Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1)

HERPUD1, or Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein, is a stress-inducible integral membrane protein of the endoplasmic reticulum. It is a component of the ER quality control machinery and ER-associated protein degradation (ERAD), participating in the recognition and ubiquitin-dependent disposal of misfolded proteins. HERPUD1 contains a pivotal ubiquitin-like domain (UBL) at its N-terminus, crucial for its regulated proteasomal degradation. Its expression is upregulated under ER stress and by the unfolded protein response (UPR). HERPUD1 interacts with ubiquilin and presenilin family members, impacting amyloid-beta production. Stabilized HERPUD1 downregulates autophagy, promotes ER remodeling into stacked tubular forms, and establishes ER-lysosome contact sites, which favor cell survival under stress conditions. It is implicated in neurodegenerative diseases due to its influence on amyloid-beta and is associated with cancer cell survival and adaptation to cellular stress, making it a relevant therapeutic target in cancer and possibly other proteinopathy-related diseases.

Other names

Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 proteinHERPUD1HERPKIAA0025MIF1 (MMF-inducible fragment protein 1)SUPMMS-inducibleHERPUD1 intronic transcript 1

Induction or inhibition of ER stress responses regulates HERPUD1 expression. Modulation of proteasomal degradation (i.e., proteasome inhibitors such as MG132 stabilize HERPUD1 levels). Possible modulation of autophagy, especially under stress or in cancer therapy.