ARNT
ARNT (skr. punog naziva na engleskom: jedarni translokator receptora aril-ugljovodonika) jest gen koji se kod ljudi nalazi na hromosomu 1. Kodira jedarni translokator receptora aril ugljovodonika, protein koji formira kompleks sa za ligand vezanim aril ugljikovodični receptor (AhR), a potreban je za funkciju receptora.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 789 aminokiselina, a molekulska težina 86.636 Da.[5]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MAATTANPEM | TSDVPSLGPA | IASGNSGPGI | QGGGAIVQRA | IKRRPGLDFD | ||||
DDGEGNSKFL | RCDDDQMSND | KERFARSDDE | QSSADKERLA | RENHSEIERR | ||||
RRNKMTAYIT | ELSDMVPTCS | ALARKPDKLT | ILRMAVSHMK | SLRGTGNTST | ||||
DGSYKPSFLT | DQELKHLILE | AADGFLFIVS | CETGRVVYVS | DSVTPVLNQP | ||||
QSEWFGSTLY | DQVHPDDVDK | LREQLSTSEN | ALTGRILDLK | TGTVKKEGQQ | ||||
SSMRMCMGSR | RSFICRMRCG | SSSVDPVSVN | RLSFVRNRCR | NGLGSVKDGE | ||||
PHFVVVHCTG | YIKAWPPAGV | SLPDDDPEAG | QGSKFCLVAI | GRLQVTSSPN | ||||
CTDMSNVCQP | TEFISRHNIE | GIFTFVDHRC | VATVGYQPQE | LLGKNIVEFC | ||||
HPEDQQLLRD | SFQQVVKLKG | QVLSVMFRFR | SKNQEWLWMR | TSSFTFQNPY | ||||
SDEIEYIICT | NTNVKNSSQE | PRPTLSNTIQ | RPQLGPTANL | PLEMGSGQLA | ||||
PRQQQQQTEL | DMVPGRDGLA | SYNHSQVVQP | VTTTGPEHSK | PLEKSDGLFA | ||||
QDRDPRFSEI | YHNINADQSK | GISSSTVPAT | QQLFSQGNTF | PPTPRPAENF | ||||
RNSGLAPPVT | IVQPSASAGQ | MLAQISRHSN | PTQGATPTWT | PTTRSGFSAQ | ||||
QVATQATAKT | RTSQFGVGSF | QTPSSFSSMS | LPGAPTASPG | AAAYPSLTNR | ||||
GSNFAPETGQ | TAGQFQTRTA | EGVGVWPQWQ | GQQPHHRSSS | SEQHVQQPPA | ||||
QQPGQPEVFQ | EMLSMLGDQS | NSYNNEEFPD | LTMFPPFSE |
Funkcija
urediKodirani protein je takođe identifikovan kao beta podjedinica heterodimernog transkripcijskog faktora, hipoksija-inducibilni faktor 1 (HIF1). Translokacija t(1;12)(q21;p13), koja rezultira fuzijom proteina TEL-ARNT, povezana je sa akutnom mijeloblastnom leukemijom. Za ovaj gen su opisane tri alternativno prerađene varijante transkripta koje kodiraju različite izoforme.
Aril-hidrokarbonski receptor (AhR) uključen je u indukciju nekoliko enzima koji učestvuju u ksenobiotskom metabolizmu. Citosolni oblik aril-ugljokovodikovog receptora bez liganda složen je u protein toplotnog šoka 90. Vezivanje liganda, koji uključuje dioksin i policiklični aromatski ugljikovodik, rezultira translokacijom podjedinice koja vezuje ligand samo u[6] jedru. Indukcija enzima uključenih u metabolizam ksenobiotika događa se vezivanjem AhR vezanog za ligand elemenata koji reaguju na ksenobiotike u promotorima gena za ove enzime.
Interakcije
urediPokazalo se da jedarni translokator receptora aril-ugljikovodika reaguje sa:
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000143437 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015522 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "UniProt, P27540" (jezik: en.). Pristupljeno 7. 12. 2021.CS1 održavanje: nepoznati jezik (link)
- ^ Hughes, D.; Guttenplan, J. B.; Marcus, C. B.; Subbaramaiah, K.; Dannenberg, A. J. (2008). "Heat Shock Protein 90 Inhibitors Suppress Aryl Hydrocarbon Receptor-Mediated Activation of CYP1A1 and CYP1B1 Transcription and DNA Adduct Formation". Cancer Prevention Research. 1 (6): 485–493. doi:10.1158/1940-6207.CAPR-08-0149. PMC 2680610. PMID 19138996.
- ^ Carver LA, Bradfield CA (april 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.
- ^ Kazlauskas A, Sundström S, Poellinger L, Pongratz I (april 2001). "The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor". Mol. Cell. Biol. 21 (7): 2594–607. doi:10.1128/MCB.21.7.2594-2607.2001. PMC 86890. PMID 11259606.
- ^ Lindebro MC, Poellinger L, Whitelaw ML (juli 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. doi:10.1002/j.1460-2075.1995.tb07359.x. PMC 394421. PMID 7628454.
- ^ Whitelaw M, Pongratz I, Wilhelmsson A, Gustafsson JA, Poellinger L (april 1993). "Ligand-dependent recruitment of the Arnt coregulator determines DNA recognition by the dioxin receptor". Mol. Cell. Biol. 13 (4): 2504–14. doi:10.1128/MCB.13.4.2504. PMC 359572. PMID 8384309.
- ^ Yamaguchi Y, Kuo MT (oktobar 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.
- ^ Mimura J, Ema M, Sogawa K, Fujii-Kuriyama Y (januar 1999). "Identification of a novel mechanism of regulation of Ah (dioxin) receptor function". Genes Dev. 13 (1): 20–5. doi:10.1101/gad.13.1.20. PMC 316371. PMID 9887096.
- ^ a b Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (mart 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.
- ^ a b c Woods SL, Whitelaw ML (mart 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. 277 (12): 10236–43. doi:10.1074/jbc.M110752200. PMID 11782478.
- ^ Beischlag TV, Wang S, Rose DW, Torchia J, Reisz-Porszasz S, Muhammad K, Nelson WE, Probst MR, Rosenfeld MG, Hankinson O (juni 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. 22 (12): 4319–33. doi:10.1128/mcb.22.12.4319-4333.2002. PMC 133867. PMID 12024042.
- ^ a b Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O (februar 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.
- ^ Ooe N, Saito K, Mikami N, Nakatuka I, Kaneko H (januar 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. 24 (2): 608–16. doi:10.1128/mcb.24.2.608-616.2004. PMC 343817. PMID 14701734.
- ^ Moffett P, Reece M, Pelletier J (septembar 1997). "The murine Sim-2 gene product inhibits transcription by active repression and functional interference". Mol. Cell. Biol. 17 (9): 4933–47. doi:10.1128/mcb.17.9.4933. PMC 232345. PMID 9271372.
Dopunska literatura
uredi- Haase VH (2006). "Hypoxia-inducible factors in the kidney". Am. J. Physiol. Renal Physiol. 291 (2): F271–81. doi:10.1152/ajprenal.00071.2006. PMC 4232221. 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. Bibcode:1992Sci...256.1193R. doi:10.1126/science.256.5060.1193. PMID 1317062. S2CID 34075046.
- Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA, Hankinson O (1991). "Cloning of a factor required for activity of the Ah (dioxin) receptor". Science. 252 (5008): 954–8. Bibcode:1991Sci...252..954H. 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. Bibcode:1995PNAS...92.5510W. doi:10.1073/pnas.92.12.5510. PMC 41725. 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. doi:10.1002/j.1460-2075.1995.tb07359.x. PMC 394421. 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. doi:10.1128/mcb.14.9.6075. PMC 359134. 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, Diep A, Mohandas T, Sparkes RS, Reyes H, Hoffman E, Lange E, Gatti RA (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, Gustafsson JA, Poellinger L (1993). "Ligand-dependent recruitment of the Arnt coregulator determines DNA recognition by the dioxin receptor". Mol. Cell. Biol. 13 (4): 2504–14. doi:10.1128/MCB.13.4.2504. PMC 359572. PMID 8384309.
- Jiang BH, Rue E, Wang GL, Roe R, Semenza GL (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, Tanaka M, Matsuda Y, Gotoh O, Saijoh Y, Fujii H, Hamada H, Kikuchi Y, Fujii-Kuriyama Y (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. doi:10.1128/MCB.16.10.5865. PMC 231588. PMID 8927054.
- Swanson HI, Yang Jh (1997). "Mapping the protein/DNA contact sites of the Ah receptor and Ah receptor nuclear translocator". J. Biol. Chem. 271 (49): 31657–65. doi:10.1074/jbc.271.49.31657. 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, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (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, Sogawa K, Matsuda Y, Fujii-Kuriyama Y (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. PMC 20712. 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. doi:10.1128/mcb.17.9.4933. PMC 232345. PMID 9271372.
Vanjski linkovi
uredi- Aryl Hydrocarbon Receptor Nuclear Translocator na US National Library of Medicine Medical Subject Headings (MeSH)
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.