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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
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 splicing 3074 67.6 617 - 2004 14593114
  • using a different splice site than variant 1
  • 16 splicing 3071 67.5 616 - 2004 14593114
    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