ID AHR_HUMAN Reviewed; 848 AA. AC P35869; A4D130; Q13728; Q13803; Q13804; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 28-JAN-2026, entry version 236. DE RecName: Full=Aryl hydrocarbon receptor {ECO:0000303|PubMed:8393992}; DE Short=Ah receptor {ECO:0000303|PubMed:8393992}; DE Short=AhR {ECO:0000303|PubMed:8393992}; DE AltName: Full=Class E basic helix-loop-helix protein 76; DE Short=bHLHe76; DE Flags: Precursor; GN Name=AHR {ECO:0000303|PubMed:8393992, ECO:0000312|HGNC:HGNC:348}; GN Synonyms=BHLHE76 {ECO:0000312|HGNC:HGNC:348}; 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]. RC TISSUE=Liver; RX PubMed=8393992; DOI=10.1093/nar/21.15.3578; RA Itoh S., Kamataki T.; RT "Human Ah receptor cDNA: analysis for highly conserved sequences."; RL Nucleic Acids Res. 21:3578-3578(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=8246913; RA Dolwick K.M., Schmidt J.V., Carver L.A., Swanson H.I., Bradfield C.A.; RT "Cloning and expression of a human Ah receptor cDNA."; RL Mol. Pharmacol. 44:911-917(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7883760; DOI=10.1093/oxfordjournals.jbchem.a124605; RA Ema M., Matsushita N., Sogawa K., Ariyama T., Inazawa J., Nemoto T., RA Ota M., Oshimura M., Fujii-Kuriyama Y.; RT "Human arylhydrocarbon receptor: functional expression and chromosomal RT assignment to 7p21."; RL J. Biochem. 116:845-851(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-235; 388-461 AND 764-848. RX PubMed=16696038; DOI=10.1136/mp.49.1.m12; RA Bennett P., Ramsden D.B., Williams A.C.; RT "Complete structural characterisation of the human aryl hydrocarbon RT receptor gene."; RL Clin. Mol. Pathol. 49:M12-M16(1996). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 236-341, AND TISSUE SPECIFICITY. RX PubMed=7515333; DOI=10.1093/carcin/15.5.801; RA Hayashi S., Watanabe J., Nakachi K., Eguchi H., Gotoh O., Kawajiri K.; RT "Interindividual difference in expression of human Ah receptor and related RT P450 genes."; RL Carcinogenesis 15:801-806(1994). RN [10] RP FUNCTION, AND MUTAGENESIS OF VAL-381. RX PubMed=7961644; DOI=10.1016/s0021-9258(18)46990-6; RA Ema M., Ohe N., Suzuki M., Mimura J., Sogawa K., Ikawa S., RA Fujii-Kuriyama Y.; RT "Dioxin binding activities of polymorphic forms of mouse and human RT arylhydrocarbon receptors."; RL J. Biol. Chem. 269:27337-27343(1994). RN [11] RP FUNCTION, AND SUBUNIT. 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 [12] RP INDUCTION. RX PubMed=11259615; DOI=10.1124/mol.59.4.716; RA Wolff S., Harper P.A., Wong J.M.Y., Mostert V., Wang Y., Abel J.; RT "Cell-specific regulation of human aryl hydrocarbon receptor expression by RT transforming growth factor-beta(1)."; RL Mol. Pharmacol. 59:716-724(2001). RN [13] RP REVIEW ON ROLE IN CELL CYCLE. RX PubMed=12213388; DOI=10.1016/s0009-2797(02)00069-8; RA Puga A., Xia Y., Elferink C.; RT "Role of the aryl hydrocarbon receptor in cell cycle regulation."; RL Chem. Biol. Interact. 141:117-130(2002). RN [14] RP INTERACTION WITH NEDD8. RX PubMed=12215427; DOI=10.1074/jbc.m202413200; RA Antenos M., Casper R.F., Brown T.J.; RT "Interaction with Nedd8, a ubiquitin-like protein, enhances the RT transcriptional activity of the aryl hydrocarbon receptor."; RL J. Biol. Chem. 277:44028-44034(2002). RN [15] RP INTERACTION WITH IVNS1ABP. RX PubMed=16582008; DOI=10.1124/mol.106.024380; RA Dunham E.E., Stevens E.A., Glover E., Bradfield C.A.; RT "The aryl hydrocarbon receptor signaling pathway is modified through RT interactions with a Kelch protein."; RL Mol. Pharmacol. 70:8-15(2006). RN [16] RP REVIEW ON VARIANTS. RX PubMed=12213390; DOI=10.1016/s0009-2797(02)00071-6; RA Harper P.A., Wong J.M.Y., Lam M.S.M., Okey A.B.; RT "Polymorphisms in the human AH receptor."; RL Chem. Biol. Interact. 141:161-187(2002). RN [17] RP REVIEW ON LIGANDS. RX PubMed=18076143; DOI=10.1021/tx7001965; RA Nguyen L.P., Bradfield C.A.; RT "The search for endogenous activators of the aryl hydrocarbon receptor."; RL Chem. Res. Toxicol. 21:102-116(2008). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [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 [19] RP FUNCTION, AND INTERACTION WITH TIPARP. RX PubMed=23275542; DOI=10.1093/nar/gks1337; RA MacPherson L., Tamblyn L., Rajendra S., Bralha F., McPherson J.P., RA Matthews J.; RT "2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymerase (TiPARP, RT ARTD14) is a mono-ADP-ribosyltransferase and repressor of aryl hydrocarbon RT receptor transactivation."; RL Nucleic Acids Res. 41:1604-1621(2013). RN [20] RP FUNCTION, AND ADP-RIBOSYLATION. RX PubMed=30373764; DOI=10.1042/bcj20180347; RA Gomez A., Bindesboell C., Somisetty V.S., Grimaldi G., Hutin D., RA MacPherson L., Ahmed S., Tamblyn L., Cho T., Nebb H.I., Moen A., RA Anonsen J.H., Grant D.M., Matthews J.; RT "Characterization of TCDD-Inducible Poly-ADP-Ribose Polymerase RT (TIPARP/ARTD14) Catalytic Activity."; RL Biochem. J. 475:3827-3846(2018). RN [21] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN RP85. RX PubMed=29726989; DOI=10.1093/hmg/ddy165; RA Zhou Y., Li S., Huang L., Yang Y., Zhang L., Yang M., Liu W., Ramasamy K., RA Jiang Z., Sundaresan P., Zhu X., Yang Z.; RT "A splicing mutation in aryl hydrocarbon receptor associated with retinitis RT pigmentosa."; RL Hum. Mol. Genet. 27:2563-2572(2018). RN [22] RP FUNCTION. RX PubMed=32818467; DOI=10.1016/j.cell.2020.07.038; RA Sadik A., Somarribas Patterson L.F., Oeztuerk S., Mohapatra S.R., RA Panitz V., Secker P.F., Pfaender P., Loth S., Salem H., Prentzell M.T., RA Berdel B., Iskar M., Faessler E., Reuter F., Kirst I., Kalter V., RA Foerster K.I., Jaeger E., Guevara C.R., Sobeh M., Hielscher T., Poschet G., RA Reinhardt A., Hassel J.C., Zapatka M., Hahn U., von Deimling A., Hopf C., RA Schlichting R., Escher B.I., Burhenne J., Haefeli W.E., Ishaque N., RA Boehme A., Schaeuble S., Thedieck K., Trump S., Seiffert M., Opitz C.A.; RT "IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes RT tumor progression."; RL Cell 182:1252-1270(2020). RN [23] RP FUNCTION. RX PubMed=32866000; DOI=10.1021/acs.jafc.0c03735; RA Zhang X., Gan M., Li J., Li H., Su M., Tan D., Wang S., Jia M., Zhang L., RA Chen G.; RT "An endogenous indole pyruvate pathway for tryptophan metabolism mediated RT by IL4I1."; RL J. Agric. Food Chem. 68:10678-10684(2020). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ARNT, AND MUTAGENESIS OF RP SER-36; HIS-39; ARG-40; LEU-50; ALA-79; PHE-82 AND 118-LEU--LEU-122. 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 [25] {ECO:0007744|PDB:5NJ8} RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 23-273 IN COMPLEXES WITH ARNT AND RP DNA, REGION, MUTAGENESIS OF ARG-40; LEU-50; VAL-74; ALA-79; PHE-82; RP LEU-118; LEU-122; PHE-136 AND ILE-154, FUNCTION, AND INTERACTION WITH ARNT. RX PubMed=28602820; DOI=10.1016/j.str.2017.05.008; RA Schulte K.W., Green E., Wilz A., Platten M., Daumke O.; RT "Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene Activation."; RL Structure 25:1025-1033(2017). RN [26] RP VARIANT LYS-554. RX PubMed=7550366; DOI=10.1097/00008571-199506000-00003; RA Kawajiri K., Watanabe J., Eguchi H., Nakachi K., Kiyohara C., Hayashi S.; RT "Polymorphisms of human Ah receptor gene are not involved in lung cancer."; RL Pharmacogenetics 5:151-158(1995). RN [27] RP VARIANTS LYS-554 AND ILE-570. RX PubMed=10739168; DOI=10.1097/00008571-200002000-00003; RA Smart J., Daly A.K.; RT "Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor RT and GSTM1 polymorphisms."; RL Pharmacogenetics 10:11-24(2000). RN [28] RP VARIANTS LYS-554 AND VAL-786. RX PubMed=11698344; DOI=10.1093/carcin/22.11.1819; RA Cauchi S., Stucker I., Solas C., Laurent-Puig P., Cenee S., Hemon D., RA Jacquet M., Kremers P., Beaune P., Massaad-Massade L.; RT "Polymorphisms of human aryl hydrocarbon receptor (AhR) gene in a French RT population: relationship with CYP1A1 inducibility and lung cancer."; RL Carcinogenesis 22:1819-1824(2001). RN [29] RP VARIANTS SER-517 AND ILE-570. RX PubMed=11689007; DOI=10.1006/bbrc.2001.5861; RA Wong J.M.Y., Okey A.B., Harper P.A.; RT "Human aryl hydrocarbon receptor polymorphisms that result in loss of RT CYP1A1 induction."; RL Biochem. Biophys. Res. Commun. 288:990-996(2001). RN [30] RP VARIANT FVH3 621-GLN--LEU-848 DEL, AND INVOLVEMENT IN FVH3. RX PubMed=31009037; DOI=10.1093/brain/awz098; RA Mayer A.K., Mahajnah M., Thomas M.G., Cohen Y., Habib A., Schulze M., RA Maconachie G.D.E., AlMoallem B., De Baere E., Lorenz B., Traboulsi E.I., RA Kohl S., Azem A., Bauer P., Gottlob I., Sharkia R., Wissinger B.; RT "Homozygous stop mutation in AHR causes autosomal recessive foveal RT hypoplasia and infantile nystagmus."; RL Brain 142:1528-1534(2019). RN [31] RP CHARACTERIZATION OF VARIANT FVH3 621-GLN--LEU-848 DEL, AND FUNCTION. RX PubMed=33193710; DOI=10.3389/fgene.2020.582796; RA Borovok N., Weiss C., Sharkia R., Reichenstein M., Wissinger B., Azem A., RA Mahajnah M.; RT "Gene and protein expression in subjects with a nystagmus-associated AHR RT mutation."; RL Front. Genet. 11:582796-582796(2020). RN [32] RP INVOLVEMENT IN FVH3. RX PubMed=35188035; DOI=10.1080/13816810.2022.2039718; RA AlMoallem B., Alharthi E.; RT "Novel biallelic AHR splice site mutation cause isolated foveal hypoplasia RT in Saudi patient: a case report."; RL Ophthalmic Genet. 43:425-429(2022). CC -!- FUNCTION: Ligand-activated transcription factor that enables cells to CC adapt to changing conditions by sensing compounds from the environment, CC diet, microbiome and cellular metabolism, and which plays important CC roles in development, immunity and cancer (PubMed:23275542, CC PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, CC translocates into the nucleus, where it heterodimerizes with ARNT and CC induces transcription by binding to xenobiotic response elements (XRE) CC (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety CC of biological processes, including angiogenesis, hematopoiesis, drug CC and lipid metabolism, cell motility and immune modulation CC (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic- CC binding, activates the expression of multiple phase I and II xenobiotic CC chemical metabolizing enzyme genes (such as the CYP1A1 gene) CC (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic CC effects of halogenated aromatic hydrocarbons (PubMed:34521881, CC PubMed:7961644). Next to xenobiotics, natural ligands derived from CC plants, microbiota, and endogenous metabolism are potent AHR agonists CC (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important CC class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). CC Acts as a negative regulator of anti-tumor immunity: indoles and CC kynurenic acid generated by Trp catabolism act as ligand and activate CC AHR, thereby promoting AHR-driven cancer cell motility and suppressing CC adaptive immunity (PubMed:32818467). Regulates the circadian clock by CC inhibiting the basal and circadian expression of the core circadian CC component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CC CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 CC (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence CC 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene CC promoters and activates their transcription (PubMed:28602820). CC {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, CC ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, CC ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, CC ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, CC ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; efficient DNA binding CC requires dimerization with another bHLH protein (PubMed:10395741, CC PubMed:28602820). Interacts with ARNT; the heterodimer ARNT:AHR binds CC to core DNA sequence 5'-TGCGTG-3' within the dioxin response element CC (DRE) of target gene promoters and activates their transcription CC (PubMed:28602820, PubMed:34521881). Binds MYBBP1A (By similarity). CC Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with CC the corepressor SMRT (PubMed:10395741). Interacts with NEDD8 and CC IVNS1ABP (PubMed:12215427, PubMed:16582008). Interacts with BMAL1 (By CC similarity). Interacts with HSP90AB1 (By similarity). Interacts with CC TIPARP; leading to mono-ADP-ribosylation of AHR and subsequent CC inhibition of AHR (PubMed:23275542, PubMed:30373764). CC {ECO:0000250|UniProtKB:P30561, ECO:0000269|PubMed:10395741, CC ECO:0000269|PubMed:12215427, ECO:0000269|PubMed:16582008, CC ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, CC ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:34521881}. CC -!- INTERACTION: CC P35869; P27540: ARNT; NbExp=7; IntAct=EBI-80780, EBI-80809; CC P35869; Q8NI08: NCOA7; NbExp=2; IntAct=EBI-80780, EBI-80799; CC P35869; Q9Y618: NCOR2; NbExp=2; IntAct=EBI-80780, EBI-80830; CC P35869; P12977: EBNA3; Xeno; NbExp=5; IntAct=EBI-80780, EBI-993115; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:34521881}. Nucleus CC {ECO:0000269|PubMed:34521881}. Note=Initially cytoplasmic; upon binding CC with ligand and interaction with a HSP90, it translocates to the CC nucleus. {ECO:0000269|PubMed:34521881}. CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested including blood, CC brain, heart, kidney, liver, lung, pancreas and skeletal muscle. CC Expressed in retinal photoreceptors (PubMed:29726989). CC {ECO:0000269|PubMed:29726989, ECO:0000269|PubMed:7515333, CC ECO:0000269|PubMed:8246913}. CC -!- INDUCTION: Induced or repressed by TGFB1 and dioxin in a cell-type CC specific fashion. Repressed by cAMP, retinoic acid, and 12-O- CC tetradecanoyl phorbol-13 acetate (TPA). {ECO:0000269|PubMed:11259615}. CC -!- DOMAIN: The PAS 1 domain is essential for dimerization and also CC required for AHR:ARNT heterodimerization. CC {ECO:0000250|UniProtKB:P30561}. CC -!- PTM: Mono-ADP-ribosylated, leading to inhibit transcription activator CC activity of AHR. {ECO:0000269|PubMed:30373764}. CC -!- DISEASE: Retinitis pigmentosa 85 (RP85) [MIM:618345]: A form of CC retinitis pigmentosa, a retinal dystrophy belonging to the group of CC pigmentary retinopathies. Retinitis pigmentosa is characterized by CC retinal pigment deposits visible on fundus examination and primary loss CC of rod photoreceptor cells followed by secondary loss of cone CC photoreceptors. Patients typically have night vision blindness and loss CC of midperipheral visual field. As their condition progresses, they lose CC their far peripheral visual field and eventually central vision as CC well. RP85 is an autosomal recessive form manifesting as early-onset CC progressive difficulty to adapt in dim light and gradually decreasing CC visual acuity in both eyes. {ECO:0000269|PubMed:29726989}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Foveal hypoplasia 3 (FVH3) [MIM:620958]: An autosomal CC recessive form of foveal hypoplasia, a developmental defect of the eye CC defined as the lack of foveal depression with continuity of all CC neurosensory retinal layers in the presumed foveal area. Clinical CC features include absence of foveal pit on optical coherence tomography, CC absence of foveal hyperpigmentation, absence of foveal avascularity, CC absence of foveal and macular reflexes, decreased visual acuity, and CC nystagmus. {ECO:0000269|PubMed:31009037, ECO:0000269|PubMed:33193710, CC ECO:0000269|PubMed:35188035}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; D16354; BAA03857.1; -; mRNA. DR EMBL; L19872; AAA16210.1; -; mRNA. DR EMBL; AC003075; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236948; EAL24281.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93686.1; -; Genomic_DNA. DR EMBL; BC069390; AAH69390.1; -; mRNA. DR EMBL; BC070080; AAH70080.1; -; mRNA. DR EMBL; U28063; AAA92082.1; -; Genomic_DNA. DR EMBL; U27656; AAA92082.1; JOINED; Genomic_DNA. DR EMBL; U27657; AAA92082.1; JOINED; Genomic_DNA. DR EMBL; U28060; AAA92082.1; JOINED; Genomic_DNA. DR EMBL; U28061; AAA92082.1; JOINED; Genomic_DNA. DR EMBL; U28062; AAA92082.1; JOINED; Genomic_DNA. DR EMBL; U28064; AAA92083.1; -; Genomic_DNA. DR EMBL; U28066; AAA92084.1; -; Genomic_DNA. DR EMBL; U28065; AAA92084.1; JOINED; Genomic_DNA. DR EMBL; D38044; BAA07235.1; -; Genomic_DNA. DR CCDS; CCDS5366.1; -. DR PIR; S59514; S59514. DR RefSeq; NP_001612.1; NM_001621.5. DR PDB; 5NJ8; X-ray; 3.30 A; A/C=23-273. DR PDB; 7ZUB; EM; 2.85 A; D=1-437. DR PDB; 8QMO; EM; 2.76 A; D=2-437. DR PDBsum; 5NJ8; -. DR PDBsum; 7ZUB; -. DR PDBsum; 8QMO; -. DR AlphaFoldDB; P35869; -. DR EMDB; EMD-14971; -. DR EMDB; EMD-18498; -. DR SMR; P35869; -. DR BioGRID; 106699; 191. DR CORUM; P35869; -. DR DIP; DIP-946N; -. DR ELM; P35869; -. DR FunCoup; P35869; 530. DR IntAct; P35869; 71. DR STRING; 9606.ENSP00000242057; -. DR BindingDB; P35869; -. DR ChEMBL; CHEMBL3201; -. DR DrugBank; DB08624; 1-[(4S)-4-amino-5-(1,3-benzothiazol-2-yl)-5-oxopentyl]guanidine. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB06732; beta-Naphthoflavone. DR DrugBank; DB12328; Cantharidin. DR DrugBank; DB13009; Carbendazim. DR DrugBank; DB08995; Diosmin. DR DrugBank; DB07715; Emodin. DR DrugBank; DB12116; Epigallocatechin gallate. DR DrugBank; DB00499; Flutamide. DR DrugBank; DB01404; Ginseng. DR DrugBank; DB16862; Indigo. DR DrugBank; DB12379; Indirubin. DR DrugBank; DB02052; Indirubin-3'-monoxime. DR DrugBank; DB11937; Kynurenic Acid. DR DrugBank; DB01097; Leflunomide. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB00393; Nimodipine. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB06436; Semaxanib. DR DrugBank; DB06083; Tapinarof. DR DrugCentral; P35869; -. DR GuidetoPHARMACOLOGY; 2951; -. DR GlyGen; P35869; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P35869; -. DR PhosphoSitePlus; P35869; -. DR BioMuta; AHR; -. DR DMDM; 3041653; -. DR jPOST; P35869; -. DR MassIVE; P35869; -. DR PaxDb; 9606-ENSP00000242057; -. DR PeptideAtlas; P35869; -. DR ProteomicsDB; 55159; -. DR Pumba; P35869; -. DR Antibodypedia; 3909; 1020 antibodies from 45 providers. DR DNASU; 196; -. DR Ensembl; ENST00000242057.9; ENSP00000242057.4; ENSG00000106546.15. DR Ensembl; ENST00000463496.1; ENSP00000436466.1; ENSG00000106546.15. DR GeneID; 196; -. DR KEGG; hsa:196; -. DR MANE-Select; ENST00000242057.9; ENSP00000242057.4; NM_001621.5; NP_001612.1. DR UCSC; uc011jxz.2; human. DR AGR; HGNC:348; -. DR ClinPGx; PA24641; -. DR CTD; 196; -. DR DisGeNET; 196; -. DR GeneCards; AHR; -. DR HGNC; HGNC:348; AHR. DR HPA; ENSG00000106546; Low tissue specificity. DR MalaCards; AHR; -. DR MIM; 600253; gene. DR MIM; 618345; phenotype. DR MIM; 620958; phenotype. DR OpenTargets; ENSG00000106546; -. DR Orphanet; 791; Retinitis pigmentosa. DR VEuPathDB; HostDB:ENSG00000106546; -. DR eggNOG; KOG3560; Eukaryota. DR GeneTree; ENSGT00940000154486; -. DR HOGENOM; CLU_010044_1_1_1; -. DR InParanoid; P35869; -. DR OMA; GCDAKGQ; -. DR OrthoDB; 6099906at2759; -. DR PAN-GO; P35869; 5 GO annotations based on evolutionary models. DR PhylomeDB; P35869; -. DR PathwayCommons; P35869; -. 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 SignaLink; P35869; -. DR SIGNOR; P35869; -. DR Agora; ENSG00000106546; -. DR BioGRID-ORCS; 196; 95 hits in 1202 CRISPR screens. DR ChiTaRS; AHR; human. DR GeneWiki; Aryl_hydrocarbon_receptor; -. DR GenomeRNAi; 196; -. DR Pharos; P35869; Tclin. DR PRO; PR:P35869; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P35869; protein. DR Bgee; ENSG00000106546; Expressed in visceral pleura and 196 other cell types or tissues. DR ExpressionAtlas; P35869; 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; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0034752; C:cytosolic aryl hydrocarbon receptor complex; TAS:DFLAT. DR GO; GO:0034753; C:nuclear aryl hydrocarbon receptor complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005667; C:transcription regulator complex; TAS:DFLAT. DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:DFLAT. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0017025; F:TBP-class protein binding; IPI:CAFA. DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; IPI:CAFA. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:DFLAT. DR GO; GO:0001223; F:transcription coactivator binding; IPI:CAFA. DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB. DR GO; GO:0001568; P:blood vessel development; NAS:DFLAT. DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; IDA:UniProtKB. DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB. DR GO; GO:1904322; P:cellular response to forskolin; IDA:UniProtKB. DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; IDA:UniProt. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProt. DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0002819; P:regulation of adaptive immune response; IDA:UniProtKB. DR GO; GO:0030888; P:regulation of B cell proliferation; IDA:DFLAT. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IDA:DFLAT. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:DFLAT. DR GO; GO:0009636; P:response to toxic substance; IDA:UniProtKB. DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:DFLAT. DR CDD; cd11436; bHLH-PAS_AhR; 1. DR CDD; cd00130; PAS; 2. DR DisProt; DP00381; -. DR FunFam; 3.30.450.20:FF:000035; Aryl hydrocarbon receptor; 1. DR FunFam; 3.30.450.20:FF:000019; Aryl hydrocarbon receptor 1; 1. DR FunFam; 4.10.280.10:FF:000024; Aryl hydrocarbon receptor 2; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 2. DR InterPro; IPR039091; AHR/AHRR. DR InterPro; IPR033348; AHR_bHLH. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR001610; PAC. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013767; PAS_fold. DR InterPro; IPR013655; PAS_fold_3. DR PANTHER; PTHR10649; ARYL HYDROCARBON RECEPTOR; 1. DR PANTHER; PTHR10649:SF9; ARYL HYDROCARBON RECEPTOR; 1. DR Pfam; PF00010; HLH; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF08447; PAS_3; 1. 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; SSF55785; PYP-like sensor domain (PAS domain); 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; ADP-ribosylation; Biological rhythms; KW Cell cycle; Cytoplasm; Disease variant; DNA-binding; Nucleus; KW Proteomics identification; Receptor; Reference proteome; Repeat; Repressor; KW Retinitis pigmentosa; Transcription; Transcription regulation. FT PROPEP 1..10 FT /evidence="ECO:0000250|UniProtKB:P30561" FT /id="PRO_0000013450" FT CHAIN 11..848 FT /note="Aryl hydrocarbon receptor" FT /id="PRO_0000013451" FT DOMAIN 27..80 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT DOMAIN 111..181 FT /note="PAS 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 275..342 FT /note="PAS 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 348..386 FT /note="PAC" FT REGION 1..39 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 38..66 FT /note="DNA-binding" FT /evidence="ECO:0000269|PubMed:28602820, FT ECO:0000269|PubMed:34521881" FT REGION 50..82 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000269|PubMed:34521881" FT REGION 118..126 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000269|PubMed:34521881" FT REGION 266..268 FT /note="Required for maintaining the overall integrity of FT the AHR:ARNT heterodimer and its transcriptional activity" FT /evidence="ECO:0000250|UniProtKB:P30561" FT REGION 824..848 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 13..16 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000269|PubMed:34521881" FT MOTIF 37..42 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000269|PubMed:34521881" FT MOTIF 64..72 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:34521881" FT COMPBIAS 1..10 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT VARIANT 517 FT /note="P -> S (in dbSNP:rs72552768)" FT /evidence="ECO:0000269|PubMed:11689007" FT /id="VAR_015516" FT VARIANT 554 FT /note="R -> K (in dbSNP:rs2066853)" FT /evidence="ECO:0000269|PubMed:10739168, FT ECO:0000269|PubMed:11698344, ECO:0000269|PubMed:7550366" FT /id="VAR_009281" FT VARIANT 570 FT /note="V -> I (in dbSNP:rs4986826)" FT /evidence="ECO:0000269|PubMed:10739168, FT ECO:0000269|PubMed:11689007" FT /id="VAR_009282" FT VARIANT 621..848 FT /note="Missing (in FVH3; likely pathogenic; decreased FT protein abundance in homozygous patient cells; results in FT decreased ligand-activated transcription activator FT activity; CYP1A1 and CYP1B1 expression levels in homozygous FT patient cells treated with benzanthracene are reduced FT compared to controls)" FT /evidence="ECO:0000269|PubMed:31009037, FT ECO:0000269|PubMed:33193710" FT /id="VAR_090031" FT VARIANT 786 FT /note="M -> V (in dbSNP:rs72552769)" FT /evidence="ECO:0000269|PubMed:11698344" FT /id="VAR_015517" FT MUTAGEN 36 FT /note="S->G: Strongly reduces transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:34521881" FT MUTAGEN 39 FT /note="H->G: Almost abolishes transcription factor FT activity. No effect on nuclear translocation upon ligand FT binding." FT /evidence="ECO:0000269|PubMed:34521881" FT MUTAGEN 40 FT /note="R->D: Abolishes transcription factor activity. FT Alters on nuclear translocation upon ligand binding." FT /evidence="ECO:0000269|PubMed:28602820, FT ECO:0000269|PubMed:34521881" FT MUTAGEN 50 FT /note="L->D: Abolishes transcription factor activity; when FT associated with D-79 and D-82." FT /evidence="ECO:0000269|PubMed:28602820, FT ECO:0000269|PubMed:34521881" FT MUTAGEN 74 FT /note="V->D: Interferes with transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:28602820" FT MUTAGEN 79 FT /note="A->D: Abolishes transcription factor activity; when FT associated with D-50 and D-82." FT /evidence="ECO:0000269|PubMed:28602820, FT ECO:0000269|PubMed:34521881" FT MUTAGEN 82 FT /note="F->D: Abolishes transcription factor activity; when FT associated with