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Protein

Steroid hormone receptor ERR1

Gene

ESRRA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.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

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173153-MONOMER.
ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-383280. Nuclear Receptor transcription pathway.
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

HGNCiHGNC:3471. ESRRA.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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.
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.

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.
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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TRRAPQ9Y4A53EBI-372412,EBI-399128

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108405. 36 interactors.
DIPiDIP-35053N.
IntActiP11474. 15 interactors.
MINTiMINT-215609.
STRINGi9606.ENSP00000000442.

Chemistry databases

BindingDBiP11474.

Structurei

Secondary structure

1423
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi195 – 204Combined sources10
Helixi224 – 244Combined sources21
Helixi249 – 251Combined sources3
Helixi254 – 277Combined sources24
Beta strandi280 – 282Combined sources3
Beta strandi284 – 287Combined sources4
Beta strandi290 – 292Combined sources3
Helixi294 – 299Combined sources6
Turni300 – 304Combined sources5
Helixi305 – 317Combined sources13
Turni318 – 320Combined sources3
Helixi323 – 335Combined sources13
Helixi345 – 364Combined sources20
Helixi377 – 382Combined sources6
Helixi385 – 400Combined sources16
Helixi404 – 406Combined sources3
Helixi410 – 421Combined sources12

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...

Miscellaneous databases

EvolutionaryTraceiP11474.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 76Repressor domainAdd BLAST76
Regioni206 – 402Ligand binding domainAdd BLAST197
Regioni403 – 423AF-2 domainAdd BLAST21

Sequence similaritiesi

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

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.
OMAiCHPGHKE.
OrthoDBiEOG091G0DYP.
PhylomeDBiP11474.
TreeFamiTF323751.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. 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.
[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]

Sequences (2)i

Sequence statusi: Complete.

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

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

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

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. 36 interactors.
DIPiDIP-35053N.
IntActiP11474. 15 interactors.
MINTiMINT-215609.
STRINGi9606.ENSP00000000442.

Chemistry databases

BindingDBiP11474.
ChEMBLiCHEMBL3429.
GuidetoPHARMACOLOGYi622.

PTM databases

iPTMnetiP11474.
PhosphoSitePlusiP11474.

Polymorphism and mutation databases

DMDMi215274146.

Proteomic databases

EPDiP11474.
PaxDbiP11474.
PeptideAtlasiP11474.
PRIDEiP11474.

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.
GeneCardsiESRRA.
HGNCiHGNC:3471. ESRRA.
HPAiHPA053785.
MIMi601998. gene.
neXtProtiNX_P11474.
OpenTargetsiENSG00000173153.
PharmGKBiPA27887.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000173153-MONOMER.
ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-383280. Nuclear Receptor transcription pathway.
SignaLinkiP11474.
SIGNORiP11474.

Miscellaneous databases

EvolutionaryTraceiP11474.
GeneWikiiEstrogen-related_receptor_alpha.
GenomeRNAii2101.
PROiP11474.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173153.
CleanExiHS_ESRRA.
ExpressionAtlasiP11474. baseline and differential.
GenevisibleiP11474. HS.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. 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.
[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]
ProtoNetiSearch...

Entry informationi

Entry nameiERR1_HUMAN
AccessioniPrimary (citable) accession number: P11474
Secondary accession number(s): Q14514
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 25, 2008
Last modified: November 30, 2016
This is version 190 of the entry and version 3 of the sequence. [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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.