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P10827 (THA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thyroid hormone receptor alpha
Alternative name(s):
Nuclear receptor subfamily 1 group A member 1
V-erbA-related protein 7
Short name=EAR-7
c-erbA-1
c-erbA-alpha
Gene names
Name:THRA
Synonyms:EAR7, ERBA1, NR1A1, THRA1, THRA2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length490 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Nuclear hormone receptor. High affinity receptor for triiodothyronine.

Subunit structure

Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Probably interacts with SFPQ. Interacts with C1D By similarity. Interacts with AKAP13. Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus.

Domain

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Uncategorizedregulation of transcription from RNA polymerase II promoter by nuclear hormone receptor

Traceable author statement. Source: Reactome

   Biological processnegative regulation of RNA polymerase II transcriptional preinitiation complex assembly

Inferred from direct assay. Source: UniProtKB

negative regulation of transcription initiation, DNA-dependent

Inferred from direct assay. Source: UniProtKB

transcription from RNA polymerase II promoter

Inferred from direct assay. Source: UniProtKB

   Cellular componentcytosol

Inferred from direct assay. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular functionTBP-class protein binding

Inferred from direct assay. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay. Source: UniProtKB

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

thyroid hormone binding

Inferred from direct assay. Source: UniProtKB

thyroid hormone receptor activity

Inferred from direct assay. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ncoa6Q9JLI42EBI-286285,EBI-286271From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-2 (identifier: P10827-1)

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 Alpha-1 (identifier: P10827-2)

The sequence of this isoform differs from the canonical sequence as follows:
     371-490: EREVQSSILY...EDLAGNAASP → VTDLRMIGAC...FLEVFEDQEV
Isoform Alpha-3 (identifier: P10827-3)

The sequence of this isoform differs from the canonical sequence as follows:
     371-409: Missing.
Isoform Alpha-4 (identifier: P10827-4)

Also known as: Alpha3;

The sequence of this isoform differs from the canonical sequence as follows:
     371-412: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 490490Thyroid hormone receptor alpha
PRO_0000053424

Regions

DNA binding53 – 12775Nuclear receptor
Zinc finger53 – 7321NR C4-type
Zinc finger91 – 11525NR C4-type
Region1 – 5252Modulating
Region190 – 370181Ligand-binding

Amino acid modifications

Cross-link190Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14

Natural variations

Alternative sequence371 – 490120EREVQ…NAASP → VTDLRMIGACHASRFLHMKV ECPTELFPPLFLEVFEDQEV in isoform Alpha-1.
VSP_003621
Alternative sequence371 – 41242Missing in isoform Alpha-4.
VSP_003623
Alternative sequence371 – 40939Missing in isoform Alpha-3.
VSP_003622

Experimental info

Sequence conflict371T → S Ref.4
Sequence conflict371T → S Ref.7
Sequence conflict1191G → A Ref.4
Sequence conflict1191G → A Ref.7
Sequence conflict2851E → A in CAB57886. Ref.1
Sequence conflict2851E → A in CAA38899. Ref.1

Secondary structure

...................................... 490
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha-2 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: C87C7D2F67B1AE49

FASTA49054,816
        10         20         30         40         50         60 
MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCSLKTSMS GYIPSYLDKD EQCVVCGDKA 

        70         80         90        100        110        120 
TGYHYRCITC EGCKGFFRRT IQKNLHPTYS CKYDSCCVID KITRNQCQLC RFKKCIAVGM 

       130        140        150        160        170        180 
AMDLVLDDSK RVAKRKLIEQ NRERRRKEEM IRSLQQRPEP TPEEWDLIHI ATEAHRSTNA 

       190        200        210        220        230        240 
QGSHWKQRRK FLPDDIGQSP IVSMPDGDKV DLEAFSEFTK IITPAITRVV DFAKKLPMFS 

       250        260        270        280        290        300 
ELPCEDQIIL LKGCCMEIMS LRAAVRYDPE SDTLTLSGEM AVKREQLKNG GLGVVSDAIF 

       310        320        330        340        350        360 
ELGKSLSAFN LDDTEVALLQ AVLLMSTDRS GLLCVDKIEK SQEAYLLAFE HYVNHRKHNI 

       370        380        390        400        410        420 
PHFWPKLLMK EREVQSSILY KGAAAEGRPG GSLGVHPEGQ QLLGMHVVQG PQVRQLEQQL 

       430        440        450        460        470        480 
GEAGSLQGPV LQHQSPKSPQ QRLLELLHRS GILHARAVCG EDDSSEADSP SSSEEEPEVC 

       490 
EDLAGNAASP 

« Hide

Isoform Alpha-1 [UniParc].

Checksum: B9FD7BFAC16D6882
Show »

FASTA41046,813
Isoform Alpha-3 [UniParc].

Checksum: 1495A3F2EE6601DD
Show »

FASTA45150,747
Isoform Alpha-4 (Alpha3) [UniParc].

