Table 1.

Endoplasmic reticulum–associated degradation (ERAD) factors implicated in lipid metabolism

Protein	Alternative name(s)	ERAD function	Domain(s)	Topology	Associated metabolic process	Regulated substrate	Reference(s)
Insig-1		Substrate-specific adaptor		M, poly	Cholesterol synthesis	HMGCR	71, 154, 155, 166
Insig-2		Substrate-specific adaptor		M, poly	Cholesterol synthesis	HMGCR	71,154
UBIAD1		Substrate-specific regulator	Prenyltransferase	M, poly	Cholesterol synthesis	HMGCR	152
Hrd1	Synoviolin	E3 ligase	RING	M, poly	Cholesterol synthesis	HMGCR	76
gp78	AMFR, RNF45	E3 ligase	RING, CUE, G2BR, VIM	M, poly	Cholesterol synthesis, SREBP processing, TAG synthesis, lipoprotein secretion	HMGCR, Insig-1, DGAT2, ApoB100	34,71,85,95, 166
Trc8	RNF138	E3 ligase	RING, sterol-binding	M, poly	Cholesterol synthesis, SREBP processing	HMGCR, Insig-1	71, 88
MARCH6	Teb4, RNF176	E3 ligase	RING	M, poly	Cholesterol synthesis	HMGCR, SM	39,44, 170
Ube2g2	Ubc7	E2-conjugating enzyme		C	Cholesterol synthesis	HMGCR	113
AUP1		Ube2g2 recruitment	CUE, G2BR	M, HP	Cholesterol synthesis	HMGCR	70
Derlin-1		Dislocation	Rhomboid, SHP box	M, poly	Lipoprotein secretion	ApoB100	174
Erlin-2	SPFH2	Scaffold	SPFH-like	M, SP	Cholesterol synthesis	HMGCR	72
TMUB1	DULP	Scaffold	UBL	M, SP	Cholesterol synthesis	HMGCR	72
UBXD8	Faf2, ETEA	VCP recruitment	UBA, UAS, UBX	M, HP	TAG synthesis, TAG degradation, SREBP processing, lipoprotein secretion	Insig-1, ApoB100, ATGL	84, 87, 133, 174
VCP	p97	AAA+ ATPase	AAA+	C	Cholesterol synthesis, TAG synthesis and degradation, lipoprotein secretion	HMGCR, Insig-1, ApoB100, SCD1	35, 74, 87, 166

Abbreviations: AAA+, ATPases associated with diverse cellular activities; ApoB100, apolipoprotein B100; ATGL, adipose triglyceride lipase; AUP1, ancient ubiquitous protein 1; C, cytosolic; CUE, coupling of ubiquitin to endoplasmic reticulum degradation; Derlin-1, degradation in endoplasmic reticulum protein 1; DGAT2, diacylglycerol acyltransferase 2; Erlin-2, endoplasmic reticulum lipid raft–associated protein 2; G2BR, Ube2g2-binding region; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; HP, hairpin; Insig-1, insulin-induced gene 1 protein; Insig-2, insulin-induced gene 2 protein; M, membrane; MARCH6, membrane-associated RING finger protein 6; poly, polytopic; SCD1, stearoyl-CoA desaturase 1; SM, squalene monooxygenase; SP, single pass; SREBP, sterol regulatory element–binding protein; TAG, triacylglycerol; TMUB1, transmembrane and ubiquitin-like domain–containing protein 1; Trc8, translocation in renal carcinoma on chromosome 8 protein; UBA, ubiquitin-associated; Ube2g2, ubiquitin-conjugating enzyme E2 G2; UBIAD1, UbiA prenyltransferase domain–containing protein 1; UBL, ubiquitin-like; UBX, ubiquitin regulatory X; UBXD8, UBX domain–containing protein 8; VCP, valosin-containing protein; VIM, VCP interacting motif.