ERLIN2
Function
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:17502376, PubMed:19240031). 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).
Involvement in disease
Spastic paraplegia 18B, autosomal recessive
SPG18B
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. SPG18B is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures.
None
The disease is caused by variants affecting the gene represented in this entry.
Spastic paraplegia 18A, autosomal dominant
SPG18A
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. SPG18A is a pure form. Age at onset of symptoms varies considerably from childhood to adulthood.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Deubiquitinated by USP25; leading to stabilization.
Sequence Similarities
Belongs to the band 7/mec-2 family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type II membrane protein
- Associated with lipid raft-like domains of the endoplasmic reticulum membrane.
Alternative names
C8orf2, SPFH2, UNQ2441/PRO5003/PRO9924, ERLIN2, Erlin-2, Endoplasmic reticulum lipid raft-associated protein 2, Stomatin-prohibitin-flotillin-HflC/K domain-containing protein 2, SPFH domain-containing protein 2