P10828 (THB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thyroid hormone receptor beta

Alternative name(s):
Nuclear receptor subfamily 1 group A member 2
c-erbA-2
c-erbA-beta

Gene names

Name:	THRB
Synonyms:	ERBA2, NR1A2, THR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	461 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	High affinity receptor for triiodothyronine. Ref.14
Subunit structure	Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with NCOA7 in a ligand-inducible manner. Interacts with C1D By similarity. Interacts with NR2F6; the interaction impairs the binding of the THRB homodimer and THRB:RXRB heterodimer to T3 response elements. Interacts with PRMT2 and THRSP. Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location	Nucleus.
Domain	Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Involvement in disease	Generalized thyroid hormone resistance (GTHR) [MIM:188570]: A disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:274300]: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. Note: The disease is caused by mutations affecting the gene represented in this entry. Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.26
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence AAA35677.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAA28412.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	female courtship behavior Inferred from electronic annotation. Source: Compara negative regulation of female receptivity Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara organ morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of heart contraction Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Traceable author statement PubMed 1618799. Source: ProtInc chromatin DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro thyroid hormone receptor activity Traceable author statement PubMed 1618799. Source: ProtInc transcription corepressor activity Traceable author statement PubMed 1618799. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Beta-1 (identifier: P10828-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Beta-2 (identifier: P10828-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MTPNSMTENG...QTFQTEEKKC → MNYCMQEIYE...QVQSPSYSQK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 461

461

Thyroid hormone receptor beta

PRO_0000053446

Regions

DNA binding

107 – 181

75

Nuclear receptor

Zinc finger

107 – 127

21

NR C4-type

Zinc finger

145 – 169

25

NR C4-type

Region

1 – 106

106

Modulating

Region

244 – 461

218

Interaction with NR2F6

Region

244 – 461

218

Ligand-binding

Natural variations

Alternative sequence

1 – 93

93

MTPNS…EEKKC → MNYCMQEIYEVHPAAGSNCY MQSTDYYAYFEDSPGYSGCD AQAVPSNNIYMEQAWAVNQP YTCSYPGNMFKSKDSDLDMA LNQYSQPEYFTEEKPTFSQV QSPSYSQK in isoform Beta-2.

VSP_031077

Natural variant

216

1

D → G.
Corresponds to variant rs9865746 [ dbSNP | Ensembl ].

VAR_050577

Natural variant

234

1

A → T in GTHR. Ref.25

VAR_004632

Natural variant

243

1

R → W in GTHR. Ref.30

VAR_004633

Natural variant

268

1

A → G in GTHR. Ref.34

VAR_059041

Natural variant

316

1

R → H in PRTH. Ref.26

VAR_004634

Natural variant

317

1

A → T in GTHR. Ref.19 Ref.27 Ref.31

VAR_004635

Natural variant

320

1

R → C in GTHR. Ref.27

VAR_004636

Natural variant

320

1

R → H in GTHR. Ref.22 Ref.27

VAR_004637

Natural variant

331

1

N → D in GTHR. Ref.34

VAR_059042

Natural variant

332

1

G → R in GTHR. Ref.19
Corresponds to variant rs28999969 [ dbSNP | Ensembl ].

VAR_004638

Natural variant

335

1

A → P in GTHR. Ref.34

VAR_059043

Natural variant

337

1

T → I. Ref.1 Ref.2
Corresponds to variant rs1054624 [ dbSNP | Ensembl ].

VAR_011784

Natural variant

337

1

Missing in GTHR. Ref.20

VAR_004639

Natural variant

338

1

R → W in GTHR. Ref.27 Ref.31 Ref.33

VAR_004640

Natural variant

340

1

Q → H in GTHR. Ref.18

VAR_004641

Natural variant

341

1

L → P in GTHR. Ref.34

VAR_059044

Natural variant

342

1

K → I in GTHR. Ref.31

VAR_004642

Natural variant

345

1

G → R in GTHR. Ref.16

VAR_004645

Natural variant

345

1

G → S in GTHR. Ref.21

VAR_004644

Natural variant

345

1

G → V in GTHR. Ref.19
Corresponds to variant rs28999970 [ dbSNP | Ensembl ].

