Conserved Protein Domain Family
RING-H2_synoviolin

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cd16479: RING-H2_synoviolin 
RING finger, H2 subclass, found in synoviolin and similar proteins
Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting the crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, Synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of Synoviolin may represent a protective response against neurodegeneration in Parkinson"s disease (PD). In addition, Synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.
Statistics
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PSSM-Id: 319393
View PSSM: cd16479
Aligned: 43 rows
Threshold Bit Score: 81.5755
Threshold Setting Gi: 300143290
Created: 2-May-2013
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding siteRING-H2 finger
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens AMFR (2LXP; also known as ubiquitin ligase GP78) binds two Zn2+ through its RING-H2 finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
Feature 1           #  #                                # #  #  #          #  # 
gi 134035039 288 DNVCIICREEMvt--------------------gaKRLPCNHIFHTSCLRSWFQRQQtCPTCR 330
gi 74626911  289 DRTCTICREEMfhpdhppentdemeplprgldmtpKRLPCGHILHFHCLRNWLERQQtCPICR 351
gi 470317224 287 DKTCIICREEMvhssikkldkn--nksqsrinstpKKLPCNHILHFNCLKNWLERQQsCPTCR 347
gi 449016284 294 DRTCIICREEMfgg------------------agaKKLVCGHIFHLRCLRSWMERSMsCPTCR 338
gi 428162867 288 DHTCIICREEMqpp-------------------haKKLPCGHIFHFDCLRSWLEEHSqCPTCR 331
gi 60465485  263 DKICIVCREDMts---------------------gKKLPCGHILHLHCLRSWLERQQtCPICR 304
gi 21622300  338 DDTCIICREEMrpwdphdp--------vrlertraKKLPCGHILHQGCLKSWLERQQvCPTCR 392
gi 158271858 289 DGVCIICREEMaea------------------gsnKRLFCGHVFHLHCLRSWLERQQnCPTCR 333
gi 440790488 273 EQICIVCREELtq---------------------gKRLPCGHILHFHCLLNWLQRQQtCPICR 314
gi 470308832 290 DNVCIICREEMta---------------------aKRLPCGHVFHLHCLRSWLERQQtCPTCR 331

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