XBP1: a transcription factor essential for hepatocyte growth, the differentiation of plasma cells, immunoglobulin secretion, and the unfolded protein response (UPR). XBP1 mRNA is spliced by IRE1 during the UPR to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis. Only the spliced form of XBP1 can activate the UPR efficiently. Activates UPR target genes via direct binding to the UPR element (UPRE). Binds DNA preferably to the CRE-like element 5'-GATGACGTG[TG]N(3)[AT]T-3', and also to some TPA response elements (TRE). Binds to the HLA DR-alpha promoter. Binds to the Tax-responsive element (TRE) of HTLV-I. Up-regulated by ATF6 via direct binding to the ERSE in response to endoplasmic reticulum stress. Genetic variations in XBP1 could be associated with susceptibility to major affective disorder type 7 (MAFD7). Major affective disorders represent a class of mental disorders characterized by a disturbance in mood as their predominant feature. Two human isoforms are produced by alternative splicing. Isoform 1 is also known as XBP-1U. Isoform 2, also known as XBP-1S, is produced by IRE1 in response to endoplasmic reticulum stress. IRE1 cleaves a 26-bp fragment causing a frameshift of the mRNA transcript.
Protein type: Transcription factor; DNA-binding
Chromosomal Location of Human Ortholog: 22q12.1|22q12
Cellular Component: nucleoplasm; endoplasmic reticulum membrane; endoplasmic reticulum; cytoplasm; integral to membrane; integral to endoplasmic reticulum membrane; nucleus; cytosol
Molecular Function: protein binding; protein homodimerization activity; protease binding; DNA binding; chromatin DNA binding; protein heterodimerization activity; ubiquitin protein ligase binding; estrogen receptor binding; protein kinase binding; transcription factor activity
Biological Process: ubiquitin-dependent protein catabolic process; transcription from RNA polymerase II promoter; muscle development; phosphoinositide 3-kinase cascade; apoptosis; positive regulation of transcription of target genes involved in unfolded protein response; exocrine pancreas development; regulation of protein stability; negative regulation of transcription from RNA polymerase II promoter; cellular response to glucose starvation; protein transport; serotonin secretion, neurotransmission; positive regulation of MHC class II biosynthetic process; positive regulation of transcription factor import into nucleus; angiogenesis; cell growth; response to electrical stimulus; fatty acid biosynthetic process; positive regulation of autophagy; positive regulation of TOR signaling pathway; response to drug; positive regulation of histone methylation; protein destabilization; unfolded protein response; organelle organization and biogenesis; cellular response to nutrient; positive regulation of immunoglobulin secretion; liver development; positive regulation of immunoglobulin production; cholesterol homeostasis; unfolded protein response, activation of signaling protein activity; cellular protein metabolic process; cellular response to insulin stimulus; positive regulation of T cell differentiation; fatty acid homeostasis; endothelial cell proliferation; positive regulation of fat cell differentiation; autophagy; positive regulation of B cell differentiation; neuron development; immune response; positive regulation of transcription from RNA polymerase II promoter; positive regulation of protein amino acid phosphorylation; sterol homeostasis; vascular endothelial growth factor receptor signaling pathway; negative regulation of apoptosis
Disease: Major Affective Disorder 7
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