dbPTM

MK12_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MK12_HUMAN
UniProt AC	P53778
Protein Name	Mitogen-activated protein kinase 12
Gene Name	MAPK12
Organism	Homo sapiens (Human).
Sequence Length	367
Subcellular Localization	Cytoplasm. Nucleus. Mitochondrion. Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma (By similarity)..
Protein Description	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 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. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration..
Protein Sequence	MSSPPPARSGFYRQEVTKTAWEVRAVYRDLQPVGSGAYGAVCSAVDGRTGAKVAIKKLYRPFQSELFAKRAYRELRLLKHMRHENVIGLLDVFTPDETLDDFTDFYLVMPFMGTDLGKLMKHEKLGEDRIQFLVYQMLKGLRYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQADSEMTGYVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKTLFKGSDHLDQLKEIMKVTGTPPAEFVQRLQSDEAKNYMKGLPELEKKDFASILTNASPLAVNLLEKMLVLDAEQRVTAGEALAHPYFESLHDTEDEPQVQKYDDSFDDVDRTLDEWKRVTYKEVLSFKPPRQLGARVSKETPL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSSPPPARS ------CCCCCCCCC	52.10	19413330
2	Phosphorylation	------MSSPPPARS ------CCCCCCCCC	52.10	23401153
3	Phosphorylation	-----MSSPPPARSG -----CCCCCCCCCC	39.88	23401153
9	Phosphorylation	SSPPPARSGFYRQEV CCCCCCCCCCCCHHH	35.05	23401153
12	Phosphorylation	PPARSGFYRQEVTKT CCCCCCCCCHHHHHH	18.21	23401153
27	Phosphorylation	AWEVRAVYRDLQPVG HHHHHHHHHCCCCCC	9.45	22817900
180	Phosphorylation	GLARQADSEMTGYVV HHHHCCCCCCCCEEE	32.08	21945579
183	Phosphorylation	RQADSEMTGYVVTRW HCCCCCCCCEEEEEE	22.70	21945579
185	Phosphorylation	ADSEMTGYVVTRWYR CCCCCCCEEEEEEEE	5.20	21945579
188	Phosphorylation	EMTGYVVTRWYRAPE CCCCEEEEEEEECHH	12.87	21945579
236	Ubiquitination	SDHLDQLKEIMKVTG CCHHHHHHHHHHHHC	39.29	-
255	Phosphorylation	EFVQRLQSDEAKNYM HHHHHHCCHHHHHHH	41.85	29759185
261	Phosphorylation	QSDEAKNYMKGLPEL CCHHHHHHHCCCHHH	10.25	29759185
350	Phosphorylation	VTYKEVLSFKPPRQL CCHHHHHHCCCCHHH	36.08	24719451
362	Phosphorylation	RQLGARVSKETPL-- HHHCCCCCCCCCC--	21.15	26437602

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
3	S	Phosphorylation	Kinase	MAPK12	P53778	GPS
183	T	Phosphorylation	Kinase	MP2K3	P46734	PhosphoELM
183	T	Phosphorylation	Kinase	MP2K6	P52564	PhosphoELM
185	Y	Phosphorylation	Kinase	MAP2K3	P46734	GPS
185	Y	Phosphorylation	Kinase	MAP2K4	P45985	GPS
185	Y	Phosphorylation	Kinase	MAP2K6	P52564	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
183	T	Phosphorylation		11010976
Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, 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 MK12_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SNTA1_HUMAN	SNTA1	physical	10212242
HTRA2_HUMAN	HTRA2	physical	17906618
MBP_HUMAN	MBP	physical	17906618
ROBO1_HUMAN	ROBO1	physical	22939629
TAB1_HUMAN	TAB1	physical	12429732
MP2K6_HUMAN	MAP2K6	physical	12761180
GCH1_HUMAN	GCH1	physical	19294699
SIAH1_HUMAN	SIAH1	physical	25416956
MK13_HUMAN	MAPK13	physical	26186194
MYLK3_HUMAN	MYLK3	physical	26186194
DLG1_HUMAN	DLG1	physical	25241761
DUS1_HUMAN	DUSP1	physical	25241761
CPZIP_HUMAN	RCSD1	physical	15850461
MK13_HUMAN	MAPK13	physical	28514442
MYLK3_HUMAN	MYLK3	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 MK12_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3 AND TYR-185, AND MASSSPECTROMETRY.	19413330 [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-185, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-27, AND MASSSPECTROMETRY.	17081983 [Abstract]

show