The ERRs are orphan nuclear receptors, meaning the identity of their endogenous ligand has yet to be unambiguously determined.
There are three human estrogen related receptors: ERRs bind enhancers throughout the genome where they exert effects on gene regulation.
The ERR family exhibit varying transcriptional activation capabilities and physically interact with the transcriptional co-activators PGC1-alpha and PGC1-beta,[1][2][3][4][5] via their AF-2 domains and the leucine-rich nuclear receptor interacting motifs (LxxLL) present in the PGC-1 proteins,[6] The ERR family have been demonstrated to control energy homeostasis,[6][7] oxidative metabolism,[1][8] and mitochondrial biogenesis,[1] while effecting mammalian physiology in the heart,[9][10][11][12] brown adipose tissue,[13][14][15] white adipose tissue,[16] placenta,[17] macrophages,[2] and demonstrated additional roles in diabetes and cancer.
[18] The contributions of individual ERRs to physiology continue to be elucidated through the generation of sophisticated tissue-specific gene knockout mouse models.
[citation needed] This article on a gene on human chromosome 14 is a stub.