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Aryl hydrocarbon receptor nuclear translocator

PDB rendering based on 1x0o.
Available structures
1x0o, 2a24, 2b02
Identifiers
Symbols ARNT; HIF-1beta; HIF1B; HIF1BETA; TANGO
External IDs OMIM126110 MGI88071 HomoloGene1261 GeneCards: ARNT Gene
RNA expression pattern
PBB GE ARNT 218221 at tn.png
PBB GE ARNT 210828 s at tn.png
PBB GE ARNT 218222 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 405 11863
Ensembl ENSG00000143437 ENSMUSG00000015522
UniProt P27540 Q3U7X2
RefSeq (mRNA) NM_001668 NM_001037737
RefSeq (protein) NP_001659 NP_001032826
Location (UCSC) Chr 1:
149.05 - 149.12 Mb
Chr 3:
95.52 - 95.58 Mb
PubMed search [1] [2]

The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.

The aryl hydrocarbon receptor (AhR) is involved in the induction of several enzymes that participate in xenobiotic metabolism. The ligand-free, cytosolic form of the aryl hydrocarbon receptor is complexed to heat shock protein 90. Binding of ligand, which includes dioxin and polycyclic aromatic hydrocarbons, results in translocation of the ligand-binding subunit only to the nucleus. Induction of enzymes involved in xenobiotic metabolism occurs through binding of the ligand-bound AhR to xenobiotic responsive elements in the promoters of genes for these enzymes.

Contents

Interactions

Aryl hydrocarbon receptor nuclear translocator has been shown to interact with HIF1A,[1][2] Src,[3] AIP,[4][5] SIM1,[6][1] Aryl hydrocarbon receptor,[7][8][9][10] EPAS1,[2] SIM2[6][11][1][12] and Nuclear receptor coactivator 2.[3]

References

  1. ^ a b c Woods, Susan L; Whitelaw Murray L (Mar. 2002). "Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors". J. Biol. Chem. (United States) 277 (12): 10236–43. doi:10.1074/jbc.M110752200. ISSN 0021-9258. PMID 11782478.  
  2. ^ a b Hogenesch, J B; Chan W K, Jackiw V H, Brown R C, Gu Y Z, Pray-Grant M, Perdew G H, Bradfield C A (Mar. 1997). "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway". J. Biol. Chem. (UNITED STATES) 272 (13): 8581–93. ISSN 0021-9258. PMID 9079689.  
  3. ^ a b Beischlag, Timothy V; Wang Song, Rose David W, Torchia Joseph, Reisz-Porszasz Suzanne, Muhammad Khurshid, Nelson Walter E, Probst Markus R, Rosenfeld Michael G, Hankinson Oliver (Jun. 2002). "Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator complex". Mol. Cell. Biol. (United States) 22 (12): 4319–33. ISSN 0270-7306. PMID 12024042.  
  4. ^ Carver, L A; Bradfield C A (Apr. 1997). "Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo". J. Biol. Chem. (UNITED STATES) 272 (17): 11452–6. ISSN 0021-9258. PMID 9111057.  
  5. ^ Kazlauskas, A; Sundström S, Poellinger L, Pongratz I (Apr. 2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor". Mol. Cell. Biol. (United States) 21 (7): 2594–607. doi:10.1128/MCB.21.7.2594-2607.2001. ISSN 0270-7306. PMID 11259606.  
  6. ^ a b Probst, M R; Fan C M, Tessier-Lavigne M, Hankinson O (Feb. 1997). "Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein". J. Biol. Chem. (UNITED STATES) 272 (7): 4451–7. ISSN 0021-9258. PMID 9020169.  
  7. ^ Lindebro, M C; Poellinger L, Whitelaw M L (Jul. 1995). "Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex". EMBO J. (ENGLAND) 14 (14): 3528–39. ISSN 0261-4189. PMID 7628454.  
  8. ^ Whitelaw, M; Pongratz I, Wilhelmsson A, Gustafsson J A, Poellinger L (Apr. 1993). "Ligand-dependent recruitment of the Arnt coregulator determines DNA recognition by the dioxin receptor". Mol. Cell. Biol. (UNITED STATES) 13 (4): 2504–14. ISSN 0270-7306. PMID 8384309.  
  9. ^ Yamaguchi, Y; Kuo M T (Oct. 1995). "Functional analysis of aryl hydrocarbon receptor nuclear translocator interactions with aryl hydrocarbon receptor in the yeast two-hybrid system". Biochem. Pharmacol. (ENGLAND) 50 (8): 1295–302. ISSN 0006-2952. PMID 7488247.  
  10. ^ Mimura, J; Ema M, Sogawa K, Fujii-Kuriyama Y (Jan. 1999). "Identification of a novel mechanism of regulation of Ah (dioxin) receptor function". Genes Dev. (UNITED STATES) 13 (1): 20–5. ISSN 0890-9369. PMID 9887096.  
  11. ^ Ooe, Norihisa; Saito Koichi, Mikami Nobuyoshi, Nakatuka Iwao, Kaneko Hideo (Jan. 2004). "Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression". Mol. Cell. Biol. (United States) 24 (2): 608–16. ISSN 0270-7306. PMID 14701734.  
  12. ^ Moffett, P; Reece M, Pelletier J (Sep. 1997). "The murine Sim-2 gene product inhibits transcription by active repression and functional interference". Mol. Cell. Biol. (UNITED STATES) 17 (9): 4933–47. ISSN 0270-7306. PMID 9271372.  

