HERPUD1

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jan 2013]

Full Name

Homocysteine Inducible ER Protein With Ubiquitin Like Domain 1

Function

Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:16289116, PubMed:28827405).

Could enhance presenilin-mediated amyloid-beta protein 40 generation. Binds to ubiquilins and this interaction is required for efficient degradation of CD3D via the ERAD pathway (PubMed:18307982).

Biological Process

Endoplasmic reticulum calcium ion homeostasis Source: ParkinsonsUK-UCL
Endoplasmic reticulum unfolded protein response Source: GO_Central
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
Negative regulation of intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
Positive regulation of ER-associated ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
Protein targeting to ER Source: Ensembl
Regulation of ER-associated ubiquitin-dependent protein catabolic process Source: GO_Central
Regulation of protein ubiquitination Source: Ensembl
Response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Response to unfolded protein Source: UniProtKB
Retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
Ubiquitin-dependent ERAD pathway Source: UniProtKB
Ubiquitin-dependent protein catabolic process Source: GO_Central

Cellular Location

Endoplasmic reticulum membrane

Topology

Cytoplasmic: 1-263
Helical: 264-284
Lumenal: 285-289
Helical: 290-310
Cytoplasmic: 311-391