ERLIN2
This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
Full Name
ER Lipid Raft Associated 2
Research Area
Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376).
Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306).
Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618).
Biological Process
Cholesterol metabolic process Source: UniProtKB-KW
Negative regulation of cholesterol biosynthetic process Source: UniProtKB
Negative regulation of fatty acid biosynthetic process Source: UniProtKB
SREBP signaling pathway Source: UniProtKB
Ubiquitin-dependent ERAD pathway Source: UniProtKB
Cellular Location
Endoplasmic reticulum membrane. Associated with lipid raft-like domains of the endoplasmic reticulum membrane.
Involvement in disease
Spastic paraplegia 18, autosomal recessive (SPG18):
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG18 is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures.
Topology
Cytoplasmic: 1-3
Helical: 4-24
Lumenal: 25-339
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