ID THB_HUMAN Reviewed; 461 AA. AC P10828; B3KU79; P37243; Q13986; Q3KP35; Q6WGL2; Q9UD41; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 2. DT 24-JAN-2024, entry version 257. DE RecName: Full=Thyroid hormone receptor beta; DE AltName: Full=Nuclear receptor subfamily 1 group A member 2; DE AltName: Full=c-erbA-2; DE AltName: Full=c-erbA-beta; GN Name=THRB; Synonyms=ERBA2, NR1A2, THR1; 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] (ISOFORM BETA-1), AND VARIANT ILE-337. RX PubMed=3034496; DOI=10.1101/sqb.1986.051.01.089; RA Weinberger C., Giguere V., Hollenberg S., Rosenfeld M.G., Evans R.M.; RT "Human steroid receptors and erbA proto-oncogene products: members of a new RT superfamily of enhancer binding proteins."; RL Cold Spring Harb. Symp. Quant. Biol. 51:759-772(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1), AND VARIANT ILE-337. RC TISSUE=Placenta; RX PubMed=2879243; DOI=10.1038/324641a0; RA Weinberger C., Thompson C.C., Ong E.S., Lebo R., Gruol D.J., Evans R.M.; RT "The c-erb-A gene encodes a thyroid hormone receptor."; RL Nature 324:641-646(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION. RX PubMed=1973914; DOI=10.1016/0303-7207(90)90245-4; RA Sakurai A., Nakai A., Degroot L.J.; RT "Structural analysis of human thyroid hormone receptor beta gene."; RL Mol. Cell. Endocrinol. 71:83-91(1990). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1). RC TISSUE=Brain; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1). 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 [MRNA] OF 1-122 (ISOFORM BETA-1). RC TISSUE=Brain, Kidney, Placenta, and Testis; RX PubMed=15105435; DOI=10.1210/me.2003-0346; RA Frankton S., Harvey C.B., Gleason L.M., Fadel A., Williams G.R.; RT "Multiple messenger ribonucleic acid variants regulate cell-specific RT expression of human thyroid hormone receptor beta1."; RL Mol. Endocrinol. 18:1631-1642(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-122 (ISOFORM BETA-2). RC TISSUE=Pituitary; RA Damm K., Berning B.; RT "Differential expression and transcriptional regulatory properties of the RT thyroid hormone receptor Beta1 and Beta2."; RL Submitted (AUG-1993) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 417-432, AND VARIANT PRTH GLN-429. RX PubMed=7528740; DOI=10.1016/s0021-9258(20)30048-x; RA Flynn T.R., Hollenberg A.N., Cohen O., Menke J.B., Usala S.J., Tollin S., RA Hegarty M.K., Wondisford F.E.; RT "A novel C-terminal domain in the thyroid hormone receptor selectively RT mediates thyroid hormone inhibition."; RL J. Biol. Chem. 269:32713-32716(1994). RN [11] RP SUBUNIT, AND INTERACTION WITH NR2F6. RX PubMed=10713182; DOI=10.1128/mcb.20.7.2604-2618.2000; RA Zhu X.G., Park K.S., Kaneshige M., Bhat M.K., Zhu Q., Mariash C.N., RA McPhie P., Cheng S.Y.; RT "The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid RT hormone nuclear receptor function."; RL Mol. Cell. Biol. 20:2604-2618(2000). RN [12] RP INTERACTION WITH PRMT2. RX PubMed=12039952; DOI=10.1074/jbc.m201053200; RA Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J.; RT "Identification of protein arginine methyltransferase 2 as a coactivator RT for estrogen receptor alpha."; RL J. Biol. Chem. 277:28624-28630(2002). RN [13] RP INTERACTION WITH NCOA7. RX PubMed=11971969; DOI=10.1128/mcb.22.10.3358-3372.2002; RA Shao W., Halachmi S., Brown M.; RT "ERAP140, a conserved tissue-specific nuclear receptor coactivator."; RL Mol. Cell. Biol. 22:3358-3372(2002). RN [14] RP INTERACTION WITH THRSP, AND FUNCTION. RX PubMed=17418816; DOI=10.1016/j.bbrc.2007.03.103; RA Chou W.Y., Cheng Y.S., Ho C.L., Liu S.T., Liu P.Y., Kuo C.C., Chang H.P., RA Chen Y.H., Chang G.G., Huang S.M.; RT "Human spot 14 protein interacts physically and functionally with the RT thyroid receptor."; RL Biochem. Biophys. Res. Commun. 357:133-138(2007). RN [15] RP INTERACTION WITH TACC1. RX PubMed=20078863; DOI=10.1186/1471-2199-11-3; RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.; RT "The transforming acidic coiled coil (TACC1) protein modulates the RT transcriptional activity of the nuclear receptors TR and RAR."; RL BMC Mol. Biol. 11:3-3(2010). RN [16] {ECO:0007744|PDB:2NLL} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 104-204 IN COMPLEX WITH ZINC RP IONS. RX PubMed=7746322; DOI=10.1038/375203a0; RA Rastinejad F., Perlmann T., Evans R.M., Sigler P.B.; RT "Structural determinants of nuclear receptor assembly on DNA direct RT repeats."; RL Nature 375:203-211(1995). RN [17] {ECO:0007744|PDB:1NAX} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 209-460 IN COMPLEX WITH SYNTHETIC RP AGONIST, AND FUNCTION. RX PubMed=12699376; DOI=10.1021/jm021080f; RA Ye L., Li Y.L., Mellstrom K., Mellin C., Bladh L.G., Koehler K., Garg N., RA Garcia Collazo A.M., Litten C., Husman B., Persson K., Ljunggren J., RA Grover G., Sleph P.G., George R., Malm J.; RT "Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid RT receptor beta1."; RL J. Med. Chem. 46:1580-1588(2003). RN [18] {ECO:0007744|PDB:1NQ0, ECO:0007744|PDB:1NQ1} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 202-461 OF VARIANT GRTHD THR-234, RP CHARACTERIZATION OF VARIANT GRTHD THR-234, AND MUTAGENESIS OF ARG-243. RX PubMed=12511610; DOI=10.1210/me.2002-0097; RA Huber B.R., Desclozeaux M., West B.L., Cunha-Lima S.T., Nguyen H.T., RA Baxter J.D., Ingraham H.A., Fletterick R.J.; RT "Thyroid hormone receptor-beta mutations conferring hormone resistance and RT reduced corepressor release exhibit decreased stability in the N-terminal RT ligand-binding domain."; RL Mol. Endocrinol. 17:107-116(2003). RN [19] {ECO:0007744|PDB:1NQ2, ECO:0007744|PDB:1NUO} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 202-461 OF VARIANT PTHR HIS-316 RP AND VARIANT GRTHD THR-317, CHARACTERIZATION OF VARIANT PTHR HIS-316, AND RP CHARACTERIZATION OF VARIANT GRTHD THR-317. RX PubMed=12554782; DOI=10.1210/me.2002-0095; RA Huber B.R., Sandler B., West B.L., Cunha Lima S.T., Nguyen H.T., RA Apriletti J.W., Baxter J.D., Fletterick R.J.; RT "Two resistance to thyroid hormone mutants with impaired hormone binding."; RL Mol. Endocrinol. 17:643-652(2003). RN [20] {ECO:0007744|PDB:1Q4X} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 209-461 IN COMPLEX WITH SYNTHETIC RP AGONIST, FUNCTION, INTERACTION WITH NCOA1; NCOA2; MED1 AND NCOR1, AND RP MUTAGENESIS OF ASN-331. RX PubMed=14673100; DOI=10.1073/pnas.2136689100; RA Borngraeber S., Budny M.J., Chiellini G., Cunha-Lima S.T., Togashi M., RA Webb P., Baxter J.D., Scanlan T.S., Fletterick R.J.; RT "Ligand selectivity by seeking hydrophobicity in thyroid hormone RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 100:15358-15363(2003). RN [21] {ECO:0007744|PDB:1XZX, ECO:0007744|PDB:1Y0X} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 202-461 IN COMPLEXES WITH RP 3,3',5-TRIIODO-L-THYRONINE AND L-THYROXINE, AND INTERACTION WITH NCOA2; RP MED1 AND NCOR1. RX PubMed=15466465; DOI=10.1074/jbc.m410124200; RA Sandler B., Webb P., Apriletti J.W., Huber B.R., Togashi M., RA Cunha Lima S.T., Juric S., Nilsson S., Wagner R., Fletterick R.J., RA Baxter J.D.; RT "Thyroxine-thyroid hormone receptor interactions."; RL J. Biol. Chem. 279:55801-55808(2004). RN [22] {ECO:0007744|PDB:3GWS} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 202-460 IN COMPLEX WITH RP 3,3',5-TRIIODO-L-THYRONINE, FUNCTION, DNA-BINDING, SUBUNIT, AND MUTAGENESIS RP OF 207-SER-ILE-208. RX PubMed=16781732; DOI=10.1016/j.jmb.2006.05.008; RA Nascimento A.S., Dias S.M., Nunes F.M., Aparicio R., Ambrosio A.L., RA Bleicher L., Figueira A.C., Santos M.A., de Oliveira Neto M., Fischer H., RA Togashi M., Craievich A.F., Garratt R.C., Baxter J.D., Webb P., RA Polikarpov I.; RT "Structural rearrangements in the thyroid hormone receptor hinge domain and RT their putative role in the receptor function."; RL J. Mol. Biol. 360:586-598(2006). RN [23] {ECO:0007744|PDB:3IMY} RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 202-461 IN COMPLEX WITH SYNTHETIC RP AGONIST, AND FUNCTION. RX PubMed=18237438; DOI=10.1186/1472-6807-8-8; RA Bleicher L., Aparicio R., Nunes F.M., Martinez L., Gomes Dias S.M., RA Figueira A.C., Santos M.A., Venturelli W.H., da Silva R., Donate P.M., RA Neves F.A., Simeoni L.A., Baxter J.D., Webb P., Skaf M.S., Polikarpov I.; RT "Structural basis of GC-1 selectivity for thyroid hormone receptor RT isoforms."; RL BMC Struct. Biol. 8:8-8(2008). RN [24] {ECO:0007744|PDB:3JZC} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 202-461, FUNCTION, AND RP MUTAGENESIS OF ASN-331. RX PubMed=19926848; DOI=10.1073/pnas.0911024106; RA Martinez L., Nascimento A.S., Nunes F.M., Phillips K., Aparicio R., RA Dias S.M., Figueira A.C., Lin J.H., Nguyen P., Apriletti J.W., Neves F.A., RA Baxter J.D., Webb P., Skaf M.S., Polikarpov I.; RT "Gaining ligand selectivity in thyroid hormone receptors via entropy."; RL Proc. Natl. Acad. Sci. U.S.A. 106:20717-20722(2009). RN [25] {ECO:0007744|PDB:3D57} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 209-460, FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF ASP-355. RX PubMed=18798561; DOI=10.1002/prot.22225; RA Jouravel N., Sablin E., Togashi M., Baxter J.D., Webb P., Fletterick R.J.; RT "Molecular basis for dimer formation of TRbeta variant D355R."; RL Proteins 75:111-117(2009). RN [26] RP VARIANT GRTHD ARG-345. RX PubMed=2510172; DOI=10.1073/pnas.86.22.8977; RA Sakurai A., Takeda K., Ain K., Ceccarelli P., Nakai A., Seino S., RA Bell G.I., Refetoff S., Degroot L.; RT "Generalized resistance to thyroid hormone associated with a mutation in RT the ligand-binding domain of the human thyroid hormone receptor beta."; RL Proc. Natl. Acad. Sci. U.S.A. 86:8977-8981(1989). RN [27] RP VARIANT GRTHD HIS-453. RX PubMed=2153155; DOI=10.1172/jci114438; RA Usala S.J., Tennyson G.E., Bale A.E., Lash R.W., Gesundheit N., RA Wondisford F.E., Accili D., Hauser P., Weintraub B.D.; RT "A base mutation of the C-erbA beta thyroid hormone receptor in a kindred RT with generalized thyroid hormone resistance. Molecular heterogeneity in two RT other kindreds."; RL J. Clin. Invest. 85:93-100(1990). RN [28] RP VARIANT GRTHD HIS-340. RX PubMed=1846005; DOI=10.1210/jcem-72-1-32; RA Usala S.J., Menke J.B., Watson T.L., Berard J., Bradley W.E.C., Bale A.E., RA Lash R.W., Weintraub B.D.; RT "A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the RT c-erbA beta thyroid hormone receptor is tightly linked to generalized RT thyroid hormone resistance."; RL J. Clin. Endocrinol. Metab. 72:32-38(1991). RN [29] RP VARIANTS GRTHD THR-317; ARG-332; VAL-345; GLU-347; VAL-442 AND THR-453. RX PubMed=1661299; DOI=10.1172/jci115542; RA Parrilla R., Mixson A.J., McPherson J.A., McClaskey J.H., Weintraub B.D.; RT "Characterization of seven novel mutations of the c-erbA beta gene in RT unrelated kindreds with generalized thyroid hormone resistance. Evidence RT for two 'hot spot' regions of the ligand binding domain."; RL J. Clin. Invest. 88:2123-2130(1991). RN [30] RP VARIANT GRTHR THR-337 DEL. RX PubMed=1653889; DOI=10.1210/mend-5-3-327; RA Usala S.J., Menke J.B., Watson T.L., Wondisford F.E., Weintraub B.D., RA Berard J., Bradley W.E.C., Ono S., Mueller O.T., Bercu B.B.; RT "A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in RT a patient with generalized thyroid hormone resistance: isolation and RT characterization of the mutant receptor."; RL Mol. Endocrinol. 5:327-335(1991). RN [31] RP VARIANT GRTHD SER-345. RX PubMed=1563081; DOI=10.1111/j.1365-2265.1992.tb01444.x; RA Adams M., Nagaya T., Tone Y., Jameson J.L., Chatterjee V.K.K.; RT "Functional properties of a novel mutant thyroid hormone receptor in a RT family with generalized thyroid hormone resistance syndrome."; RL Clin. Endocrinol. (Oxf.) 36:281-289(1992). RN [32] RP VARIANT GRTHD HIS-320. RX PubMed=1314846; DOI=10.1210/jcem.74.5.1314846; RA Cugini C.D. Jr., Leidy J.W. Jr., Chertow B.S., Berard J., Bradley W.E.C., RA Menke J.B., Hao E.-H., Usala S.J.; RT "An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid RT hormone receptor in a kindred with generalized resistance to thyroid RT hormones results in a receptor with significant 3,5,3'-triiodothyronine RT binding activity."; RL J. Clin. Endocrinol. Metab. 74:1164-1170(1992). RN [33] RP VARIANT GRTHD THR-453. RX PubMed=1619012; DOI=10.1210/jcem.75.1.1619012; RA Shuto Y., Wakabayashi I., Amuro N., Minami S., Okazaki T.; RT "A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid RT hormone receptor-beta associated with a family with generalized resistance RT to thyroid hormone."; RL J. Clin. Endocrinol. Metab. 75:213-217(1992). RN [34] RP VARIANT GRTHD GLU-443. RX PubMed=1587388; DOI=10.1016/0303-7207(92)90026-3; RA Sasaki S., Nakamura H., Tagami T., Miyoshi Y., Tanaka K., Imura H.; RT "A point mutation of the T3 receptor beta 1 gene in a kindred of RT generalized resistance to thyroid hormone."; RL Mol. Cell. Endocrinol. 84:159-166(1992). RN [35] RP VARIANT GRTHD THR-234. RX PubMed=1324420; DOI=10.1210/mend.6.7.1324420; RA Behr M., Loos U.; RT "A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA beta RT thyroid hormone receptor gene in a family with generalized thyroid hormone RT resistance."; RL Mol. Endocrinol. 6:1119-1126(1992). RN [36] RP VARIANT PRTH HIS-316. RX PubMed=8381821; DOI=10.1172/jci116233; RA Geffner M.E., Su F., Ross N.S., Hershman J.M., van Dop C., Menke J.B., RA Hao E., Stanzak R.K., Eaton T., Samuels H.H., Usala S.J.; RT "An arginine to histidine mutation in codon 311 of the C-erbA beta gene RT results in a mutant thyroid hormone receptor that does not mediate a RT dominant negative phenotype."; RL J. Clin. Invest. 91:538-546(1993). RN [37] RP VARIANTS GRTHD THR-317; CYS-320; HIS-320; TRP-338; HIS-438 AND THR-453. RX PubMed=8514853; DOI=10.1172/jci116474; RA Weiss R.E., Weinberg M., Refetoff S.; RT "Identical mutations in unrelated families with generalized resistance to RT thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone RT receptor beta gene. Analysis of 15 families."; RL J. Clin. Invest. 91:2408-2415(1993). RN [38] RP VARIANT GRTHD ARG-446. RX PubMed=8175986; DOI=10.1210/jcem.78.5.8175986; RA Weiss R.E., Chyna B., Duell P.B., Hayashi Y., Sunthornthepvarakul T., RA Refetoff S.; RT "A new point mutation (C446R) in the thyroid hormone receptor-beta gene of RT a family with resistance to thyroid hormone."; RL J. Clin. Endocrinol. Metab. 78:1253-1256(1994). RN [39] RP VARIANT GRTHD SER-453. RX PubMed=7833659; DOI=10.1089/thy.1994.4.249; RA Refetoff S., Weiss R.E., Wing J.R., Sarne D., Chyna B., Hayashi Y.; RT "Resistance to thyroid hormone in subjects from two unrelated families is RT associated with a point mutation in the thyroid hormone receptor beta gene RT resulting in the replacement of the normal proline 453 with serine."; RL Thyroid 4:249-254(1994). RN [40] RP VARIANT GRTHD TRP-243. RX PubMed=8664910; RX DOI=10.1002/(sici)1098-1004(1996)7:1<79::aid-humu15>3.0.co;2-p; RA Pohlenz J., Schoenberger W., Wemme H., Winterpacht A., Wirth S., Zabel B.; RT "New point mutation (R243W) in the hormone binding domain of the c-erbA RT beta 1 gene in a family with generalized resistance to thyroid hormone."; RL Hum. Mutat. 7:79-81(1996). RN [41] RP VARIANTS GRTHD THR-317; TRP-338; ILE-342 AND GLU-348. RX PubMed=8889584; RX DOI=10.1002/(sici)1098-1004(1996)8:3<247::aid-humu8>3.0.co;2-6; RA Seto D., Weintraub B.D.; RT "Rapid molecular diagnosis of mutations associated with generalized thyroid RT hormone resistance by PCR-coupled automated direct sequencing of genomic RT DNA: detection of two novel mutations."; RL Hum. Mutat. 8:247-257(1996). RN [42] RP VARIANT GRTHD ILE-426. RX PubMed=10660344; RA Menzaghi C., di Paola R., Corrias A., Einaudi S., Trischitta V., RA de Sanctis C., de Filippis V.; RT "T426I a new mutation in the thyroid hormone receptor gene in a sporadic RT patient with resistance to thyroid hormone and dysmorphism."; RL Hum. Mutat. 12:289-289(1998). RN [43] RP VARIANT GRTHD TRP-338. RX PubMed=16804041; DOI=10.1210/jc.2006-0727; RA Mamanasiri S., Yesil S., Dumitrescu A.M., Liao X.-H., Demir T., Weiss R.E., RA Refetoff S.; RT "Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance RT to thyroid hormone."; RL J. Clin. Endocrinol. Metab. 91:3471-3477(2006). RN [44] RP VARIANTS GRTHD GLY-268; ASP-331; PRO-335; PRO-341; PHE-346; MET-431; RP THR-447; LEU-453; THR-453 AND CYS-459. RX PubMed=19268523; DOI=10.1016/j.mcp.2009.02.002; RA Rivolta C.M., Olcese M.C., Belforte F.S., Chiesa A., RA Gruneiro-Papendieck L., Iorcansky S., Herzovich V., Cassorla F., Gauna A., RA Gonzalez-Sarmiento R., Targovnik H.M.; RT "Genotyping of resistance to thyroid hormone in South American population. RT Identification of seven novel missense mutations in the human thyroid RT hormone receptor beta gene."; RL Mol. Cell. Probes 23:148-153(2009). CC -!- FUNCTION: Nuclear hormone receptor that can act as a repressor or CC activator of transcription. High affinity receptor for thyroid CC hormones, including triiodothyronine and thyroxine. CC {ECO:0000269|PubMed:12699376, ECO:0000269|PubMed:14673100, CC ECO:0000269|PubMed:16781732, ECO:0000269|PubMed:17418816, CC ECO:0000269|PubMed:18237438, ECO:0000269|PubMed:18798561, CC ECO:0000269|PubMed:19926848}. CC -!- SUBUNIT: Binds DNA as a dimer; homodimer and heterodimer with RXRA. CC Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, NCOA7 and CC MED1/TRAP220 in a ligand-inducible manner. Interacts with the CC corepressor NCOR1 in absence of ligand. Interacts with C1D (By CC similarity). Interacts with NR2F6; the interaction impairs the binding CC of the THRB homodimer and THRB:RXRB heterodimer to T3 response CC elements. Interacts with PRMT2 and THRSP. Interacts with TACC1; this CC interaction is decreased in the presence of thyroid hormone T3 CC (PubMed:20078863). {ECO:0000250, ECO:0000269|PubMed:10713182, CC ECO:0000269|PubMed:11971969, ECO:0000269|PubMed:12039952, CC ECO:0000269|PubMed:12699376, ECO:0000269|PubMed:14673100, CC ECO:0000269|PubMed:15466465, ECO:0000269|PubMed:16781732, CC ECO:0000269|PubMed:17418816, ECO:0000269|PubMed:18237438, CC ECO:0000269|PubMed:18798561, ECO:0000269|PubMed:20078863, CC ECO:0000269|PubMed:7746322}. CC -!- INTERACTION: CC P10828; Q60974: Ncor1; Xeno; NbExp=2; IntAct=EBI-78558, EBI-349004; CC P10828-1; Q9Y618: NCOR2; NbExp=3; IntAct=EBI-3955784, EBI-80830; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta-1; CC IsoId=P10828-1; Sequence=Displayed; CC Name=Beta-2; CC IsoId=P10828-2, P37243-1; Sequence=VSP_031077; CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain. CC -!- DISEASE: Thyroid hormone resistance, generalized, autosomal dominant CC (GRTHD) [MIM:188570]: An autosomal dominant disease characterized by CC high levels of circulating thyroid hormones (T3-T4), goiter, abnormal CC mental functions, increased susceptibility to infections, abnormal CC growth and bone maturation, tachycardia and deafness. Affected CC individuals may also have attention deficit-hyperactivity disorders CC (ADHD) and language difficulties. Patients have normal or slightly CC elevated thyroid stimulating hormone (TSH). CC {ECO:0000269|PubMed:10660344, ECO:0000269|PubMed:12511610, CC ECO:0000269|PubMed:12554782, ECO:0000269|PubMed:1314846, CC ECO:0000269|PubMed:1324420, ECO:0000269|PubMed:1563081, CC ECO:0000269|PubMed:1587388, ECO:0000269|PubMed:1619012, CC ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:16804041, CC ECO:0000269|PubMed:1846005, ECO:0000269|PubMed:19268523, CC ECO:0000269|PubMed:2153155, ECO:0000269|PubMed:2510172, CC ECO:0000269|PubMed:7833659, ECO:0000269|PubMed:8175986, CC ECO:0000269|PubMed:8514853, ECO:0000269|PubMed:8664910, CC ECO:0000269|PubMed:8889584}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Thyroid hormone resistance, generalized, autosomal recessive CC (GRTHR) [MIM:274300]: An autosomal recessive disorder characterized by CC goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid CC hormone, abnormal growth and bone maturation, and deafness. Patients CC also have high levels of circulating thyroid hormones, with elevated CC thyroid stimulating hormone. {ECO:0000269|PubMed:1653889}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Selective pituitary thyroid hormone resistance (PRTH) CC [MIM:145650]: Variant form of thyroid hormone resistance and is CC characterized by clinical hyperthyroidism, with elevated free thyroid CC hormones, but inappropriately normal serum TSH. Unlike GRTH, where the CC syndrome usually segregates with a dominant allele, the mode of CC inheritance in PRTH has not been established. CC {ECO:0000269|PubMed:7528740, ECO:0000269|PubMed:8381821}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35677.