O75582 (KS6A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribosomal protein S6 kinase alpha-5
Short name=S6K-alpha-5
EC=2.7.11.1

Alternative name(s):
90 kDa ribosomal protein S6 kinase 5
Nuclear mitogen- and stress-activated protein kinase 1
RSK-like protein kinase
Short name=RSKL

Gene names

Name:	RPS6KA5
Synonyms:	MSK1

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	802 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and 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 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.2 Ref.7
Cofactor	Magnesium. Ref.1 Ref.2 Ref.7
Enzyme regulation	Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region. Ref.1 Ref.12
Subunit structure	Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 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. Interacts with CREBBP and EP300. Ref.7 Ref.10
Subcellular location	Nucleus. Cytoplasm. Note: Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid. Ref.1 Ref.14
Tissue specificity	Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver. Ref.1 Ref.2
Post-translational modification	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. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain. Ref.12 Ref.13 Ubiquitinated. Ref.18
Miscellaneous	Enzyme activity requires the presence of both kinase domains. Ref.1
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 AAC69577.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Inflammatory response Stress response
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
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 axon guidance Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement Ref.2. Source: UniProtKB histone H2A-S1 phosphorylation Inferred from direct assay Ref.11. Source: UniProtKB histone H3-S10 phosphorylation Inferred from mutant phenotype Ref.8. Source: UniProtKB histone H3-S28 phosphorylation Inferred from mutant phenotype Ref.8. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome interleukin-1-mediated signaling pathway Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL negative regulation of cytokine production Traceable author statement Ref.15. Source: UniProtKB negative regulation of transcription, DNA-templated Inferred from direct assay Ref.11. Source: UniProtKB neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of CREB transcription factor activity Traceable author statement Ref.15. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.7Ref.14. Source: UniProtKB positive regulation of histone acetylation Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL positive regulation of histone phosphorylation Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20018936. Source: BHF-UCL stress-activated MAPK cascade 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
Cellular_component	cytoplasm Inferred from direct assay Ref.14. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MLTK	Q9NYL2	4	EBI-73869,EBI-602273

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75582-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75582-2)

The sequence of this isoform differs from the canonical sequence as follows:
     549-549: N → V
     550-802: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 802

802

Ribosomal protein S6 kinase alpha-5

PRO_0000086207

Regions

Domain

49 – 318

270

Protein kinase 1

Domain

319 – 387

69

AGC-kinase C-terminal

Domain

426 – 687

262

Protein kinase 2

Nucleotide binding

55 – 63

9

ATP By similarity UniProtKB Q15418

Nucleotide binding

432 – 440

9

ATP By similarity UniProtKB Q15418

Sites

Active site

177

1

Proton acceptor By similarity UniProtKB Q15418

Active site

544

1

Proton acceptor By similarity UniProtKB Q15418

Binding site

81

1

ATP By similarity UniProtKB Q15418

Binding site

455

1

ATP By similarity UniProtKB Q15418

Amino acid modifications

Modified residue

212

1

Phosphoserine; by autocatalysis Ref.12 UniProtKB Q15418

Modified residue

360

1

Phosphoserine; by MAPK1, MAPK3 and MAPK14 Ref.12 UniProtKB Q15418

Modified residue

376

1

Phosphoserine; by autocatalysis Ref.12 Ref.16 Ref.19 UniProtKB Q15418

Modified residue

381

1

Phosphoserine; by autocatalysis Ref.12 Ref.19

Modified residue

581

1

Phosphothreonine; by MAPK1, MAPK3 and MAPK14 Ref.12 UniProtKB Q15418

Modified residue

647

1

Phosphoserine Ref.13

Modified residue

657

1

Phosphoserine Ref.13

Modified residue

695

1

Phosphoserine Ref.13

Modified residue

700

1

Phosphothreonine; by MAPK1, MAPK3 and MAPK14 Ref.13

Modified residue

750

1

Phosphoserine; by autocatalysis Ref.12 UniProtKB Q15418

Modified residue

752

1

Phosphoserine; by autocatalysis Ref.12

Modified residue

758

1

Phosphoserine; by autocatalysis Ref.12

Natural variations

Alternative sequence

549

1

N → V in isoform 2.

VSP_041837

Alternative sequence

550 – 802

253

Missing in isoform 2.

VSP_041838

Natural variant

190

1

H → R.
Corresponds to variant rs34699345 [ dbSNP | Ensembl ].

VAR_051634

Natural variant

554

1

D → N. Ref.23
Corresponds to variant rs55911249 [ dbSNP | Ensembl ].

VAR_040634

Natural variant

574

1

P → L. Ref.23
Corresponds to variant rs34604933 [ dbSNP | Ensembl ].

VAR_040635

Natural variant

599

1

Y → C. Ref.23
Corresponds to variant rs55968863 [ dbSNP | Ensembl ].

VAR_040636

Experimental info

Mutagenesis

195

1

D → A: Loss of kinase activity. Ref.1

Mutagenesis

212

1

S → A: Inactivates the N-terminal kinase domain. Ref.12

Mutagenesis

360

1

S → A: Decreases kinase activity by 60% in response to PMA and UV-C. Ref.12

Mutagenesis

376

1

S → A: Loss of kinase activity, and decreases the phosphorylation of S-360 and T-581. Ref.12

Mutagenesis

565

1

D → A: Loss of kinase activity. Ref.1

Mutagenesis

581

1

T → A: Loss of kinase activity, and blocks phosphorylation of S-212; S-376 and S-381 in response to PMA and UV-C. Ref.12

Mutagenesis

700

1

T → A or D: Strongly reduces phosphorylation of T-581 in response to PMA and UV-C. Ref.13

Sequence conflict

452 – 453

2

FA → LQ in AAC69577. Ref.3

Sequence conflict

532

1

V → L in AAC69577. Ref.3

Sequence conflict

538

1

V → L in AAC69577. Ref.3

Sequence conflict

757 – 758

2

SS → RG in AAC69577. Ref.3

Secondary structure

1

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802

Helix Strand Turn

Details...