Checksum: 15FD778790B4D26B
Show »

FASTA44850,465

References

« Hide 'large scale' references
[1]"Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene."
Laudet V., Begue A., Henry C., Joubel A., Martin P., Stehelin D., Saule S.
Nucleic Acids Res. 19:1105-1112(1991) [PubMed: 1850510] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
[2]"Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus."
Miyajima N., Horiuchi R., Shibuya Y., Fukushige S., Matsubara K., Toyoshima K., Yamamoto T.
Cell 57:31-39(1989) [PubMed: 2539258] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
[3]"Characterization of a thyroid hormone receptor expressed in human kidney and other tissues."
Nakai A., Seino S., Sakurai A., Szilak I., Bell G.I., Degroot L.J.
Proc. Natl. Acad. Sci. U.S.A. 85:2781-2785(1988) [PubMed: 3357890] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
Tissue: Kidney.
[4]"Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor."
Pfahl M., Benbrook D.
Nucleic Acids Res. 15:9613-9613(1987) [PubMed: 3684612] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
Tissue: Testis.
[5]"Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues."
Nakai A., Sakurai A., Bell G.I., Degroot L.J.
Mol. Endocrinol. 2:1087-1092(1988) [PubMed: 2464749] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM ALPHA-1).
[6]"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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-2).
Tissue: Brain.
[7]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].
[8]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-2 AND ALPHA-3).
Tissue: Brain, Hippocampus and Muscle.
[9]"A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library."
Benbrook D., Pfahl M.
Science 238:788-791(1987) [PubMed: 3672126] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-370.
[10]Liu C., Li L., Liu B., Zang X.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE OF 280-451 (ISOFORM ALPHA-4).
Tissue: Brain cortex.
[11]"Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300."
Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M.
Cell 90:569-580(1997) [PubMed: 9267036] [Abstract]
Cited for: INTERACTION WITH NCOA3.
[12]"Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action."
Rubino D., Driggers P., Arbit D., Kemp L., Miller B., Coso O., Pagliai K., Gray K., Gutkind S., Segars J.
Oncogene 16:2513-2526(1998) [PubMed: 9627117] [Abstract]
Cited for: INTERACTION WITH AKAP13.
[13]"A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo."
Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K., Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H., Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W.
J. Biol. Chem. 274:34283-34293(1999) [PubMed: 10567404] [Abstract]
Cited for: INTERACTION WITH NCOA6.
[14]"Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells."
Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.
Proteomics 8:2885-2896(2008) [PubMed: 18655026] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-190, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X55074 expand/collapse EMBL AC list , X55073, X55070, X55071, X55004, X55069, X55068, X55066 Genomic DNA. Translation: CAB57886.1.
X55005 mRNA. Translation: CAA38749.1.
X55074 expand/collapse EMBL AC list , X55073, X55070, X55071, X55004, X55069, X55068 Genomic DNA. Translation: CAA38899.1.
M24899 mRNA. Translation: AAA35783.1.
M24900 mRNA. Translation: AAA52333.1.
J03239 mRNA. Translation: AAA61176.1.
Y00479 mRNA. Translation: CAA68539.1.
M24748 Genomic DNA. Translation: AAA66021.1.
AK290530 mRNA. Translation: BAF83219.1.
CH471152 Genomic DNA. Translation: EAW60632.1.
BC000261 mRNA. Translation: AAH00261.1.
BC002728 mRNA. Translation: AAH02728.1.
BC035137 mRNA. Translation: AAH35137.1.
AF522368 mRNA. Translation: AAM77692.1.
IPIIPI00022991.
IPI00219099.
IPI00219100.
IPI00219101.
PIRA30893.
A40917.
S06163.
RefSeqNP_001177847.1. NM_001190918.1.
NP_001177848.1. NM_001190919.1.
NP_003241.2. NM_003250.5.
NP_955366.1. NM_199334.3.
UniGeneHs.724.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NAVX-ray2.50A148-370[»]
2H77X-ray2.33A148-370[»]
2H79X-ray1.87A148-370[»]
3HZFX-ray2.50A148-370[»]
3ILZX-ray1.85A148-370[»]
3JZBX-ray2.01A148-370[»]
ProteinModelPortalP10827.
SMRP10827. Positions 50-413.
ModBaseSearch...

Protein-protein interaction databases

IntActP10827. 9 interactions.
STRINGP10827.

PTM databases

PhosphoSiteP10827.

Polymorphism databases

DMDM135705.

Proteomic databases

PRIDEP10827.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264637; ENSP00000264637; ENSG00000126351.
GeneID7067.
KEGGhsa:7067.
UCSCuc002htw.1. human.
uc002htx.2. human.

Organism-specific databases

CTD7067.
GeneCardsGC17P038219.
HGNCHGNC:11796. THRA.
HPACAB023349.
HPA009654.
MIM190120. gene.
neXtProtNX_P10827.
PharmGKBPA36507.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG06097.
GeneTreeENSGT00590000082832.
HOGENOMHBG713785.
HOVERGENHBG005606.
InParanoidP10827.
OMAKRKNSQC.
OrthoDBEOG4B2SX0.
PhylomeDBP10827.

Enzyme and pathway databases

Pathway_Interaction_DBrxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressP10827.
BgeeP10827.
CleanExHS_THRA.
GenevestigatorP10827.
GermOnlineENSG00000126351. Homo sapiens.

Family and domain databases

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]
Gene3DG3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 2 hits.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.
KOK05547.
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. Str_ncl_receptor. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00451. Levothyroxine.
DB00279. Liothyronine.
NextBio27631.
SOURCESearch...

Entry information

Entry nameTHA_HUMAN
AccessionPrimary (citable) accession number: P10827
Secondary accession number(s): A8K3B5 expand/collapse secondary AC list , P21205, Q8N6A1, Q96H73
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: January 25, 2012
This is version 154 of the entry and version 1 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

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families