Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Associates with chromatin to the HERPUD1 promoter. Also induces transcriptional activation of chemokine receptors. Functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Also decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells. This is the transcriptionally active form that translocates to the nucleus and activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many promoters to activate transcription of the genes. Binds to the unfolded protein response element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Homodimer. Interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Interacts with CREBZF; the interaction occurs only in combination with HCFC1. Interacts (via central part and transmembrane region) with DCSTAMP (via C-terminus cytoplasmic domain). Interacts with OS9. Interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Interacts (via C-terminal domain) with CCR1. Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia. Colocalizes with DCSTAMP in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Upon RIP activation the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB). Expressed in trigeminal ganglia (at protein level). First proteolytically cleaved by site-1 protease (S1P) that generates membrane-associated N-terminus and a luminal C-terminus forms. The membrane-associated N-terminus form is further proteolytically processed probably by the site-2 protease (S2P) through a regulated intramembrane proteolysis (RIP), releasing the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form, which is transported to the nucleus. The proteolytic cleavage is strongly induced during dendritic cell (DC) maturation and inhibited by DCSTAMP. That form is rapidly degraded. N-glycosylated. Belongs to the bZIP family. ATF subfamily.