9o9u

Structural highlights

Disease

ERLN1_HUMAN Autosomal recessive spastic paraplegia type 62. The disease is caused by variants affecting the gene represented in this entry.

Function

ERLN1_HUMAN Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway (PubMed:37683630). Binds cholesterol and may promote ER retention of the SCAP-SREBF complex (PubMed:24217618).^{[1] [2] [3]} (Microbial infection) Required early in hepatitis C virus (HCV) infection to initiate RNA replication, and later in the infection to support infectious virus production.^[4]

References

1. ↑ Pearce MM, Wormer DB, Wilkens S, Wojcikiewicz RJ. An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors. J Biol Chem. 2009 Apr 17;284(16):10433-45. PMID:19240031 doi:10.1074/jbc.M809801200
2. ↑ Huber MD, Vesely PW, Datta K, Gerace L. Erlins restrict SREBP activation in the ER and regulate cellular cholesterol homeostasis. J Cell Biol. 2013 Nov 11;203(3):427-36. PMID:24217618 doi:10.1083/jcb.201305076
3. ↑ Teo QW, Wong HH, Heunis T, Stancheva V, Hachim A, Lv H, Siu L, Ho J, Lan Y, Mok CKP, Ulferts R, Sanyal S. Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection. Dev Cell. 2023 Nov 20;58(22):2495-2509.e6. PMID:37683630 doi:10.1016/j.devcel.2023.08.013
4. ↑ Whitten-Bauer C, Chung J, Gómez-Moreno A, Gomollón-Zueco P, Huber MD, Gerace L, Garaigorta U. The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection. Cells. 2019 Dec 2;8(12):1555. PMID:31810281 doi:10.3390/cells8121555