dbPTM

KS6A4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KS6A4_HUMAN
UniProt AC	O75676
Protein Name	Ribosomal protein S6 kinase alpha-4
Gene Name	RPS6KA4
Organism	Homo sapiens (Human).
Sequence Length	772
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..
Protein Sequence	MGDEDDDESCAVELRITEANLTGHEEKVSVENFELLKVLGTGAYGKVFLVRKAGGHDAGKLYAMKVLRKAALVQRAKTQEHTRTERSVLELVRQAPFLVTLHYAFQTDAKLHLILDYVSGGEMFTHLYQRQYFKEAEVRVYGGEIVLALEHLHKLGIIYRDLKLENVLLDSEGHIVLTDFGLSKEFLTEEKERTFSFCGTIEYMAPEIIRSKTGHGKAVDWWSLGILLFELLTGASPFTLEGERNTQAEVSRRILKCSPPFPPRIGPVAQDLLQRLLCKDPKKRLGAGPQGAQEVRNHPFFQGLDWVALAARKIPAPFRPQIRSELDVGNFAEEFTRLEPVYSPPGSPPPGDPRIFQGYSFVAPSILFDHNNAVMTDGLEAPGAGDRPGRAAVARSAMMQDSPFFQQYELDLREPALGQGSFSVCRRCRQRQSGQEFAVKILSRRLEANTQREVAALRLCQSHPNVVNLHEVHHDQLHTYLVLELLRGGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEAGVVHRDLKPENILYADDTPGAPVKIIDFGFARLRPQSPGVPMQTPCFTLQYAAPELLAQQGYDESCDLWSLGVILYMMLSGQVPFQGASGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRGLLTVDPAKRLKLEGLRGSSWLQDGSARSSPPLRTPDVLESSGPAVRSGLNATFMAFNRGKREGFFLKSVENAPLAKRRKQKLRSATASRRGSPAPANPGRAPVASKGAPRRANGPLPPS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
9	Phosphorylation	GDEDDDESCAVELRI CCCCCCHHCEEEEEE	17.86	20873877
22	Phosphorylation	RITEANLTGHEEKVS EEEECCCCCCCEEEC	35.98	25106551
27	Ubiquitination	NLTGHEEKVSVENFE CCCCCCEEECHHHHH	36.50	-
29	Phosphorylation	TGHEEKVSVENFELL CCCCEEECHHHHHHH	34.48	19835603
37	Ubiquitination	VENFELLKVLGTGAY HHHHHHHHHHCCCCC	48.30	21890473
37 (in isoform 2)	Ubiquitination	-	48.30	21890473
37 (in isoform 1)	Ubiquitination	-	48.30	21890473
41	Phosphorylation	ELLKVLGTGAYGKVF HHHHHHCCCCCCEEE	17.93	19835603
44	Phosphorylation	KVLGTGAYGKVFLVR HHHCCCCCCEEEEEE	20.87	19835603
69	Ubiquitination	YAMKVLRKAALVQRA HHHHHHHHHHHHHHH	33.57	-
84	Phosphorylation	KTQEHTRTERSVLEL HHCCCCHHHHHHHHH	36.58	23312004
87	Phosphorylation	EHTRTERSVLELVRQ CCCHHHHHHHHHHHH	25.48	23312004
128	Phosphorylation	GEMFTHLYQRQYFKE CHHHHHHHHHHHHCC	8.27	27259358
134	Ubiquitination	LYQRQYFKEAEVRVY HHHHHHHCCCEEEEE	51.59	-
141	Phosphorylation	KEAEVRVYGGEIVLA CCCEEEEECHHHHHH	14.62	-
178	Phosphorylation	SEGHIVLTDFGLSKE CCCCEEEECCCCCHH	20.56	21082442
183	Phosphorylation	VLTDFGLSKEFLTEE EEECCCCCHHHCCCH	30.44	21082442
184	Ubiquitination	LTDFGLSKEFLTEEK EECCCCCHHHCCCHH	58.49	-
191 (in isoform 2)	Ubiquitination	-	46.38	21890473
191	Ubiquitination	KEFLTEEKERTFSFC HHHCCCHHHHHCEEC	46.38	21906983
191 (in isoform 1)	Ubiquitination	-	46.38	21890473
194	Phosphorylation	LTEEKERTFSFCGTI CCCHHHHHCEECCCH	25.40	28102081
196	Phosphorylation	EEKERTFSFCGTIEY CHHHHHCEECCCHHH	21.00	17429437
200	Phosphorylation	RTFSFCGTIEYMAPE HHCEECCCHHHHCHH	16.30	28102081
279	Ubiquitination	LLQRLLCKDPKKRLG HHHHHHCCCHHHHCC	76.63	-
313	Ubiquitination	WVALAARKIPAPFRP HHHHHHCCCCCCCCH	48.60	-
324	Phosphorylation	PFRPQIRSELDVGNF CCCHHHHCCCCCCCC	44.11	23090842
336	Phosphorylation	GNFAEEFTRLEPVYS CCCHHHHHCCCCCCC	37.31	23090842
342	Phosphorylation	FTRLEPVYSPPGSPP HHCCCCCCCCCCCCC	26.61	29255136
