Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Identification of major proteins in the lipid droplet-enriched fraction isolated from the human hepatocyte cell line HuH7.
SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins.
UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover.
The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER.
Defining human ERAD networks through an integrative mapping strategy.
Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid droplet turnover.
-
UBXD8/FAF2 recruits p97/VCP to lipid droplets, binds directly to ATGL and promotes dissociation of its coactivator CGI-58, inhibiting lipolysis and increasing lipid-droplet size.
-
Association of UBXD8 with the ER-resident rhomboid pseudoprotease UBAC2 restricts trafficking of UBXD8 from the ER to lipid droplets.
Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and disrupts endoplasmic reticulum-associated protein degradation.
Identification of ERAD components essential for dislocation of the null Hong Kong variant of α-1-antitrypsin (NHK).
Architecture of the human interactome defines protein communities and disease networks.
The AAA+ ATPase p97, a cellular multitool.
LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
LMBR1L regulates lymphopoiesis through Wnt/β-catenin signaling.
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner.
Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.
Multimodal cell maps as a foundation for structural and functional genomics.
Exocytosis of azurophil granule lumen proteins
UniProt entry Q96CS3 (FAF2_HUMAN), FAS-associated factor 2 / UBXD8
-
FAF2/UBXD8 is a UBA-UAS-UBX p97/VCP cofactor at the ER membrane and lipid droplets, functioning in ERAD substrate dislocation, ATGL inhibition/lipid-droplet regulation, and stress-granule disassembly.
Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.
-
Systematic AP-MS of the human VCP/p97-UBXD adaptor network places FAF2/UBXD8 among the membrane-tethered UBXD adaptors linked to ERAD and lipid-droplet homeostasis, recovering interactors such as AMFR, DERLIN2, AUP1, BAG6 and UBAC2 and the shared UFD1L/NPLOC4 module.
Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
-
In reconstituted CMG-helicase disassembly assays, FAF2 (together with UBXN7 and FAF1) acts as a UBX cofactor that lowers the high ubiquitin-chain-length threshold of mammalian p97-UFD1-NPL4, stabilising productive interactions between UFD1-NPL4 and K48-linked chains of at least five ubiquitins; FAF1/FAF2 use a previously uncharacterised coiled-coil domain rather than the UBA domain.
The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition.
-
The p97-UBXD8/FAF2 complex localises to ER-mitochondria contact sites (ERMCS) and limits excessive contacts in a p97-catalytic-activity-dependent manner; loss of UBXD8 increases membrane lipid saturation via the SREBP1-SCD1 axis, and aberrant contacts are rescued by unsaturated fatty acids or SCD1 overexpression.
AAA+ ATPase chaperone p97/VCP(FAF2) governs basal pexophagy.
-
FAF2/UBXD8, with p97/VCP (NPLOC4/UFD1), maintains peroxisome homeostasis by extracting ubiquitylated peroxisomal membrane proteins such as PMP70; in FAF2-deficient cells PMP70 accumulates, recruiting the autophagy adaptor OPTN to peroxisomes and inducing basal pexophagy, so FAF2-p97 negatively regulates pexophagy rather than acting in peroxisome biogenesis.
A UBH-UBX module amplifies p97/VCP's unfolding power to facilitate protein extraction and degradation.
-
FAF2 contains a conserved ubiquitin-binding helix (UBH) adjacent to its UBX domain; the UBH-UBX module enhances engagement of ubiquitinated substrates with p97-UFD1L-NPLOC4 and boosts the motor's ATPase and unfolding activities ~2-fold, with reconstituted p97-UFD1L-NPLOC4-FAF2 sufficient to extract membrane proteins from the ER and mitochondria. FAF2 knockout stabilised the ERAD client CD4.