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P10828 (THB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 182. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length461 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Ref.14 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24

Subunit structure

Binds DNA as a dimer; homodimer and heterodimer with RXRA. Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, NCOA7 and MED1/TRAP220 in a ligand-inducible manner. Interacts with the corepressor NCOR1 in absence of ligand. 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 Ref.19 Ref.20 Ref.21 Ref.24

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.17 Ref.18 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43

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.35

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 processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDeafness
Disease mutation
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processType I pneumocyte differentiation

Inferred from electronic annotation. Source: Ensembl

female courtship behavior

Inferred from electronic annotation. Source: Ensembl

gene expression

Traceable author statement. Source: Reactome

intracellular receptor signaling pathway

Inferred from direct assay Ref.20. Source: GOC

negative regulation of female receptivity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Traceable author statement PubMed 1618799. Source: ProtInc

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement PubMed 1618799. Source: ProtInc

   Molecular_functionDNA binding

Traceable author statement PubMed 1618799. Source: ProtInc

chromatin DNA binding

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction Ref.12. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15100213PubMed 15625236PubMed 7870181. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Non-traceable author statement PubMed 1618799. Source: ProtInc

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

thyroid hormone binding

Inferred from direct assay Ref.20. Source: UniProtKB

thyroid hormone receptor activity

Inferred from direct assay Ref.20. Source: UniProtKB

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 461461Thyroid hormone receptor beta
PRO_0000053446

Regions

DNA binding107 – 18175Nuclear receptor Ref.21
Zinc finger107 – 12721NR C4-type
Zinc finger145 – 16925NR C4-type
Region1 – 106106Modulating
Region244 – 461218Interaction with NR2F6
Region244 – 461218Ligand-binding

Sites

Binding site2821Thyroid hormone
Binding site3201Thyroid hormone
Binding site3311Thyroid hormone; via amide nitrogen
Binding site4351Thyroid hormone

Natural variations

Alternative sequence1 – 9393MTPNS…EEKKC → MNYCMQEIYEVHPAAGSNCY MQSTDYYAYFEDSPGYSGCD AQAVPSNNIYMEQAWAVNQP YTCSYPGNMFKSKDSDLDMA LNQYSQPEYFTEEKPTFSQV QSPSYSQK in isoform Beta-2.
VSP_031077
Natural variant2161D → G.
Corresponds to variant rs9865746 [ dbSNP | Ensembl ].
VAR_050577
Natural variant2341A → T in GTHR; impairs hormone binding and ligand-dependent conformational changes. Ref.17 Ref.34
VAR_004632
Natural variant2431R → W in GTHR. Ref.39
VAR_004633
Natural variant2681A → G in GTHR. Ref.43
VAR_059041
Natural variant3161R → H in PRTH; impairs hormone binding. Ref.18 Ref.35
VAR_004634
Natural variant3171A → T in GTHR; impairs hormone binding. Ref.18 Ref.28 Ref.36 Ref.40
VAR_004635
Natural variant3201R → C in GTHR. Ref.36
VAR_004636
Natural variant3201R → H in GTHR. Ref.31 Ref.36
VAR_004637
Natural variant3311N → D in GTHR. Ref.43
VAR_059042
Natural variant3321G → R in GTHR. Ref.28
Corresponds to variant rs28999969 [ dbSNP | Ensembl ].
VAR_004638
Natural variant3351A → P in GTHR. Ref.43
VAR_059043
Natural variant3371T → I. Ref.1 Ref.2
Corresponds to variant rs1054624 [ dbSNP | Ensembl ].
VAR_011784
Natural variant3371Missing in GTHR. Ref.29
VAR_004639
Natural variant3381R → W in GTHR. Ref.36 Ref.40 Ref.42
VAR_004640
Natural variant3401Q → H in GTHR. Ref.27
VAR_004641
Natural variant3411L → P in GTHR. Ref.43
VAR_059044
Natural variant3421K → I in GTHR. Ref.40
VAR_004642
Natural variant3451G → R in GTHR. Ref.25
VAR_004645
Natural variant3451G → S in GTHR. Ref.30
VAR_004644
Natural variant3451G → V in GTHR. Ref.28
Corresponds to variant rs28999970 [ dbSNP | Ensembl ].
VAR_004643
Natural variant3461L → F in GTHR. Ref.43
VAR_059045
Natural variant3471G → E in GTHR. Ref.28
Corresponds to variant rs28999971 [ dbSNP | Ensembl ].
VAR_004646
Natural variant3481V → E in GTHR. Ref.40
VAR_004647
Natural variant4261T → I in GTHR. Ref.41
VAR_004648
Natural variant4291R → Q in PRTH. Ref.10
VAR_058508
Natural variant4311I → M in GTHR. Ref.43
VAR_059046
Natural variant4381R → H in GTHR. Ref.36
VAR_004649
Natural variant4421M → V in GTHR. Ref.28
VAR_004650
Natural variant4431K → E in GTHR. Ref.33
VAR_004651
Natural variant4461C → R in GTHR. Ref.37
VAR_004652
Natural variant4471P → T in GTHR. Ref.43
VAR_059047
Natural variant4531P → H in GTHR. Ref.26
VAR_004653
Natural variant4531P → L in GTHR. Ref.43
VAR_059048
Natural variant4531P → S in GTHR. Ref.38
VAR_004654
Natural variant4531P → T in GTHR. Ref.28 Ref.32 Ref.36 Ref.43
Corresponds to variant rs28933408 [ dbSNP | Ensembl ].
VAR_004655
Natural variant4591F → C in GTHR. Ref.43
VAR_059049

Experimental info

Mutagenesis207 – 2082SI → AA: Modestly inhibits homodimer formation on a minimal response element (in vitro). Ref.21
Mutagenesis207 – 2082SI → KK: Inhibits homodimer formation on a minimal response element (in vitro). Ref.21
Mutagenesis2431R → Q: Impairs hormone binding and ligand-dependent conformational changes. Ref.17 Ref.21
Mutagenesis3311N → S: No effect on thyroid hormone binding. Ref.19 Ref.21 Ref.23
Mutagenesis3551D → R: Stabilizes homodimer. Ref.21 Ref.24
Sequence conflict2431R → P in AAA35677. Ref.1
Sequence conflict2431R → P in CAA28412. Ref.2
Sequence conflict4511F → L in AAA35677. Ref.1
Sequence conflict4511F → L in CAA28412. Ref.2

Secondary structure

........................................................... 461
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Beta-1 [UniParc].

Last modified October 1, 1994. Version 2.
Checksum: 6770BB0D372A7CAA

FASTA46152,788
        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 

« Hide

Isoform Beta-2 [UniParc] [UniParc].

Checksum: 21755292507335D8
Show »

FASTA47654,449

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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 (1.90 ANGSTROMS) OF 104-204 IN COMPLEX WITH ZINC IONS.
[16]"Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1."
Ye L., Li Y.L., Mellstrom K., Mellin C., Bladh L.G., Koehler K., Garg N., Garcia Collazo A.M., Litten C., Husman B., Persson K., Ljunggren J., Grover G., Sleph P.G., George R., Malm J.
J. Med. Chem. 46:1580-1588(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 209-460 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION.
[17]"Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain."
Huber B.R., Desclozeaux M., West B.L., Cunha-Lima S.T., Nguyen H.T., Baxter J.D., Ingraham H.A., Fletterick R.J.
Mol. Endocrinol. 17:107-116(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 202-461 OF VARIANT GTHR THR-234, CHARACTERIZATION OF VARIANT GTHR THR-234, MUTAGENESIS OF ARG-243.
[18]"Two resistance to thyroid hormone mutants with impaired hormone binding."
Huber B.R., Sandler B., West B.L., Cunha Lima S.T., Nguyen H.T., Apriletti J.W., Baxter J.D., Fletterick R.J.
Mol. Endocrinol. 17:643-652(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 202-461 OF VARIANT PTHR HIS-316 AND VARIANT GTHR THR-317, CHARACTERIZATION OF VARIANT PTHR HIS-316, CHARACTERIZATION OF VARIANT GTHR THR-317.
[19]"Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor."
Borngraeber S., Budny M.J., Chiellini G., Cunha-Lima S.T., Togashi M., Webb P., Baxter J.D., Scanlan T.S., Fletterick R.J.
Proc. Natl. Acad. Sci. U.S.A. 100:15358-15363(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 209-461 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1; NCOA2; MED1 AND NCOR1, MUTAGENESIS OF ASN-331.
[20]"Thyroxine-thyroid hormone receptor interactions."
Sandler B., Webb P., Apriletti J.W., Huber B.R., Togashi M., Cunha Lima S.T., Juric S., Nilsson S., Wagner R., Fletterick R.J., Baxter J.D.
J. Biol. Chem. 279:55801-55808(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 202-461 IN COMPLEX WITH SYNTHETIC AGONIST, INTERACTION WITH NCOA2; MED1 AND NCOR1.
[21]"Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function."
Nascimento A.S., Dias S.M., Nunes F.M., Aparicio R., Ambrosio A.L., Bleicher L., Figueira A.C., Santos M.A., de Oliveira Neto M., Fischer H., Togashi M., Craievich A.F., Garratt R.C., Baxter J.D., Webb P., Polikarpov I.
J. Mol. Biol. 360:586-598(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 202-460 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, DNA-BINDING, SUBUNIT, MUTAGENESIS OF 207-SER-ILE-208.
[22]"Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms."
Bleicher L., Aparicio R., Nunes F.M., Martinez L., Gomes Dias S.M., Figueira A.C., Santos M.A., Venturelli W.H., da Silva R., Donate P.M., Neves F.A., Simeoni L.A., Baxter J.D., Webb P., Skaf M.S., Polikarpov I.
BMC Struct. Biol. 8:8-8(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 202-461 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION.
[23]"Gaining ligand selectivity in thyroid hormone receptors via entropy."
Martinez L., Nascimento A.S., Nunes F.M., Phillips K., Aparicio R., Dias S.M., Figueira A.C., Lin J.H., Nguyen P., Apriletti J.W., Neves F.A., Baxter J.D., Webb P., Skaf M.S., Polikarpov I.
Proc. Natl. Acad. Sci. U.S.A. 106:20717-20722(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 202-461, FUNCTION, MUTAGENESIS OF ASN-331.
[24]"Molecular basis for dimer formation of TRbeta variant D355R."
Jouravel N., Sablin E., Togashi M., Baxter J.D., Webb P., Fletterick R.J.
Proteins 75:111-117(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 209-460, FUNCTION, SUBUNIT, MUTAGENESIS OF ASP-355.
[25]"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.
[26]"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.
[27]"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.
[28]"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.
[29]"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.
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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.
[35]"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.
[36]"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.
[37]"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.
[38]"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.
[39]"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.
[40]"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.
[41]"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.
[42]"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.
[43]"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.

