CREB3L3

CREB3L3 (CAMP Responsive Element Binding Protein 3 Like 3) is a Protein Coding gene. Diseases associated with CREB3L3 include Hyperlipoproteinemia, Type V and Hepatocellular Carcinoma. Among its related pathways are Aldosterone synthesis and secretion and Circadian entrainment. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is CREB3L4.

Full Name

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).

Biological Process

Endoplasmic reticulum unfolded protein response Source: Reactome
Positive regulation of acute inflammatory response Source: ParkinsonsUK-UCL
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
Regulation of transcription by RNA polymerase II Source: GO_Central

Cellular Location

Endoplasmic reticulum membrane
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.

Topology

Cytoplasmic: 1-322
Helical: 323-343
Lumenal: 344-461

PTM

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.