UniProt Accession

 KS6A4_HUMAN; O75676; A8K7Z8; O75585; Q53ES8 

Genbank Protein ID

 AJ010119; AK223561; AK292163; CH471076; AF074715 

Genbank Nucleotide ID

 CAA09009.1; BAD97281.1; BAF84852.1; EAW74260.1; AAC67395.1 

Protein Name

 Ribosomal protein S6 kinase alpha-4 

Protein Synonyms/Alias

 S6K-alpha-4; 90 kDa ribosomal protein S6 kinase 4; Nuclear mitogen- and stress-activated protein kinase 2; Ribosomal protein kinase B; RSKB 

Gene Name

 RPS6KA4 

Gene Synonyms/Alias

 MSK2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
37	VENFELLKVLGTGAY	ubiquitination	[1, 2, 3, 4]
134	LYQRQYFKEAEVRVY	ubiquitination	[3]
191	KEFLTEEKERTFSFC	ubiquitination	[2]
279	LLQRLLCKDPKKRLG	ubiquitination	[3]
313	WVALAARKIPAPFRP	ubiquitination	[3]
440	SGQEFAVKILSRRLE	ubiquitination	[1, 4]
532	GVVHRDLKPENILYA	ubiquitination	[2, 3]
548	DTPGAPVKIIDFGFA	ubiquitination	[2]
661	LLTVDPAKRLKLEGL	ubiquitination	[3]
664	VDPAKRLKLEGLRGS	ubiquitination	[3]
720	KREGFFLKSVENAPL	ubiquitination	[3]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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 factor RELA, 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. 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. 

Sequence Annotation

 DOMAIN 33 301 Protein kinase 1.
 DOMAIN 302 371 AGC-kinase C-terminal.
 DOMAIN 411 674 Protein kinase 2.
 NP_BIND 39 47 ATP (By similarity).
 NP_BIND 417 425 ATP (By similarity).
 REGION 725 772 Required for nuclear targeting and
 ACT_SITE 161 161 Proton acceptor (By similarity).
 ACT_SITE 530 530 Proton acceptor (By similarity).
 BINDING 65 65 ATP (By similarity).
 BINDING 440 440 ATP (By similarity).
 MOD_RES 196 196 Phosphoserine; by autocatalysis (By
 MOD_RES 343 343 Phosphoserine; by MAPK1, MAPK3 and MAPK14
 MOD_RES 347 347 Phosphoserine.
 MOD_RES 360 360 Phosphoserine; by autocatalysis (By
 MOD_RES 365 365 Phosphoserine; by autocatalysis (By
 MOD_RES 542 542 Phosphothreonine.
 MOD_RES 568 568 Phosphothreonine; by MAPK1, MAPK3 and
 MOD_RES 634 634 Phosphoserine.
 MOD_RES 678 678 Phosphoserine.
 MOD_RES 687 687 Phosphothreonine.
 MOD_RES 737 737 Phosphoserine; by autocatalysis
 MOD_RES 745 745 Phosphoserine.  

Keyword

 Alternative splicing; ATP-binding; Complete proteome; Inflammatory response; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Stress response; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 772 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0048273; F:mitogen-activated protein kinase p38 binding; IGI:UniProtKB.
 GO:0004711; F:ribosomal protein S6 kinase activity; NAS:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0043987; P:histone H3-S10 phosphorylation; IMP:UniProtKB.
 GO:0043988; P:histone H3-S28 phosphorylation; IMP:UniProtKB.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
 GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
 GO:0001818; P:negative regulation of cytokine production; TAS:UniProtKB.
 GO:0032793; P:positive regulation of CREB transcription factor activity; TAS:UniProtKB.
 GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
 GO:0033129; P:positive regulation of histone phosphorylation; IMP:BHF-UCL.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. 

Interpro

 IPR000961; AGC-kinase_C.
 IPR011009; Kinase-like_dom.
 IPR017892; Pkinase_C.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR016239; Ribosomal_S6_kinase_II.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase
 PF00433; Pkinase_C 

SMART

 SM00133; S_TK_X
 SM00220; S_TKc 

PROSITE

 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS