylation of histone H2A inhibits transcription on chromatin templates."; J. Biol. Chem. 279:21866-21872(2004).
[9]	ENZYME REGULATION, PHOSPHORYLATION AT SER-212; SER-376; SER-381; SER-750; SER-752 AND SER-758, AND MUTAGENESIS OF SER-212; SER-360; SER-376 AND THR-581. DOI=10.1042/BJ20041501; PubMed=15568999 [NCBI, ExPASy, EBI, Israel, Japan] McCoy C.E., Campbell D.G., Deak M., Bloomberg G.B., Arthur J.S.C.; "MSK1 activity is controlled by multiple phosphorylation sites."; Biochem. J. 387:507-517(2005).
[10]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.
[11]	VARIANTS [LARGE SCALE ANALYSIS] ASN-554; LEU-574 AND CYS-599. DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Patterns of somatic mutation in human cancer genomes."; Nature 446:153-158(2007).

Comments

FUNCTION: Serine/threonine kinase required for the mitogen or stress-induced phosphorylation of the transcription factors CREB (cAMP response element-binding protein) and ATF1 (activating transcription factor-1). Essential role in the control of RELA transcriptional activity in response to TNF. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and epidemal growth-factor (EGF), which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 14 (HMG-14).
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
ENZYME REGULATION: Appears to be activated by multiple phosphorylations on threonine and serine residues. ERK1/2 and MAPK14/p38-alpha may play a role in this process.
SUBUNIT: Forms a complex with either ERK1 or ERK2 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA.
INTERACTION:
Q04206:RELA; NbExp=1; IntAct=EBI-73869, EBI-73886;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly nuclear. Partially cytoplasmic.
TISSUE SPECIFICITY: Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.
PTM: Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain.
MISCELLANEOUS: Enzyme activity requires the presence of both kinase domains.
SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
SIMILARITY: Contains 2 protein kinase domains.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF074393; AAC31171.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF080000; AAD23915.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF090421; AAC69577.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC017187; AAH17187.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00335101; -.

PIR

T13149; T13149.

RefSeq

NP_004746.2; -.
NP_872198.1; -.

UniGene

Hs.510225

3D structure databases

PDB

1VZO; X-ray; 1.80 A; A=2-348.

[ExPASy / RCSB / EBI]

PDBsum

1VZO; -.

ModBase

O75582.

Protein-protein interaction databases

IntAct

O75582; 1.

PTM databases

PhosphoSite

O75582; -.

Enzyme and pathway databases

BRENDA

2.7.11.1; 247.

Pathway_Interaction_DB

lpa4_pathway; LPA4-mediated signaling events.
p38alphabetadownstreampathway; Signaling mediated by p38-alpha and p38-beta.
mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_11061; Signalling by NGF.

Organism-specific databases

GC14M090406; -.

HIX0020495; -.

HGNC:10434; RPS6KA5.

HPA001274; -.

603607; gene. [NCBI / EBI]

PharmGKB

PA34849; -.

Gene expression databases

O75582; -.

O75582; -.

HS_RPS6KA5; -.

ENSG00000100784; Homo sapiens.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005654;	Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0005524;	Molecular function: ATP binding (inferred from direct assay from UniProtKB).
GO:0000287;	Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004674;	Molecular function: protein serine/threonine kinase activity (inferred from direct assay from UniProtKB).
GO:0007173;	Biological process: epidermal growth factor receptor signaling pathway (traceable author statement from UniProtKB).
GO:0016572;	Biological process: histone phosphorylation (inferred from direct assay from UniProtKB).
GO:0007243;	Biological process: protein kinase cascade (inferred from direct assay from UniProtKB).
GO:0006355;	Biological process: regulation of transcription, DNA-dependent (inferred from direct assay from UniProtKB).
GO:0042221;	Biological process: response to chemical stimulus (inferred from expression pattern from UniProtKB).
GO:0009605;	Biological process: response to external stimulus (inferred from expression pattern from UniProtKB).
GO:0006950;	Biological process: response to stress (inferred from expression pattern from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR000961; AGC-kinase_C.
IPR017892; Pkinase_C.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_BS.
IPR016239; Ribosomal_S6_kinase_II.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
IPR002290; Ser_thr_pkinase.
Graphical view of domain structure.

Pfam

PF00069; Pkinase; 2.
PF00433; Pkinase_C; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000606; Ribsml_S6_kin_2; 1.

ProDom

PD000001; Prot_kinase; 2.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00133; S_TK_X; 1.
SM00220; S_TKc; 2.
SMART graphical view of domain structure.

PROSITE

PS51285; AGC_KINASE_CTER; 1.
PS00107; PROTEIN_KINASE_ATP; 2.
PS50011; PROTEIN_KINASE_DOM; 2.
PS00108; PROTEIN_KINASE_ST; 2.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

O75582; -.

Genome annotation databases

Ensembl

ENSG00000100784; Homo sapiens. [Contig view]

GeneID

9252; -.

KEGG

hsa:9252; -.

Phylogenomic databases

HOGENOM

O75582; -.

HOVERGEN

O75582; -.

OMA

O75582; DSGHDKA.

Other

NextBio

34679; -.

SOURCE

RPS6KA5; Homo sapiens.

