RNF216 : ring finger protein 216

Description

The RNF216 (ring finger protein 216) is a protein-coding gene located on chromosome 7.

The RNF216 gene provides instructions for making a protein that plays a role in the ubiquitin-proteasome system, which is the cell machinery that breaks down (degrades) unwanted proteins. Specifically, this protein functions as an E3 ubiquitin ligase. E3 ubiquitin ligases form part of a protein complex that tags damaged or excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them.The RNF216 protein tags proteins involved in an early immune response called inflammation to help control the response. RNF216 also regulates the amount of a protein in nerve cells (neurons) called Arc, which plays a role in a process called synaptic plasticity. Synaptic plasticity is the ability of the connections between neurons (synapses) to change and adapt over time in response to experience. This process is critical for learning and memory. It is likely that the RNF216 protein also regulates proteins involved in other body processes, although these proteins have not been identified.

Isoform 1: This protein acts as an E3 ubiquitin ligase, accepting ubiquitin from specific E2 enzymes and transferring it to target proteins. This process promotes the degradation of these target proteins. This isoform plays a crucial role in regulating antiviral responses by promoting the degradation of TRAF3, TLR4, and TLR9. This, in turn, downregulates NF-kappa-B and IRF3 activation, as well as beta interferon production. Additionally, this isoform participates in the regulation of autophagy by ubiquitinating BECN1, leading to its degradation and inhibition of autophagy. This isoform also plays a role in ARC-dependent synaptic plasticity by mediating ARC ubiquitination, resulting in its rapid degradation via the proteasome. Finally, this isoform plays an essential role in spermatogenesis and male fertility. Mechanistically, it regulates meiosis by promoting the degradation of PRKACB through the ubiquitin-mediated lysosome pathway. It also modulates the gonadotropin-releasing hormone signal pathway by affecting the stability of STAU2, which is required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite.

RNF216 is also known as CAHH, TRIAD3, U7I1, UBCE7IP1, ZIN.

Associated Diseases

• Cerebellar ataxia and hypogonadotropic hypogonadism
• Cerebellar ataxia-hypogonadism syndrome
• Gordon Holmes syndrome