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P63058 (THA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 alpha
Alternative name(s):
Nuclear receptor subfamily 1 group A member 1
c-erbA-1
c-erbA-alpha
Gene names
Name:Thra
Synonyms:C-erba-alpha, Nr1a1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length492 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. Isoform Alpha-deltaE6 does not bind DNA, inhibits the activity of isoform Alpha-1, and stimulates myoblast differentiation. Ref.9

Subunit structure

Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Probably interacts with SFPQ. Interacts with AKAP13. Interacts with C1D. Interacts with TP53INP2. Interacts with PER2. Ref.7 Ref.8 Ref.10

Subcellular location

Nucleus.

Isoform Alpha-deltaE6: Cytoplasm. Note: Sequesters isoform Alpha-1 into this compartment.

Tissue specificity

Ubiquitous (Isoform Alpha-deltaE6) Ref.9

Domain

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Isoform Alpha-deltaE6 lacks the hinge region that connects the modulating domain and the DNA binding domain.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR1 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence CAM46188.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
RNA editing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMIsopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processType I pneumocyte differentiation

Inferred from genetic interaction PubMed 22001906. Source: MGI

cartilage condensation

Inferred from mutant phenotype PubMed 9250685. Source: MGI

cytoplasmic sequestering of transcription factor

Inferred from direct assay Ref.9. Source: MGI

erythrocyte differentiation

Inferred from mutant phenotype PubMed 18203951. Source: MGI

female courtship behavior

Inferred from mutant phenotype PubMed 10769387. Source: MGI

intracellular receptor signaling pathway

Inferred from direct assay PubMed 15322135. Source: GOC

learning or memory

Inferred from mutant phenotype PubMed 17129617. Source: MGI

negative regulation of DNA-templated transcription, initiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of RNA polymerase II transcriptional preinitiation complex assembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11641275PubMed 15062575PubMed 15322135. Source: MGI

organ morphogenesis

Inferred from mutant phenotype PubMed 9927422. Source: MGI

ossification

Inferred from mutant phenotype PubMed 9250685PubMed 9927422. Source: MGI

positive regulation of female receptivity

Inferred from mutant phenotype PubMed 10769387. Source: MGI

positive regulation of myotube differentiation

Inferred from direct assay Ref.9. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15340084. Source: MGI

regulation of heart contraction

Inferred from mutant phenotype PubMed 15240882PubMed 9430637. Source: MGI

regulation of lipid catabolic process

Inferred from mutant phenotype PubMed 12869545. Source: MGI

regulation of myeloid cell apoptotic process

Inferred from mutant phenotype PubMed 18203951. Source: MGI

regulation of thyroid hormone mediated signaling pathway

Inferred from mutant phenotype PubMed 12869545. Source: MGI

response to cold

Inferred from mutant phenotype PubMed 12869545. Source: MGI

thyroid gland development

Inferred from genetic interaction PubMed 11773436. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: MGI

cytosol

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 17952069. Source: MGI

   Molecular_functionchromatin DNA binding

Inferred from direct assay PubMed 17952069. Source: MGI

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 15322135. Source: MGI

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

protein complex binding

Inferred from direct assay PubMed 15340084. Source: MGI

single-stranded RNA binding

Inferred from direct assay PubMed 15180993. Source: MGI

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

steroid receptor RNA activator RNA binding

Inferred from direct assay PubMed 15180993. Source: MGI

thyroid hormone binding

Inferred from sequence or structural similarity. Source: UniProtKB

thyroid hormone receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-2 (identifier: P63058-1)

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: P63058-2)

The sequence of this isoform differs from the canonical sequence as follows:
     371-492: EREVQSSILY...EDQAGKAASP → VTDLRMIGAC...FLEVFEDQEV
Isoform Alpha-3 (identifier: P63058-3)

The sequence of this isoform differs from the canonical sequence as follows:
     371-409: Missing.
Isoform Alpha-deltaE6 (identifier: P63058-4)

The sequence of this isoform differs from the canonical sequence as follows:
     121-197: AMDLVLDDSK...RRKFLPDDIG → GTSP
     371-492: EREVQSSILY...EDQAGKAASP → VTDLRMIGAC...FLEVFEDQEV
Note: Due to mismatches with the underlying genomic sequence that lie within a microexon, this isoform has been proposed to undergo RNA editing involving both base insertion and deletion.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 492492Thyroid hormone receptor alpha
PRO_0000053425

Regions

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

Sites

Binding site2281Thyroid hormone By similarity
Binding site2771Thyroid hormone; via amide nitrogen By similarity

Amino acid modifications

Cross-link190Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence121 – 19777AMDLV…PDDIG → GTSP in isoform Alpha-deltaE6.
VSP_038640
Alternative sequence371 – 492122EREVQ…KAASP → VTDLRMIGACHASRFLHMKV ECPTELFPPLFLEVFEDQEV in isoform Alpha-1 and isoform Alpha-deltaE6.
VSP_003624
Alternative sequence371 – 40939Missing in isoform Alpha-3.
VSP_003625

Experimental info

Sequence conflict1061Q → H in CAA36241. Ref.2

Sequences

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

Last modified January 19, 2010. Version 2.
Checksum: 870100FCB5C34A10

FASTA49255,023
        10         20         30         40         50         60 
MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCPLKSSMS GYIPSYLDKD EQCVVCGDKA 

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

       130        140        150        160        170        180 
AMDLVLDDSK RVAKRKLIEQ NRERRRKEEM IRSLQQRPEP TPEEWDLIHV 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 
GEAGSLRGPV LQHQSPKSPQ QRLLELLHRS GILHSRAVCG EDDSSEASSL SSSSDTEDTE 

       490 
VCEDQAGKAA SP 

« Hide

Isoform Alpha-1 [UniParc] [UniParc].

Checksum: EC0240EF1ECF4111
Show »

FASTA41046,795
Isoform Alpha-3 [UniParc] [UniParc].

Checksum: 6DE1FECA97686CAF
Show »

FASTA45350,954
Isoform Alpha-deltaE6 [UniParc].

Checksum: 27137623BED67783
Show »

FASTA33737,926

References

« Hide 'large scale' references
[1]"Multiple sequences encoding potential thyroid hormone receptors isolated from mouse skeletal muscle cDNA libraries."
Prost E., Koenig R.J., Moore D.D., Larsen P.R., Whalen R.G.
Nucleic Acids Res. 16:6248-6248(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1), NUCLEOTIDE SEQUENCE [MRNA] OF 1-452 (ISOFORMS ALPHA-2 AND ALPHA-3).
Strain: C3H.
Tissue: Muscle.
[2]"Nucleotide sequence of the murine thyroid hormone receptor (alpha-1) cDNA."
Masuda M., Yasuhara S., Yamashita M., Shibuya M., Odaka T.
Nucleic Acids Res. 18:3055-3055(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
Strain: C3H.
Tissue: Testis.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
Strain: C57BL/6J.
Tissue: Olfactory bulb.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 ALPHA-2).
Strain: C57BL/6.
Tissue: Brain.
[7]"Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex."
Zamir I., Dawson J., Lavinsky R.M., Glass C.K., Rosenfeld M.G., Lazar M.A.
Proc. Natl. Acad. Sci. U.S.A. 94:14400-14405(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH C1D.
[8]"Cloning and characterization of RAP250, a nuclear receptor coactivator."
Caira F., Antonson P., Pelto-Huikko M., Treuter E., Gustafsson J.-A.
J. Biol. Chem. 275:5308-5317(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA6.
[9]"Characterization of a novel thyroid hormone receptor alpha variant involved in the regulation of myoblast differentiation."
Casas F., Busson M., Grandemange S., Seyer P., Carazo A., Pessemesse L., Wrutniak-Cabello C., Cabello G.
Mol. Endocrinol. 20:749-763(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS ALPHA-1 AND ALPHA-DELTAE6), POTENTIAL RNA EDITING OF ISOFORM ALPHA-DELTAE6, FUNCTION, TISSUE SPECIFICITY.
[10]"The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07750 mRNA. Translation: CAA30575.1.
X07751 mRNA. Translation: CAA30576.1.
X07752 mRNA. Translation: CAA30577.1.
X51983 mRNA. Translation: CAA36241.1.
AK078233 mRNA. Translation: BAC37186.1.
AL590963 Genomic DNA. Translation: CAM46188.1. Sequence problems.
AL590963 Genomic DNA. Translation: CAM46189.1.
AL590963 Genomic DNA. Translation: CAM46190.1.
CH466556 Genomic DNA. Translation: EDL16164.1.
CH466556 Genomic DNA. Translation: EDL16165.1.
BC046795 mRNA. Translation: AAH46795.1.
CCDSCCDS25362.1. [P63058-2]
PIRS14416.
S14417.
S14418.
QRMSA1. S14690.
RefSeqNP_835161.1. NM_178060.3. [P63058-2]
UniGeneMm.265917.
Mm.442648.

3D structure databases

ProteinModelPortalP63058.
SMRP63058. Positions 49-409.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204183. 4 interactions.
DIPDIP-43752N.
IntActP63058. 1 interaction.
MINTMINT-3374329.

Chemistry

GuidetoPHARMACOLOGY588.

PTM databases

PhosphoSiteP63058.

Proteomic databases

PRIDEP63058.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000064187; ENSMUSP00000068281; ENSMUSG00000058756. [P63058-1]
ENSMUST00000103139; ENSMUSP00000099428; ENSMUSG00000058756. [P63058-2]
ENSMUST00000124072; ENSMUSP00000115323; ENSMUSG00000058756.
GeneID21833.
KEGGmmu:21833.
UCSCuc007lhe.1. mouse. [P63058-2]
uc007lhf.1. mouse.
uc007lhg.1. mouse. [P63058-3]

Organism-specific databases

CTD7067.
MGIMGI:98742. Thra.

Phylogenomic databases

eggNOGNOG272726.
GeneTreeENSGT00740000114969.
HOVERGENHBG005606.
InParanoidQ80Y90.
KOK05547.
OMAWLNGPKR.
OrthoDBEOG7TBC2V.
PhylomeDBP63058.
TreeFamTF328382.

Gene expression databases

ArrayExpressP63058.
BgeeP63058.
CleanExMM_THRA.
GenevestigatorP63058.

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

NextBio301282.
PROP63058.
SOURCESearch...

Entry information

Entry nameTHA_MOUSE
AccessionPrimary (citable) accession number: P63058
Secondary accession number(s): A3KFN4 expand/collapse secondary AC list , P10685, P15827, P16416, P37241, Q542U8, Q63107, Q63195, Q63196, Q80Y90, Q99146
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: January 19, 2010
Last modified: July 9, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot