Structural highlights
Function
[FOS_HUMAN] Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation.[1] [2] [3] [NFAC2_HUMAN] Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The nuclear factor of activated T cells (NFAT) and the AP-1 heterodimer, Fos-Jun, cooperatively bind a composite DNA site and synergistically activate the expression of many immune-response genes. A 2.7-A-resolution crystal structure of the DNA-binding domains of NFAT, Fos and Jun, in a quaternary complex with a DNA fragment containing the distal antigen-receptor response element from the interleukin-2 gene promoter, shows an extended interface between NFAT and AP-1, facilitated by the bending of Fos and DNA. The tight association of the three proteins on DNA creates a continuous groove for the recognition of 15 base pairs.
Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA.,Chen L, Glover JN, Hogan PG, Rao A, Harrison SC Nature. 1998 Mar 5;392(6671):42-8. PMID:9510247[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Okazaki K, Sagata N. The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells. EMBO J. 1995 Oct 16;14(20):5048-59. PMID:7588633
- ↑ Zhang Y, Feng XH, Derynck R. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 1998 Aug 27;394(6696):909-13. PMID:9732876 doi:10.1038/29814
- ↑ Bossis G, Malnou CE, Farras R, Andermarcher E, Hipskind R, Rodriguez M, Schmidt D, Muller S, Jariel-Encontre I, Piechaczyk M. Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation. Mol Cell Biol. 2005 Aug;25(16):6964-79. PMID:16055710 doi:http://dx.doi.org/10.1128/MCB.25.16.6964-6979.2005
- ↑ Yiu GK, Kaunisto A, Chin YR, Toker A. NFAT promotes carcinoma invasive migration through glypican-6. Biochem J. 2011 Nov 15;440(1):157-66. doi: 10.1042/BJ20110530. PMID:21871017 doi:10.1042/BJ20110530
- ↑ Chen L, Glover JN, Hogan PG, Rao A, Harrison SC. Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature. 1998 Mar 5;392(6671):42-8. PMID:9510247 doi:10.1038/32100
