activating transcription factor-6; cAMP-dependent transcription factor ATF-6 alpha (ATF6)

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 Expression: ubiquitous

Properties

SIZE: MW = 75 kD entity length = 670 aa COMPARTMENT: cytoplasm cellular membrane MOTIF: serine residue {124-127} (4) DNA-binding motif SITE: 308-328 MOTIF: lysine residue {325-328} (4) basic region leucine zipper SITE: 334-369 FOR-BINDING-VIA: leucine zipper transmembrane domain {378-398} proteolytic site {419-420} proline residue {463-466} (4) N-glycosylation site {N472} N-glycosylation site {N584} N-glycosylation site {N643}

Database Correlations

OMIM 605537 UniProt P18850 Pfam PF00170 Entrez Gene 22926 Kegg hsa:22926