ProtoNet

O75582.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Repeat; Serine/threonine-protein kinase; Transferase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 802`	`802`	`Ribosomal protein S6 kinase alpha-5.`	`PRO_0000086207`
`DOMAIN`	`49 318`	`270`	`Protein kinase 1.`
`DOMAIN`	`319 387`	`69`	`AGC-kinase C-terminal.`
`DOMAIN`	`426 687`	`262`	`Protein kinase 2.`
`NP_BIND`	`55 63`	`9`	`ATP (By similarity).`
`NP_BIND`	`432 440`	`9`	`ATP (By similarity).`
`ACT_SITE`	`177 177`		`Proton acceptor (By similarity).`
`ACT_SITE`	`544 544`		`Proton acceptor (By similarity).`
`BINDING`	`81 81`		`ATP (By similarity).`
`BINDING`	`455 455`		`ATP (By similarity).`
`MOD_RES`	`212 212`		`Phosphoserine; by autocatalysis.`
`MOD_RES`	`360 360`		`Phosphoserine; by MAPK3, MAPK1 and MAPK14.`
`MOD_RES`	`376 376`		`Phosphoserine; by autocatalysis.`
`MOD_RES`	`381 381`		`Phosphoserine; by autocatalysis.`
`MOD_RES`	`581 581`		`Phosphothreonine; by MAPK1, MAPK3 and MAPK14.`
`MOD_RES`	`750 750`		`Phosphoserine; by autocatalysis.`
`MOD_RES`	`752 752`		`Phosphoserine; by autocatalysis.`
`MOD_RES`	`758 758`		`Phosphoserine; by autocatalysis.`
`VARIANT`	`190 190`	`1`	`H -> R (in dbSNP:rs34699345 [NCBI]).`	`VAR_051634`
`VARIANT`	`554 554`	`1`	`D -> N.`	`VAR_040634`
`VARIANT`	`574 574`	`1`	`P -> L.`	`VAR_040635`
`VARIANT`	`599 599`	`1`	`Y -> C.`	`VAR_040636`
`MUTAGEN`	`195 195`		`D->A: Loss of kinase activity.`
`MUTAGEN`	`212 212`		`S->A: Inactives the N-terminal kinase domain.`
`MUTAGEN`	`360 360`		`S->A: Decreases kinase activity by 60% in response to PMA and UV-C.`
`MUTAGEN`	`376 376`		`S->A: Loss of kinase activity, and decreases the phosphorylation of S-360 and T-581.`
`MUTAGEN`	`565 565`		`D->A: Loss of kinase activity.`
`MUTAGEN`	`581 581`		`T->A: Loss of kinase activity, and blocks phosphorylation of S-212; S-376 and S-381 in response to PMA and UV-C.`
`CONFLICT`	`452 453`		`FA -> LQ (in Ref. 3; AAC69577).`
`CONFLICT`	`508 511`		`ERIK -> DALR (in Ref. 3; AAC69577).`
`CONFLICT`	`532 532`		`V -> L (in Ref. 3; AAC69577).`
`CONFLICT`	`538 538`		`V -> L (in Ref. 3; AAC69577).`
`CONFLICT`	`549 549`		`N -> V (in Ref. 4; AAH17187).`
`CONFLICT`	`588 590`		`YAA -> SCR (in Ref. 3; AAC69577).`
`CONFLICT`	`757 758`		`SS -> RG (in Ref. 3; AAC69577).`
`CONFLICT`	`801 802`		`VA -> ELRHGRSDQ (in Ref. 3; AAC69577).`
`STRAND`	`26 31`	`6`
`HELIX`	`46 48`	`3`
`STRAND`	`49 57`	`9`
`TURN`	`58 60`	`3`
`STRAND`	`61 68`	`8`
`TURN`	`72 75`	`4`
`STRAND`	`77 94`	`18`
`HELIX`	`95 97`	`3`
`HELIX`	`101 109`	`9`
`STRAND`	`117 123`	`7`
`STRAND`	`126 131`	`6`
`HELIX`	`139 146`	`8`
`HELIX`	`151 170`	`20`
`HELIX`	`180 182`	`3`
`STRAND`	`183 185`	`3`
`STRAND`	`191 194`	`4`
`STRAND`	`196 201`	`6`
`HELIX`	`204 210`	`7`
`HELIX`	`212 214`	`3`
`HELIX`	`222 225`	`4`
`HELIX`	`235 250`	`16`
`HELIX`	`264 273`	`10`
`HELIX`	`284 293`	`10`
`HELIX`	`298 300`	`3`
`TURN`	`306 308`	`3`
`HELIX`	`309 313`	`5`
`HELIX`	`316 318`	`3`
`HELIX`	`323 327`	`5`

Sequence information

Length: 802 AA [This is the length of the unprocessed precursor]

Molecular weight: 89865 Da [This is the MW of the unprocessed precursor]

CRC64: 76C27D0F6639BFA4 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE LLKVLGTGAY 

        70         80         90        100        110        120 
GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT ERQVLEHIRQ SPFLVTLHYA 

       130        140        150        160        170        180 
FQTETKLHLI LDYINGGELF THLSQRERFT EHEVQIYVGE IVLALEHLHK LGIIYRDIKL 

       190        200        210        220        230        240 
ENILLDSNGH VVLTDFGLSK EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS 

       250        260        270        280        290        300 
LGVLMYELLT GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK 

       310        320        330        340        350        360 
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE EFTEMDPTYS 

       370        380        390        400        410        420 
PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV ERPGVTNVAR SAMMKDSPFY 

       430        440        450        460        470        480 
QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ AFAVKIISKR MEANTQKEIT ALKLCEGHPN 

       490        500        510        520        530        540 
IVKLHEVFHD QLHTFLVMEL LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV 

       550        560        570        580        590        600 
VHRDLKPENL LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD 

       610        620        630        640        650        660 
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG EAWKNVSQEA 

       670        680        690        700        710        720 
KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT PDILGSSGAA VHTCVKATFH 

       730        740        750        760        770        780 
AFNKYKREGF CLQNVDKAPL AKRRKMKKTS TSTETRSSSS ESSHSSSSHS HGKTTPTKTL 

       790        800 
QPSNPADSNN PETLFQFSDS VA

O75582 in FASTA format

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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools