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O08580

- ERR1_MOUSE

UniProt

O08580 - ERR1_MOUSE

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Protein

Steroid hormone receptor ERR1

Gene

Esrra

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei124 – 1241Required for DNA-dependent dimerizationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi76 – 15176Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri79 – 9921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri115 – 13420NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: NTNU_SB
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  5. sequence-specific DNA binding Source: UniProtKB
  6. sequence-specific DNA binding transcription factor activity Source: MGI
  7. steroid binding Source: InterPro
  8. steroid hormone receptor activity Source: InterPro
  9. zinc ion binding Source: InterPro

GO - Biological processi

  1. cartilage development Source: Ensembl
  2. negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  3. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  4. regulation of cell proliferation Source: Ensembl
  5. regulation of osteoblast differentiation Source: Ensembl
  6. regulation of osteoclast differentiation Source: Ensembl
  7. regulation of transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_198602. PPARA activates gene expression.
REACT_205251. Transcriptional activation of mitochondrial biogenesis.
REACT_234105. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Esrra
Synonyms:Err1, Estrra, Nr3b1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:1346831. Esrra.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. intercellular bridge Source: Ensembl
  2. microtubule cytoskeleton Source: Ensembl
  3. nucleolus Source: Ensembl
  4. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 422422Steroid hormone receptor ERR1PRO_0000053661Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki14 – 14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei19 – 191Phosphoserine2 Publications
Modified residuei22 – 221PhosphoserineBy similarity
Modified residuei129 – 1291N6-acetyllysine; by PCAF/KAT2BBy similarity
Modified residuei138 – 1381N6-acetyllysine; by PCAF/KAT2BBy similarity
Modified residuei160 – 1601N6-acetyllysine; by PCAF/KAT2BBy similarity
Modified residuei162 – 1621N6-acetyllysine; by PCAF/KAT2BBy similarity
Cross-linki402 – 402Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO08580.
PaxDbiO08580.
PRIDEiO08580.

PTM databases

PhosphoSiteiO08580.

Expressioni

Tissue specificityi

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

Developmental stagei

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

Inductioni

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

Gene expression databases

BgeeiO08580.
CleanExiMM_ESRRA.
ExpressionAtlasiO08580. baseline and differential.
GenevestigatoriO08580.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi204937. 7 interactions.
IntActiO08580. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliO08580.
SMRiO08580. Positions 71-421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7676Repressor domainAdd
BLAST
Regioni205 – 401197Ligand binding domainBy similarityAdd
BLAST
Regioni402 – 42221AF-2 domainBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri79 – 9921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri115 – 13420NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG282629.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000233467.
HOVERGENiHBG108344.
InParanoidiO08580.
KOiK08552.
OMAiGPGEQGS.
OrthoDBiEOG7288S1.
TreeFamiTF323751.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR008946. 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]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08580-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSSQVVGIEP LYIKAEPASP DSPKGSSETE TEPPVTLASG PAPARCLPGH
60 70 80 90 100
KEEEDGEGAG SGEQGSGKLV LSSLPKRLCL VCGDVASGYH YGVASCEACK
110 120 130 140 150
AFFKRTIQGS IEYSCPASNE CEITKRRRKA CQACRFTKCL RVGMLKEGVR
160 170 180 190 200
LDRVRGGRQK YKRRPEVDPL PFPGPFPAGP LAVAGGPRKT APVNALVSHL
210 220 230 240 250
LVVEPEKLYA MPDPASPDGH LPAVATLCDL FDREIVVTIS WAKSIPGFSS
260 270 280 290 300
LSLSDQMSVL QSVWMEVLVL GVAQRSLPLQ DELAFAEDLV LDEEGARAAG
310 320 330 340 350
LGDLGAALLQ LVRRLQALRL EREEYVLLKA LALANSDSVH IEDAEAVEQL
360 370 380 390 400
REALHEALLE YEAGRAGPGG GAERRRAGRL LLTLPLLRQT AGKVLAHFYG
410 420
VKLEGKVPMH KLFLEMLEAM MD
Length:422
Mass (Da):45,464
Last modified:July 27, 2011 - v4
Checksum:i2F54EEA1BD3B511D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti275 – 2751R → G in AAB51250. (PubMed:9271417)Curated
Sequence conflicti308 – 3081Missing in AAB51250. (PubMed:9271417)Curated
Sequence conflicti408 – 4125PMHKL → HAQV in AAB51250. (PubMed:9271417)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85259 mRNA. Translation: AAB51250.1.
AK156371 mRNA. Translation: BAE33690.1.
BC138586 mRNA. Translation: AAI38587.1.
BC171958 mRNA. Translation: AAI71958.1.
CCDSiCCDS29509.1.
RefSeqiNP_031979.2. NM_007953.2.
UniGeneiMm.386776.

Genome annotation databases

EnsembliENSMUST00000025906; ENSMUSP00000025906; ENSMUSG00000024955.
GeneIDi26379.
KEGGimmu:26379.
UCSCiuc008gjg.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85259 mRNA. Translation: AAB51250.1 .
AK156371 mRNA. Translation: BAE33690.1 .
BC138586 mRNA. Translation: AAI38587.1 .
BC171958 mRNA. Translation: AAI71958.1 .
CCDSi CCDS29509.1.
RefSeqi NP_031979.2. NM_007953.2.
UniGenei Mm.386776.

3D structure databases

ProteinModelPortali O08580.
SMRi O08580. Positions 71-421.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204937. 7 interactions.
IntActi O08580. 2 interactions.

Chemistry

ChEMBLi CHEMBL1914280.
GuidetoPHARMACOLOGYi 622.

PTM databases

PhosphoSitei O08580.

Proteomic databases

MaxQBi O08580.
PaxDbi O08580.
PRIDEi O08580.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025906 ; ENSMUSP00000025906 ; ENSMUSG00000024955 .
GeneIDi 26379.
KEGGi mmu:26379.
UCSCi uc008gjg.1. mouse.

Organism-specific databases

CTDi 2101.
MGIi MGI:1346831. Esrra.

Phylogenomic databases

eggNOGi NOG282629.
GeneTreei ENSGT00760000118887.
HOGENOMi HOG000233467.
HOVERGENi HBG108344.
InParanoidi O08580.
KOi K08552.
OMAi GPGEQGS.
OrthoDBi EOG7288S1.
TreeFami TF323751.

Enzyme and pathway databases

Reactomei REACT_198602. PPARA activates gene expression.
REACT_205251. Transcriptional activation of mitochondrial biogenesis.
REACT_234105. Nuclear Receptor transcription pathway.

Miscellaneous databases

ChiTaRSi Esrra. mouse.
NextBioi 304289.
PROi O08580.
SOURCEi Search...

Gene expression databases

Bgeei O08580.
CleanExi MM_ESRRA.
ExpressionAtlasi O08580. baseline and differential.
Genevestigatori O08580.

Family and domain databases

Gene3Di 1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProi IPR008946. 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 ]
Pfami PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PIRSFi PIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.
PRINTSi PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 2 hits.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiERR1_MOUSE
AccessioniPrimary (citable) accession number: O08580
Secondary accession number(s): B2RRU9, Q3U110
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 133 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3