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E3 ubiquitin-protein ligase synoviolin (synovial apoptosis inhibitor 1, SYVN1, HRD1, KIAA1810)
Function:
1) E3 ubiquitin-protein ligase
2) accepts ubiquitin specifically from endoplasmic reticulum- associated UBC7 E2 ligase & transfers it to substrates, promoting their degradation
3) 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
4) also promotes the degradation of normal but naturally short-lived proteins, including SGK
5) protects cells from ER stress-induced apoptosis
6) protects neurons from apoptosis induced by polyglutamine- expanded huntingtin or unfolded GPR37 by promoting their degradation
7) sequesters TP53 in cytoplasm & promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation & apoptosis
8) ubiquitin conjugation, 3rd step
9) interacts with VCP, SEL1L, HERPUD1 & DERL1
10) component of a complex containing SYVN1, HERPUD1, SELS & DERL1, which probably transfers misfolded proteins to VCP
11) 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)
General
ring finger protein
transmembrane 5 protein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
Properties
SIZE: MW = 68 kD
entity length = 617 aa
COMPARTMENT: endoplasmic reticulum
MOTIF: signal sequence {1-22}
exoplasmic domain {23-41}
transmembrane domain {42-62}
cytoplasmic loop {63-98}
transmembrane domain {99-119}
exoplasmic loop {120-140}
transmembrane domain {141-161}
cytoplasmic loop {162-169}
transmembrane domain {170-190}
exoplasmic loop {191-224}
transmembrane domain {225-245}
interaction with TP53 {236-270}
cytoplasmic domain {246-617}
MOTIF: RING-finger {291-330}
EFFECTOR-BOUND: Zn+2
FOR-BINDING-OF: DNA motif
proline-rich region
SITE: 339-478
MOTIF: proline residue (SEVERAL)
Database Correlations
OMIM 608046
UniProt Q86TM6
Pfam PF00097
References
UniProt :accession Q86TM6