ESRRG

Protein identityUniProt · HPA

UniProt accession

P62508

Gene

ESRRG

Ensembl

ENSG00000196482

Chromosome

1

Canonical length

458 aa

Protein class

FDA approved drug targets, Nuclear receptors, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the estrogen receptor-related receptor (ESRR) family, which belongs to the nuclear hormone receptor superfamily. All members of the ESRR family share an almost identical DNA binding domain, which is composed of two C4-type zinc finger motifs. The ESRR members are orphan nuclear receptors; they bind to the estrogen response element and steroidogenic factor 1 response element, and activate genes controlled by both response elements in the absence of any ligands. The ESRR family is closely related to the estrogen receptor (ER) family. They share target genes, co-regulators and promoters, and by targeting the same set of genes, the ESRRs seem to interfere with the ER-mediated estrogen response in various ways. It has been reported that the family member encoded by this gene functions as a transcriptional activator of DNA cytosine-5-methyltransferases 1 (Dnmt1) expression by direct binding to its response elements in the DNMT1 promoters, modulates cell proliferation and estrogen signaling in breast cancer, and negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation and bone formation. Multiple alternatively spliced transcript variants have been identified, which mainly differ at the 5' end and some of which encode protein isoforms differing in the N-terminal region. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

458 residues, UniProt reviewed canonical sequence.

>P62508|ESRRG
     1  MDSVELCLPE SFSLHYEEEL LCRMSNKDRH IDSSCSSFIK TEPSSPASLT DSVNHHSPGG
    61  SSDASGSYSS TMNGHQNGLD SPPLYPSAPI LGGSGPVRKL YDDCSSTIVE DPQTKCEYML
   121  NSMPKRLCLV CGDIASGYHY GVASCEACKA FFKRTIQGNI EYSCPATNEC EITKRRRKSC
   181  QACRFMKCLK VGMLKEGVRL DRVRGGRQKY KRRIDAENSP YLNPQLVQPA KKPYNKIVSH
   241  LLVAEPEKIY AMPDPTVPDS DIKALTTLCD LADRELVVII GWAKHIPGFS TLSLADQMSL
   301  LQSAWMEILI LGVVYRSLSF EDELVYADDY IMDEDQSKLA GLLDLNNAIL QLVKKYKSMK
   361  LEKEEFVTLK AIALANSDSM HIEDVEAVQK LQDVLHEALQ DYEAGQHMED PRRAGKMLMT
   421  LPLLRQTSTK AVQHFYNIKL EGKVPMHKLF LEMLEAKV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ESRRG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

44 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ESRRG.

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 56 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Movement disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0.07

gnomAD missense Z

2.56

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• positive regulation of cold-induced thermogenesis
• positive regulation of transcription by RNA polymerase II
• regulation of DNA-templated transcription
• regulation of transcription by RNA polymerase II
• retinoic acid receptor signaling pathway

Molecular functions

• AF-2 domain binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• estrogen response element binding
• identical protein binding
• nuclear receptor activity
• nuclear steroid receptor activity
• sequence-specific double-stranded DNA binding
• steroid binding
• zinc ion binding

Cellular components

• chromatin
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Nuclear hormone receptor, ligand-binding domain
• Zinc finger, nuclear hormone receptor-type
• Nuclear hormone receptor
• Retinoic acid receptor
• Zinc finger, NHR/GATA-type
• Estrogen receptor/oestrogen-related receptor
• Oestrogen-related receptor
• Nuclear hormone receptor-like domain superfamily
• Nuclear hormone receptor family NR3 subfamily
• Ligand-binding domain of nuclear hormone receptor
• Double treble clef zinc finger, C4 type

KeywordsUniProt

• Acetylation
• Activator
• DNA-binding
• Isopeptide bond
• Metal-binding
• Nucleus
• Phosphoprotein
• Receptor
• Transcription
• Transcription regulation
• Ubl conjugation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of ESRRG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NCOA1
• NCOR2
• NRIP1
• PNRC1
• PNRC2
• NR0B1
• PPARGC1A