3a
Domain
The second or the third transmembrane region are responsible for Golgi localization.
Function
Plays a role in viral egress via lysosomal trafficking (PubMed:33157038, PubMed:33422265). Forms homotetrameric ion channels (viroporins) localized at endosomes and lysosomes, that may induce deacidification of lysosomes, allowing safe egress of virions via lysosomal trafficking (PubMed:33157038, PubMed:33422265, PubMed:34158638). Also blocks autolysosome formation by binding and sequestering the host component VPS39 for homotypic fusion and protein sorting (HOPS) on late endosomes (PubMed:33422265). This prevents fusion of autophagosomes with lysosomes, disrupting autophagy and facilitating virus egress (PubMed:33422265). Induces host RETREG1/FAM134B-dependent reticulophagy by interacting with host HMGB1 and enhancing the association between HMGB1 and host BECN1 (PubMed:35239449). This induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449).
Post-translational modifications
Exists in both O-glycosylated and non-glycosylated forms. The glycosylated form is associated with the virion.
Cellular localization
- Virion
- Host cell membrane
- Multi-pass membrane protein
- Host endoplasmic reticulum membrane
- Multi-pass membrane protein
- Secreted
- Host cytoplasm
- Host endosome
- Host lysosome
- The cell surface expressed protein can undergo endocytosis. The protein is secreted in association with membranous structures.
Alternative names
ORF3a protein, ORF3a, Accessory protein 3a, Protein 3a, Protein U274, Protein X1, 3a