343	Phosphorylation	TRLEPVYSPPGSPPP HCCCCCCCCCCCCCC	25.50	29255136
347	Phosphorylation	PVYSPPGSPPPGDPR CCCCCCCCCCCCCCC	39.75	29255136
359	Phosphorylation	DPRIFQGYSFVAPSI CCCCCCCCEEECCEE	6.53	22322096
360	Phosphorylation	PRIFQGYSFVAPSIL CCCCCCCEEECCEEE	21.77	22322096
365	Phosphorylation	GYSFVAPSILFDHNN CCEEECCEEEECCCC	23.37	22322096
376	Phosphorylation	DHNNAVMTDGLEAPG CCCCCEECCCCCCCC	21.95	22322096
433	Phosphorylation	RRCRQRQSGQEFAVK HHHHHHCCCCHHHHH	44.63	22210691
434 (in isoform 2)	Ubiquitination	-	23.77	21890473
440	Ubiquitination	SGQEFAVKILSRRLE CCCHHHHHHHHHHHH	34.20	21890473
440 (in isoform 1)	Ubiquitination	-	34.20	21890473
443	Phosphorylation	EFAVKILSRRLEANT HHHHHHHHHHHHHHC	20.87	22210691
502	Phosphorylation	IRKKRHFSESEASQI HHHHCCCCHHHHHHH	33.80	23312004
526 (in isoform 2)	Ubiquitination	-	4.17	21890473
532	Ubiquitination	GVVHRDLKPENILYA CCCCCCCCHHHEEEC	55.35	21906983
532 (in isoform 1)	Ubiquitination	-	55.35	21890473
542 (in isoform 2)	Ubiquitination	-	24.95	21890473
542	Phosphorylation	NILYADDTPGAPVKI HEEECCCCCCCCEEE	24.95	21082442
548 (in isoform 1)	Ubiquitination	-	32.65	21890473
548	Ubiquitination	DTPGAPVKIIDFGFA CCCCCCEEEEEEEEC	32.65	2190698
568	Phosphorylation	SPGVPMQTPCFTLQY CCCCCCCCCCEEHHH	18.77	22817900
613	Phosphorylation	QVPFQGASGQGGQSQ CCCCCCCCCCCCHHH	38.17	26657352
634	Phosphorylation	KIREGRFSLDGEAWQ HHCCCCCCCCCCHHC	24.96	21082442
648	Ubiquitination	QGVSEEAKELVRGLL CCCCHHHHHHHHHHC	55.66	-
661	Ubiquitination	LLTVDPAKRLKLEGL HCCCCHHHCCCCCCC	64.75	-
664	Sumoylation	VDPAKRLKLEGLRGS CCHHHCCCCCCCCCC	48.83	-
664	Ubiquitination	VDPAKRLKLEGLRGS CCHHHCCCCCCCCCC	48.83	-
664	Sumoylation	VDPAKRLKLEGLRGS CCHHHCCCCCCCCCC	48.83	-
671	Phosphorylation	KLEGLRGSSWLQDGS CCCCCCCCCCCCCCC	16.35	23090842
672	Phosphorylation	LEGLRGSSWLQDGSA CCCCCCCCCCCCCCC	34.33	18691976
678	Phosphorylation	SSWLQDGSARSSPPL CCCCCCCCCCCCCCC	28.88	23898821
681	Phosphorylation	LQDGSARSSPPLRTP CCCCCCCCCCCCCCC	47.08	20201521
682	Phosphorylation	QDGSARSSPPLRTPD CCCCCCCCCCCCCCH	25.61	23927012
687	Phosphorylation	RSSPPLRTPDVLESS CCCCCCCCCHHHHCC	31.37	19664994
693	Phosphorylation	RTPDVLESSGPAVRS CCCHHHHCCCHHHHH	36.11	23927012
694	Phosphorylation	TPDVLESSGPAVRSG CCHHHHCCCHHHHHC	39.15	23927012
700	Phosphorylation	SSGPAVRSGLNATFM CCCHHHHHCCCEEEE	40.82	28555341
705	Phosphorylation	VRSGLNATFMAFNRG HHHCCCEEEEEECCC	16.93	28555341
720	Ubiquitination	KREGFFLKSVENAPL CCCCEECCCCCCCCH	47.50	-
721	Phosphorylation	REGFFLKSVENAPLA CCCEECCCCCCCCHH	36.49	25159151
729	Ubiquitination	VENAPLAKRRKQKLR CCCCCHHHHHHHHHH	61.49	-
737	Phosphorylation	RRKQKLRSATASRRG HHHHHHHHHHHHCCC	40.17	28102081
739	Phosphorylation	KQKLRSATASRRGSP HHHHHHHHHHCCCCC	26.81	26699800
743	Methylation	RSATASRRGSPAPAN HHHHHHCCCCCCCCC	47.66	83364677
745	Phosphorylation	ATASRRGSPAPANPG HHHHCCCCCCCCCCC	18.97	23927012
759	Acetylation	GRAPVASKGAPRRAN CCCCCCCCCCCCCCC	49.72	25953088
772	Phosphorylation	ANGPLPPS------- CCCCCCCC-------	51.41	23312004

