ATF6

This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]

Activating Transcription Factor 6

Cyclic AMP-dependent transcription factor ATF-6 alpha: Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane (PubMed:10564271, PubMed:11158310, PubMed:11779464).
Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR) (PubMed:10564271, PubMed:11158310, PubMed:11779464).
Processed cyclic AMP-dependent transcription factor ATF-6 alpha: Transcription factor that initiates the unfolded protein response (UPR) during endoplasmic reticulum stress by activating transcription of genes involved in the UPR (PubMed:10564271, PubMed:11163209, PubMed:11158310, PubMed:11779464).
Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N9-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3') (PubMed:10564271, PubMed:11158310, PubMed:11779464).
Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor (PubMed:10564271, PubMed:11158310, PubMed:11779464).
May play a role in foveal development and cone function in the retina (PubMed:26029869).

ATF6-mediated unfolded protein response Source: ParkinsonsUK-UCL
Endoplasmic reticulum unfolded protein response Source: GO_Central
Eye development Source: UniProtKB
Positive regulation of apoptotic process Source: ParkinsonsUK-UCL
Positive regulation of ATF6-mediated unfolded protein response Source: UniProtKB
Positive regulation of autophagy Source: MGI
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Protein folding Source: ProtInc
Regulation of transcription by RNA polymerase II Source: GO_Central
Signal transduction Source: ProtInc
Visual perception Source: UniProtKB

Golgi apparatus membrane; Endoplasmic reticulum membrane. Translocates from the endoplasmic reticulum to the Golgi, where it is processed.
Processed cyclic AMP-dependent transcription factor ATF-6 alpha: Nucleus. Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus (PubMed:10564271, PubMed:12782636). THBS4 promotes its nuclear shuttling (By similarity).

Achromatopsia 7 (ACHM7): A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.

Cytoplasmic: 1-377 aa
Helical: 378-398 aa
Lumenal: 399-670 aa

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 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) 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).