D-50 and D-79." FT /evidence="ECO:0000269|PubMed:28602820, FT ECO:0000269|PubMed:34521881" FT MUTAGEN 118..122 FT /note="LLQAL->ELQDE: Strongly reduces transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:34521881" FT MUTAGEN 118 FT /note="L->D: Interferes with transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:28602820" FT MUTAGEN 122 FT /note="L->D: Interferes with transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:28602820" FT MUTAGEN 136 FT /note="F->D: Interferes with transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:28602820" FT MUTAGEN 154 FT /note="I->D: Interferes with transcription factor FT activity." FT /evidence="ECO:0000269|PubMed:28602820" FT MUTAGEN 381 FT /note="V->A: Increases specific ligand binding." FT /evidence="ECO:0000269|PubMed:7961644" FT MUTAGEN 381 FT /note="V->D: Abolishes specific ligand binding." FT /evidence="ECO:0000269|PubMed:7961644" FT MUTAGEN 381 FT /note="V->L,G: No effect on specific ligand binding." FT /evidence="ECO:0000269|PubMed:7961644" FT CONFLICT 191 FT /note="E -> EG (in Ref. 8; AAA92082)" FT /evidence="ECO:0000305" FT CONFLICT 340..341 FT /note="MI -> SD (in Ref. 9)" FT /evidence="ECO:0000305" FT CONFLICT 807..848 FT /note="LNETYPAELNNINNTQTTTHLQPLHHPSEARPFPDLTSSGFL -> FK (in FT Ref. 1; BAA03857)" FT /evidence="ECO:0000305" FT HELIX 35..52 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 58..61 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 66..86 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 113..121 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 126..130 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 142..146 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 150..152 FT /evidence="ECO:0007829|PDB:5NJ8" FT TURN 153..155 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 158..161 FT /evidence="ECO:0007829|PDB:5NJ8" FT HELIX 164..174 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 217..224 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 235..246 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 262..270 FT /evidence="ECO:0007829|PDB:5NJ8" FT STRAND 287..291 FT /evidence="ECO:0007829|PDB:8QMO" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 302..307 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 312..316 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 330..343 FT /evidence="ECO:0007829|PDB:8QMO" FT STRAND 344..354 FT /evidence="ECO:0007829|PDB:8QMO" FT STRAND 360..386 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 388..396 FT /evidence="ECO:0007829|PDB:8QMO" FT TURN 411..415 FT /evidence="ECO:0007829|PDB:8QMO" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:8QMO" SQ SEQUENCE 848 AA; 96147 MW; 1BFE022871B7B028 CRC64; MNSSSANITY ASRKRRKPVQ KTVKPIPAEG IKSNPSKRHR DRLNTELDRL ASLLPFPQDV INKLDKLSVL RLSVSYLRAK SFFDVALKSS PTERNGGQDN CRAANFREGL NLQEGEFLLQ ALNGFVLVVT TDALVFYASS TIQDYLGFQQ SDVIHQSVYE LIHTEDRAEF QRQLHWALNP SQCTESGQGI EEATGLPQTV VCYNPDQIPP ENSPLMERCF ICRLRCLLDN SSGFLAMNFQ GKLKYLHGQK KKGKDGSILP PQLALFAIAT PLQPPSILEI RTKNFIFRTK HKLDFTPIGC DAKGRIVLGY TEAELCTRGS GYQFIHAADM LYCAESHIRM IKTGESGMIV FRLLTKNNRW TWVQSNARLL YKNGRPDYII VTQRPLTDEE GTEHLRKRNT KLPFMFTTGE AVLYEATNPF PAIMDPLPLR TKNGTSGKDS ATTSTLSKDS LNPSSLLAAM MQQDESIYLY PASSTSSTAP FENNFFNESM NECRNWQDNT APMGNDTILK HEQIDQPQDV NSFAGGHPGL FQDSKNSDLY SIMKNLGIDF EDIRHMQNEK FFRNDFSGEV DFRDIDLTDE ILTYVQDSLS KSPFIPSDYQ QQQSLALNSS CMVQEHLHLE QQQQHHQKQV VVEPQQQLCQ KMKHMQVNGM FENWNSNQFV PFNCPQQDPQ QYNVFTDLHG ISQEFPYKSE MDSMPYTQNF ISCNQPVLPQ HSKCTELDYP MGSFEPSPYP TTSSLEDFVT CLQLPENQKH GLNPQSAIIT PQTCYAGAVS MYQCQPEPQH THVGQMQYNP VLPGQQAFLN KFQNGVLNET YPAELNNINN TQTTTHLQPL HHPSEARPFP DLTSSGFL //