XBP1

X-box binding protein 1
Identifiers
Symbols	XBP1 ; TREB5; XBP2
External IDs	Template:OMIM5 Template:MGI HomoloGene: 3722
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE XBP1 200670 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

X-box binding protein 1, also known as XBP1, is a human gene.

Function

The transcription factor X-box binding protein 1 (XBP-1) is a bZIP transcription factor first identified by its ability to bind to the x-box, a conserved transcriptional element, in the human leukocyte antigen (HLA) DR alpha promoter. XBP-1 is also essential for plasma cell differentiation. This differentiation requires not only the expression of XBP-1 but the expression of the spliced isoform of XBP-1s. This protein has also been identified as a cellular transcription factor that binds to an enhancer in the promoter of the T cell leukemia virus type 1 promoter. The generation of XBP-1s during plasma cell differentiation also seems to be the cue for Kaposi's sarcoma-associated herpesvirus and Epstein Barr virus reactivation from latency.

XBP-1 is upregulated as part of the ER stress response, the unfolded protein response (UPR). This increase in transcription requires an ER stress response consensus binding element in the promoter. XBP-1u is ubiquitously expressed but under conditions of ER-stress, the XBP-1u mRNA is processed by IRE1. Activated IRE1 oligomerises and activates its ribonuclease domain through autophosphorylation. Because the lumen of the ER is continuous with the perinuclear space, the activated ribonuclease domains can penetrate the inner leaflet of the nuclear envelope. Within the nucleus, activated IRE1 catalyses the excision of a 26 nucleotide unconventional intron from XBP-1 mRNA, in a manner mechanistically similar to pre-tRNA splicing. Removal of this intron causes a frame shift in the XBP-1 coding sequence resulting in the translation of a 371 amino acid, 54 kDa, XBP-1s isoform rather than the 261 amino acid, 33 kDa, XBP-1u isoform.

Finally, a pseudogene has been identified and localized to chromosome 5.

Further reading

• Clarke R, Liu MC, Bouker KB; et al. (2003). "Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling". Oncogene. 22 (47): 7316–39. doi:10.1038/sj.onc.1206937. PMID 14576841.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Nekrutenko A, He J (2007). "Functionality of unspliced XBP1 is required to explain evolution of overlapping reading frames". Trends Genet. 22 (12): 645–8. doi:10.1016/j.tig.2006.09.012. PMID 17034899.
• Liou HC, Eddy R, Shows T; et al. (1991). "An HLA-DR alpha promoter DNA-binding protein is expressed ubiquitously and maps to human chromosomes 22 and 5". Immunogenetics. 34 (5): 286–92. PMID 1718857.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ono SJ, Liou HC, Davidon R; et al. (1991). "Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4309–12. PMID 1903538.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Yoshimura T, Fujisawa J, Yoshida M (1990). "Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain". EMBO J. 9 (8): 2537–42. PMID 2196176.CS1 maint: Multiple names: authors list (link)
• Liou HC, Boothby MR, Finn PW; et al. (1990). "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter". Science. 247 (4950): 1581–4. PMID 2321018.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ponath PD, Fass D, Liou HC; et al. (1993). "The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes". J. Biol. Chem. 268 (23): 17074–82. PMID 8349596.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Clauss IM, Chu M, Zhao JL, Glimcher LH (1996). "The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core". Nucleic Acids Res. 24 (10): 1855–64. PMID 8657566.CS1 maint: Multiple names: authors list (link)
• Kishimoto T, Kokura K, Ohkawa N; et al. (1998). "Enhanced expression of a new class of liver-enriched b-Zip transcription factors, hepatocarcinogenesis-related transcription factor, in hepatocellular carcinomas of rats and humans". Cell Growth Differ. 9 (4): 337–44. PMID 9563853.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dunham I, Shimizu N, Roe BA; et al. (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Reimold AM, Etkin A, Clauss I; et al. (2000). "An essential role in liver development for transcription factor XBP-1". Genes Dev. 14 (2): 152–7. PMID 10652269.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. PMID 11076863.CS1 maint: Multiple names: authors list (link)
• Yoshida H, Matsui T, Yamamoto A; et al. (2002). "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor". Cell. 107 (7): 881–91. PMID 11779464.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Takahashi S, Suzuki S, Inaguma S; et al. (2002). "Down-regulation of human X-box binding protein 1 (hXBP-1) expression correlates with tumor progression in human prostate cancers". Prostate. 50 (3): 154–61. PMID 11813207.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gu Z, Lee RY, Skaar TC; et al. (2002). "Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780)". Cancer Res. 62 (12): 3428–37. PMID 12067985.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Yoshida H, Matsui T, Hosokawa N; et al. (2003). "A time-dependent phase shift in the mammalian unfolded protein response". Dev. Cell. 4 (2): 265–71. PMID 12586069.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Shuda M, Kondoh N, Imazeki N; et al. (2004). "Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis". J. Hepatol. 38 (5): 605–14. PMID 12713871.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Newman JR, Keating AE (2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science. 300 (5628): 2097–101. doi:10.1126/science.1084648. PMID 12805554.
• Kakiuchi C, Iwamoto K, Ishiwata M; et al. (2003). "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder". Nat. Genet. 35 (2): 171–5. doi:10.1038/ng1235. PMID 12949534.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)