VAR_004643

Natural variant

346

1

L → F in GTHR. Ref.34

VAR_059045

Natural variant

347

1

G → E in GTHR. Ref.19
Corresponds to variant rs28999971 [ dbSNP | Ensembl ].

VAR_004646

Natural variant

348

1

V → E in GTHR. Ref.31

VAR_004647

Natural variant

426

1

T → I in GTHR. Ref.32

VAR_004648

Natural variant

429

1

R → Q in PRTH. Ref.10

VAR_058508

Natural variant

431

1

I → M in GTHR. Ref.34

VAR_059046

Natural variant

438

1

R → H in GTHR. Ref.27

VAR_004649

Natural variant

442

1

M → V in GTHR. Ref.19

VAR_004650

Natural variant

443

1

K → E in GTHR. Ref.24

VAR_004651

Natural variant

446

1

C → R in GTHR. Ref.28

VAR_004652

Natural variant

447

1

P → T in GTHR. Ref.34

VAR_059047

Natural variant

453

1

P → H in GTHR. Ref.17

VAR_004653

Natural variant

453

1

P → L in GTHR. Ref.34

VAR_059048

Natural variant

453

1

P → S in GTHR. Ref.29

VAR_004654

Natural variant

453

1

P → T in GTHR. Ref.19 Ref.23 Ref.27 Ref.34
Corresponds to variant rs28933408 [ dbSNP | Ensembl ].

VAR_004655

Natural variant

459

1

F → C in GTHR. Ref.34

VAR_059049

Experimental info

Sequence conflict

243

1

R → P in AAA35677. Ref.1

Sequence conflict

243

1

R → P in CAA28412. Ref.2

Sequence conflict

451

1

F → L in AAA35677. Ref.1

Sequence conflict

451

1

F → L in CAA28412. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

461

Helix Strand Turn

Details...

