P45983 (MK08_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 8
Short name=MAP kinase 8
Short name=MAPK 8
EC=2.7.11.24

Alternative name(s):
JNK-46
Stress-activated protein kinase 1c
Short name=SAPK1c
Stress-activated protein kinase JNK1
c-Jun N-terminal kinase 1

Gene names

Name:	MAPK8
Synonyms:	JNK1, PRKM8, SAPK1, SAPK1C

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Ref.11 Ref.14 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.27 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. Ref.11 Ref.14 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.27
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.7
Enzyme regulation	Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3. Ref.19
Subunit structure	Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with TP53 and WWOX. Interacts with JAMP. Forms a complex with MAPK8IP1 and ARHGEF28 By similarity. Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells By similarity. Interacts with NFATC4. Interacts with MECOM; regulates JNK signaling. Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.19 Ref.24
Subcellular location	Cytoplasm. Nucleus Ref.26.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Phosphorylated by TAOK2. Ref.13
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from direct assay Ref.25. Source: UniProtKB negative regulation of protein binding Inferred from direct assay Ref.25. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome ossification Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from direct assay Ref.25. Source: UniProtKB peptidyl-threonine phosphorylation Inferred from direct assay Ref.25. Source: UniProtKB positive regulation of apoptotic signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of deacetylase activity Inferred from mutant phenotype Ref.21. Source: BHF-UCL positive regulation of determination of dorsal identity Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from mutant phenotype PubMed 22065586. Source: BHF-UCL regulation of protein localization Inferred from direct assay Ref.21. Source: BHF-UCL regulation of sequence-specific DNA binding transcription factor activity Traceable author statement. Source: Reactome response to UV Inferred from direct assay PubMed 14967141. Source: MGI response to cadmium ion Inferred from electronic annotation. Source: Compara toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase activity Inferred from direct assay Ref.25Ref.2. Source: UniProtKB histone deacetylase regulator activity Inferred from mutant phenotype Ref.21. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
JUN	P05412	3	EBI-286483,EBI-852823
MAP2K7	O14733-2	3	EBI-286483,EBI-492627
Mapk8ip1	Q9WVI9-1	2	EBI-286483,EBI-288461	From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P45983-1)

Also known as: JNK1-alpha-2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P45983-2)

Also known as: JNK1-alpha-1;

The sequence of this isoform differs from the canonical sequence as follows:
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Note: Contains a phosphoserine at position 377.

Isoform 3 (identifier: P45983-3)

Also known as: JNK1-beta-1;

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH
     380-427: GAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR → AQVQQ

Note: Contains a phosphoserine at position 377.

Isoform 4 (identifier: P45983-4)

Also known as: JNK1-beta-2;

The sequence of this isoform differs from the canonical sequence as follows:
     208-208: L → I
     219-230: VCHKILFPGRDY → IKGGVLFPGTDH

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 427

427

Mitogen-activated protein kinase 8

PRO_0000186262

Regions

Domain

26 – 321

296

Protein kinase

Nucleotide binding

32 – 40

9

ATP By similarity

Motif

183 – 185

3

TXY

Sites

Active site

151

1

Proton acceptor By similarity

Binding site

55

1

ATP By similarity

Amino acid modifications

Modified residue

183

1

Phosphothreonine; by MAP2K7

Modified residue

185

1

Phosphotyrosine; by MAP2K4

Modified residue

377

1

Phosphoserine By similarity

Natural variations

Alternative sequence

208

1

L → I in isoform 3 and isoform 4.

VSP_004831

Alternative sequence

219 – 230

12

VCHKI…PGRDY → IKGGVLFPGTDH in isoform 3 and isoform 4.

VSP_004832

Alternative sequence

380 – 427

48

GAAVI…LGCCR → AQVQQ in isoform 1 and isoform 3.

VSP_004833

Natural variant

171

1

G → S in a renal clear cell carcinoma sample; somatic mutation. Ref.29

VAR_042258

Natural variant

177

1

G → R in a glioblastoma multiforme sample; somatic mutation. Ref.29

VAR_042259

Natural variant

365

1

E → K.
Corresponds to variant rs45483593 [ dbSNP | Ensembl ].

VAR_050592

Experimental info

Mutagenesis

183

1

T → A: Phosphorylation blocked.

Mutagenesis

185

1

Y → F: Phosphorylation blocked.

Secondary structure

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427

Helix Strand Turn

Details...

Helix

4 – 9

6

Beta strand

10 – 15

6

Beta strand

18 – 23

6

Beta strand

26 – 34

9

Beta strand

36 – 45

10

Turn

46 – 49

4

Beta strand

50 – 58

9

Helix

60 – 62

3

Helix

64 – 79

16

Beta strand

83 – 85

3

Beta strand

88 – 92

5

Beta strand

94 – 97

4

Turn

98 – 100

3

Beta strand

103 – 109

7

Beta strand

112 – 114

3

Helix

115 – 120

6

Helix

125 – 144

20

Helix

154 – 156

3

Beta strand

157 – 159

3

Turn

161 – 163

3

Beta strand

165 – 167

3

Beta strand

174 – 177

4

Beta strand

178 – 180

3

Beta strand

182 – 184

3

Beta strand

185 – 187

3

Helix

189 – 191

3

Helix

194 – 197

4

Helix

206 – 220

15

Helix

230 – 241

12

Helix

246 – 249

4

Helix

254 – 261

8

Helix

271 – 274

4

Helix

277 – 279

3

Helix

285 – 301

17

Helix

306 – 308

3

Helix

312 – 317

6

Helix

319 – 322

4

Helix

327 – 330

4

Turn

339 – 342

4

Helix

349 – 363

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (JNK1-alpha-2) [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 94FB6BE0358B9B60	FASTA	427	48,296
	10 20 30 40 50 60 MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ 250 260 270 280 290 300 LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 310 320 330 340 350 360 MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 370 380 390 400 410 420 MDLEERTKNG VIRGQPSPLG AAVINGSQHP SSSSSVNDVS SMSTDPTLAS DTDSSLEAAA GPLGCCR
	Isoform 1 (JNK1-alpha-1) [UniParc]. Checksum: A7320EF933E9CF85	FASTA	384	44,229
	10 20 30 40 50 60 MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDLWS VGCIMGEMVC HKILFPGRDY IDQWNKVIEQ 250 260 270 280 290 300 LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 310 320 330 340 350 360 MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 370 380 MDLEERTKNG VIRGQPSPLA QVQQ
	Isoform 3 (JNK1-beta-1) [UniParc]. Checksum: 76E49A950E64C1A1	FASTA	384	44,022
	10 20 30 40 50 60 MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGEMIK GGVLFPGTDH IDQWNKVIEQ 250 260 270 280 290 300 LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 310 320 330 340 350 360 MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 370 380 MDLEERTKNG VIRGQPSPLA QVQQ
	Isoform 4 (JNK1-beta-2) [UniParc]. Checksum: 3F5CC3F6A4F3EF2D	FASTA	427	48,088
	10 20 30 40 50 60 MSRSKRDNNF YSVEIGDSTF TVLKRYQNLK PIGSGAQGIV CAAYDAILER NVAIKKLSRP 70 80 90 100 110 120 FQNQTHAKRA YRELVLMKCV NHKNIIGLLN VFTPQKSLEE FQDVYIVMEL MDANLCQVIQ 130 140 150 160 170 180 MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTAGTSF 190 200 210 220 230 240 MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGEMIK GGVLFPGTDH IDQWNKVIEQ 250 260 270 280 290 300 LGTPCPEFMK KLQPTVRTYV ENRPKYAGYS FEKLFPDVLF PADSEHNKLK ASQARDLLSK 310 320 330 340 350 360 MLVIDASKRI SVDEALQHPY INVWYDPSEA EAPPPKIPDK QLDEREHTIE EWKELIYKEV 370 380 390 400 410 420 MDLEERTKNG VIRGQPSPLG AAVINGSQHP SSSSSVNDVS SMSTDPTLAS DTDSSLEAAA GPLGCCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain." Derijard B., Hibi M., Wu I.-H., Barrett T., Su B., Deng T., Karin M., Davis R.J. Cell 76:1025-1037(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"Selective interaction of JNK protein kinase isoforms with transcription factors." Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., Derijard B., Davis R.J. EMBO J. 15:2760-2770(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Brain.
[3]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[6]	"Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms." Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J. Science 267:682-685(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[7]	"Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7." Fleming Y., Armstrong C.G., Morrice N., Paterson A., Goedert M., Cohen P. Biochem. J. 352:145-154(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REGULATION BY MAP2K4 AND MAP2K7, COFACTOR.
[8]	"The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death." Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H. EMBO J. 19:2958-2968(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MECOM.
[9]	"JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis." Chang N.-S., Doherty J., Ensign A. J. Biol. Chem. 278:9195-9202(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WWOX AND TP53.
[10]	"Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein." Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., Herr J.C., Okumura K., Hasegawa A., Koyama K., Suri A. Biochem. J. 389:73-82(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPAG9.
[11]	"Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26." Hu Y., Mivechi N.F. Mol. Cell. Biol. 26:3282-3294(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HSF4.
[12]	"Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation." Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y., Bode A.M., Dong Z. Cancer Res. 67:8725-8735(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFATC4.
[13]	"Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis. JNK-and caspase-dependent nuclear localization is a requirement for membrane blebbing." Zihni C., Mitsopoulos C., Tavares I.A., Baum B., Ridley A.J., Morris J.D. J. Biol. Chem. 282:6484-6493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY TAOK2.
[14]	"Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to activation of the transcription factor Elk-1." Zhang L., Yang S.H., Sharrocks A.D. Mol. Cell. Biol. 27:2861-2869(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ELK1.
[15]	"Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in Escherichia coli by Jun N-terminal kinase 1." Murata T., Shinozuka Y., Obata Y., Yokoyama K.K. Anal. Biochem. 376:115-121(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF JDP2.
[16]	"JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy." Wei Y., Pattingre S., Sinha S., Bassik M., Levine B. Mol. Cell 30:678-688(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BCL2.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the 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) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[19]	"Crystal structure of SCCA1 and insight about the interaction with JNK1." Zheng B., Matoba Y., Kumagai T., Katagiri C., Hibino T., Sugiyama M. Biochem. Biophys. Res. Commun. 380:143-147(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SERPINB3, ENZYME REGULATION.
[20]	"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) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 (ISOFORMS 1 AND 3), MASS SPECTROMETRY.
[21]	"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity." Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R., Bordone L. PLoS ONE 4:E8414-E8414(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF SIRT1.
[22]	"JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis." Tomlinson V., Gudmundsdottir K., Luong P., Leung K.Y., Knebel A., Basu S. Cell Death Dis. 1:E29-E29(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF YAP1.
[23]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"A critical step for JNK activation: isomerization by the prolyl isomerase Pin1." Park J.E., Lee J.A., Park S.G., Lee D.H., Kim S.J., Kim H.J., Uchida C., Uchida T., Park B.C., Cho S. Cell Death Differ. 19:153-161(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIN1.
[25]	"Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin-dependent cells." Deng H., Zhang J., Yoon T., Song D., Li D., Lin A. Int. J. Biochem. Cell Biol. 43:409-415(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[26]	"Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis." Wang J., Tang R., Lv M., Wang Q., Zhang X., Guo Y., Chang H., Qiao C., Xiao H., Li X., Li Y., Shen B., Zhang J. Mol. Biol. Cell 22:117-127(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[27]	"JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress." Miotto B., Struhl K. Mol. Cell 44:62-71(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CDT1.
[28]	"Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125." Heo Y.S., Kim S.K., Seo C.I., Kim Y.K., Sung B.J., Lee H.S., Lee J.I., Park S.Y., Kim J.H., Hwang K.Y., Hyun Y.L., Jeon Y.H., Ro S., Cho J.M., Lee T.G., Yang C.H. EMBO J. 23:2185-2195(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-363.
[29]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-171 AND ARG-177.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

C-Jun N-terminal kinases entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L26318 mRNA. Translation: AAA36131.1.
U34822 mRNA. Translation: AAC50607.1.
U35004 mRNA. Translation: AAC50610.1.
U35005 mRNA. Translation: AAC50611.1.
AB451231 mRNA. Translation: BAG70045.1.
CH471187 Genomic DNA. Translation: EAW93132.1.
CH471187 Genomic DNA. Translation: EAW93129.1.
CH471187 Genomic DNA. Translation: EAW93130.1.
CH471187 Genomic DNA. Translation: EAW93133.1.
CH471187 Genomic DNA. Translation: EAW93134.1.
CH471187 Genomic DNA. Translation: EAW93136.1.
BC144063 mRNA. Translation: AAI44064.1.

IPI

IPI00003145.
IPI00024672.
IPI00220305.
IPI00220306.

PIR

S71097.
S71099.

RefSeq

NP_002741.1. NM_002750.2.
NP_620634.1. NM_139046.1.
NP_620635.1. NM_139047.1.
NP_620637.1. NM_139049.1.

UniGene

Hs.138211.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UKH	X-ray	2.35	A	1-363	[»]
1UKI	X-ray	2.70	A	1-363	[»]
2G01	X-ray	3.50	A/B	1-364	[»]
2GMX	X-ray	3.50	A/B	1-364	[»]
2H96	X-ray	3.00	A/B	1-364	[»]
2NO3	X-ray	3.20	A/B	1-364	[»]
2XRW	X-ray	1.33	A	2-364	[»]
2XS0	X-ray	2.60	A	1-379	[»]
3ELJ	X-ray	1.80	A	1-364	[»]
3O17	X-ray	3.00	A/B	1-364	[»]
3O2M	X-ray	2.70	A/B	1-364	[»]
3PZE	X-ray	2.00	A	7-364	[»]
3V3V	X-ray	2.70	A	1-363	[»]
3VUD	X-ray	3.50	A	1-364	[»]
3VUG	X-ray	3.24	A	1-364	[»]
3VUH	X-ray	2.70	A	1-364	[»]
3VUI	X-ray	2.80	A	1-364	[»]
3VUK	X-ray	2.95	A	1-364	[»]
3VUL	X-ray	2.81	A	1-364	[»]
3VUM	X-ray	2.69	A	1-364	[»]

ProteinModelPortal

P45983.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-249N.

IntAct

P45983. 25 interactions.

MINT

MINT-1211982.

STRING

9606.ENSP00000353483.

PTM databases

PhosphoSite

P45983.

Polymorphism databases

DMDM

2507195.

Proteomic databases

PaxDb

P45983.

PRIDE

P45983.

Protocols and materials databases

DNASU

5599.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360332; ENSP00000353483; ENSG00000107643.
ENST00000374176; ENSP00000363291; ENSG00000107643.
ENST00000374179; ENSP00000363294; ENSG00000107643.
ENST00000374182; ENSP00000363297; ENSG00000107643.
ENST00000374189; ENSP00000363304; ENSG00000107643.

GeneID

5599.

KEGG

hsa:5599.

UCSC

uc001jgo.3. human.
uc001jgp.3. human.
uc001jgq.3. human.

Organism-specific databases

CTD

5599.

GeneCards

GC10P049514.

HGNC

HGNC:6881. MAPK8.

HPA

CAB004463.

MIM

601158. gene.

neXtProt

NX_P45983.

PharmGKB

PA283.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG014652.

InParanoid

P45983.

KO

K04440.

OMA

AMINGSQ.

Enzyme and pathway databases

BRENDA

2.7.11.24. 2681.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
bcr_5pathway. BCR signaling pathway.
ceramidepathway. Ceramide signaling pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
ephrinbrevpathway. Ephrin B reverse signaling.
epopathway. EPO signaling pathway.
faspathway. FAS signaling pathway (CD95).
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
foxopathway. FoxO family signaling.
glypican_3pathway. Glypican 3 network.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il1pathway. IL1-mediated signaling events.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il2_1pathway. IL2-mediated signaling events.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
avb3_opn_pathway. Osteopontin-mediated events.
p75ntrpathway. p75(NTR)-mediated signaling.
reelinpathway. Reelin signaling pathway.
ar_tf_pathway. Regulation of Androgen receptor activity.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
s1p_s1p2_pathway. S1P2 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
trail_pathway. TRAIL signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_578. Apoptosis.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P45983.

Bgee

P45983.

CleanEx

HS_MAPK8.

Genevestigator

P45983.

GermOnline

ENSG00000107643. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008351. MAPK_JNK.
IPR000719. Prot_kinase_cat_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR01772. JNKMAPKINASE.

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P45983.

ChEMBL

CHEMBL2276.

EvolutionaryTrace

P45983.

GenomeRNAi

5599.

NextBio

21738.

SOURCE

Search...

Entry information

Entry name

MK08_HUMAN

Accession

Primary (citable) accession number: P45983
Secondary accession number(s): B5BTZ5 , B7ZLV4, D3DX88, D3DX92, Q15709, Q15712, Q15713

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 150 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.