Further reading

  • Haase VH (2006). "Hypoxia-inducible factors in the kidney.". Am. J. Physiol. Renal Physiol. 291 (2): F271–81. doi:10.1152/ajprenal.00071.2006. PMID 16554418.  
  • Reyes H, Reisz-Porszasz S, Hankinson O (1992). "Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor.". Science 256 (5060): 1193–5. doi:10.1126/science.256.5060.1193. PMID 1317062.  
  • Hoffman EC, Reyes H, Chu FF, et al. (1991). "Cloning of a factor required for activity of the Ah (dioxin) receptor.". Science 252 (5008): 954–8. doi:10.1126/science.1852076. PMID 1852076.  
  • Yamaguchi Y, Kuo MT (1995). "Functional analysis of aryl hydrocarbon receptor nuclear translocator interactions with aryl hydrocarbon receptor in the yeast two-hybrid system.". Biochem. Pharmacol. 50 (8): 1295–302. doi:10.1016/0006-2952(95)02016-6. PMID 7488247.  
  • Wang GL, Jiang BH, Rue EA, Semenza GL (1995). "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.". Proc. Natl. Acad. Sci. U.S.A. 92 (12): 5510–4. doi:10.1073/pnas.92.12.5510. PMID 7539918.  
  • Lindebro MC, Poellinger L, Whitelaw ML (1995). "Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex.". Embo J. 14 (14): 3528–39. PMID 7628454.  
  • Abbott BD, Probst MR, Perdew GH (1995). "Immunohistochemical double-staining for Ah receptor and ARNT in human embryonic palatal shelves.". Teratology 50 (5): 361–6. doi:10.1002/tera.1420500507. PMID 7716743.  
  • Reisz-Porszasz S, Probst MR, Fukunaga BN, Hankinson O (1994). "Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).". Mol. Cell. Biol. 14 (9): 6075–86. PMID 8065341.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.  
  • Johnson B, Brooks BA, Heinzmann C, et al. (1993). "The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3.". Genomics 17 (3): 592–8. doi:10.1006/geno.1993.1377. PMID 8244375.  
  • Whitelaw M, Pongratz I, Wilhelmsson A, et al. (1993). "Ligand-dependent recruitment of the Arnt coregulator determines DNA recognition by the dioxin receptor.". Mol. Cell. Biol. 13 (4): 2504–14. PMID 8384309.  
  • Jiang BH, Rue E, Wang GL, et al. (1996). "Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1.". J. Biol. Chem. 271 (30): 17771–8. doi:10.1074/jbc.271.30.17771. PMID 8663540.  
  • Rowlands JC, McEwan IJ, Gustafsson JA (1996). "Trans-activation by the human aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator proteins: direct interactions with basal transcription factors.". Mol. Pharmacol. 50 (3): 538–48. PMID 8794892.  
  • Ema M, Morita M, Ikawa S, et al. (1996). "Two new members of the murine Sim gene family are transcriptional repressors and show different expression patterns during mouse embryogenesis.". Mol. Cell. Biol. 16 (10): 5865–75. PMID 8927054.  
  • Swanson HI, Yang J (1997). "Mapping the protein/DNA contact sites of the Ah receptor and Ah receptor nuclear translocator.". J. Biol. Chem. 271 (49): 31657–65. PMID 8940186.  
  • Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O (1997). "Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein.". J. Biol. Chem. 272 (7): 4451–7. doi:10.1074/jbc.272.7.4451. PMID 9020169.  
  • Hogenesch JB, Chan WK, Jackiw VH, et al. (1997). "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway.". J. Biol. Chem. 272 (13): 8581–93. doi:10.1074/jbc.272.13.8581. PMID 9079689.  
  • Carver LA, Bradfield CA (1997). "Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.". J. Biol. Chem. 272 (17): 11452–6. doi:10.1074/jbc.272.17.11452. PMID 9111057.  
  • Ema M, Taya S, Yokotani N, et al. (1997). "A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development.". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4273–8. doi:10.1073/pnas.94.9.4273. PMID 9113979.  
  • Moffett P, Reece M, Pelletier J (1997). "The murine Sim-2 gene product inhibits transcription by active repression and functional interference.". Mol. Cell. Biol. 17 (9): 4933–47. PMID 9271372.  

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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