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MAPK8

From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens
MAPK8
Available structures
PDBOrtholog search:PDBeRCSB
List of PDB id codes

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

Identifiers
AliasesMAPK8, Mapk8, AI849689, JNK, JNK1, Prkm8, SAPK1, JNK-46, JNK1A2, JNK21B1/2, SAPK1c, mitogen-activated protein kinase 8
External IDsOMIM:601158;MGI:1346861;HomoloGene:56760;GeneCards:MAPK8;OMA:MAPK8 - orthologs
Gene location (Human)
Chromosome 10 (human)
Chr.Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for MAPK8
Genomic location for MAPK8
Band10q11.22Start48,306,639bp[1]
End48,439,360bp[1]
Gene location (Mouse)
Chromosome 14 (mouse)
Chr.Chromosome 14 (mouse)[2]
Chromosome 14 (mouse)
Genomic location for MAPK8
Genomic location for MAPK8
Band14|14 BStart33,099,855bp[2]
End33,169,115bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • ganglionic eminence

  • tendon of biceps brachii

  • Achilles tendon

  • stromal cell of endometrium

  • buccal mucosa cell

  • ventricular zone

  • islet of Langerhans

  • internal globus pallidus

  • gallbladder

  • epithelium of colon
Top expressed in
  • zygote

  • secondary oocyte

  • primary oocyte

  • barrel cortex

  • superior cervical ganglion

  • ganglionic eminence

  • perirhinal cortex

  • visual cortex

  • genital tubercle

  • piriform cortex
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5599

26419

Ensembl

ENSG00000107643

ENSMUSG00000021936

UniProt

P45983

Q91Y86

RefSeq (mRNA)
NM_001278547
NM_001278548
NM_002750
NM_139046
NM_139049

NM_001323302
NM_001323320
NM_001323321
NM_001323322
NM_001323323
NM_001323324
NM_001323325
NM_001323326
NM_001323327
NM_001323328
NM_001323329
NM_001323330
NM_001323331

NM_001310452
NM_001310453
NM_001310454
NM_016700

RefSeq (protein)
NP_001265476
NP_001265477
NP_001310231
NP_001310249
NP_001310250

NP_001310251
NP_001310252
NP_001310253
NP_001310254
NP_001310255
NP_001310256
NP_001310257
NP_001310258
NP_001310259
NP_001310260
NP_620634
NP_620637

NP_001297381
NP_001297382
NP_001297383
NP_057909

Location (UCSC)Chr 10: 48.31 – 48.44 MbChr 14: 33.1 – 33.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitousenzyme that in humans is encoded by theMAPK8gene.[5][6]

Function

[edit]

The protein encoded by this gene is a member of theMAP kinase andJNK family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such asproliferation,differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specifictranscription factors, and thus mediates immediate-earlygene expression in response to cell stimuli. The activation of this kinase bytumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha-inducedapoptosis. Thiskinase is also involved in UV radiation-induced apoptosis, which is thought to be related to thecytochrome c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role inT cell proliferation, apoptosis and differentiation. Fouralternately spliced transcript variants encoding distinctisoforms have been reported.[7] MAPK8 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[8]

Interactions

[edit]

MAPK8 has been shown tointeract with:

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000107643Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000021936Ensembl, May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^abDérijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ (April 1994). "JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain".Cell.76 (6):1025–37.doi:10.1016/0092-8674(94)90380-8.PMID 8137421.S2CID 6797795.
  6. ^Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Dérijard B, Davis RJ (July 1996)."Selective interaction of JNK protein kinase isoforms with transcription factors".EMBO J.15 (11):2760–70.doi:10.1002/j.1460-2075.1996.tb00636.x.PMC 450211.PMID 8654373.
  7. ^"Entrez Gene: MAPK8 mitogen-activated protein kinase 8".
  8. ^"JNK1 (human)".www.phosphosite.org. Retrieved2020-10-28.
  9. ^Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (March 1995)."Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine".J. Biol. Chem.270 (13):7420–6.doi:10.1074/jbc.270.13.7420.PMID 7535770.
  10. ^Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (December 1997)."c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors".J. Biol. Chem.272 (51):32163–8.doi:10.1074/jbc.272.51.32163.PMID 9405416.
  11. ^abChen Z, Cobb MH (May 2001)."Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2".J. Biol. Chem.276 (19):16070–5.doi:10.1074/jbc.M100681200.PMID 11279118.
  12. ^abcdTournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997)."Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase".Proc. Natl. Acad. Sci. U.S.A.94 (14):7337–42.Bibcode:1997PNAS...94.7337T.doi:10.1073/pnas.94.14.7337.PMC 23822.PMID 9207092.
  13. ^abMeyer CF, Wang X, Chang C, Templeton D, Tan TH (April 1996)."Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation".J. Biol. Chem.271 (15):8971–6.doi:10.1074/jbc.271.15.8971.PMID 8621542.
  14. ^Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H,Gaynor RB, Matsumoto K (December 2003)."Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling".EMBO J.22 (23):6277–88.doi:10.1093/emboj/cdg605.PMC 291846.PMID 14633987.
  15. ^Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H (September 1998)."ASK1 is essential for JNK/SAPK activation by TRAF2".Mol. Cell.2 (3):389–95.doi:10.1016/s1097-2765(00)80283-x.PMID 9774977.
  16. ^Yazgan O, Pfarr CM (August 2002)."Regulation of two JunD isoforms by Jun N-terminal kinases".J. Biol. Chem.277 (33):29710–8.doi:10.1074/jbc.M204552200.PMID 12052834.
  17. ^Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (September 2001)."Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death".J. Biol. Chem.276 (39):36530–4.doi:10.1074/jbc.M104837200.PMID 11479302.
  18. ^Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction".J. Cell Sci.108 (11):3599–609.doi:10.1242/jcs.108.11.3599.PMID 8586671.
  19. ^Girardin SE, Yaniv M (July 2001)."A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation".EMBO J.20 (13):3437–46.doi:10.1093/emboj/20.13.3437.PMC 125507.PMID 11432831.
  20. ^Tanoue T, Moriguchi T, Nishida E (July 1999)."Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5".J. Biol. Chem.274 (28):19949–56.doi:10.1074/jbc.274.28.19949.PMID 10391943.
  21. ^Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001)."Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1".J. Biol. Chem.276 (19):16491–500.doi:10.1074/jbc.M010966200.PMID 11278799.
  22. ^Wang T, Arifoglu P, Ronai Z, Tew KD (June 2001)."Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus".J. Biol. Chem.276 (24):20999–1003.doi:10.1074/jbc.M101355200.PMID 11279197.
  23. ^Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF (January 2002)."Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action".J. Biol. Chem.277 (2):1531–7.doi:10.1074/jbc.M101521200.PMID 11606564.
  24. ^Aguirre V, Uchida T, Yenush L, Davis R, White MF (March 2000)."The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)".J. Biol. Chem.275 (12):9047–54.doi:10.1074/jbc.275.12.9047.PMID 10722755.
  25. ^Gao M, Labuda T, Xia Y, Gallagher E, Fang D, Liu YC, Karin M (October 2004)."Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch".Science.306 (5694):271–5.Bibcode:2004Sci...306..271G.doi:10.1126/science.1099414.PMID 15358865.S2CID 31876966.
  26. ^Gallagher E, Gao M, Liu YC, Karin M (February 2006)."Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change".Proceedings of the National Academy of Sciences of the United States of America.103 (6):1717–22.Bibcode:2006PNAS..103.1717G.doi:10.1073/pnas.0510664103.PMC 1413664.PMID 16446428.
  27. ^abcCheng J, Yang J, Xia Y, Karin M, Su B (April 2000)."Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation".Mol. Cell. Biol.20 (7):2334–42.doi:10.1128/mcb.20.7.2334-2342.2000.PMC 85399.PMID 10713157.
  28. ^Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (October 2002)."JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors".Proc. Natl. Acad. Sci. U.S.A.99 (22):14189–94.Bibcode:2002PNAS...9914189L.doi:10.1073/pnas.232310199.PMC 137859.PMID 12391307.
  29. ^Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ (January 2002)."Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation".J. Biol. Chem.277 (4):2573–8.doi:10.1074/jbc.M110299200.PMID 11707464.
  30. ^Xu S, Cobb MH (December 1997)."MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases".J. Biol. Chem.272 (51):32056–60.doi:10.1074/jbc.272.51.32056.PMID 9405400.
  31. ^Elion EA (September 1998). "Routing MAP kinase cascades".Science.281 (5383):1625–6.doi:10.1126/science.281.5383.1625.PMID 9767029.S2CID 28868990.
  32. ^Cai Y, Lechner MS, Nihalani D, Prindle MJ, Holzman LB, Dressler GR (January 2002)."Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation".J. Biol. Chem.277 (2):1217–22.doi:10.1074/jbc.M109663200.PMID 11700324.
  33. ^Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI (November 1999)."JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway".Mol. Cell. Biol.19 (11):7539–48.doi:10.1128/mcb.19.11.7539.PMC 84763.PMID 10523642.
  34. ^Kelkar N, Gupta S, Dickens M, Davis RJ (February 2000)."Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3".Mol. Cell. Biol.20 (3):1030–43.doi:10.1128/mcb.20.3.1030-1043.2000.PMC 85220.PMID 10629060.
  35. ^Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y (November 1999)."Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase".J. Biol. Chem.274 (46):32580–7.doi:10.1074/jbc.274.46.32580.PMID 10551811.
  36. ^Wiltshire C, Matsushita M, Tsukada S, Gillespie DA, May GH (November 2002)."A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria".Biochem. J.367 (Pt 3):577–85.doi:10.1042/BJ20020553.PMC 1222945.PMID 12167088.
  37. ^Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F (February 1996). "Differential phosphorylations of Spi-B and Spi-1 transcription factors".Oncogene.12 (4):863–73.PMID 8632909.

Further reading

[edit]

External links

[edit]

This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.


PDB gallery
  • 1jnk: THE C-JUN N-TERMINAL KINASE (JNK3S) COMPLEXED WITH MGAMP-PNP
    1jnk: THE C-JUN N-TERMINAL KINASE (JNK3S) COMPLEXED WITH MGAMP-PNP
  • 1pmn: Crystal structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
    1pmn: Crystal structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
  • 1pmq: The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
    1pmq: The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
  • 1pmu: The crystal structure of JNK3 in complex with a phenantroline inhibitor
    1pmu: The crystal structure of JNK3 in complex with a phenantroline inhibitor
  • 1pmv: The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor
    1pmv: The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor
  • 1ukh: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
    1ukh: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
  • 1uki: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
    1uki: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
  • 2b1p: inhibitor complex of JNK3
    2b1p: inhibitor complex of JNK3
  • 2exc: Inhibitor complex of JNK3
    2exc: Inhibitor complex of JNK3
  • 2g01: Pyrazoloquinolones as Novel, Selective JNK1 inhibitors
    2g01: Pyrazoloquinolones as Novel, Selective JNK1 inhibitors
  • 2gmx: Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
    2gmx: Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
  • 2h96: Discovery of Potent, Highly Selective, and Orally Bioavailable Pyridine Carboxamide C-jun NH2-terminal Kinase Inhibitors
    2h96: Discovery of Potent, Highly Selective, and Orally Bioavailable Pyridine Carboxamide C-jun NH2-terminal Kinase Inhibitors
  • 2no3: Novel 4-anilinopyrimidines as potent JNK1 Inhibitors
    2no3: Novel 4-anilinopyrimidines as potent JNK1 Inhibitors
  • 2o0u: Crystal structure of human JNK3 complexed with N-{3-cyano-6-[3-(1-piperidinyl)propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl}-1-naphthalenecarboxamide
    2o0u: Crystal structure of human JNK3 complexed with N-{3-cyano-6-[3-(1-piperidinyl)propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl}-1-naphthalenecarboxamide
  • 2o2u: Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
    2o2u: Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
  • 2ok1: Crystal structure of JNK3 bound to N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
    2ok1: Crystal structure of JNK3 bound to N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide
Non-specific serine/threonine protein kinases (EC 2.7.11.1)
Pyruvate dehydrogenase kinase (EC 2.7.11.2)
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)
Myosin-heavy-chain kinase (EC 2.7.11.7)
Fas-activated serine/threonine kinase (EC 2.7.11.8)
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)
  • -
IκB kinase (EC 2.7.11.10)
cAMP-dependent protein kinase (EC 2.7.11.11)
cGMP-dependent protein kinase (EC 2.7.11.12)
Protein kinase C (EC 2.7.11.13)
Rhodopsin kinase (EC 2.7.11.14)
Beta adrenergic receptor kinase (EC 2.7.11.15)
G-protein coupled receptor kinases (EC 2.7.11.16)
Ca2+/calmodulin-dependent (EC 2.7.11.17)
Myosin light-chain kinase (EC 2.7.11.18)
Phosphorylase kinase (EC 2.7.11.19)
Elongation factor 2 kinase (EC 2.7.11.20)
Polo kinase (EC 2.7.11.21)
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21)
Cyclin-dependent kinase (EC 2.7.11.22)
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)
Mitogen-activated protein kinase (EC 2.7.11.24)
MAP3K (EC 2.7.11.25)
Tau-protein kinase (EC 2.7.11.26)
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)
  • -
Tropomyosin kinase (EC 2.7.11.28)
  • -
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)
  • -
Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
Activity
Regulation
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