NR4A2

Protein identityUniProt · HPA

UniProt accession

P43354

Gene

NR4A2

Ensembl

ENSG00000153234

Chromosome

2

Canonical length

598 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Nuclear receptors, Predicted intracellular proteins, Transcription factors

Subcellular location

Nuclear speckles

OverviewNCBI Gene

This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcription factor. Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson disease, schizophernia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

598 residues, UniProt reviewed canonical sequence.

>P43354|NR4A2
     1  MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE ITATTSLPSF
    61  STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY QQHSHLPPQS EEMMPHSGSV
   121  YYKPSSPPTP TTPGFQVQHS PMWDDPGSLH NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ
   181  SPPGTPVSSC QMRFDGPLHV PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA
   241  SQLLDTQVPS PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL
   301  ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK SPQEPSPPSP
   361  PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT QHIQQFYDLL TGSMEIIRGW
   421  AEKIPGFADL PKADQDLLFE SAFLELFVLR LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG
   481  EWIDSIVEFS SNLQNMNIDI SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT
   541  FNNGGLNRPN YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NR4A2 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)

0.48

Highest tissue expression

126 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NR4A2.

Disease | AllUniProt

Conditions NR4A2 is implicated in, by any mechanism.

• Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism (IDLDP) MIM:619911

Disease | GeneticClinVar

52 pathogenic / likely-pathogenic of 251 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
• Inborn genetic diseases
• Epilepsy
• Neurodevelopmental disorder
• Autism spectrum 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)

0.13

gnomAD pLI

1

gnomAD missense Z

2.24

DepMap mean gene effect

-0.05

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

• adult locomotory behavior
• canonical Wnt signaling pathway
• cellular response to corticotropin-releasing hormone stimulus
• cellular response to oxidative stress
• central nervous system neuron differentiation
• central nervous system projection neuron axonogenesis
• DNA-templated transcription
• dopamine biosynthetic process
• dopaminergic neuron differentiation
• fat cell differentiation
• habenula development
• midbrain dopaminergic neuron differentiation
• negative regulation of apoptotic signaling pathway
• negative regulation of neuron apoptotic process
• negative regulation of transcription by RNA polymerase II
• neuron apoptotic process
• neuron maturation
• neuron migration
• positive regulation of transcription by RNA polymerase II
• post-embryonic development
• regulation of dopamine metabolic process
• regulation of respiratory gaseous exchange
• regulation of transcription by RNA polymerase II
• response to amphetamine
• response to hypoxia
• transcription by RNA polymerase II
• general adaptation syndrome

Molecular functions

• beta-catenin binding
• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• nuclear glucocorticoid receptor binding
• nuclear receptor activity
• nuclear retinoid X receptor binding
• protein heterodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• zinc ion binding

Cellular components

• chromatin
• cytoplasm
• nuclear speck
• nucleoplasm
• nucleus
• protein-containing complex
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Nuclear hormone receptor, ligand-binding domain
• Zinc finger, nuclear hormone receptor-type
• Nuclear hormone receptor
• Nuclear receptor subfamily 4 group A member 1-3
• Zinc finger, NHR/GATA-type
• Nuclear hormone receptor-like domain superfamily
• Ligand-binding domain of nuclear hormone receptor
• Double treble clef zinc finger, C4 type
• Nuclear receptor subfamily 4 group A member 2

KeywordsUniProt

• Cytoplasm
• DNA-binding
• Dystonia
• Intellectual disability
• Metal-binding
• Nucleus
• Parkinsonism
• Receptor
• Transcription
• Transcription regulation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of NR4A2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HADC1
• NCOR2
• PER2
• SFPQ
• SIN3A