Turn

108 – 110

3

Beta strand

116 – 118

3

Helix

125 – 136

12

Helix

140 – 142

3

Turn

155 – 159

5

Helix

162 – 171

10

Helix

176 – 178

3

Helix

182 – 195

14

Helix

198 – 204

7

Helix

205 – 208

4

Helix

216 – 230

15

Turn

234 – 237

4

Helix

239 – 242

4

Turn

248 – 251

4

Beta strand

260 – 263

4

Helix

266 – 273

8

Helix

276 – 288

13

Helix

293 – 295

3

Helix

298 – 319

22

Turn

323 – 326

4

Beta strand

327 – 330

4

Turn

331 – 333

3

Beta strand

334 – 336

3

Helix

338 – 343

6

Turn

344 – 348

5

Helix

349 – 360

12

Helix

361 – 363

3

Helix

367 – 378

12

Helix

389 – 410

22

Beta strand

413 – 416

4

Helix

417 – 445

29

Helix

448 – 450

3

Helix

453 – 459

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Beta-1 [UniParc]. Last modified October 1, 1994. Version 2. Checksum: 6770BB0D372A7CAA	FASTA	461	52,788
	10 20 30 40 50 60 MTPNSMTENG LTAWDKPKHC PDREHDWKLV GMSEACLHRK SHSERRSTLK NEQSSPHLIQ 70 80 90 100 110 120 TTWTSSIFHL DHDDVNDQSV SSAQTFQTEE KKCKGYIPSY LDKDELCVVC GDKATGYHYR 130 140 150 160 170 180 CITCEGCKGF FRRTIQKNLH PSYSCKYEGK CVIDKVTRNQ CQECRFKKCI YVGMATDLVL 190 200 210 220 230 240 DDSKRLAKRK LIEENREKRR REELQKSIGH KPEPTDEEWE LIKTVTEAHV ATNAQGSHWK 250 260 270 280 290 300 QKRKFLPEDI GQAPIVNAPE GGKVDLEAFS HFTKIITPAI TRVVDFAKKL PMFCELPCED 310 320 330 340 350 360 QIILLKGCCM EIMSLRAAVR YDPESETLTL NGEMAVTRGQ LKNGGLGVVS DAIFDLGMSL 370 380 390 400 410 420 SSFNLDDTEV ALLQAVLLMS SDRPGLACVE RIEKYQDSFL LAFEHYINYR KHHVTHFWPK 430 440 450 460 LLMKVTDLRM IGACHASRFL HMKVECPTEL FPPLFLEVFE D
	Isoform Beta-2 [UniParc] [UniParc]. Checksum: 21755292507335D8	FASTA	476	54,449
	10 20 30 40 50 60 MNYCMQEIYE VHPAAGSNCY MQSTDYYAYF EDSPGYSGCD AQAVPSNNIY MEQAWAVNQP 70 80 90 100 110 120 YTCSYPGNMF KSKDSDLDMA LNQYSQPEYF TEEKPTFSQV QSPSYSQKKG YIPSYLDKDE 130 140 150 160 170 180 LCVVCGDKAT GYHYRCITCE GCKGFFRRTI QKNLHPSYSC KYEGKCVIDK VTRNQCQECR 190 200 210 220 230 240 FKKCIYVGMA TDLVLDDSKR LAKRKLIEEN REKRRREELQ KSIGHKPEPT DEEWELIKTV 250 260 270 280 290 300 TEAHVATNAQ GSHWKQKRKF LPEDIGQAPI VNAPEGGKVD LEAFSHFTKI ITPAITRVVD 310 320 330 340 350 360 FAKKLPMFCE LPCEDQIILL KGCCMEIMSL RAAVRYDPES ETLTLNGEMA VTRGQLKNGG 370 380 390 400 410 420 LGVVSDAIFD LGMSLSSFNL DDTEVALLQA VLLMSSDRPG LACVERIEKY QDSFLLAFEH 430 440 450 460 470 YINYRKHHVT HFWPKLLMKV TDLRMIGACH ASRFLHMKVE CPTELFPPLF LEVFED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human steroid receptors and erbA proto-oncogene products: members of a new superfamily of enhancer binding proteins." Weinberger C., Giguere V., Hollenberg S., Rosenfeld M.G., Evans R.M. Cold Spring Harb. Symp. Quant. Biol. 51:759-772(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1), VARIANT ILE-337.
[2]	"The c-erb-A gene encodes a thyroid hormone receptor." Weinberger C., Thompson C.C., Ong E.S., Lebo R., Gruol D.J., Evans R.M. Nature 324:641-646(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1), VARIANT ILE-337. Tissue: Placenta.
[3]	"Structural analysis of human thyroid hormone receptor beta gene." Sakurai A., Nakai A., Degroot L.J. Mol. Cell. Endocrinol. 71:83-91(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SEQUENCE REVISION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1). Tissue: Brain.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1).
[8]	"Multiple messenger ribonucleic acid variants regulate cell-specific expression of human thyroid hormone receptor beta1." Frankton S., Harvey C.B., Gleason L.M., Fadel A., Williams G.R. Mol. Endocrinol. 18:1631-1642(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-122 (ISOFORM BETA-1). Tissue: Brain, Kidney, Placenta and Testis.
[9]	"Differential expression and transcriptional regulatory properties of the thyroid hormone receptor Beta1 and Beta2." Damm K., Berning B. Submitted (AUG-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-122 (ISOFORM BETA-2). Tissue: Pituitary.
[10]	"A novel C-terminal domain in the thyroid hormone receptor selectively mediates thyroid hormone inhibition." Flynn T.R., Hollenberg A.N., Cohen O., Menke J.B., Usala S.J., Tollin S., Hegarty M.K., Wondisford F.E. J. Biol. Chem. 269:32713-32716(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 417-432, VARIANT PRTH GLN-429.
[11]	"The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function." Zhu X.G., Park K.S., Kaneshige M., Bhat M.K., Zhu Q., Mariash C.N., McPhie P., Cheng S.Y. Mol. Cell. Biol. 20:2604-2618(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, INTERACTION WITH NR2F6.
[12]	"Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha." Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J. J. Biol. Chem. 277:28624-28630(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRMT2.
[13]	"ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCOA7.
[14]	"Human spot 14 protein interacts physically and functionally with the thyroid receptor." Chou W.Y., Cheng Y.S., Ho C.L., Liu S.T., Liu P.Y., Kuo C.C., Chang H.P., Chen Y.H., Chang G.G., Huang S.M. Biochem. Biophys. Res. Commun. 357:133-138(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THRSP, FUNCTION.
[15]	"Structural determinants of nuclear receptor assembly on DNA direct repeats." Rastinejad F., Perlmann T., Evans R.M., Sigler P.B. Nature 375:203-211(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 102-212.
[16]	"Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta." Sakurai A., Takeda K., Ain K., Ceccarelli P., Nakai A., Seino S., Bell G.I., Refetoff S., Degroot L. Proc. Natl. Acad. Sci. U.S.A. 86:8977-8981(1989) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR ARG-345.
[17]	"A base mutation of the C-erbA beta thyroid hormone receptor in a kindred with generalized thyroid hormone resistance. Molecular heterogeneity in two other kindreds." Usala S.J., Tennyson G.E., Bale A.E., Lash R.W., Gesundheit N., Wondisford F.E., Accili D., Hauser P., Weintraub B.D. J. Clin. Invest. 85:93-100(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR HIS-453.
[18]	"A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance." Usala S.J., Menke J.B., Watson T.L., Berard J., Bradley W.E.C., Bale A.E., Lash R.W., Weintraub B.D. J. Clin. Endocrinol. Metab. 72:32-38(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR HIS-340.
[19]	"Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two 'hot spot' regions of the ligand binding domain." Parrilla R., Mixson A.J., McPherson J.A., McClaskey J.H., Weintraub B.D. J. Clin. Invest. 88:2123-2130(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GTHR THR-317; ARG-332; VAL-345; GLU-347; VAL-442 AND THR-453.
[20]	"A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor." Usala S.J., Menke J.B., Watson T.L., Wondisford F.E., Weintraub B.D., Berard J., Bradley W.E.C., Ono S., Mueller O.T., Bercu B.B. Mol. Endocrinol. 5:327-335(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR THR-337 DEL.
[21]	"Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome." Adams M., Nagaya T., Tone Y., Jameson J.L., Chatterjee V.K.K. Clin. Endocrinol. (Oxf.) 36:281-289(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR SER-345.
[22]	"An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid hormone receptor in a kindred with generalized resistance to thyroid hormones results in a receptor with significant 3,5,3'-triiodothyronine binding activity." Cugini C.D. Jr., Leidy J.W. Jr., Chertow B.S., Berard J., Bradley W.E.C., Menke J.B., Hao E.-H., Usala S.J. J. Clin. Endocrinol. Metab. 74:1164-1170(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR HIS-320.
[23]	"A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone." Shuto Y., Wakabayashi I., Amuro N., Minami S., Okazaki T. J. Clin. Endocrinol. Metab. 75:213-217(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR THR-453.
[24]	"A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone." Sasaki S., Nakamura H., Tagami T., Miyoshi Y., Tanaka K., Imura H. Mol. Cell. Endocrinol. 84:159-166(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR GLU-443.
