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O08580 (ERR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Steroid hormone receptor ERR1
Alternative name(s):
Estrogen receptor-like 1
Estrogen-related receptor alpha
Short name=ERR-alpha
Nuclear receptor subfamily 3 group B member 1
Gene names
Name:Esrra
Synonyms:Err1, Estrra, Nr3b1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length422 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle By similarity.

Subunit structure

Binds DNA as a monomer or a homodimer. Interacts (via the AF2 domain) with coactivator PPARGC1A (via the L3 motif); the interaction greatly enhances transriptional activity of genes involved in energy metabolism. Interacts with PIAS4; the interaction enhances sumoylation By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Most highly expressed in kidney, heart, and brown adipocytes. Also found in utERus, cervix and vagina.

Developmental stage

Expressed in an organ specific mannER through mid-to late embryonic development with persistent high-level expression in brown adipose tissue and intestinal mucosa.

Induction

Activated by diethylstilbestrol (DES) and estradiol in the uterus.

Post-translational modification

Phosphorylation on Ser-19 enhances sumoylation on Lys-14 increasing repression of transcriptional activity By similarity. Ref.7

Sumoylated with SUMO2. Main site is Lys-14 which is enhanced by phosphorylation on Ser-19, cofactor activation, and by interaction with PIAS4. Sumoylation enhances repression of transcriptional activity, but has no effect on subcellular location nor on DNA binding By similarity. Ref.7

Reversibly acetylated. Acetylation by PCAF/KAT2 at Lys-129, Lys-138, Lys-160 and Lys-162 and PCAF/KAT2 decreases transcriptional activity probably by inhibiting DNA-binding activity; deacetylation involves SIRT1 and HDAC8 and increases DNA-binding By similarity. Ref.8

Disruption phenotype

No visible phenotype; mice are viable, fertile and display no gross anatomical alterations, with the exception of reduced body weight and peripheral fat deposits. Mice are resistant to a high-fat diet-induced obesity. Ref.5

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcartilage development

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 21106753. Source: BHF-UCL

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay PubMed 18234909. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 18234909. Source: MGI

sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 18234909. Source: MGI

steroid binding

Inferred from electronic annotation. Source: InterPro

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 422422Steroid hormone receptor ERR1
PRO_0000053661

Regions

DNA binding76 – 15176Nuclear receptor
Zinc finger79 – 9921NR C4-type
Zinc finger115 – 13420NR C4-type
Region1 – 7676Repressor domain
Region205 – 401197Ligand binding domain By similarity
Region402 – 42221AF-2 domain By similarity

Sites

Site1241Required for DNA-dependent dimerization By similarity

Amino acid modifications

Modified residue191Phosphoserine Ref.6 Ref.7
Modified residue221Phosphoserine By similarity
Modified residue1291N6-acetyllysine; by PCAF/KAT2B By similarity
Modified residue1381N6-acetyllysine; by PCAF/KAT2B By similarity
Modified residue1601N6-acetyllysine; by PCAF/KAT2B By similarity
Modified residue1621N6-acetyllysine; by PCAF/KAT2B By similarity
Cross-link14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link402Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Sequence conflict2751R → G in AAB51250. Ref.1
Sequence conflict3081Missing in AAB51250. Ref.1
Sequence conflict408 – 4125PMHKL → HAQV in AAB51250. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O08580 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: 2F54EEA1BD3B511D

FASTA42245,464
        10         20         30         40         50         60 
MSSQVVGIEP LYIKAEPASP DSPKGSSETE TEPPVTLASG PAPARCLPGH KEEEDGEGAG 

        70         80         90        100        110        120 
SGEQGSGKLV LSSLPKRLCL VCGDVASGYH YGVASCEACK AFFKRTIQGS IEYSCPASNE 

       130        140        150        160        170        180 
CEITKRRRKA CQACRFTKCL RVGMLKEGVR LDRVRGGRQK YKRRPEVDPL PFPGPFPAGP 

       190        200        210        220        230        240 
LAVAGGPRKT APVNALVSHL LVVEPEKLYA MPDPASPDGH LPAVATLCDL FDREIVVTIS 

       250        260        270        280        290        300 
WAKSIPGFSS LSLSDQMSVL QSVWMEVLVL GVAQRSLPLQ DELAFAEDLV LDEEGARAAG 

       310        320        330        340        350        360 
LGDLGAALLQ LVRRLQALRL EREEYVLLKA LALANSDSVH IEDAEAVEQL REALHEALLE 

       370        380        390        400        410        420 
YEAGRAGPGG GAERRRAGRL LLTLPLLRQT AGKVLAHFYG VKLEGKVPMH KLFLEMLEAM 


MD 

« Hide

References

« Hide 'large scale' references
[1]"The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene."
Sladek R., Bader J.-A., Giguere V.
Mol. Cell. Biol. 17:5400-5409(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[2]"The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness."
Shigeta H., Zuo W., Yang N., DiAugustine R., Teng C.T.
J. Mol. Endocrinol. 19:299-309(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Kidney.
[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].
Strain: NOD.
Tissue: Spleen.
[4]"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].
Tissue: Brain.
[5]"Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha."
Luo J., Sladek R., Carrier J., Bader J.A., Richard D., Giguere V.
Mol. Cell. Biol. 23:7947-7956(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif."
Tremblay A.M., Wilson B.J., Yang X.-J., Giguere V.
Mol. Endocrinol. 22:570-584(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, PHOSPHORYLATION AT SER-19.
[8]"An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha."
Wilson B.J., Tremblay A.M., Deblois G., Sylvain-Drolet G., Giguere V.
Mol. Endocrinol. 24:1349-1358(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION BY PCAF/KAT2B, DEACETYLATION BY SIRT1 AND HDAC8.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U85259 mRNA. Translation: AAB51250.1.
AK156371 mRNA. Translation: BAE33690.1.
BC138586 mRNA. Translation: AAI38587.1.
BC171958 mRNA. Translation: AAI71958.1.
CCDSCCDS29509.1.
RefSeqNP_031979.2. NM_007953.2.
UniGeneMm.386776.

3D structure databases

ProteinModelPortalO08580.
SMRO08580. Positions 71-421.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204937. 7 interactions.
IntActO08580. 2 interactions.

Chemistry

ChEMBLCHEMBL1914280.
GuidetoPHARMACOLOGY622.

PTM databases

PhosphoSiteO08580.

Proteomic databases

PaxDbO08580.
PRIDEO08580.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025906; ENSMUSP00000025906; ENSMUSG00000024955.
GeneID26379.
KEGGmmu:26379.
UCSCuc008gjg.1. mouse.

Organism-specific databases

CTD2101.
MGIMGI:1346831. Esrra.

Phylogenomic databases

eggNOGNOG282629.
GeneTreeENSGT00730000110346.
HOGENOMHOG000233467.
HOVERGENHBG108344.
InParanoidB2RRU9.
KOK08552.
OMAGPGEQGS.
OrthoDBEOG7288S1.
TreeFamTF323751.

Gene expression databases

ArrayExpressO08580.
BgeeO08580.
CleanExMM_ESRRA.
GenevestigatorO08580.

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.
IPR027289. Oest-rel_rcp.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFPIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 2 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio304289.
PROO08580.
SOURCESearch...

Entry information

Entry nameERR1_MOUSE
AccessionPrimary (citable) accession number: O08580
Secondary accession number(s): B2RRU9, Q3U110
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 129 of the entry and version 4 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