activating transcription factor-6; cAMP-dependent transcription factor ATF-6 alpha (ATF6)
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Function
- transcription facto
- acts during endoplasmic reticulum stress by activating unfolded protein response target genes
- binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') & of ERSE II (5'-ATTGG-N-CCACG-3')
- binding to ERSE requires binding of NF-Y to ERSE
- may also be involved in activation of transcription by the serum response factor
- during unfolded protein response an approximative 50 kDa fragment containing the cytoplasmic transcription factor domain is released by proteolysis
- phosphorylated in vitro by MAPK14/P38MAPK
- homodimer & heterodimer with ATF6-beta
- the dimer interacts with the nuclear transcription factor Y (NF-Y) trimer through direct binding to NF-Y subunit C (NF-YC)
- interacts also with the transcription factors GTF2I, YY1 & SRF
Structure
- N-glycosylated
- the glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR)
- the basic domain functions as a nuclear localization signal
- the basic leucine-zipper domain is sufficient for association with the NF-Y trimer & binding to ERSE
- belongs to the bZIP family, ATF subfamily
- contains 1 bZIP domain
Compartment
- endoplasmic reticulum membrane
- single-pass type 2 membrane protein
- processed ATF6: nucleus
- under ER stress the cleaved N- terminal cytoplasmic domain translocates into the nucleus