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.
CCDSCCDS2641.1. [P10828-1]
PIRTVHUAR. A25237.
S40152.
RefSeqNP_000452.2. NM_000461.4. [P10828-1]
NP_001121648.1. NM_001128176.2. [P10828-1]
NP_001121649.1. NM_001128177.1. [P10828-1]
NP_001239563.1. NM_001252634.1. [P10828-1]
XP_005265477.1. XM_005265420.2. [P10828-2]
XP_005265478.1. XM_005265421.2. [P10828-1]
XP_005265480.1. XM_005265423.2. [P10828-1]
XP_005265481.1. XM_005265424.2. [P10828-1]
XP_005265482.1. XM_005265425.2. [P10828-1]
XP_006713380.1. XM_006713317.1. [P10828-1]
XP_006713381.1. XM_006713318.1. [P10828-1]
UniGeneHs.187861.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BSXX-ray3.70A/B202-461[»]
1N46X-ray2.20A/B204-461[»]
1NAXX-ray2.70A209-460[»]
1NQ0X-ray2.40A202-461[»]
1NQ1X-ray2.90A202-461[»]
1NQ2X-ray2.40A202-461[»]
1NUOX-ray3.10A202-461[»]
1Q4XX-ray2.80A209-461[»]
1R6GX-ray3.00A203-461[»]
1XZXX-ray2.50X202-461[»]
1Y0XX-ray3.10X202-461[»]
2J4AX-ray2.20A209-461[»]
2NLLX-ray1.90B104-204[»]
2PINX-ray2.30A/B209-461[»]
3D57X-ray2.20A/B209-460[»]
3GWSX-ray2.20X202-460[»]
3IMYX-ray2.55A202-461[»]
3JZCX-ray2.50A202-461[»]
ProteinModelPortalP10828.
SMRP10828. Positions 94-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112924. 49 interactions.
DIPDIP-5991N.
IntActP10828. 10 interactions.
MINTMINT-1508903.
STRING9606.ENSP00000348827.

Chemistry

BindingDBP10828.
ChEMBLCHEMBL1947.
DrugBankDB00451. Levothyroxine.
DB00279. Liothyronine.
GuidetoPHARMACOLOGY589.

PTM databases

PhosphoSiteP10828.

Polymorphism databases

DMDM586092.

Proteomic databases

PaxDbP10828.
PRIDEP10828.

Protocols and materials databases

DNASU7068.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280696; ENSP00000280696; ENSG00000151090. [P10828-2]
ENST00000356447; ENSP00000348827; ENSG00000151090. [P10828-1]
ENST00000396671; ENSP00000379904; ENSG00000151090. [P10828-1]
ENST00000415021; ENSP00000404898; ENSG00000151090.
ENST00000416420; ENSP00000414444; ENSG00000151090. [P10828-1]
ENST00000447875; ENSP00000388467; ENSG00000151090.
GeneID7068.
KEGGhsa:7068.
UCSCuc003ccx.4. human. [P10828-1]

Organism-specific databases

CTD7068.
GeneCardsGC03M024158.
HGNCHGNC:11799. THRB.
HPACAB002008.
CAB002009.
MIM145650. phenotype.
188570. phenotype.
190160. gene.
274300. phenotype.
neXtProtNX_P10828.
Orphanet3221. Generalized resistance to thyroid hormone.
97927. Peripheral resistance to thyroid hormones.
165994. Selective pituitary resistance to thyroid hormone.
PharmGKBPA36508.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG272726.
HOGENOMHOG000010313.
HOVERGENHBG005606.
KOK08362.
OMALYEVHPA.
OrthoDBEOG7TBC2V.
PhylomeDBP10828.
TreeFamTF328382.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP10828.

Gene expression databases

ArrayExpressP10828.
BgeeP10828.
CleanExHS_THRB.
GenevestigatorP10828.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR008946. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10828.
GeneWikiThyroid_hormone_receptor_beta.
GenomeRNAi7068.
NextBio27637.
PROP10828.
SOURCESearch...

Entry information

Entry nameTHB_HUMAN
AccessionPrimary (citable) accession number: P10828
Secondary accession number(s): B3KU79 expand/collapse secondary AC list , P37243, Q13986, Q3KP35, Q6WGL2, Q9UD41
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM