ID ARNT_HUMAN Reviewed; 789 AA. AC P27540; B2R9H1; C4AMA1; F8WAP6; Q59ED4; Q5QP39; Q8NDC7; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 27-MAR-2024, entry version 236. DE RecName: Full=Aryl hydrocarbon receptor nuclear translocator {ECO:0000305}; DE Short=ARNT protein; DE AltName: Full=Class E basic helix-loop-helix protein 2; DE Short=bHLHe2; DE AltName: Full=Dioxin receptor, nuclear translocator; DE AltName: Full=Hypoxia-inducible factor 1-beta; DE Short=HIF-1-beta; DE Short=HIF1-beta; GN Name=ARNT {ECO:0000312|HGNC:HGNC:700}; Synonyms=BHLHE2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RX PubMed=1852076; DOI=10.1126/science.1852076; RA Hoffman E.C., Reyes H., Chu F.-F., Sander F., Conley L.H., Brooks B.A., RA Hankinson O.; RT "Cloning of a factor required for activity of the Ah (dioxin) receptor."; RL Science 252:954-958(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Scheel J.; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis, Thalamus, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Aortic endothelium; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-517. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP PROTEIN SEQUENCE OF 186-203 AND 662-694. RX PubMed=7539918; DOI=10.1073/pnas.92.12.5510; RA Wang G.L., Jiang B.-H., Rue E.A., Semenza G.L.; RT "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer RT regulated by cellular O2 tension."; RL Proc. Natl. Acad. Sci. U.S.A. 92:5510-5514(1995). RN [10] RP CHARACTERIZATION. RX PubMed=1317062; DOI=10.1126/science.256.5060.1193; RA Reyes H., Reisz-Porszasz S., Hankinson O.; RT "Identification of the Ah receptor nuclear translocator protein (Arnt) as a RT component of the DNA binding form of the Ah receptor."; RL Science 256:1193-1195(1992). RN [11] RP DNA-BINDING, AND MUTAGENESIS OF ARG-91; ASN-93; HIS-94; GLU-98; ARG-99; RP ARG-101 AND ARG-102. RX PubMed=8621524; DOI=10.1074/jbc.271.15.8843; RA Bacsi S.G., Hankinson O.; RT "Functional characterization of DNA-binding domains of the subunits of the RT heterodimeric aryl hydrocarbon receptor complex imputing novel and RT canonical basic helix-loop-helix protein-DNA interactions."; RL J. Biol. Chem. 271:8843-8850(1996). RN [12] RP INTERACTION WITH NOCA7. RX PubMed=10395741; DOI=10.1006/abbi.1999.1282; RA Nguyen T.A., Hoivik D., Lee J.-E., Safe S.; RT "Interactions of nuclear receptor coactivator/corepressor proteins with the RT aryl hydrocarbon receptor complex."; RL Arch. Biochem. Biophys. 367:250-257(1999). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP INTERACTION WITH HIF1A. RX PubMed=20699359; DOI=10.1242/jcs.068122; RA Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., Simos G.; RT "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."; RL J. Cell Sci. 123:2976-2986(2010). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP INTERACTION WITH AHRR. RX PubMed=28904176; DOI=10.1074/jbc.m117.812974; RA Sakurai S., Shimizu T., Ohto U.; RT "The crystal structure of the AhRR-ARNT heterodimer reveals the structural RT basis of the repression of AhR-mediated transcription."; RL J. Biol. Chem. 292:17609-17616(2017). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-58, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [20] RP FUNCTION, AND INTERACTION WITH ARNT. RX PubMed=34521881; DOI=10.1038/s41598-021-97507-w; RA Haidar R., Henkler F., Kugler J., Rosin A., Genkinger D., Laux P., Luch A.; RT "The role of DNA-binding and ARNT dimerization on the nucleo-cytoplasmic RT translocation of the aryl hydrocarbon receptor."; RL Sci. Rep. 11:18194-18194(2021). RN [21] {ECO:0007744|PDB:1X0O, ECO:0007744|PDB:2A24} RP STRUCTURE BY NMR OF 356-470 IN COMPLEX WITH EPAS1, SUBUNIT, AND INTERACTION RP WITH EPAS1. RX PubMed=16181639; DOI=10.1016/j.jmb.2005.08.043; RA Card P.B., Erbel P.J., Gardner K.H.; RT "Structural basis of ARNT PAS-B dimerization: use of a common beta-sheet RT interface for hetero- and homodimerization."; RL J. Mol. Biol. 353:664-677(2005). RN [22] {ECO:0007744|PDB:2K7S} RP STRUCTURE BY NMR OF 356-470. RX PubMed=19196990; DOI=10.1073/pnas.0808270106; RA Evans M.R., Card P.B., Gardner K.H.; RT "ARNT PAS-B has a fragile native state structure with an alternative beta- RT sheet register nearby in sequence space."; RL Proc. Natl. Acad. Sci. U.S.A. 106:2617-2622(2009). RN [23] {ECO:0007744|PDB:5V0L} RP X-RAY CRYSTALLOGRAPHY (4.00 ANGSTROMS) OF 70-346 IN COMPLEXES WITH AHR AND RP DNA, FUNCTION, INTERACTION WITH AHR, AND REGION. RX PubMed=28396409; DOI=10.1073/pnas.1617035114; RA Seok S.H., Lee W., Jiang L., Molugu K., Zheng A., Li Y., Park S., RA Bradfield C.A., Xing Y.; RT "Structural hierarchy controlling dimerization and target DNA recognition RT in the AHR transcriptional complex."; RL Proc. Natl. Acad. Sci. U.S.A. 114:5431-5436(2017). CC -!- FUNCTION: Required for activity of the AHR. Upon ligand binding, AHR CC translocates into the nucleus, where it heterodimerizes with ARNT and CC induces transcription by binding to xenobiotic response elements (XRE). CC Not required for the ligand-binding subunit to translocate from the CC cytosol to the nucleus after ligand binding (PubMed:34521881). The CC complex initiates transcription of genes involved in the regulation of CC a variety of biological processes, including angiogenesis, CC hematopoiesis, drug and lipid metabolism, cell motility and immune CC modulation (Probable). The heterodimer binds to core DNA sequence 5'- CC TACGTG-3' within the hypoxia response element (HRE) of target gene CC promoters and functions as a transcriptional regulator of the adaptive CC response to hypoxia (By similarity). The heterodimer ARNT:AHR binds to CC core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) CC of target gene promoters and activates their transcription CC (PubMed:28396409). {ECO:0000250|UniProtKB:P53762, CC ECO:0000269|PubMed:28396409, ECO:0000269|PubMed:34521881, CC ECO:0000305|PubMed:34521881}. CC -!- SUBUNIT: Monomer. Homodimer only upon binding to a DNA (By similarity). CC Efficient DNA binding requires dimerization with another bHLH protein. CC Interacts with TACC3 (By similarity). Interacts with HIF1A, EPAS1, CC NPAS1 and NPAS3; forms a heterodimer that binds core DNA sequence 5'- CC TACGTG-3' within the hypoxia response element (HRE) of target gene CC promoters (PubMed:20699359, PubMed:16181639) (By similarity). Forms a CC heterodimer with AHRR, as well as with other bHLH proteins (Probable). CC Interacts with NOCA7 (PubMed:10395741). Interacts with TACC3 (By CC similarity). Interacts with AHR; the heterodimer ARNT:AHR binds to core CC DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of CC target gene promoters and activates their transcription CC (PubMed:28396409, PubMed:34521881). Interacts with SIM1 and NPAS4 (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P53762, CC ECO:0000269|PubMed:10395741, ECO:0000269|PubMed:16181639, CC ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:28396409, CC ECO:0000269|PubMed:34521881, ECO:0000305|PubMed:28904176}. CC -!- INTERACTION: CC P27540; P35869: AHR; NbExp=6; IntAct=EBI-80809, EBI-80780; CC P27540; Q99814: EPAS1; NbExp=8; IntAct=EBI-80809, EBI-447470; CC P27540; Q16665: HIF1A; NbExp=12; IntAct=EBI-80809, EBI-447269; CC P27540; Q8NI08: NCOA7; NbExp=2; IntAct=EBI-80809, EBI-80799; CC P27540; Q9Y618: NCOR2; NbExp=2; IntAct=EBI-80809, EBI-80830; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:34521881}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Long; CC IsoId=P27540-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P27540-2; Sequence=VSP_002092; CC Name=3; CC IsoId=P27540-3; Sequence=VSP_036532, VSP_036533; CC Name=4; CC IsoId=P27540-4; Sequence=VSP_055030; CC -!- SEQUENCE CAUTION: CC Sequence=BAD93114.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD38953.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/223/ARNT"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/arnt/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M69238; AAA51777.1; -; mRNA. DR EMBL; Y18859; CAC21446.1; -; Genomic_DNA. DR EMBL; AJ251863; CAC21446.1; JOINED; Genomic_DNA. DR EMBL; AJ404851; CAC21446.1; JOINED; Genomic_DNA. DR EMBL; AJ404852; CAC21446.1; JOINED; Genomic_DNA. DR EMBL; AJ404853; CAC21446.1; JOINED; Genomic_DNA. DR EMBL; AJ404854; CAC21446.1; JOINED; Genomic_DNA. DR EMBL; AK290177; BAF82866.1; -; mRNA. DR EMBL; AK293027; BAF85716.1; -; mRNA. DR EMBL; AK313780; BAG36518.1; -; mRNA. DR EMBL; AB209877; BAD93114.1; ALT_INIT; mRNA. DR EMBL; AL834279; CAD38953.1; ALT_INIT; mRNA. DR EMBL; AY430083; AAQ96598.1; -; Genomic_DNA. DR EMBL; AL355860; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53510.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53513.1; -; Genomic_DNA. DR CCDS; CCDS65641.1; -. [P27540-3] DR CCDS; CCDS65642.1; -. [P27540-4] DR CCDS; CCDS970.1; -. [P27540-1] DR CCDS; CCDS971.1; -. [P27540-2] DR PIR; I59550; I59550. DR RefSeq; NP_001184254.1; NM_001197325.1. DR RefSeq; NP_001272964.1; NM_001286035.1. [P27540-3] DR RefSeq; NP_001272965.1; NM_001286036.1. [P27540-4] DR RefSeq; NP_001659.1; NM_001668.3. [P27540-1] DR RefSeq; NP_848514.1; NM_178427.2. [P27540-2] DR RefSeq; XP_016856778.1; XM_017001289.1. [P27540-3] DR PDB; 1X0O; NMR; -; A=356-470. DR PDB; 2A24; NMR; -; B=358-465. DR PDB; 2B02; X-ray; 1.50 A; A=354-470. DR PDB; 2HV1; NMR; -; A/B=356-470. DR PDB; 2K7S; NMR; -; A=356-470. DR PDB; 3F1N; X-ray; 1.48 A; B=356-470. DR PDB; 3F1O; X-ray; 1.60 A; B=356-470. DR PDB; 3F1P; X-ray; 1.17 A; B=356-470. DR PDB; 3H7W; X-ray; 1.65 A; B=356-470. DR PDB; 3H82; X-ray; 1.50 A; B=356-470. DR PDB; 4EQ1; X-ray; 1.60 A; A/B=357-464. DR PDB; 4GHI; X-ray; 1.50 A; B=356-470. DR PDB; 4GS9; X-ray; 1.72 A; B=356-470. DR PDB; 4H6J; X-ray; 1.52 A; B=357-470. DR PDB; 4LPZ; X-ray; 3.15 A; A/B=356-470. DR PDB; 4PKY; X-ray; 3.20 A; A/D=356-470. DR PDB; 4XT2; X-ray; 1.70 A; B/D=356-470. DR PDB; 5TBM; X-ray; 1.85 A; B=356-467. DR PDB; 5UFP; X-ray; 1.90 A; B=356-467. DR PDB; 5V0L; X-ray; 4.00 A; A=70-346. DR PDB; 6CZW; X-ray; 1.60 A; B=356-470. DR PDB; 6D09; X-ray; 1.85 A; B=356-470. DR PDB; 6D0B; X-ray; 1.60 A; B=356-470. DR PDB; 6D0C; X-ray; 1.50 A; B=356-470. DR PDB; 6X21; X-ray; 1.54 A; B=356-467. DR PDB; 6X28; X-ray; 1.92 A; B=356-467. DR PDB; 6X2H; X-ray; 2.00 A; B=356-467. DR PDB; 6X37; X-ray; 1.94 A; B=356-467. DR PDB; 6X3D; X-ray; 2.00 A; B=356-467. DR PDB; 8CK3; X-ray; 1.71 A; B=356-470. DR PDB; 8CK4; X-ray; 2.29 A; B=356-470. DR PDB; 8CK8; X-ray; 2.30 A; B=356-470. DR PDBsum; 1X0O; -. DR PDBsum; 2A24; -. DR PDBsum; 2B02; -. DR PDBsum; 2HV1; -. DR PDBsum; 2K7S; -. DR PDBsum; 3F1N; -. DR PDBsum; 3F1O; -. DR PDBsum; 3F1P; -. DR PDBsum; 3H7W; -. DR PDBsum; 3H82; -. DR PDBsum; 4EQ1; -. DR PDBsum; 4GHI; -. DR PDBsum; 4GS9; -. DR PDBsum; 4H6J; -. DR PDBsum; 4LPZ; -. DR PDBsum; 4PKY; -. DR PDBsum; 4XT2; -. DR PDBsum; 5TBM; -. DR PDBsum; 5UFP; -. DR PDBsum; 5V0L; -. DR PDBsum; 6CZW; -. DR PDBsum; 6D09; -. DR PDBsum; 6D0B; -. DR PDBsum; 6D0C; -. DR PDBsum; 6X21; -. DR PDBsum; 6X28; -. DR PDBsum; 6X2H; -. DR PDBsum; 6X37; -. DR PDBsum; 6X3D; -. DR PDBsum; 8CK3; -. DR PDBsum; 8CK4; -. DR PDBsum; 8CK8; -. DR AlphaFoldDB; P27540; -. DR BMRB; P27540; -. DR SMR; P27540; -. DR BioGRID; 106898; 240. DR ComplexPortal; CPX-2385; Hypoxia-inducible transcription factor complex, HIF2. DR ComplexPortal; CPX-7381; Hypoxia-inducible transcription factor complex, HIF1. DR CORUM; P27540; -. DR DIP; DIP-30886N; -. DR ELM; P27540; -. DR IntAct; P27540; 45. DR MINT; P27540; -. DR STRING; 9606.ENSP00000351407; -. DR ChEMBL; CHEMBL5618; -. DR MoonDB; P27540; Predicted. DR GlyCosmos; P27540; 4 sites, 2 glycans. DR GlyGen; P27540; 8 sites, 2 O-linked glycans (8 sites). DR iPTMnet; P27540; -. DR PhosphoSitePlus; P27540; -. DR BioMuta; ARNT; -. DR DMDM; 114163; -. DR EPD; P27540; -. DR jPOST; P27540; -. DR MassIVE; P27540; -. DR MaxQB; P27540; -. DR PaxDb; 9606-ENSP00000351407; -. DR PeptideAtlas; P27540; -. DR ProteomicsDB; 30540; -. DR ProteomicsDB; 54398; -. [P27540-1] DR ProteomicsDB; 54399; -. [P27540-2] DR ProteomicsDB; 54400; -. [P27540-3] DR Pumba; P27540; -. DR Antibodypedia; 916; 798 antibodies from 43 providers. DR DNASU; 405; -. DR Ensembl; ENST00000354396.6; ENSP00000346372.2; ENSG00000143437.21. [P27540-4] DR Ensembl; ENST00000358595.10; ENSP00000351407.5; ENSG00000143437.21. [P27540-1] DR Ensembl; ENST00000505755.5; ENSP00000427571.1; ENSG00000143437.21. [P27540-2] DR Ensembl; ENST00000515192.5; ENSP00000423851.1; ENSG00000143437.21. [P27540-3] DR GeneID; 405; -. DR KEGG; hsa:405; -. DR MANE-Select; ENST00000358595.10; ENSP00000351407.5; NM_001668.4; NP_001659.1. DR UCSC; uc001evr.2; human. [P27540-1] DR AGR; HGNC:700; -. DR CTD; 405; -. DR DisGeNET; 405; -. DR GeneCards; ARNT; -. DR HGNC; HGNC:700; ARNT. DR HPA; ENSG00000143437; Low tissue specificity. DR MIM; 126110; gene. DR neXtProt; NX_P27540; -. DR OpenTargets; ENSG00000143437; -. DR PharmGKB; PA24994; -. DR VEuPathDB; HostDB:ENSG00000143437; -. DR eggNOG; KOG3561; Eukaryota. DR GeneTree; ENSGT00940000157585; -. DR HOGENOM; CLU_011864_1_1_1; -. DR InParanoid; P27540; -. DR OMA; LXSDDEQ; -. DR OrthoDB; 2872674at2759; -. DR PhylomeDB; P27540; -. DR TreeFam; TF319983; -. DR PathwayCommons; P27540; -. DR Reactome; R-HSA-1234158; Regulation of gene expression by Hypoxia-inducible Factor. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds. DR Reactome; R-HSA-211976; Endogenous sterols. DR Reactome; R-HSA-211981; Xenobiotics. DR Reactome; R-HSA-8937144; Aryl hydrocarbon receptor signalling. DR Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR SignaLink; P27540; -. DR SIGNOR; P27540; -. DR BioGRID-ORCS; 405; 74 hits in 1190 CRISPR screens. DR ChiTaRS; ARNT; human. DR EvolutionaryTrace; P27540; -. DR GeneWiki; Aryl_hydrocarbon_receptor_nuclear_translocator; -. DR GenomeRNAi; 405; -. DR Pharos; P27540; Tbio. DR PRO; PR:P27540; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P27540; Protein. DR Bgee; ENSG00000143437; Expressed in colonic epithelium and 201 other cell types or tissues. DR ExpressionAtlas; P27540; baseline and differential. DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0034753; C:nuclear aryl hydrocarbon receptor complex; IDA:UniProtKB. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0017162; F:aryl hydrocarbon receptor binding; IPI:BHF-UCL. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProt. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0004879; F:nuclear receptor activity; IEA:Ensembl. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:BHF-UCL. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProt. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IC:BHF-UCL. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IC:BHF-UCL. DR GO; GO:0045821; P:positive regulation of glycolytic process; IC:BHF-UCL. DR GO; GO:0046886; P:positive regulation of hormone biosynthetic process; IDA:BHF-UCL. DR GO; GO:0033235; P:positive regulation of protein sumoylation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IDA:BHF-UCL. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IC:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL. DR CDD; cd18947; bHLH-PAS_ARNT; 1. DR CDD; cd00130; PAS; 2. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR001067; Nuc_translocat. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013767; PAS_fold. DR NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR23042:SF50; ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR; 1. DR PANTHER; PTHR23042; CIRCADIAN PROTEIN CLOCK/ARNT/BMAL/PAS; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF14598; PAS_11; 1. DR PRINTS; PR00785; NCTRNSLOCATR. DR SMART; SM00353; HLH; 1. DR SMART; SM00086; PAC; 1. DR SMART; SM00091; PAS; 2. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR SUPFAM; SSF88633; Positive stranded ssRNA viruses; 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 2. DR Genevisible; P27540; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Direct protein sequencing; DNA-binding; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..789 FT /note="Aryl hydrocarbon receptor nuclear translocator" FT /id="PRO_0000127118" FT DOMAIN 89..142 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT DOMAIN 161..235 FT /note="PAS 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 349..419 FT /note="PAS 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 424..467 FT /note="PAC" FT REGION 1..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 88..128 FT /note="DNA-binding" FT /evidence="ECO:0000269|PubMed:28396409" FT REGION 112..264 FT /note="Required for heterodimer formation with EPAS1" FT /evidence="ECO:0000250|UniProtKB:P53762" FT REGION 112..168 FT /note="Required for heterodimer formation with HIF1A" FT /evidence="ECO:0000250|UniProtKB:P53762" FT REGION 167..171 FT /note="Mediates the transcription activity and dimerization FT of the AHR:ARNT complex" FT /evidence="ECO:0000250|UniProtKB:P53762" FT REGION 465..492 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 672..789 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 43..97 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 465..485 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 692..723 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 731..778 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 77 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 58 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..9 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11230166" FT /id="VSP_036532" FT VAR_SEQ 77..91 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1852076" FT /id="VSP_002092" FT VAR_SEQ 319..323 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11230166" FT /id="VSP_036533" FT VAR_SEQ 601..602 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_055030" FT VARIANT 430 FT /note="R -> Q (in dbSNP:rs2229175)" FT /id="VAR_024280" FT VARIANT 511 FT /note="D -> N (in dbSNP:rs1805133)" FT /id="VAR_014819" FT VARIANT 517 FT /note="D -> E (in dbSNP:rs10305741)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_018906" FT VARIANT 706 FT /note="P -> L (in dbSNP:rs2275237)" FT /id="VAR_020189" FT MUTAGEN 91 FT /note="R->A: Diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 93 FT /note="N->A: Diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 94 FT /note="H->A: Severely diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 98 FT /note="E->A: Severely diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 99 FT /note="R->A: Diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 101 FT /note="R->A: Severely diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT MUTAGEN 102 FT /note="R->A: Severely diminishes DNA interaction." FT /evidence="ECO:0000269|PubMed:8621524" FT CONFLICT 627 FT /note="R -> H (in Ref. 3; BAG36518)" FT /evidence="ECO:0000305" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:2K7S" FT STRAND 362..367 FT /evidence="ECO:0007829|PDB:3F1P" FT STRAND 371..376 FT /evidence="ECO:0007829|PDB:3F1P" FT HELIX 380..384 FT /evidence="ECO:0007829|PDB:3F1P" FT HELIX 388..390 FT /evidence="ECO:0007829|PDB:3F1P" FT TURN 391..393 FT /evidence="ECO:0007829|PDB:3F1P" FT HELIX 396..399 FT /evidence="ECO:0007829|PDB:3F1P" FT TURN 402..404 FT /evidence="ECO:0007829|PDB:3F1P" FT HELIX 405..415 FT /evidence="ECO:0007829|PDB:3F1P" FT TURN 416..420 FT /evidence="ECO:0007829|PDB:3F1N" FT STRAND 423..430 FT /evidence="ECO:0007829|PDB:3F1P" FT STRAND 436..446 FT /evidence="ECO:0007829|PDB:3F1P" FT TURN 449..451 FT /evidence="ECO:0007829|PDB:2B02" FT STRAND 456..463 FT /evidence="ECO:0007829|PDB:3F1P" SQ SEQUENCE 789 AA; 86636 MW; 2E278F8E62BFBF6D CRC64; 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 //