MK08_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MK08_MOUSE
• UniProt AC: Q91Y86
• Protein Name: Mitogen-activated protein kinase 8
• Gene Name: Mapk8
• Organism: Mus musculus (Mouse).
• Sequence Length: 384
• Subcellular Localization: Cytoplasm . Nucleus . Colocalizes with POU5F1 in the nucleus.
• Protein Description: Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock. [PubMed: 22441692 Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (By similarity Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation]
• Protein Sequence: MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLAQVQQ

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
116	S-nitrosocysteine	ELMDANLCQVIQMEL HHCCCCHHHHHHCCC	2.81	-
116	S-nitrosylation	ELMDANLCQVIQMEL HHCCCCHHHHHHCCC	2.81	-
129	Phosphorylation	ELDHERMSYLLYQML CCCHHHHHHHHHHHH	20.89	16483929
153	Ubiquitination	GIIHRDLKPSNIVVK CCCCCCCCHHHEEEE	51.17	-
166	Ubiquitination	VKSDCTLKILDFGLA EECCCEEEECCHHCC	24.06	-
175	Phosphorylation	LDFGLARTAGTSFMM CCHHCCCCCCCCCCC	24.67	22499769
178	Phosphorylation	GLARTAGTSFMMTPY HCCCCCCCCCCCCCH	19.14	22499769
179	Phosphorylation	LARTAGTSFMMTPYV CCCCCCCCCCCCCHH	15.38	22499769
183	Phosphorylation	AGTSFMMTPYVVTRY CCCCCCCCCHHEEEH	10.32	22322096
185	Phosphorylation	TSFMMTPYVVTRYYR CCCCCCCHHEEEHHC	9.82	22322096
188	Phosphorylation	MMTPYVVTRYYRAPE CCCCHHEEEHHCCCH	11.69	22322096
308	Acetylation	MLVIDASKRISVDEA HHHHCHHHCCCHHHH	56.31	7670877
377	Phosphorylation	GVIRGQPSPLAQVQQ CCCCCCCCCCHHCCC	25.34	25521595

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
129	S	Phosphorylation	Kinase	PRKCD	P28867	GPS
183	T	Phosphorylation	Kinase	MAP2K4	P47809	GPS
183	T	Phosphorylation	Kinase	MAP2K7	Q8CE90	Uniprot
185	Y	Phosphorylation	Kinase	MKK4	P47809	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
183	T	Phosphorylation	Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme.	11562351
183	T	Phosphorylation	May be phosphorylated at Thr-183 and Tyr-185 by MAP3K1/MEKK1.	11562351

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MK08_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NFE2_MOUSE	Nfe2	physical	19966288
JUN_MOUSE	Jun	physical	21538482
JUN_MOUSE	Jun	physical	17276034
JUN_MOUSE	Jun	physical	17158449
P53_MOUSE	Trp53	physical	9732264
DAXX_MOUSE	Daxx	physical	18932217
GTR4_MOUSE	Slc2a4	physical	18932217
JUN_MOUSE	Jun	physical	10748240
MABP1_MOUSE	Mapkbp1	physical	10471813
JUN_MOUSE	Jun	physical	15288121
SARM1_MOUSE	Sarm1	physical	17724133
JUN_MOUSE	Jun	physical	15218018
JIP3_MOUSE	Mapk8ip3	physical	15767678
JIP4_MOUSE	Spag9	physical	15767678
JUN_MOUSE	Jun	physical	15767678
P53_MOUSE	Trp53	physical	15580310
WWOX_MOUSE	Wwox	physical	15580310
JUN_MOUSE	Jun	physical	12223491
MCL1_MOUSE	Mcl1	physical	22976837
JUN_MOUSE	Jun	physical	9687507
ZBT7C_MOUSE	Zbtb7c	physical	27646874

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Phosphoproteomic analysis of the developing mouse brain.";
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
Mol. Cell. Proteomics 3:1093-1101(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND MASSSPECTROMETRY.
PubMed: 15345747

"Requirement of the JIP1 scaffold protein for stress-induced JNKactivation.";
Whitmarsh A.J., Kuan C.-Y., Kennedy N.J., Kelkar N., Haydar T.F.,Mordes J.P., Appel M., Rossini A.A., Jones S.N., Flavell R.A.,Rakic P., Davis R.J.;
Genes Dev. 15:2421-2432(2001).
Cited for: SUBUNIT, AND PHOSPHORYLATION AT THR-183 AND TYR-185.
PubMed: 11562351