E3 ubiquitin-protein ligase synoviolin (synovial apoptosis inhibitor 1, SYVN1, HRD1, KIAA1810)
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Function
- E3 ubiquitin-protein ligase
- accepts ubiquitin specifically from endoplasmic reticulum- associated UBC7 E2 ligase & transfers it to substrates, promoting their degradation
- component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins
- also promotes the degradation of normal but naturally short-lived proteins, including SGK
- protects cells from ER stress-induced apoptosis
- protects neurons from apoptosis induced by polyglutamine- expanded huntingtin or unfolded GPR37 by promoting their degradation
- sequesters TP53 in cytoplasm & promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation & apoptosis
- ubiquitin conjugation, 3rd step
- interacts with VCP, SEL1L, HERPUD1 & DERL1
- component of a complex containing SYVN1, HERPUD1, SELS & DERL1, which probably transfers misfolded proteins to VCP
- part of a complex containing SYVN1, SEL1L & DERL2.
Structure
- homodimer
- not N-glycosylated
- auto-ubiquitinated
- belongs to the HRD1 family
- contains 1 RING-type zinc finger required for E3 ligase activity
Compartment
endoplasmic reticulum membrane
Alternative splicing
named isoforms=3
Expression
- ubiquitously expressed
- highest levels in liver & kidney (at protein level)
- induced by ER-stress-inducing agents such as thapsigargin, tunicamycin or brefeldin A, but not by heat shock.
Pathology
- up-regulated in synovial tissues from patients with rheumatoid arthritis (at protein level)