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
196	S	Phosphorylation	Kinase	RPS6KA4	O75676	GPS
196	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
324	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
343	S	Phosphorylation	Kinase	MAPK1	P28482	Uniprot
343	S	Phosphorylation	Kinase	MAPK3	P27361	Uniprot
343	S	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
347	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
360	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
568	T	Phosphorylation	Kinase	MAPK1	P28482	Uniprot
568	T	Phosphorylation	Kinase	MAPK3	P27361	Uniprot
568	T	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	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	18691976
Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.
737	S	Phosphorylation	-
Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).
745	S	Phosphorylation	18691976
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.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of KS6A4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK14_HUMAN	MAPK14	physical	9792677
MK14_HUMAN	MAPK14	genetic	9792677
CREB1_HUMAN	CREB1	physical	9792677
FOS_HUMAN	FOS	physical	9792677
MK01_HUMAN	MAPK1	physical	11035004
MK01_HUMAN	MAPK1	physical	10922375
MK14_HUMAN	MAPK14	physical	10922375

Drug and Disease Associations

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

Regulatory Network of KS6A4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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 TYR-342; SER-343; SER-347;THR-542; SER-678; SER-681; THR-687 AND SER-745, AND MASS SPECTROMETRY.	19369195 [Abstract]
"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 SER-343; SER-347; SER-634;SER-678; SER-737 AND SER-745, AND MASS SPECTROMETRY.	18691976 [Abstract]
"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-681 AND SER-682, ANDMASS SPECTROMETRY.	17192257 [Abstract]

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