KS6A4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KS6A4_MOUSE
• UniProt AC: Q9Z2B9
• Protein Name: Ribosomal protein S6 kinase alpha-4
• Gene Name: Rps6ka4
• Organism: Mus musculus (Mouse).
• Sequence Length: 773
• Subcellular Localization: Nucleus.
• Protein 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 (By similarity)..
• Protein Sequence: MGDEDEDEGCAVELQITEANLTGHEEKVSVENFALLKVLGTGAYGKVFLVRKTGGHDAGKLYAMKVLRKAALVQRAKTQEHTRTERSVLELVRQAPFLVTLHYAFQTDAKLHLILDYVSGGEMFTHLYQRQYFKEAEVRVYGGEIVLALEHLHKLGIIYRDLKLENVLLDSEGHIVLTDFGLSKEFLTEEKERTFSFCGTIEYMAPEIIRSKAGHGKAVDWWSLGILLFELLTGASPFTLEGERNTQAEVSRRILKCSPPFPLRIGPVAQDLLQRLLCKDPKKRLGAGPQGAQEVKSHPFFQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPAGSPPPGDPRIFQGYSFVAPSILFDHNNAVMADVLQAPGAGYRPGRAAVARSAMMQDSPFFQQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEENTQREVAALRLCQSHPNVVNLHEVLHDQLHTYLVLELLRGGELLEHIRKKRLFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPAEPMQTPCFTLQYAAPELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEGLRSSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSAAASRRGSPVPASSGRLPASAAKGTTRRANGPLSPS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
87	Phosphorylation	EHTRTERSVLELVRQ CCCHHHHHHHHHHHH	25.48	-
160	Methylation	HKLGIIYRDLKLENV HHCCCEECCCCCCCE	32.17	30988155
183	Phosphorylation	VLTDFGLSKEFLTEE EEECCCCCHHHCCCH	30.44	23737553
196	Phosphorylation	EEKERTFSFCGTIEY CHHHHHCEECCCHHH	21.00	-
342	Phosphorylation	FTRLEPVYSPAGSPP HHCCCCCCCCCCCCC	21.47	25168779
343	Phosphorylation	TRLEPVYSPAGSPPP HCCCCCCCCCCCCCC	14.44	27087446
347	Phosphorylation	PVYSPAGSPPPGDPR CCCCCCCCCCCCCCC	36.02	27087446
360	Phosphorylation	PRIFQGYSFVAPSIL CCCCCCCEEECCEEE	21.77	25338131
365	Phosphorylation	GYSFVAPSILFDHNN CCEEECCEEEECCCC	23.37	25338131
502	Phosphorylation	IRKKRLFSESEASQI HHHHCCCCHHHHHHH	44.82	22817900
504	Phosphorylation	KKRLFSESEASQILR HHCCCCHHHHHHHHH	36.95	22817900
507	Phosphorylation	LFSESEASQILRSLV CCCHHHHHHHHHHHH	17.44	22817900
542	Phosphorylation	NILYADDTPGAPVKI HEEECCCCCCCCEEE	24.95	25619855
568	Phosphorylation	SPAEPMQTPCFTLQY CCCCCCCCCCEEHHH	18.77	-
634	Phosphorylation	KIREGRFSLDGEAWQ HHCCCCCCCCCCHHC	24.96	28833060
670	Phosphorylation	LKLEGLRSSSWLQDG CCCCCCCCCCCCCCC	33.49	23984901
671	Phosphorylation	KLEGLRSSSWLQDGS CCCCCCCCCCCCCCC	21.06	23984901
672	Phosphorylation	LEGLRSSSWLQDGSA CCCCCCCCCCCCCCC	32.81	23984901
678	Phosphorylation	SSWLQDGSARSSPPL CCCCCCCCCCCCCCC	28.88	26060331
681	Phosphorylation	LQDGSARSSPPLRTP CCCCCCCCCCCCCCC	47.08	21082442
682	Phosphorylation	QDGSARSSPPLRTPD CCCCCCCCCCCCCCH	25.61	22942356
687	Phosphorylation	RSSPPLRTPDVLESS CCCCCCCCCHHHHCC	31.37	26824392
693	Phosphorylation	RTPDVLESSGPAVRS CCCHHHHCCCHHHHH	36.11	25619855
694	Phosphorylation	TPDVLESSGPAVRSG CCHHHHCCCHHHHHC	39.15	25619855
721	Phosphorylation	REGFFLKSVENAPLA CCCEECCCCCCCCHH	36.49	29514104
737	Phosphorylation	RRKQKLRSAAASRRG HHHHHHHHHHHHHCC	32.47	29472430
741	Phosphorylation	KLRSAAASRRGSPVP HHHHHHHHHCCCCCC	20.13	29514104
745	Phosphorylation	AAASRRGSPVPASSG HHHHHCCCCCCCCCC	22.40	26824392
750	Phosphorylation	RGSPVPASSGRLPAS CCCCCCCCCCCCCCH	27.53	24453211
751	Phosphorylation	GSPVPASSGRLPASA CCCCCCCCCCCCCHH	30.00	24453211
757	Phosphorylation	SSGRLPASAAKGTTR CCCCCCCHHCCCCCC	27.16	22322096
771	Phosphorylation	RRANGPLSPS----- CCCCCCCCCC-----	26.65	25521595
773	Phosphorylation	ANGPLSPS------- CCCCCCCC-------	49.86	26824392

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
343	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
343	S	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
343	S	Phosphorylation	Kinase	MAPK14	P47811	Uniprot
568	T	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
568	T	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
568	T	Phosphorylation	Kinase	MAPK14	P47811	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
196	S	Phosphorylation	Ser-343 and Ser-196 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain.	-
343	S	Phosphorylation	Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.	-
343	S	Phosphorylation	Ser-343 and Ser-196 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain.	-
343	S	Phosphorylation	Ser-343 and Thr-568 phosphorylation is required for kinase activity.	-
568	T	Phosphorylation	Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.	-
568	T	Phosphorylation	Ser-343 and Thr-568 phosphorylation is required for kinase activity.	-
687	T	Phosphorylation	Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.	21183079
737	S	Phosphorylation	Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).	-
745	S	Phosphorylation	Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of KS6A4_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of KS6A4_MOUSE !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale phosphorylation analysis of mouse liver.";
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343 AND SER-347, ANDMASS SPECTROMETRY.
PubMed: 17242355