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FLASH GENE
Symbol SYVN1 contributors: mct/pgu - updated : 18-01-2017
HGNC name synovial apoptosis inhibitor 1, synoviolin
HGNC id 20738
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly
Endocrineneuroendocrinepituitary  moderately
 pancreas   highly
Lymphoid/Immunelymph node   highly
Nervousbrainmidbrainsubstantia nigra highly Homo sapiens
Respiratorylung   highly
Skin/Tegumentskin   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousdopaminergic neuron Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text moderately in umbilical cord
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 22 aa signal peptide
  • six transmembrane domains
  • a cytosolic RING-H2-type zinc finger domain required for E3 ligase activity
  • proline-rich region
    • conjugated PhosphoP , Other
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to rattus Syvn1 (96.2 pc)
    homolog to murine Syvn1 (95.9 pc)
    Homologene
    FAMILY
  • HRD1 family
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    text
  • multi-pass membrane protein
    • basic FUNCTION
  • involved in endoplasmic reticulum (ER)-associated degradation, using the ubiquitin-proteasome system for additional degradation of unfolded proteins
  • protecting cells from apoptosis by inducing degradation of abnormally processed proteins that accumulate in the ER
  • involved in the elimination of two model ER-associated degradation substrates, TCR-alpha and CD3-delta
  • acting as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation
  • also promoting the degradation of normal but naturally short-lived proteins such as SGK
  • protecting neurons from apoptosis induced by polyglutamine-expanded huntingtin (HD) or unfolded GPR37 by promoting their degradation
  • sequestering TP53 in the cytoplasm and promoting its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis
  • in addition to Parkin, is also involved in the degradation of GPR37
  • E3 ubiquitin ligase implicated in endoplasmic reticulum-associated degradation, involved in the degradation of endogenous immature nicastrin, and affecting amyloid beta-protein generation
  • its level was negatively correlated with the Abeta level, suggesting the possible involvement of SYVN1 in Abeta generation
  • importance of the E3 ubiquitin ligase synoviolin in liver fibrosis
  • essential role for SYVN1 together with the E2 ubiquitin-conjugating enzyme UBE2J1 in the ubiquitination and dislocation of misfolded MHC class I heavy chains
  • physiological role for SYVN1 and UBE2J1 in the homeostatic regulation of MHC class I assembly and expression
  • potential role in the pathogenesis of hemochromatosis
  • regulation of the stability and assembly of the SYVN1-SEL1L complex is critical to optimize the degradation kinetics of ERAD substrates
  • stabilization and assembly of the SYVN1-SEL1L complex thus play a central role in mammalian ERAD regulation
  • SYVN1 serves critical roles in synovial hyperplasia
    • CELLULAR PROCESS protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism protein
    signaling
  • ER-associated protein catabolic process
    • a component
  • 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
  • part of a complex containing SYVN1, HERPUD1, SELS and DERL1 which probably transfer misfolded proteins from the ER to VCP
  • part of a complex containing SYVN1, SEL1L and DERL2
  • auto-ubiquitinated
  • SYVN1 and UBE2J1 form a functional E3–E2 pair for the turnover of other ERAD cellular substrates
  • SYVN1-SEL1L complex provides a scaffold for endoplasmic reticulum (ER)-associated degradation (ERAD)
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • interacting with TP53 and HD
  • interacting with VCP, SEL1L, HERPUD1 and DERL1
  • interacting with GPR37, through its proline-rich region, promoting the ubiquitylation and degradation of GPR37
  • interacting with NCSTN (SYVN1-mediated ubiquitination is involved in the degradation of immature nicastrin, and probably regulates amyloid beta-protein generation)
  • promoted APP ubiquitination and degradation, resulting in decreased generation of Abeta
  • HERPUD1 interacts directly with the ubiquitin ligase SYVN1, which is found in high molecular mass complexes of the ER membrane
  • NRF1 is degraded and suppressed by the ER-associated degradation (ERAD) ubiquitin ligase SYVN1 and valosin-containing protein (VCP) under normal conditions
  • both BTRC- and SYVN1-dependent degradation mechanisms regulate the transcriptional activity of NRF1 to maintain cellular homeostasis
  • USP25 counteracts ubiquitination of ERAD substrates by the ubiquitin ligase SYVN1, rescuing them from degradation by the proteasome
  • critical scaffolding function for HEY1, HEY2 that is required for forming an active retrotranslocation complex containing SYVN1, SEL1L, and DERL2
  • SYVN1 and RNF5 may be negative regulators of disease-associated transporter ABCG5/ABCG8
  • enhanced phosphorylation of a negative regulator of secretion, STXBP5L, in response to insulin secretagogues targets it to degradation by the SYVN1 E3-ubiquitin ligase
  • USP19 regulates the stability of SYVN1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases
  • PADI4 interacted with SYVN1 directly and overexpression of PADI4 suppressed the ubiquitination of proteins
    • cell & other
    REGULATION
    activated by to protect against ER stress-induced apoptosis by degrading unfolded proteins accumulated in the ER
    induced by ER-stress-inducing agents such as thapsigargin, tunicamycin or brefeldin A, but not by heat shock
    Other regulated by ERN1-XBP1 pathway (dependency of its induction on the ERN1-XBP1 pathway
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS