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c-jun proto-oncogene protein; v-jun avian sarcoma virus 17 oncogene homolog; p39 (JUN)

Function: - transcription factor - recognizes & binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3' - basic amino acids flanking Cys-269 probably stablilize anionic form of Cys; oxidation of Cys-269, presumably to sulfenic (RSOH) or sulfinic (RSO2H) acid or disulfide, may inactivate DNA-binding capacity - p39Jun forms homodimers & heterodimers with fos, fra, jun-B, CRE-BP1, BATF3 - interacts with HIVEP3 (putative) - interacts with SMAD3/SMAD4 heterodimers - interacts with MYBBP1A, SPIB & TCF20 - interacts with COPS5 indirectly leading to its phosphorylation - interacts with DSIPI; this interaction inhibits binding of active p39jun to its target DNA - phosphorylation enhances the transcriptional activity - phosphorylated by PRKDC Structure: - belongs to the bZIP family, Jun subfamily - contains 1 bZIP domain Compartment: nucleus Pathology: - c-jun protein is produced in high amounts in end-stage fibrosis of many organs in both mice & humans, including: - idiopathic pulmonary fibrosis - scleroderma - cirrhosis - myelofibrosis [9] - c-jun protein converts cells into pathologic fibroblasts, stimulates fibroblast proliferation, & causes the wayward fibroblasts to produce a molecule that protects them from destruction by macrophages [9]

Interactions

molecular events

Related

jun proto-oncogene

General

jun protein family phosphoprotein proto oncogene protein

Properties

SIZE: entity length = 331 aa MW = 36 kD COMPARTMENT: cell nucleus MOTIF: Thr phosphorylation site {T2} Thr phosphorylation site {T8} Ser phosphorylation site {S58} Thr phosphorylation site {T62} Ser phosphorylation site {S63} Ser phosphorylation site {S73} Thr phosphorylation site {T89} Thr phosphorylation site {T93} Thr phosphorylation site {T239} Ser phosphorylation site {S243} Ser phosphorylation site {S249} hinge region DNA-binding motif SITE: 257-276 MOTIF: cysteine residue {269} arginine residue {272} helix-loop-helix NAME: helix-loop-helix FOR-BINDING-VIA: helix-loop-helix leucine zipper SITE: 280-308 FOR-BINDING-VIA: leucine zipper MOTIF: Thr phosphorylation site {T286}

Database Correlations

OMIM 165160 UniProt P05412 PFAM correlations Entrez Gene 3725 KEGG correlations

References

  1. Kouzarides T, Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature. 1988 Dec 15;336(6200):646-51. PMID: 2974122
  2. Dwarki VJ, Montminy M, Verma IM. Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO J. 1990 Jan;9(1):225-32. PMID: 2136830
  3. Abate C, Patel L, Rauscher FJ 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157-61. PMID: 2118682
  4. Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Oct 4;254(5028):11. PMID: 1925549 - Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490-3. Erratum in: Science. 1991 Oct 4;254(5028):11. PMID: 2006423
  5. Bintruy B, Smeal T, Karin M. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature. 1991 May 9;351(6322):122-7. PMID: 1903181
  6. Allende JE, Allende CC. Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 1995 Mar;9(5):313-23. Review. PMID: 7896000
  7. Morgan & Curran The Neuroscientist 1:68 1995
  8. Herschman HR Extracellular signals, transcriptional responses and cellular specificity TIBS 14:455 1989 PMID: 2696174
  9. Wernig G, Chen SY, Cui L et al. Unifying mechanism for different fibrotic diseases. Proc Natl Acad Sci U S A 2017 May 2; 114:4757. PMID: 28424250
  10. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/JUNID151.html
  11. UniProt :accession P05412
  12. NIEHS-SNPs http://egp.gs.washington.edu/data/jun/

Component-of

activating protein 1 (AP1)