Beta strand

26 – 31

6

Helix

46 – 48

3

Beta strand

49 – 57

9

Turn

58 – 60

3

Beta strand

61 – 68

8

Turn

72 – 75

4

Beta strand

77 – 94

18

Helix

95 – 97

3

Helix

101 – 109

9

Beta strand

117 – 123

7

Beta strand

126 – 131

6

Helix

139 – 146

8

Helix

151 – 170

20

Helix

180 – 182

3

Beta strand

183 – 185

3

Beta strand

191 – 194

4

Beta strand

196 – 201

6

Helix

204 – 210

7

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

Helix

418 – 422

5

Beta strand

423 – 425

3

Beta strand

432 – 435

4

Beta strand

438 – 445

8

Turn

446 – 448

3

Beta strand

451 – 458

8

Helix

459 – 461

3

Helix

462 – 474

13

Turn

475 – 477

3

Beta strand

484 – 489

6

Beta strand

491 – 498

8

Helix

506 – 512

7

Helix

518 – 537

20

Helix

547 – 549

3

Beta strand

550 – 553

4

Beta strand

560 – 563

4

Helix

602 – 617

16

Helix

634 – 641

8

Turn

642 – 644

3

Helix

651 – 654

4

Helix

658 – 668

11

Turn

672 – 674

3

Turn

678 – 680

3

Helix

685 – 687

3

Helix

700 – 728

29

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 76C27D0F6639BFA4	FASTA	802	89,865
	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
	Isoform 2 [UniParc]. Checksum: 3CED0A0C50E96C78	FASTA	549	61,769
	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 VHRDLKPEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB." Deak M., Clifton A.D., Lucocq J.M., Alessi D.R. EMBO J. 17:4426-4441(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-195 AND ASP-565. Tissue: Pancreas.
[2]	"Cloning and characterization of RLPK, a novel RSK-related protein kinase." New L., Zhao M., Li Y., Bassett W.W., Feng Y., Ludwig S., Padova F.D., Gram H., Han J. J. Biol. Chem. 274:1026-1032(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Placenta.
[3]	"Assignment of a member of the ribosomal protein S6 kinase family, RPS6KA5, to human chromosome 14q31-q32.1 by radiation hybrid mapping." Jiang C., Yu L., Tu Q., Zhao Y., Zhang H., Zhao S. Cytogenet. Cell Genet. 87:261-262(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL LOCATION.
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [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] (ISOFORM 2). Tissue: Placenta.
[6]	"MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts." Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P., Arthur J.S. Mol. Cell. Biol. 22:2871-2881(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)." Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G. EMBO J. 22:1313-1324(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RELA.
[8]	"MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14." Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H., Hazzalin C.A., Mahadevan L.C., Arthur J.S. EMBO J. 22:2788-2797(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMGN1/HMG14.
[9]	"Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway." Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E. Exp. Hematol. 31:398-405(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3.
[10]	"Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1)." Janknecht R. Oncogene 22:746-755(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, INTERACTION WITH CREBBP AND EP300.
[11]	"Phosphorylation of histone H2A inhibits transcription on chromatin templates." Zhang Y., Griffin K., Mondal N., Parvin J.D. J. Biol. Chem. 279:21866-21872(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H2A.
[12]	"MSK1 activity is controlled by multiple phosphorylation sites." McCoy C.E., Campbell D.G., Deak M., Bloomberg G.B., Arthur J.S.C. Biochem. J. 387:507-517(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-212; SER-360; SER-376; SER-381; THR-581; SER-750; SER-752 AND SER-758, MUTAGENESIS OF SER-212; SER-360; SER-376 AND THR-581.
[13]	"Identification of novel phosphorylation sites in MSK1 by precursor ion scanning MS." McCoy C.E., Macdonald A., Morrice N.A., Campbell D.G., Deak M., Toth R., McIlrath J., Arthur J.S. Biochem. J. 402:491-501(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-647; SER-657; SER-695 AND THR-700, MUTAGENESIS OF THR-700.
[14]	"Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition." Beck I.M., Vanden Berghe W., Vermeulen L., Bougarne N., Vander Cruyssen B., Haegeman G., De Bosscher K. EMBO J. 27:1682-1693(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]	"MSK activation and physiological roles." Arthur J.S. Front. Biosci. 13:5866-5879(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[16]	"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-376, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"The versatile role of MSKs in transcriptional regulation." Vermeulen L., Vanden Berghe W., Beck I.M., De Bosscher K., Haegeman G. Trends Biochem. Sci. 34:311-318(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[18]	"Development and validation of a method for profiling post-translational modification activities using protein microarrays." Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C. PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[19]	"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-376 AND SER-381, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"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].
[21]	"The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein." Smith K.J., Carter P.S., Bridges A., Horrocks P., Lewis C., Pettman G., Clarke A., Brown M., Hughes J., Wilkinson M., Bax B., Reith A. Structure 12:1067-1077(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-348.
[22]	"The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1." Malakhova M., D'Angelo I., Kim H.G., Kurinov I., Bode A.M., Dong Z. J. Mol. Biol. 399:41-52(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 414-738.
[23]	"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] ASN-554; LEU-574 AND CYS-599.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF074393 mRNA. Translation: AAC31171.1.
AF080000 mRNA. Translation: AAD23915.1.
AF090421 mRNA. Translation: AAC69577.1. Frameshift.
AL121784 Genomic DNA. No translation available.
AL133454 Genomic DNA. No translation available.
AL159191 Genomic DNA. No translation available.
BC017187 mRNA. Translation: AAH17187.1.

PIR

T13149.

RefSeq

NP_004746.2. NM_004755.2.
NP_872198.1. NM_182398.1.

UniGene

Hs.510225.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VZO	X-ray	1.80	A	2-348	[»]
3KN5	X-ray	2.40	A/B	414-738	[»]
3KN6	X-ray	2.00	A/B	414-738	[»]

ProteinModelPortal

O75582.

SMR

O75582. Positions 24-729.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

114676. 50 interactions.

IntAct

O75582. 31 interactions.

MINT

MINT-261060.

STRING

9606.ENSP00000261991.

Chemistry

BindingDB

O75582.

ChEMBL

CHEMBL4237.

GuidetoPHARMACOLOGY

1523.

PTM databases

PhosphoSite

O75582.

Proteomic databases

PaxDb

O75582.

PRIDE

O75582.

Protocols and materials databases

DNASU

9252.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261991; ENSP00000261991; ENSG00000100784.
ENST00000418736; ENSP00000402787; ENSG00000100784.

GeneID

9252.

KEGG

hsa:9252.

UCSC

uc001xys.2. human.

Organism-specific databases

CTD

9252.

GeneCards

GC14M091337.

HGNC

HGNC:10434. RPS6KA5.

HPA

CAB025458.
HPA001274.

MIM

603607. gene.

neXtProt

NX_O75582.

PharmGKB

PA34849.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

InParanoid

O75582.

KO

K04445.

OMA

FQSHDKS.

OrthoDB

EOG76HQ0Z.

PhylomeDB

O75582.

TreeFam

TF313438.

Enzyme and pathway databases

Reactome

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

SignaLink

O75582.

Gene expression databases

ArrayExpress

O75582.

Bgee

O75582.

CleanEx

HS_RPS6KA5.

Genevestigator

O75582.

Family and domain databases

InterPro

IPR000961. 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]

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. SSF56112. 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

ChiTaRS

RPS6KA5. human.

EvolutionaryTrace

O75582.

GeneWiki

RPS6KA5.

GenomeRNAi

9252.

NextBio

34679.

PRO

O75582.

SOURCE

Search...

Entry information

Entry name

KS6A5_HUMAN

Accession

Primary (citable) accession number: O75582
Secondary accession number(s): O95316, Q96AF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	November 1, 1998
Last modified:	February 19, 2014
This is version 142 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.