NBR1

NBR1, short for neighbor of BRCA1 gene 1, is a protein encoded by the NBR1 gene in humans. It is a selective autophagy receptor that participates in the cellular process of autophagy by linking ubiquitinated cargo to the autophagy machinery.

Like other selective autophagy receptors, NBR1 binds to ubiquitinated substrates and to Atg8 family proteins such as LC3 and GABARAP through an LC3-interacting region (LIR). This enables the cargo to be enclosed by an autophagosome for delivery to lysosomes for degradation. NBR1 functions in coordination with p62/SQSTM1 and contributes to the clearance of protein aggregates, damaged organelles, and other ubiquitin-tagged cargo. It has been implicated in selective autophagy pathways such as aggrephagy (protein aggregates) and pexophagy (peroxisomes).

Structurally, NBR1 possesses regions that promote self-association or dimerization and domains that recognize ubiquitin and interact with ATG8 family proteins, facilitating cargo recognition and autophagosome recruitment.

Physiologically, NBR1 operates in mammalian cells under stress to maintain cellular homeostasis. Disruption of NBR1 function can impair selective autophagy and lead to accumulation of ubiquitinated material, contributing to cellular stress responses. Given the central role of autophagy in disease, NBR1 is often studied in the context of neurodegenerative diseases and cancer where protein quality control is compromised.