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Protein

Steroid hormone receptor ERR1

Gene

Esrra

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Sitei124Required for DNA-dependent dimerizationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi76 – 151Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri79 – 99NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri115 – 134NR C4-typePROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1346831 Esrra

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, 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. Cardiomyocyte-specific double konckout for ESRRA and ESRRG are slower at gaining weight, smaller and shorter from 5 to 7 days of age compared to controls. They show decreased absolute weight of most internal organs except the heart. They have about 70% decreased plasma IGF1 levels but normal plasma growth hormone levels. At 14-15 days, mutants develop lethal dilated cardiomyopathy and heart failure (PubMed:28572090).2 Publications

Chemistry databases

ChEMBLiCHEMBL1914280
GuidetoPHARMACOLOGYi622

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536611 – 422Steroid hormone receptor ERR1Add BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei19PhosphoserineCombined sources1 Publication1
Modified residuei22PhosphoserineCombined sources1
Modified residuei129N6-acetyllysine; by PCAF/KAT2BBy similarity1
Modified residuei138N6-acetyllysine; by PCAF/KAT2BBy similarity1
Modified residuei160N6-acetyllysine; by PCAF/KAT2BBy similarity1
Modified residuei162N6-acetyllysine; by PCAF/KAT2BBy similarity1
Cross-linki189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki402Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki402Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy 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

EPDiO08580
MaxQBiO08580
PaxDbiO08580
PeptideAtlasiO08580
PRIDEiO08580

PTM databases

iPTMnetiO08580
PhosphoSitePlusiO08580

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

BgeeiENSMUSG00000024955
CleanExiMM_ESRRA
ExpressionAtlasiO08580 baseline and differential
GenevisibleiO08580 MM

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 transcriptional activity of genes involved in energy metabolism. Interacts with PIAS4; the interaction enhances sumoylation (By similarity). Interacts with MAPK15; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity (PubMed:21190936).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204937, 6 interactors
IntActiO08580, 2 interactors
STRINGi10090.ENSMUSP00000025906

Structurei

3D structure databases

ProteinModelPortaliO08580
SMRiO08580
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini192 – 420NR LBDPROSITE-ProRule annotationAdd BLAST229

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 76Repressor domainAdd BLAST76
Regioni402 – 422AF-2 domainBy similarityAdd BLAST21

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri79 – 99NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri115 – 134NR C4-typePROSITE-ProRule annotationAdd BLAST20

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000233467
HOVERGENiHBG108344
InParanoidiO08580
KOiK08552
OMAiCHPGHKE
OrthoDBiEOG091G0DYP
TreeFamiTF323751

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR027289 Oest-rel_rcp
IPR024178 Oest_rcpt/oest-rel_rcp
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PIRSFiPIRSF002527 ER-like_NR, 1 hit
PIRSF500939 ERR1-2-3, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 2 hits
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti275R → G in AAB51250 (PubMed:9271417).Curated1
Sequence conflicti308Missing in AAB51250 (PubMed:9271417).Curated1
Sequence conflicti408 – 412PMHKL → HAQV in AAB51250 (PubMed:9271417).Curated5

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

Similar proteinsi

Entry informationi

Entry nameiERR1_MOUSE
AccessioniPrimary (citable) accession number: O08580
Secondary accession number(s): B2RRU9, Q3U110
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 162 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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