[25]	"A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA beta thyroid hormone receptor gene in a family with generalized thyroid hormone resistance." Behr M., Loos U. Mol. Endocrinol. 6:1119-1126(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR THR-234.
[26]	"An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype." Geffner M.E., Su F., Ross N.S., Hershman J.M., van Dop C., Menke J.B., Hao E., Stanzak R.K., Eaton T., Samuels H.H., Usala S.J. J. Clin. Invest. 91:538-546(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PRTH HIS-316.
[27]	"Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families." Weiss R.E., Weinberg M., Refetoff S. J. Clin. Invest. 91:2408-2415(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GTHR THR-317; CYS-320; HIS-320; TRP-338; HIS-438 AND THR-453.
[28]	"A new point mutation (C446R) in the thyroid hormone receptor-beta gene of a family with resistance to thyroid hormone." Weiss R.E., Chyna B., Duell P.B., Hayashi Y., Sunthornthepvarakul T., Refetoff S. J. Clin. Endocrinol. Metab. 78:1253-1256(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR ARG-446.
[29]	"Resistance to thyroid hormone in subjects from two unrelated families is associated with a point mutation in the thyroid hormone receptor beta gene resulting in the replacement of the normal proline 453 with serine." Refetoff S., Weiss R.E., Wing J.R., Sarne D., Chyna B., Hayashi Y. Thyroid 4:249-254(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR SER-453.
[30]	"New point mutation (R243W) in the hormone binding domain of the c-erbA beta 1 gene in a family with generalized resistance to thyroid hormone." Pohlenz J., Schoenberger W., Wemme H., Winterpacht A., Wirth S., Zabel B. Hum. Mutat. 7:79-81(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR TRP-243.
[31]	"Rapid molecular diagnosis of mutations associated with generalized thyroid hormone resistance by PCR-coupled automated direct sequencing of genomic DNA: detection of two novel mutations." Seto D., Weintraub B.D. Hum. Mutat. 8:247-257(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GTHR THR-317; TRP-338; ILE-342 AND GLU-348.
[32]	"T426I a new mutation in the thyroid hormone receptor gene in a sporadic patient with resistance to thyroid hormone and dysmorphism." Menzaghi C., di Paola R., Corrias A., Einaudi S., Trischitta V., de Sanctis C., de Filippis V. Hum. Mutat. 12:289-289(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR ILE-426.
[33]	"Mosaicism of a thyroid hormone receptor-beta gene mutation in resistance to thyroid hormone." Mamanasiri S., Yesil S., Dumitrescu A.M., Liao X.-H., Demir T., Weiss R.E., Refetoff S. J. Clin. Endocrinol. Metab. 91:3471-3477(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GTHR TRP-338.
[34]	"Genotyping of resistance to thyroid hormone in South American population. Identification of seven novel missense mutations in the human thyroid hormone receptor beta gene." Rivolta C.M., Olcese M.C., Belforte F.S., Chiesa A., Gruneiro-Papendieck L., Iorcansky S., Herzovich V., Cassorla F., Gauna A., Gonzalez-Sarmiento R., Targovnik H.M. Mol. Cell. Probes 23:148-153(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GTHR GLY-268; ASP-331; PRO-335; PRO-341; PHE-346; MET-431; THR-447; LEU-453; THR-453 AND CYS-459.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M26747 mRNA. Translation: AAA35677.1. Different initiation.
X04707 mRNA. Translation: CAA28412.1. Different initiation.
AK096628 mRNA. Translation: BAG53341.1.
AC012087 Genomic DNA. No translation available.
AC093927 Genomic DNA. No translation available.
AC098971 Genomic DNA. No translation available.
AC099054 Genomic DNA. No translation available.
AC112217 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64345.1.
BC106929 mRNA. Translation: AAI06930.1.
BC106930 mRNA. Translation: AAI06931.1.
AY286465 mRNA. Translation: AAQ23704.1.
AY286466 mRNA. Translation: AAQ23705.1.
AY286467 mRNA. Translation: AAQ23706.1.
AY286468 mRNA. Translation: AAQ23707.1.
AY286469 mRNA. Translation: AAQ23708.1.
AY286470 mRNA. Translation: AAQ23709.1.
AY286471 mRNA. Translation: AAQ23710.1.
X74497 mRNA. Translation: CAA52606.1.

