dbPTM

MK13_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK13_HUMAN
UniProt AC	O15264
Protein Name	Mitogen-activated protein kinase 13
Gene Name	MAPK13
Organism	Homo sapiens (Human).
Sequence Length	365
Subcellular Localization
Protein Description	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells..
Protein Sequence	MSLIRKKGFYKQDVNKTAWELPKTYVSPTHVGSGAYGSVCSAIDKRSGEKVAIKKLSRPFQSEIFAKRAYRELLLLKHMQHENVIGLLDVFTPASSLRNFYDFYLVMPFMQTDLQKIMGMEFSEEKIQYLVYQMLKGLKYIHSAGVVHRDLKPGNLAVNEDCELKILDFGLARHADAEMTGYVVTRWYRAPEVILSWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTGVPGTEFVQKLNDKAAKSYIQSLPQTPRKDFTQLFPRASPQAADLLEKMLELDVDKRLTAAQALTHPFFEPFRDPEEETEAQQPFDDSLEHEKLTVDEWKQHIYKEIVNFSPIARKDSRRRSGMKL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSLIRKKGF ------CCCHHCCCC	32.29	24719451
10	Phosphorylation	LIRKKGFYKQDVNKT CHHCCCCCCCCCCCC	19.19	-
24	Phosphorylation	TAWELPKTYVSPTHV CHHHCCCCEECCCCC	27.50	23312004
25	Phosphorylation	AWELPKTYVSPTHVG HHHCCCCEECCCCCC	12.69	23312004
27	Phosphorylation	ELPKTYVSPTHVGSG HCCCCEECCCCCCCC	17.42	24719451
29	Phosphorylation	PKTYVSPTHVGSGAY CCCEECCCCCCCCCC	22.99	28348404
33	Phosphorylation	VSPTHVGSGAYGSVC ECCCCCCCCCCHHHH	21.11	23312004
36	Phosphorylation	THVGSGAYGSVCSAI CCCCCCCCHHHHHHH	17.29	23312004
38	Phosphorylation	VGSGAYGSVCSAIDK CCCCCCHHHHHHHHC	13.79	23312004
47	Phosphorylation	CSAIDKRSGEKVAIK HHHHHCCCCCEEEEE	57.98	22817900
123	Phosphorylation	KIMGMEFSEEKIQYL HHHCCCCCHHHHHHH	31.38	29116813
129	Phosphorylation	FSEEKIQYLVYQMLK CCHHHHHHHHHHHHH	11.12	29116813
143	Phosphorylation	KGLKYIHSAGVVHRD HCCCHHHHCCEECCC	19.70	-
180	Phosphorylation	RHADAEMTGYVVTRW HHCCHHHCCEEEEEE	19.50	27273156
182	Phosphorylation	ADAEMTGYVVTRWYR CCHHHCCEEEEEEEE	5.20	27273156
185	Phosphorylation	EMTGYVVTRWYRAPE HHCCEEEEEEEECCH	12.87	23927012
226	Ubiquitination	GKTLFKGKDYLDQLT CCCCCCCHHHHHHHH	43.73	21906983
261	Phosphorylation	AAKSYIQSLPQTPRK HHHHHHHCCCCCCCC	32.24	27251275
265	Phosphorylation	YIQSLPQTPRKDFTQ HHHCCCCCCCCCHHH	24.11	29496963
350	Phosphorylation	YKEIVNFSPIARKDS HHHHHCCCCCCCCHH	15.36	22617229
357	Phosphorylation	SPIARKDSRRRSGMK CCCCCCHHCHHCCCC	30.62	-
361	Phosphorylation	RKDSRRRSGMKL--- CCHHCHHCCCCC---	41.23	-

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
180	T	Phosphorylation	Kinase	MKK3	P46734	PSP
180	T	Phosphorylation	Kinase	MAP2K4	P45985	Uniprot
180	T	Phosphorylation	Kinase	MKK6	P52564	PSP
180	T	Phosphorylation	Kinase	MAP2K7	O14733	Uniprot
182	Y	Phosphorylation	Kinase	MKK3	P46734	PSP
182	Y	Phosphorylation	Kinase	MAP2K4	P45985	Uniprot
182	Y	Phosphorylation	Kinase	MKK6	P52564	PSP
182	Y	Phosphorylation	Kinase	MAP2K7	O14733	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
180	T	Phosphorylation		9374491
Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme.

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 MK13_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ATF2_HUMAN	ATF2	physical	12244047
FGF12_HUMAN	FGF12	physical	12244047
AKIP1_HUMAN	AKIP1	physical	18624398
ANKL2_HUMAN	ANKLE2	physical	18624398
MBP_HUMAN	MBP	physical	17906618
HTRA2_HUMAN	HTRA2	physical	17906618
A4_HUMAN	APP	physical	21832049
TAU_HUMAN	MAPT	physical	9199504
POTEF_HUMAN	POTEF	physical	26186194
M3K4_HUMAN	MAP3K4	physical	25241761
MAPK3_HUMAN	MAPKAPK3	physical	25241761
SQSTM_HUMAN	SQSTM1	physical	26279575
POTEF_HUMAN	POTEF	physical	28514442

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 MK13_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 SER-350, AND MASSSPECTROMETRY.	19369195 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND MASSSPECTROMETRY.	18088087 [Abstract]
"Characterization of the structure and function of the fourth memberof p38 group mitogen-activated protein kinases, p38delta."; Jiang Y., Gram H., Zhao M., New L., Gu J., Feng L., Di Padova F.,Ulevitch R.J., Han J.; J. Biol. Chem. 272:30122-30128(1997). Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-180 AND TYR-182,MUTAGENESIS OF THR-180 AND TYR-182, ENZYME REGULATION, AND TISSUESPECIFICITY.	9374491 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, AND MASSSPECTROMETRY.	18083107 [Abstract]

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