THB_HUMAN
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 03-AUG-2022, entry version 249.
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 -!- 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;
CC 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. [P10828-1]
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. [P10828-1]
DR RefSeq; XP_016862597.1; XM_017007108.1.
DR RefSeq; XP_016862598.1; XM_017007109.1. [P10828-1]
DR RefSeq; XP_016862599.1; XM_017007110.1.
DR RefSeq; XP_016862600.1; XM_017007111.1. [P10828-1]
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 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 AlphaFoldDB; P10828; -.
DR SMR; P10828; -.
DR BioGRID; 112924; 63.
DR ComplexPortal; CPX-654; RXRalpha-TRbeta nuclear hormone receptor complex.
DR CORUM; P10828; -.
DR DIP; DIP-5991N; -.
DR IntAct; P10828; 21.
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; P10828; -.
DR PeptideAtlas; P10828; -.
DR PRIDE; P10828; -.
DR ProteomicsDB; 52661; -. [P10828-1]
DR ProteomicsDB; 52662; -. [P10828-2]
DR ABCD; P10828; 3 sequenced antibodies.
DR Antibodypedia; 4548; 505 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 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; YCMQELY; -.
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 1103 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 186 other tissues.
DR ExpressionAtlas; P10828; baseline and differential.
DR Genevisible; P10828; HS.
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:0008050; P:female courtship behavior; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
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:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0002154; P:thyroid hormone mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; TAS:ProtInc.
DR GO; GO:0060509; P:type I pneumocyte differentiation; IEA:Ensembl.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
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 HELIX 389..410
FT /evidence="ECO:0007829|PDB:6KKB"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:1R6G"
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
