Testicular Receptor 4 (TR4) (NR2C2) Antibody – Rabbit Polyclonal

Function: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during expression during the late phase of spermatogenesis. Activates transcriptional activity of LHCG and is antagonist of PPARA-mediated transactivation

By similarity. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subunit structure: Homodimer; can bind DNA as homodimer

By similarity. Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity

By similarity. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain. Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity. Interacts with NLRP10. Ref.5 Ref.7 Ref.9

Subcellular location: Nucleus

By similarity Ref.5.

Tissue specificity: Expressed, during embryogenesis, in perichondrium, developing glomeruli structures and tubules of kidney, as well as in intestiinal villi. Also expressed in lung and hair follicles. Ref.4 Ref.6 Ref.8

Induction: Induced by retinoic acid. Ref.10

Post-translational modification: Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non-phosphorylated form preferentially recruits the coactivator, PCAF. Ref.7

Disruption phenotype: Impaired spermatogenesis. Mutant animals have smaller cerebellums with disruption of lobes VI-VII. They exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells 7 days after birth. Deficiencies in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Also responses to novel environmental situations are inhibited. NR2C1 and NR2C2 double knockout results in embryonic lethality around 7.5 dpc and increased apoptosis. Ref.6 Ref.8 Ref.10 Ref.11

Sequence similarities: Belongs to the nuclear hormone receptor family. NR2 subfamily.Contains 1 nuclear receptor DNA-binding domain.

Sequence caution: The sequence AAB33314.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAC18408.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.