SPFH2 is a ubiquitously expressed 339 amino acid protein that belongs to the band 7/mec-2 family. Localized to lipid raft-like domains in the membrane of the endoplasmic reticulum (ER), SPFH2 plays a crucial role in the ER-associated degradation (ERAD) pathway that removes metabolically regulated and aberrant proteins from the ER. Specifically, SPFH2 associates with IP3R-I (Inositol 1,4,5-triphosphate receptor I), a substrate of the ERAD pathway, and facilitates its polyubiquitination and subsequent degradation. Three isoforms of SPFH2 are expressed due to alternative splicing events.
Function:
Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Also involved in ITPR1 degradation by the ERAD pathway.
Subunit:
Interacts with activated ITPR1, independently of the degree of ITPR1 polyubiquitination (By similarity). Forms a heteromeric complex with ERLIN1. In complex with ERLIN1, interacts with RNF170.
Subcellular Location:
Endoplasmic reticulum membrane. Associated with lipid raft-like domains of the endoplasmic reticulum membrane.
Tissue Specificity:
Ubiquitous.
DISEASE:
Defects in ERLIN2 are the cause of spastic paraplegia autosomal recessive type 18 (SPG18) [MIM:611225]. 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.
Similarity:
Belongs to the band 7/mec-2 family.
SWISS:
O94905
Gene ID:
11160
Database links:
Entrez Gene: 11160 Human
Entrez Gene: 244373 Mouse
Entrez Gene: 290823 Rat
Omim: 611605 Human
SwissProt: O94905 Human
SwissProt: Q8SFZ9 Mouse
SwissProt: B5DEH2 Rat
Unigene: 705490 Human
Unigene: 277699 Mouse
Unigene: 12619 Rat
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