MAPK8 (mitogen-activated protein kinase 8)

Gene

• Entrez ID: 5599
• Gene name: Mitogen-activated protein kinase 8
• Gene symbol: MAPK8
• Synonyms: JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8, SAPK1, SAPK1c
• Chromosome: 10
• Chromosome location: 10q11.22
• Summary: The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003985	hsa-miR-199a-3p	Western blot	18456660
MIRT005427	hsa-miR-214-3p	GFP reporter assay, Microarray, qRT-PCR, Western blot, Reporter assay;qRT-PCR;Microarray;Other	19859982
MIRT016104	hsa-miR-421	Sequencing	20371350
MIRT016104	hsa-miR-421	CLASH	23622248
MIRT016510	hsa-miR-193b-3p	Microarray	20304954
MIRT016510	hsa-miR-193b-3p	PAR-CLIP	23592263
MIRT016510	hsa-miR-193b-3p	PAR-CLIP	21572407
MIRT021289	hsa-miR-125a-5p	Sequencing	20371350
MIRT021678	hsa-miR-140-3p	Sequencing	20371350
MIRT025602	hsa-miR-10a-5p	Sequencing	20371350
MIRT028235	hsa-miR-33a-5p	Sequencing	20371350
MIRT028235	hsa-miR-33a-5p	PAR-CLIP	24398324
MIRT037323	hsa-miR-877-5p	CLASH	23622248
MIRT437964	hsa-miR-92a-3p	qRT-PCR, Luciferase reporter assay, Western blot	24705900
MIRT441783	hsa-miR-3163	PAR-CLIP	22100165
MIRT441784	hsa-miR-4480	PAR-CLIP	22100165
MIRT441784	hsa-miR-4480	PAR-CLIP	22012620
MIRT441785	hsa-miR-1277-5p	PAR-CLIP	22100165
MIRT441785	hsa-miR-1277-5p	PAR-CLIP	22012620
MIRT441786	hsa-miR-3662	PAR-CLIP	22100165
MIRT441786	hsa-miR-3662	PAR-CLIP	22012620
MIRT473685	hsa-miR-374b-3p	PAR-CLIP	23592263
MIRT473685	hsa-miR-374b-3p	PAR-CLIP	21572407
MIRT473686	hsa-miR-548s	PAR-CLIP	23592263
MIRT473686	hsa-miR-548s	PAR-CLIP	21572407
MIRT473687	hsa-miR-4524b-5p	PAR-CLIP	23592263
MIRT473687	hsa-miR-4524b-5p	PAR-CLIP	21572407
MIRT473688	hsa-miR-4524a-5p	PAR-CLIP	23592263
MIRT473688	hsa-miR-4524a-5p	PAR-CLIP	21572407
MIRT473689	hsa-miR-3926	PAR-CLIP	23592263
MIRT473689	hsa-miR-3926	PAR-CLIP	21572407
MIRT473690	hsa-miR-3190-5p	PAR-CLIP	23592263
MIRT473690	hsa-miR-3190-5p	PAR-CLIP	21572407
MIRT473691	hsa-miR-4280	PAR-CLIP	23592263
MIRT473691	hsa-miR-4280	PAR-CLIP	21572407
MIRT473692	hsa-miR-892b	PAR-CLIP	23592263
MIRT473692	hsa-miR-892b	PAR-CLIP	21572407
MIRT473693	hsa-miR-193a-3p	PAR-CLIP	23592263
MIRT473693	hsa-miR-193a-3p	PAR-CLIP	21572407
MIRT473694	hsa-miR-497-3p	PAR-CLIP	23592263
MIRT473694	hsa-miR-497-3p	PAR-CLIP	20371350
MIRT473695	hsa-miR-30b-5p	PAR-CLIP	23592263
MIRT473695	hsa-miR-30b-5p	PAR-CLIP	21572407
MIRT473696	hsa-miR-30e-5p	PAR-CLIP	23592263
MIRT473696	hsa-miR-30e-5p	PAR-CLIP	21572407
MIRT473697	hsa-miR-30c-5p	PAR-CLIP	23592263
MIRT473697	hsa-miR-30c-5p	PAR-CLIP	21572407
MIRT473698	hsa-miR-30d-5p	PAR-CLIP	23592263
MIRT473698	hsa-miR-30d-5p	PAR-CLIP	21572407
MIRT473699	hsa-miR-30a-5p	PAR-CLIP	23592263
MIRT473699	hsa-miR-30a-5p	PAR-CLIP	21572407
MIRT501958	hsa-miR-3680-3p	PAR-CLIP	24398324
MIRT501958	hsa-miR-3680-3p	PAR-CLIP	22012620
MIRT501959	hsa-miR-433-3p	PAR-CLIP	24398324
MIRT501960	hsa-miR-7154-5p	PAR-CLIP	24398324
MIRT501961	hsa-miR-4795-3p	PAR-CLIP	24398324
MIRT501962	hsa-miR-8060	PAR-CLIP	24398324
MIRT501963	hsa-miR-496	PAR-CLIP	24398324
MIRT501964	hsa-miR-664a-3p	PAR-CLIP	24398324
MIRT501965	hsa-miR-126-5p	PAR-CLIP	24398324
MIRT501966	hsa-miR-203a-3p	PAR-CLIP	24398324
MIRT501967	hsa-miR-33b-5p	PAR-CLIP	24398324
MIRT536119	hsa-miR-557	PAR-CLIP	22012620
MIRT536120	hsa-miR-507	PAR-CLIP	22012620
MIRT536121	hsa-miR-450b-5p	PAR-CLIP	22012620
MIRT536122	hsa-miR-4325	PAR-CLIP	22012620
MIRT536123	hsa-miR-7703	PAR-CLIP	22012620
MIRT536124	hsa-miR-4775	PAR-CLIP	22012620
MIRT536125	hsa-miR-616-5p	PAR-CLIP	22012620
MIRT536126	hsa-miR-373-5p	PAR-CLIP	22012620
MIRT536127	hsa-miR-371b-5p	PAR-CLIP	22012620
MIRT536128	hsa-miR-3613-3p	PAR-CLIP	22012620
MIRT536128	hsa-miR-3613-3p	PAR-CLIP	20371350
MIRT536129	hsa-miR-888-5p	PAR-CLIP	22012620
MIRT536130	hsa-miR-590-3p	PAR-CLIP	22012620
MIRT566815	hsa-miR-548aw	PAR-CLIP	20371350
MIRT566816	hsa-miR-1468-3p	PAR-CLIP	20371350
MIRT566817	hsa-miR-548x-5p	PAR-CLIP	20371350
MIRT566818	hsa-miR-548g-5p	PAR-CLIP	20371350
MIRT566819	hsa-miR-548f-5p	PAR-CLIP	20371350
MIRT566820	hsa-miR-548aj-5p	PAR-CLIP	20371350
MIRT566821	hsa-miR-4282	PAR-CLIP	20371350

Transcription factors

Transcription factor	Regulation	Reference
E2F1	Unknown	20800677
E2F3	Unknown	20800677
HSF2	Repression	11557063
JUN	Activation	19324081
JUN	Unknown	16397260

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	14967141, 15850461, 20027304, 21095239, 22966201
GO:0004705	Function	JUN kinase activity	IBA	21873635
GO:0004705	Function	JUN kinase activity	IDA	8654373, 21095239
GO:0004705	Function	JUN kinase activity	TAS
GO:0004707	Function	MAP kinase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	10393177, 10490659, 10747973, 10856240, 11517249, 15334056, 15894542, 16291755, 16533805, 16840345, 16982329, 18003900, 18286207, 19234442, 19527717, 22966201, 23397142, 25241761, 25284480, 27043084
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	20027304, 30878395
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IDA	21856198
GO:0006468	Process	Protein phosphorylation	IMP	22441692
GO:0006979	Process	Response to oxidative stress	IDA	22966201
GO:0007254	Process	JNK cascade	IBA	21873635
GO:0007254	Process	JNK cascade	IDA	8654373
GO:0007254	Process	JNK cascade	TAS
GO:0007258	Process	JUN phosphorylation	IDA	14967141, 21095239
GO:0009411	Process	Response to UV	IDA	14967141
GO:0009612	Process	Response to mechanical stimulus	IBA	21873635
GO:0010628	Process	Positive regulation of gene expression	IMP	22065586
GO:0016241	Process	Regulation of macroautophagy	TAS	26546165
GO:0016301	Function	Kinase activity	TAS
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	15850461, 20027304, 21095239, 22966201
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	21095239
GO:0018107	Process	Peptidyl-threonine phosphorylation	IMP	20027304
GO:0019899	Function	Enzyme binding	IPI	14615289
GO:0030424	Component	Axon	ISS	22683681
GO:0031063	Process	Regulation of histone deacetylation	IEA
GO:0031281	Process	Positive regulation of cyclase activity	IMP	22027397
GO:0032091	Process	Negative regulation of protein binding	IDA	21095239
GO:0032880	Process	Regulation of protein localization	IDA	20027304
GO:0034198	Process	Cellular response to amino acid starvation	IDA	11096076
GO:0034614	Process	Cellular response to reactive oxygen species	IMP	26514923
GO:0035033	Function	Histone deacetylase regulator activity	IMP	20027304
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0042826	Function	Histone deacetylase binding	IPI	20027304
GO:0043065	Process	Positive regulation of apoptotic process	IBA	21873635
GO:0043065	Process	Positive regulation of apoptotic process	TAS
GO:0043066	Process	Negative regulation of apoptotic process	IDA	14967141, 21095239
GO:0045202	Component	Synapse	ISS
GO:0048511	Process	Rhythmic process	IEA
GO:0051090	Process	Regulation of DNA-binding transcription factor activity	TAS
GO:0051247	Process	Positive regulation of protein metabolic process	IMP	22027397
GO:0051403	Process	Stress-activated MAPK cascade	IDA	11096076
GO:0071222	Process	Cellular response to lipopolysaccharide	IDA	23776175
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0071276	Process	Cellular response to cadmium ion	IMP	26514923
GO:0071345	Process	Cellular response to cytokine stimulus	TAS
GO:0090045	Process	Positive regulation of deacetylase activity	IMP	20027304
GO:0097441	Component	Basal dendrite	ISS	22683681
GO:1900740	Process	Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway	TAS
GO:1902595	Process	Regulation of DNA replication origin binding	IMP	21856198

Other IDs

• MIM: 601158
• HGNC: 6881
• e!Ensembl: ENSG00000107643

Protein

• UniProt ID: P45983
• Protein name: Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1)
• Protein function: 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 (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). 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 (PubMed:21364637). 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 (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). 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. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:20027304, PubMed:17296730, PubMed:16581800). 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 (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). ; JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.
• PDB: 1UKH, 1UKI, 2G01, 2GMX, 2H96, 2NO3, 2XRW, 2XS0, 3ELJ, 3O17, 3O2M, 3PZE, 3V3V, 3VUD, 3VUG, 3VUH, 3VUI, 3VUK, 3VUL, 3VUM, 4AWI, 4E73, 4G1W, 4HYS, 4HYU, 4IZY, 4L7F, 4QTD, 4UX9, 4YR8, 5LW1, 6F5E, 6ZR5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	26 → 321	Protein kinase domain	Domain

• Sequence:

  MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP
  FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ
  MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF
  MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ
  LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK
  MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV
  MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA
  GPLGCCR

• Sequence length: 427