IPI

IPI00444844.
IPI00446999.

PIR

TVHUAR. A25237.
S40152.

RefSeq

NP_000452.2. NM_000461.4.
NP_001121648.1. NM_001128176.2.
NP_001121649.1. NM_001128177.1.
NP_001239563.1. NM_001252634.1.

UniGene

Hs.187861.
Hs.713754.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BSX	X-ray	3.70	A/B	202-461	[»]
1N46	X-ray	2.20	A/B	204-461	[»]
1NAX	X-ray	2.70	A	209-460	[»]
1NQ0	X-ray	2.40	A	202-461	[»]
1NQ1	X-ray	2.90	A	202-461	[»]
1NQ2	X-ray	2.40	A	202-461	[»]
1NUO	X-ray	3.10	A	202-461	[»]
1Q4X	X-ray	2.80	A	209-461	[»]
1R6G	X-ray	3.00	A	203-461	[»]
1XZX	X-ray	2.50	X	202-461	[»]
1Y0X	X-ray	3.10	X	202-461	[»]
2J4A	X-ray	2.20	A	209-461	[»]
2NLL	X-ray	1.90	B	104-204	[»]
2PIN	X-ray	2.30	A/B	209-461	[»]
3D57	X-ray	2.20	A/B	209-460	[»]
3GWS	X-ray	2.20	X	202-460	[»]
3IMY	X-ray	2.55	A	202-461	[»]
3JZC	X-ray	2.50	A	202-461	[»]

ProteinModelPortal

P10828.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5991N.

IntAct

P10828. 8 interactions.

MINT

MINT-1508903.

STRING

9606.ENSP00000348827.

PTM databases

PhosphoSite

P10828.

Polymorphism databases

DMDM

586092.

Proteomic databases

PaxDb

P10828.

PRIDE

P10828.

Protocols and materials databases

DNASU

7068.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000280696; ENSP00000280696; ENSG00000151090.
ENST00000356447; ENSP00000348827; ENSG00000151090.
ENST00000396671; ENSP00000379904; ENSG00000151090.
ENST00000415021; ENSP00000404898; ENSG00000151090.
ENST00000416420; ENSP00000414444; ENSG00000151090.
ENST00000447875; ENSP00000388467; ENSG00000151090.

GeneID

7068.

KEGG

hsa:7068.

UCSC

uc003ccx.4. human.

Organism-specific databases

CTD

7068.

GeneCards

GC03M024158.

HGNC

HGNC:11799. THRB.

HPA

CAB002008.
CAB002009.

MIM

145650. phenotype.
188570. phenotype.
190160. gene.
274300. phenotype.

neXtProt

NX_P10828.

Orphanet

3221. Generalized resistance to thyroid hormone.
97927. Peripheral resistance to thyroid hormones.
165994. Selective pituitary resistance to thyroid hormone.

PharmGKB

PA36508.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG272726.

HOGENOM

HOG000010313.

HOVERGEN

HBG005606.

KO

K08362.

OMA

HLIQATW.

OrthoDB

EOG4Z8XWB.

Enzyme and pathway databases

Pathway_Interaction_DB

rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Reactome

REACT_71. Gene Expression.

SignaLink

P10828.

Gene expression databases

ArrayExpress

P10828.

Bgee

P10828.

CleanEx

HS_THRB.

Genevestigator

P10828.

GermOnline

ENSG00000151090. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P10828.

ChEMBL

CHEMBL1947.

DrugBank

DB00451. Levothyroxine.
DB00279. Liothyronine.

EvolutionaryTrace

P10828.

GenomeRNAi

7068.

NextBio

27637.

SOURCE

Search...

Entry information

Entry name

THB_HUMAN

Accession

Primary (citable) accession number: P10828
Secondary accession number(s): B3KU79 , P37243, Q13986, Q3KP35, Q6WGL2, Q9UD41

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 1, 1994
Last modified:	May 29, 2013
This is version 170 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.