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA28412.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; M26747; AAA35677.1; ALT_INIT; mRNA. DR EMBL; X04707; CAA28412.1; ALT_INIT; mRNA. DR EMBL; AK096628; BAG53341.1; -; mRNA. DR EMBL; AC012087; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093927; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC098971; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC099054; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC112217; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471055; EAW64345.1; -; Genomic_DNA. DR EMBL; BC106929; AAI06930.1; -; mRNA. DR EMBL; BC106930; AAI06931.1; -; mRNA. DR EMBL; AY286465; AAQ23704.1; -; mRNA. DR EMBL; AY286466; AAQ23705.1; -; mRNA. DR EMBL; AY286467; AAQ23706.1; -; mRNA. DR EMBL; AY286468; AAQ23707.1; -; mRNA. DR EMBL; AY286469; AAQ23708.1; -; mRNA. DR EMBL; AY286470; AAQ23709.1; -; mRNA. DR EMBL; AY286471; AAQ23710.1; -; mRNA. DR EMBL; X74497; CAA52606.1; -; mRNA. DR CCDS; CCDS2641.1; -. [P10828-1] DR PIR; A25237; TVHUAR. DR PIR; S40152; S40152. DR RefSeq; NP_000452.2; NM_000461.4. [P10828-1] DR RefSeq; NP_001121648.1; NM_001128176.2. [P10828-1] DR RefSeq; NP_001121649.1; NM_001128177.1. [P10828-1] DR RefSeq; NP_001239563.1; NM_001252634.1. [P10828-1] DR RefSeq; XP_005265478.1; XM_005265421.4. DR RefSeq; XP_005265480.1; XM_005265423.4. DR RefSeq; XP_005265481.1; XM_005265424.3. DR RefSeq; XP_006713380.1; XM_006713317.3. DR RefSeq; XP_006713381.1; XM_006713318.3. DR RefSeq; XP_011532348.1; XM_011534046.2. DR RefSeq; XP_011532349.1; XM_011534047.2. [P10828-1] DR RefSeq; XP_011532350.1; XM_011534048.2. DR RefSeq; XP_011532351.1; XM_011534049.2. DR RefSeq; XP_011532352.1; XM_011534050.2. [P10828-1] DR RefSeq; XP_011532353.1; XM_011534051.2. DR RefSeq; XP_011532354.1; XM_011534052.2. DR RefSeq; XP_016862597.1; XM_017007108.1. DR RefSeq; XP_016862598.1; XM_017007109.1. DR RefSeq; XP_016862599.1; XM_017007110.1. DR RefSeq; XP_016862600.1; XM_017007111.1. DR RefSeq; XP_016862601.1; XM_017007112.1. DR PDB; 1BSX; X-ray; 3.70 A; A/B=202-461. DR PDB; 1N46; X-ray; 2.20 A; A/B=204-461. DR PDB; 1NAX; X-ray; 2.70 A; A=209-460. DR PDB; 1NQ0; X-ray; 2.40 A; A=202-461. DR PDB; 1NQ1; X-ray; 2.90 A; A=202-461. DR PDB; 1NQ2; X-ray; 2.40 A; A=202-461. DR PDB; 1NUO; X-ray; 3.10 A; A=202-461. DR PDB; 1Q4X; X-ray; 2.80 A; A=209-461. DR PDB; 1R6G; X-ray; 3.00 A; A=203-461. DR PDB; 1XZX; X-ray; 2.50 A; X=202-461. DR PDB; 1Y0X; X-ray; 3.10 A; X=202-461. DR PDB; 2J4A; X-ray; 2.20 A; A=209-461. DR PDB; 2NLL; X-ray; 1.90 A; B=104-204. DR PDB; 2PIN; X-ray; 2.30 A; A/B=209-461. DR PDB; 3D57; X-ray; 2.20 A; A/B=209-460. DR PDB; 3GWS; X-ray; 2.20 A; X=202-460. DR PDB; 3IMY; X-ray; 2.55 A; A=202-461. DR PDB; 3JZC; X-ray; 2.50 A; A=202-461. DR PDB; 4ZO1; X-ray; 3.22 A; X=210-461. DR PDB; 6KKB; X-ray; 1.70 A; X=211-460. DR PDB; 6KKE; X-ray; 2.58 A; A=211-459. DR PDB; 6KNU; X-ray; 2.70 A; A=211-460. DR PDB; 6KNV; X-ray; 2.80 A; A=211-460. DR PDB; 6KNW; X-ray; 2.67 A; A=211-460. DR PDB; 7WLX; X-ray; 2.39 A; A=202-461. DR PDB; 7WMG; X-ray; 2.93 A; A=202-461. DR PDB; 7WMH; X-ray; 1.97 A; A=202-461. DR PDB; 7WMJ; X-ray; 2.81 A; A=202-461. DR PDB; 7WML; X-ray; 2.67 A; A=202-461. DR PDB; 7WMN; X-ray; 2.57 A; A=202-461. DR PDB; 7WMO; X-ray; 2.56 A; A=202-461. DR PDBsum; 1BSX; -. DR PDBsum; 1N46; -. DR PDBsum; 1NAX; -. DR PDBsum; 1NQ0; -. DR PDBsum; 1NQ1; -. DR PDBsum; 1NQ2; -. DR PDBsum; 1NUO; -. DR PDBsum; 1Q4X; -. DR PDBsum; 1R6G; -. DR PDBsum; 1XZX; -. DR PDBsum; 1Y0X; -. DR PDBsum; 2J4A; -. DR PDBsum; 2NLL; -. DR PDBsum; 2PIN; -. DR PDBsum; 3D57; -. DR PDBsum; 3GWS; -. DR PDBsum; 3IMY; -. DR PDBsum; 3JZC; -. DR PDBsum; 4ZO1; -. DR PDBsum; 6KKB; -. DR PDBsum; 6KKE; -. DR PDBsum; 6KNU; -. DR PDBsum; 6KNV; -. DR PDBsum; 6KNW; -. DR PDBsum; 7WLX; -. DR PDBsum; 7WMG; -. DR PDBsum; 7WMH; -. DR PDBsum; 7WMJ; -. DR PDBsum; 7WML; -. DR PDBsum; 7WMN; -. DR PDBsum; 7WMO; -. DR AlphaFoldDB; P10828; -. DR SMR; P10828; -. DR BioGRID; 112924; 64. DR ComplexPortal; CPX-654; RXRalpha-TRbeta nuclear hormone receptor complex. DR CORUM; P10828; -. DR DIP; DIP-5991N; -. DR IntAct; P10828; 22. DR MINT; P10828; -. DR STRING; 9606.ENSP00000379904; -. DR BindingDB; P10828; -. DR ChEMBL; CHEMBL1947; -. DR DrugBank; DB08085; 1-(4-HEXYLPHENYL)PROP-2-EN-1-ONE. DR DrugBank; DB03181; 2-[4-(4-Hydroxy-3-Isopropyl-Phenoxy)-3,5-Dimethyl-Phenyl]-2h-[1,2,4]Triazine-3,5-Dione. DR DrugBank; DB02106; [3,5-Dibromo-4-(4-Hydroxy-3-Phenethylcarbamoyl-Phenoxy)-Phenyl]-Acetic Acid. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB00509; Dextrothyroxine. DR DrugBank; DB05035; Eprotirome. DR DrugBank; DB03788; GC-24. DR DrugBank; DB03176; KB-141. DR DrugBank; DB00451; Levothyroxine. DR DrugBank; DB00279; Liothyronine. DR DrugBank; DB01583; Liotrix. DR DrugBank; DB05192; MB07811. DR DrugBank; DB07425; Sobetirome. DR DrugBank; DB09100; Thyroid, porcine. DR DrugBank; DB03604; Tiratricol. DR DrugCentral; P10828; -. DR GuidetoPHARMACOLOGY; 589; -. DR iPTMnet; P10828; -. DR PhosphoSitePlus; P10828; -. DR BioMuta; THRB; -. DR DMDM; 586092; -. DR MassIVE; P10828; -. DR MaxQB; P10828; -. DR PaxDb; 9606-ENSP00000379904; -. DR PeptideAtlas; P10828; -. DR ProteomicsDB; 52661; -. [P10828-1] DR ProteomicsDB; 52662; -. [P10828-2] DR ABCD; P10828; 3 sequenced antibodies. DR Antibodypedia; 4548; 586 antibodies from 42 providers. DR DNASU; 7068; -. DR Ensembl; ENST00000280696.9; ENSP00000280696.5; ENSG00000151090.20. [P10828-2] DR Ensembl; ENST00000356447.9; ENSP00000348827.4; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000396671.7; ENSP00000379904.2; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000416420.5; ENSP00000414444.1; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000642307.1; ENSP00000494618.1; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000643772.1; ENSP00000496029.1; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000644321.1; ENSP00000496616.1; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000645139.1; ENSP00000493709.1; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000646209.2; ENSP00000496686.2; ENSG00000151090.20. [P10828-1] DR Ensembl; ENST00000646432.1; ENSP00000496509.1; ENSG00000151090.20. [P10828-1] DR GeneID; 7068; -. DR KEGG; hsa:7068; -. DR MANE-Select; ENST00000646209.2; ENSP00000496686.2; NM_001354712.2; NP_001341641.1. DR UCSC; uc003ccx.5; human. [P10828-1] DR AGR; HGNC:11799; -. DR CTD; 7068; -. DR DisGeNET; 7068; -. DR GeneCards; THRB; -. DR HGNC; HGNC:11799; THRB. DR HPA; ENSG00000151090; Low tissue specificity. DR MalaCards; THRB; -. DR MIM; 145650; phenotype. DR MIM; 188570; phenotype. DR MIM; 190160; gene. DR MIM; 274300; phenotype. DR neXtProt; NX_P10828; -. DR OpenTargets; ENSG00000151090; -. DR Orphanet; 566243; Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta. DR PharmGKB; PA36508; -. DR VEuPathDB; HostDB:ENSG00000151090; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000156809; -. DR HOGENOM; CLU_007368_18_2_1; -. DR InParanoid; P10828; -. DR OMA; AASSNCY; -. DR OrthoDB; 5390715at2759; -. DR PhylomeDB; P10828; -. DR TreeFam; TF328382; -. DR PathwayCommons; P10828; -. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR SignaLink; P10828; -. DR SIGNOR; P10828; -. DR BioGRID-ORCS; 7068; 13 hits in 1191 CRISPR screens. DR ChiTaRS; THRB; human. DR EvolutionaryTrace; P10828; -. DR GeneWiki; Thyroid_hormone_receptor_beta; -. DR GenomeRNAi; 7068; -. DR Pharos; P10828; Tclin. DR PRO; PR:P10828; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P10828; Protein. DR Bgee; ENSG00000151090; Expressed in Brodmann (1909) area 23 and 188 other cell types or tissues. DR ExpressionAtlas; P10828; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:ComplexPortal. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0070324; F:thyroid hormone binding; IDA:UniProtKB. DR GO; GO:0001223; F:transcription coactivator binding; IPI:ARUK-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IDA:ARUK-UCL. DR GO; GO:0006351; P:DNA-templated transcription; TAS:ProtInc. DR GO; GO:0008050; P:female courtship behavior; IEA:Ensembl. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0007621; P:negative regulation of female receptivity; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0002157; P:positive regulation of thyroid hormone mediated signaling pathway; IDA:ComplexPortal. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl. DR GO; GO:0097474; P:retinal cone cell apoptotic process; IEA:Ensembl. DR GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl. DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:0002154; P:thyroid hormone mediated signaling pathway; IBA:GO_Central. DR GO; GO:0060509; P:type I pneumocyte differentiation; IEA:Ensembl. DR CDD; cd06961; NR_DBD_TR; 1. DR CDD; cd06935; NR_LBD_TR; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1. DR IDEAL; IID00539; -. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR001728; ThyrH_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1. DR PANTHER; PTHR24082:SF210; THYROID HORMONE RECEPTOR BETA; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR PRINTS; PR00546; THYROIDHORMR. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P10828; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Deafness; Disease variant; DNA-binding; KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..461 FT /note="Thyroid hormone receptor beta" FT /id="PRO_0000053446" FT DOMAIN 217..461 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 107..181 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 107..127 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 145..169 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..106 FT /note="Modulating" FT REGION 244..461 FT /note="Interaction with NR2F6" FT /evidence="ECO:0000269|PubMed:10713182" FT BINDING 107 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 110 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 124 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 145 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 151 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 164 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:7746322, FT ECO:0007744|PDB:2NLL" FT BINDING 282 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0000269|PubMed:16781732, ECO:0007744|PDB:1XZX, FT ECO:0007744|PDB:3GWS" FT BINDING 282 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0007744|PDB:1Y0X" FT BINDING 331 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0000269|PubMed:16781732, ECO:0007744|PDB:1XZX, FT ECO:0007744|PDB:3GWS" FT BINDING 331 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0007744|PDB:1Y0X" FT BINDING 435 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0000269|PubMed:16781732, ECO:0007744|PDB:1XZX, FT ECO:0007744|PDB:3GWS" FT BINDING 435 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000269|PubMed:15466465, FT ECO:0007744|PDB:1Y0X" FT VAR_SEQ 1..93 FT /note="MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNE FT QSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKC -> MNYCMQEIYEVHPA FT AGSNCYMQSTDYYAYFEDSPGYSGCDAQAVPSNNIYMEQAWAVNQPYTCSYPGNMFKSK FT DSDLDMALNQYSQPEYFTEEKPTFSQVQSPSYSQK (in isoform Beta-2)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_031077" FT VARIANT 216 FT /note="D -> G (in dbSNP:rs9865746)" FT /id="VAR_050577" FT VARIANT 234 FT /note="A -> T (in GRTHD; impairs hormone binding and FT ligand-dependent conformational changes; FT dbSNP:rs121918694)" FT /evidence="ECO:0000269|PubMed:12511610, FT ECO:0000269|PubMed:1324420" FT /id="VAR_004632" FT VARIANT 243 FT /note="R -> W (in GRTHD; dbSNP:rs121918707)" FT /evidence="ECO:0000269|PubMed:8664910" FT /id="VAR_004633" FT VARIANT 268 FT /note="A -> G (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059041" FT VARIANT 316 FT /note="R -> H (in PRTH; impairs hormone binding; FT dbSNP:rs121918695)" FT /evidence="ECO:0000269|PubMed:12554782, FT ECO:0000269|PubMed:8381821" FT /id="VAR_004634" FT VARIANT 317 FT /note="A -> T (in GRTHD; impairs hormone binding; FT dbSNP:rs121918690)" FT /evidence="ECO:0000269|PubMed:12554782, FT ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:8514853, FT ECO:0000269|PubMed:8889584" FT /id="VAR_004635" FT VARIANT 320 FT /note="R -> C (in GRTHD; dbSNP:rs121918696)" FT /evidence="ECO:0000269|PubMed:8514853" FT /id="VAR_004636" FT VARIANT 320 FT /note="R -> H (in GRTHD; dbSNP:rs121918693)" FT /evidence="ECO:0000269|PubMed:1314846, FT ECO:0000269|PubMed:8514853" FT /id="VAR_004637" FT VARIANT 331 FT /note="N -> D (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059042" FT VARIANT 332 FT /note="G -> R (in GRTHD; dbSNP:rs28999969)" FT /evidence="ECO:0000269|PubMed:1661299" FT /id="VAR_004638" FT VARIANT 335 FT /note="A -> P (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059043" FT VARIANT 337 FT /note="T -> I (in dbSNP:rs1054624)" FT /evidence="ECO:0000269|PubMed:2879243, FT ECO:0000269|PubMed:3034496" FT /id="VAR_011784" FT VARIANT 337 FT /note="Missing (in GRTHR)" FT /evidence="ECO:0000269|PubMed:1653889" FT /id="VAR_004639" FT VARIANT 338 FT /note="R -> W (in GRTHD; dbSNP:rs121918697)" FT /evidence="ECO:0000269|PubMed:16804041, FT ECO:0000269|PubMed:8514853, ECO:0000269|PubMed:8889584" FT /id="VAR_004640" FT VARIANT 340 FT /note="Q -> H (in GRTHD; dbSNP:rs121918688)" FT /evidence="ECO:0000269|PubMed:1846005" FT /id="VAR_004641" FT VARIANT 341 FT /note="L -> P (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059044" FT VARIANT 342 FT /note="K -> I (in GRTHD)" FT /evidence="ECO:0000269|PubMed:8889584" FT /id="VAR_004642" FT VARIANT 345 FT /note="G -> R (in GRTHD; dbSNP:rs121918686)" FT /evidence="ECO:0000269|PubMed:2510172" FT /id="VAR_004645" FT VARIANT 345 FT /note="G -> S (in GRTHD; dbSNP:rs121918686)" FT /evidence="ECO:0000269|PubMed:1563081" FT /id="VAR_004644" FT VARIANT 345 FT /note="G -> V (in GRTHD; dbSNP:rs28999970)" FT /evidence="ECO:0000269|PubMed:1661299" FT /id="VAR_004643" FT VARIANT 346 FT /note="L -> F (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059045" FT VARIANT 347 FT /note="G -> E (in GRTHD; dbSNP:rs28999971)" FT /evidence="ECO:0000269|PubMed:1661299" FT /id="VAR_004646" FT VARIANT 348 FT /note="V -> E (in GRTHD)" FT /evidence="ECO:0000269|PubMed:8889584" FT /id="VAR_004647" FT VARIANT 426 FT /note="T -> I (in GRTHD)" FT /evidence="ECO:0000269|PubMed:10660344" FT /id="VAR_004648" FT VARIANT 429 FT /note="R -> Q (in PRTH; dbSNP:rs1553609210)" FT /evidence="ECO:0000269|PubMed:7528740" FT /id="VAR_058508" FT VARIANT 431 FT /note="I -> M (in GRTHD; dbSNP:rs1553609195)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059046" FT VARIANT 438 FT /note="R -> H (in GRTHD; dbSNP:rs121918698)" FT /evidence="ECO:0000269|PubMed:8514853" FT /id="VAR_004649" FT VARIANT 442 FT /note="M -> V (in GRTHD; dbSNP:rs121918691)" FT /evidence="ECO:0000269|PubMed:1661299" FT /id="VAR_004650" FT VARIANT 443 FT /note="K -> E (in GRTHD; dbSNP:rs121918692)" FT /evidence="ECO:0000269|PubMed:1587388" FT /id="VAR_004651" FT VARIANT 446 FT /note="C -> R (in GRTHD; dbSNP:rs121918703)" FT /evidence="ECO:0000269|PubMed:8175986" FT /id="VAR_004652" FT VARIANT 447 FT /note="P -> T (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059047" FT VARIANT 453 FT /note="P -> H (in GRTHD; dbSNP:rs121918687)" FT /evidence="ECO:0000269|PubMed:2153155" FT /id="VAR_004653" FT VARIANT 453 FT /note="P -> L (in GRTHD)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059048" FT VARIANT 453 FT /note="P -> S (in GRTHD; dbSNP:rs28933408)" FT /evidence="ECO:0000269|PubMed:7833659" FT /id="VAR_004654" FT VARIANT 453 FT /note="P -> T (in GRTHD; dbSNP:rs28933408)" FT /evidence="ECO:0000269|PubMed:1619012, FT ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:19268523, FT ECO:0000269|PubMed:8514853" FT /id="VAR_004655" FT VARIANT 459 FT /note="F -> C (in GRTHD; dbSNP:rs121918702)" FT /evidence="ECO:0000269|PubMed:19268523" FT /id="VAR_059049" FT MUTAGEN 207..208 FT /note="SI->AA: Modestly inhibits homodimer formation on a FT minimal response element (in vitro)." FT /evidence="ECO:0000269|PubMed:16781732" FT MUTAGEN 207..208 FT /note="SI->KK: Inhibits homodimer formation on a minimal FT response element (in vitro)." FT /evidence="ECO:0000269|PubMed:16781732" FT MUTAGEN 243 FT /note="R->Q: Impairs hormone binding and ligand-dependent FT conformational changes." FT /evidence="ECO:0000269|PubMed:12511610" FT MUTAGEN 331 FT /note="N->S: No effect on thyroid hormone binding." FT /evidence="ECO:0000269|PubMed:14673100, FT ECO:0000269|PubMed:19926848" FT MUTAGEN 355 FT /note="D->R: Stabilizes homodimer." FT /evidence="ECO:0000269|PubMed:18798561" FT CONFLICT 243 FT /note="R -> P (in Ref. 1; AAA35677 and 2; CAA28412)" FT /evidence="ECO:0000305" FT CONFLICT 451 FT /note="F -> L (in Ref. 1; AAA35677 and 2; CAA28412)" FT /evidence="ECO:0000305" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:2NLL" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 125..136 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 140..142 FT /evidence="ECO:0007829|PDB:2NLL" FT TURN 155..159 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 162..171 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 182..195 FT /evidence="ECO:0007829|PDB:2NLL" FT HELIX 198..205 FT /evidence="ECO:0007829|PDB:2NLL" FT TURN 207..209 FT /evidence="ECO:0007829|PDB:1Y0X" FT HELIX 216..230 FT /evidence="ECO:0007829|PDB:6KKB" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:1NQ2" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 239..242 FT /evidence="ECO:0007829|PDB:6KKB" FT TURN 248..251 FT /evidence="ECO:0007829|PDB:1N46" FT STRAND 260..263 FT /evidence="ECO:0007829|PDB:1N46" FT HELIX 266..288 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 291..294 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 298..318 FT /evidence="ECO:0007829|PDB:6KKB" FT TURN 323..326 FT /evidence="ECO:0007829|PDB:6KKB" FT STRAND 327..330 FT /evidence="ECO:0007829|PDB:6KKB" FT TURN 331..333 FT /evidence="ECO:0007829|PDB:6KKB" FT STRAND 334..337 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 338..343 FT /evidence="ECO:0007829|PDB:6KKB" FT TURN 344..347 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 348..360 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 361..363 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 367..378 FT /evidence="ECO:0007829|PDB:6KKB" FT STRAND 381..383 FT /evidence="ECO:0007829|PDB:7WMG" FT HELIX 389..410 FT /evidence="ECO:0007829|PDB:6KKB" FT STRAND 413..416 FT /evidence="ECO:0007829|PDB:7WMH" FT HELIX 417..445 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 448..450 FT /evidence="ECO:0007829|PDB:6KKB" FT HELIX 453..459 FT /evidence="ECO:0007829|PDB:6KKB" SQ SEQUENCE 461 AA; 52788 MW; 6770BB0D372A7CAA CRC64; MTPNSMTENG LTAWDKPKHC PDREHDWKLV GMSEACLHRK SHSERRSTLK NEQSSPHLIQ TTWTSSIFHL DHDDVNDQSV SSAQTFQTEE KKCKGYIPSY LDKDELCVVC GDKATGYHYR CITCEGCKGF FRRTIQKNLH PSYSCKYEGK CVIDKVTRNQ CQECRFKKCI YVGMATDLVL DDSKRLAKRK LIEENREKRR REELQKSIGH KPEPTDEEWE LIKTVTEAHV ATNAQGSHWK QKRKFLPEDI GQAPIVNAPE GGKVDLEAFS HFTKIITPAI TRVVDFAKKL PMFCELPCED QIILLKGCCM EIMSLRAAVR YDPESETLTL NGEMAVTRGQ LKNGGLGVVS DAIFDLGMSL SSFNLDDTEV ALLQAVLLMS SDRPGLACVE RIEKYQDSFL LAFEHYINYR KHHVTHFWPK LLMKVTDLRM IGACHASRFL HMKVECPTEL FPPLFLEVFE D //