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Protein

Steroid hormone receptor ERR1

Gene

ESRRA

Organism
Homo sapiens (Human)
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.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei124Required for DNA-dependent dimerization1

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-HSA-1989781 PPARA activates gene expression
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-8939902 Regulation of RUNX2 expression and activity
SignaLinkiP11474
SIGNORiP11474

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, ESRL1, NR3B1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000173153.13
HGNCiHGNC:3471 ESRRA
MIMi601998 gene
neXtProtiNX_P11474

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14K → R: Some loss of sumoylation. Complete loss of sumoylation; when associated with R-403. 2 Publications1
Mutagenesisi19S → A: 50% loss of phosphorylation but represses transactivation activity in the absence of coactivator. Almost complete loss of phosphorylation and 2-fold loss of repression of transactivation activity in response to coactivator; when associated with A-22. 2 Publications1
Mutagenesisi19S → D: Represses transactivation activity in response to coactivator as for wild type; when associated with D-22. 2 Publications1
Mutagenesisi22S → A: 15% loss of phosphorylation but little transactivating activity. Almost complete loss of phosphorylation and 2-fold loss of repression of transactivation activity in the presence of coactivator; when associated with A-19. 2 Publications1
Mutagenesisi22S → D: Represses transactivation activity in response to coactivator as for wild type; when associated with D-19. 2 Publications1
Mutagenesisi118S → A: Binds DNA as a monomer or as a dimer as for wild type. No effect on interaction with PPARGC1A. 1 Publication1
Mutagenesisi124T → A: Binds DNA predominantly as a monomer. Loss of interaction with PPARGC1A. 1 Publication1
Mutagenesisi129K → R: Abolishes acetylation by PCAF/KAT2B; when associated with R-138, R-160 and R-162. 1 Publication1
Mutagenesisi138K → R: Abolishes acetylation by PCAF/KAT2B; when associated with R-129, R-160 and R-162. 1 Publication1
Mutagenesisi160K → R: Abolishes acetylation by PCAF/KAT2B; when associated with R-129, R-138 and R-162. 1 Publication1
Mutagenesisi162K → R: Abolishes acetylation by PCAF/KAT2B; when associated with R-129, R-138 and R-160. 1 Publication1
Mutagenesisi258 – 262MSVLQ → VSVLE: Almost complete loss of interaction to L2 or to L3 of PPARGC1A. 1 Publication5
Mutagenesisi259S → H: Little effect on binding L2 of PPARGC1A. Greatly reduced binding to L3 of PPARGC1A. 1 Publication1
Mutagenesisi315R → A: Almost complete loss of interaction to L2 or to L3 of PPARGC1A. 1 Publication1
Mutagenesisi338D → A: Almost complete loss of interaction to L2 or to L3 of PPARGC1A. 1 Publication1
Mutagenesisi341H → A: Little effect on binding L3 of PPARGC1A. 1 Publication1
Mutagenesisi343E → A: No effect on binding L3 of PPARGC1A. 1 Publication1
Mutagenesisi403K → R: Decrease in sumoylation. No effect on transcriptional activity. Complete loss of sumoylation; when associated with R-14. 2 Publications1
Mutagenesisi413L → A: Loss of coactivation activity; when associated with A-418. Loss of increased response to coactivator; when associated with A-19 and A-418. 1 Publication1
Mutagenesisi418L → A: Loss of coactivation activity; when associated with A-413. Loss of increased response to coactivator activity; when associated with A-19 and A-413. 1 Publication1
Mutagenesisi421 – 423Missing : Greatly reduced interaction with L3 motif of PPARGC1A. Less effect on binding to L2 motif of PPARGC1A. 1 Publication3
Mutagenesisi423D → A: Little effect on binding L3 of PPARGC1A. 1

Organism-specific databases

DisGeNETi2101
OpenTargetsiENSG00000173153
PharmGKBiPA27887

Chemistry databases

ChEMBLiCHEMBL3429
DrugBankiDB06833 1-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-INDOL-3-YL]METHYL}METHANAMINE
DB00197 Troglitazone
GuidetoPHARMACOLOGYi622

Polymorphism and mutation databases

DMDMi215274146

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536601 – 423Steroid hormone receptor ERR1Add BLAST423

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)2 Publications
Modified residuei19PhosphoserineCombined sources2 Publications1
Modified residuei22PhosphoserineCombined sources2 Publications1
Modified residuei129N6-acetyllysine; by PCAF/KAT2B1 Publication1
Modified residuei138N6-acetyllysine; by PCAF/KAT2B1 Publication1
Modified residuei160N6-acetyllysine; by PCAF/KAT2B1 Publication1
Modified residuei162N6-acetyllysine; by PCAF/KAT2B1 Publication1
Cross-linki189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate2 Publications
Cross-linki403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources

Post-translational modificationi

Phosphorylation on Ser-19 enhances sumoylation on Lys-14 increasing repression of transcriptional activity.2 Publications
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.2 Publications
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.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP11474
PaxDbiP11474
PeptideAtlasiP11474
PRIDEiP11474
ProteomicsDBi52781
52782 [P11474-2]

PTM databases

iPTMnetiP11474
PhosphoSitePlusiP11474

Expressioni

Inductioni

Induced by PGC1alpha in a number of specific cell types including heart, kidney and muscle.1 Publication

Gene expression databases

BgeeiENSG00000173153 Expressed in 207 organ(s), highest expression level in apex of heart
CleanExiHS_ESRRA
ExpressionAtlasiP11474 baseline and differential
GenevisibleiP11474 HS

Organism-specific databases

HPAiHPA053785

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. Interacts with MAPK15; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108405, 38 interactors
DIPiDIP-35053N
IntActiP11474, 28 interactors
MINTiP11474
STRINGi9606.ENSP00000000442

Chemistry databases

BindingDBiP11474

Structurei

Secondary structure

1423
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP11474
SMRiP11474
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11474

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini193 – 421NR LBDPROSITE-ProRule annotationAdd BLAST229

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 76Repressor domainAdd BLAST76
Regioni403 – 423AF-2 domainAdd 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
InParanoidiP11474
KOiK08552
OMAiCHSGHKE
OrthoDBiEOG091G0DYP
PhylomeDBiP11474
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, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P11474-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSSQVVGIEP LYIKAEPASP DSPKGSSETE TEPPVALAPG PAPTRCLPGH
60 70 80 90 100
KEEEDGEGAG PGEQGGGKLV LSSLPKRLCL VCGDVASGYH YGVASCEACK
110 120 130 140 150
AFFKRTIQGS IEYSCPASNE CEITKRRRKA CQACRFTKCL RVGMLKEGVR
160 170 180 190 200
LDRVRGGRQK YKRRPEVDPL PFPGPFPAGP LAVAGGPRKT AAPVNALVSH
210 220 230 240 250
LLVVEPEKLY AMPDPAGPDG HLPAVATLCD LFDREIVVTI SWAKSIPGFS
260 270 280 290 300
SLSLSDQMSV LQSVWMEVLV LGVAQRSLPL QDELAFAEDL VLDEEGARAA
310 320 330 340 350
GLGELGAALL QLVRRLQALR LEREEYVLLK ALALANSDSV HIEDAEAVEQ
360 370 380 390 400
LREALHEALL EYEAGRAGPG GGAERRRAGR LLLTLPLLRQ TAGKVLAHFY
410 420
GVKLEGKVPM HKLFLEMLEA MMD
Length:423
Mass (Da):45,510
Last modified:November 25, 2008 - v3
Checksum:iBAE62DAF0BE6BA96
GO
Isoform 2 (identifier: P11474-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     191-191: Missing.

Note: No experimental confirmation available.
Show »
Length:422
Mass (Da):45,439
Checksum:i482E152354383842
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GWT5F5GWT5_HUMAN
Steroid hormone receptor ERR1
ESRRA
109Annotation score:
H0YGT3H0YGT3_HUMAN
Steroid hormone receptor ERR1
ESRRA
198Annotation score:
F5H0E9F5H0E9_HUMAN
Steroid hormone receptor ERR1
ESRRA
162Annotation score:

Sequence cautioni

The sequence AAB17015 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA35778 differs from that shown. Reason: Frameshift at positions 345 and 354.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035756191Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51416 mRNA Translation: CAA35778.1 Frameshift.
L38487 mRNA Translation: AAB17015.1 Different initiation.
AP001453 Genomic DNA No translation available.
CCDSiCCDS41667.1 [P11474-1]
CCDS60830.1 [P11474-2]
PIRiA29345
RefSeqiNP_001269379.1, NM_001282450.1 [P11474-1]
NP_001269380.1, NM_001282451.1 [P11474-2]
NP_004442.3, NM_004451.4 [P11474-1]
UniGeneiHs.110849

Genome annotation databases

EnsembliENST00000000442; ENSP00000000442; ENSG00000173153 [P11474-1]
ENST00000405666; ENSP00000384851; ENSG00000173153 [P11474-1]
ENST00000406310; ENSP00000385971; ENSG00000173153 [P11474-2]
GeneIDi2101
KEGGihsa:2101
UCSCiuc001nzr.3 human [P11474-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51416 mRNA Translation: CAA35778.1 Frameshift.
L38487 mRNA Translation: AAB17015.1 Different initiation.
AP001453 Genomic DNA No translation available.
CCDSiCCDS41667.1 [P11474-1]
CCDS60830.1 [P11474-2]
PIRiA29345
RefSeqiNP_001269379.1, NM_001282450.1 [P11474-1]
NP_001269380.1, NM_001282451.1 [P11474-2]
NP_004442.3, NM_004451.4 [P11474-1]
UniGeneiHs.110849

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XB7X-ray2.50A194-423[»]
2PJLX-ray2.30A/B193-423[»]
3D24X-ray2.11A/C192-423[»]
3K6PX-ray2.00A193-423[»]
ProteinModelPortaliP11474
SMRiP11474
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108405, 38 interactors
DIPiDIP-35053N
IntActiP11474, 28 interactors
MINTiP11474
STRINGi9606.ENSP00000000442

Chemistry databases

BindingDBiP11474
ChEMBLiCHEMBL3429
DrugBankiDB06833 1-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-INDOL-3-YL]METHYL}METHANAMINE
DB00197 Troglitazone
GuidetoPHARMACOLOGYi622

PTM databases

iPTMnetiP11474
PhosphoSitePlusiP11474

Polymorphism and mutation databases

DMDMi215274146

Proteomic databases

EPDiP11474
PaxDbiP11474
PeptideAtlasiP11474
PRIDEiP11474
ProteomicsDBi52781
52782 [P11474-2]

Protocols and materials databases

DNASUi2101
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000000442; ENSP00000000442; ENSG00000173153 [P11474-1]
ENST00000405666; ENSP00000384851; ENSG00000173153 [P11474-1]
ENST00000406310; ENSP00000385971; ENSG00000173153 [P11474-2]
GeneIDi2101
KEGGihsa:2101
UCSCiuc001nzr.3 human [P11474-1]

Organism-specific databases

CTDi2101
DisGeNETi2101
EuPathDBiHostDB:ENSG00000173153.13
GeneCardsiESRRA
HGNCiHGNC:3471 ESRRA
HPAiHPA053785
MIMi601998 gene
neXtProtiNX_P11474
OpenTargetsiENSG00000173153
PharmGKBiPA27887
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000233467
HOVERGENiHBG108344
InParanoidiP11474
KOiK08552
OMAiCHSGHKE
OrthoDBiEOG091G0DYP
PhylomeDBiP11474
TreeFamiTF323751

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-8939902 Regulation of RUNX2 expression and activity
SignaLinkiP11474
SIGNORiP11474

Miscellaneous databases

EvolutionaryTraceiP11474
GeneWikiiEstrogen-related_receptor_alpha
GenomeRNAii2101
PROiPR:P11474
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173153 Expressed in 207 organ(s), highest expression level in apex of heart
CleanExiHS_ESRRA
ExpressionAtlasiP11474 baseline and differential
GenevisibleiP11474 HS

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, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiERR1_HUMAN
AccessioniPrimary (citable) accession number: P11474
Secondary accession number(s): Q14514
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 25, 2008
Last modified: November 7, 2018
This is version 207 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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