The nuclear receptor 4A2 (NR4A2) (nuclear receptor subfamily 4 group A member 2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene.[5] NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.
NR4A2 plays a key role in the maintenance of the dopaminergic system of the brain.[6] Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson's disease and schizophrenia. Misregulation of this gene may be associated with rheumatoid arthritis. Four transcript variants encoding four distinct isoforms have been identified for this gene. Additional alternate splice variants may exist, but their full-length nature has not been determined.[7]
This protein is thought to be critical to development of the dopamine phenotype in the midbrain, as mice without NR4A2 are lacking expression of this phenotype. This is further confirmed by studies showing that when forcing NR4A2 expression in naïve precursor cells, there is complete dopamine phenotype gene expression.[8]
While NR4A2 is a key protein, there are other factors required as research shows that solely expressing NR4A2 fails to stimulate this phenotypic gene expression. One of these suggested factors is winged-helix transcription factor 2 (Foxa2). Studies have found these two factors to be within the same region of developing dopaminergic neurons, both of these factors were present in order to have expression for the dopamine phenotype. [8]