CREB3L3
Function
Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). May function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. Regulates FGF21 transcription (By similarity). Plays a crucial role in the regulation of triglyceride metabolism and is required for the maintenance of normal plasma triglyceride concentrations (PubMed:21666694).
Involvement in disease
Hypertriglyceridemia 2
HYTG2
An autosomal dominant form of hypertriglyceridemia, a disorder characterized by elevated plasma triglyceride levels. HYTG2 patients also have increased total cholesterol levels and low levels of high density lipoprotein (HDL) cholesterol. Reduced penetrance has been observed.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2).
N- and O-glycosylated. N-glycosylation is required for optimal proteolytic activation. O-glycosylated with core 1 or possibly core 8 glycans.
Ubiquitinated at Lys-294 by SYNV1/HRD1 via 'Lys-27'-linked ubiquitin.
Sequence Similarities
Belongs to the bZIP family. ATF subfamily.
Tissue Specificity
Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type II membrane protein
- Processed cyclic AMP-responsive element-binding protein 3-like protein 3
- Nucleus
- Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus.
Alternative names
CREBH, HYST1481, CREB3L3, Cyclic AMP-responsive element-binding protein 3-like protein 3, cAMP-responsive element-binding protein 3-like protein 3, Transcription factor CREB-H