XBP-1 (XBP1) Antibody – Mouse Monoclonal

This gene encodes a transcription factor that regulates MHC class II genes by binding to a promoter element referred to as an X box. This gene product is a bZIP protein, which was also identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. It may increase expression of viral proteins by acting as the DNA binding partner of a viral transactivator. It has been found that upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), the mRNA of this gene is processed to an active form by an unconventional splicing mechanism that is mediated by the endonuclease inositol-requiring enzyme 1 (IRE1). The resulting loss of 26 nt from the spliced mRNA causes a frame-shift and an isoform XBP1(S), which is the functionally active transcription factor. The isoform encoded by the unspliced mRNA, XBP1(U), is constitutively expressed, and thought to function as a negative feedback regulator of XBP1(S), which shuts off transcription of target genes during the recovery phase of ER stress. A pseudogene of XBP1 has been identified and localized to chromosome 5. [provided by RefSeq, Jul 2008]

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: DNA-binding; Transcription factor

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: transcription from RNA polymerase II promoter; ubiquitin-dependent protein catabolic process; 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; response to electrical stimulus; cell growth; positive regulation of TOR signaling pathway; fatty acid biosynthetic process; positive regulation of autophagy; 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; cellular protein metabolic process; unfolded protein response, activation of signaling protein activity; positive regulation of T cell differentiation; cellular response to insulin stimulus; endothelial cell proliferation; fatty acid homeostasis; neuron development; positive regulation of fat cell differentiation; autophagy; positive regulation of B cell differentiation; immune response; positive regulation of transcription from RNA polymerase II promoter; positive regulation of protein amino acid phosphorylation; vascular endothelial growth factor receptor signaling pathway; sterol homeostasis; negative regulation of apoptosis

Disease: Major Affective Disorder 7