Phospho-ATF6 (Thr166) Antibody - #AF4507

Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.

During unfolded protein response, a fragment of approximately 50 kDa containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases.

N-glycosylated. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR).

Phosphorylated in vitro by MAPK14/P38MAPK.

Endoplasmic reticulum membrane>Single-pass type II membrane protein.

Nucleus.
Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus. THBS4 promotes its nuclear shuttling.

Ubiquitous.

Homodimer and 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 and SRF. Interacts (via lumenal domain) with THBS1 (By similarity). Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation. Interacts with XBP1 isoform 2; the interaction occurs in a ER stress-dependent manner.

The basic domain functions as a nuclear localization signal.

The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE.

Belongs to the bZIP family. ATF subfamily.