ER-phagy (Selective ER Autophagy) Project

SCOPING BIOLOGY_DOMAINFLAGSHIP

Species: human

Genes: SEC62 ATL3 ULK1 ATG9A EIF2AK3

Warnings (1)

ER-phagy (Selective ER Autophagy) Project

Bottom line: scoped, not yet started as a project. ER-phagy is the selective
autophagy of endoplasmic reticulum, carried out by ER-membrane receptors
(FAM134B/RETREG1, RTN3, SEC62, CCPG1, TEX264, ATL3) that bind ATG8-family
proteins such as LC3B and GABARAP. The candidate table below lists 12 human genes, but
no ER-phagy-specific work has been done: there is no module and no gene review
made for this project. Five candidates were reviewed for other projects (SEC62
and ATL3 for Proteostasis, ULK1 and ATG9A for the CONDENSATES phagophore audit,
EIF2AK3 as a Proteostasis review). Of those, SEC62 keeps its IMP reticulophagy
(GO:0061709) annotation as non-core, and the ATL3 review declined to add
reticulophagy without better evidence. The receptors that define the field,
RETREG1, RTN3, CCPG1 and TEX264, have no review yet.

Overview

ER-phagy is the selective autophagy of endoplasmic reticulum, mediated by specific receptor proteins that link ER membranes to the autophagy machinery. Most receptors were characterized 2017-2023, making this a relatively new field with recent discoveries.

Model Species

Primary: Homo sapiens (human)
- Most receptors characterized in human cells
- Disease relevance (neurodegeneration, viral infection)

Core Pathway Architecture

ER-phagy Receptors

Proteins that bridge ER to autophagosomes via LC3-interacting regions (LIRs):
- FAM134B (RETREG1) - Reticulon-like, sheet ER-phagy
- RTN3 - Reticulon 3, tubular ER
- SEC62 - Translocon-associated, recovER-phagy
- CCPG1 - Cell cycle progression gene 1
- TEX264 - Three-way junction ER-phagy
- ATL3 - Atlastin-3, tubular ER

Core Autophagy Machinery

ER Stress Connection

Candidate Genes (12)

Gene UniProt Function
FAM134B Q9H6L5 ER-phagy receptor (sheets)
RTN3 O95197 ER-phagy receptor (tubules)
SEC62 Q99442 RecovER-phagy receptor
CCPG1 Q9ULG6 ER-phagy receptor
TEX264 Q9Y6I9 ER-phagy receptor
ATL3 Q6DD88 ER-phagy receptor
MAP1LC3B Q9GZQ8 Autophagosome protein
GABARAP O95166 ATG8 family
ULK1 O75385 Autophagy kinase
ATG9A Q7Z3C6 Membrane trafficking
ERN1 O75460 IRE1α, ER stress sensor
EIF2AK3 Q9NZJ5 PERK, ER stress kinase

Key Recent Discoveries (2020+)

Disease Relevance

Project Status

Slides