Conserved Protein Domain Family
RING-HC_RBR_RNF19A
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cd16775: RING-HC_RBR_RNF19A 
RING finger, HC subclass, found in RING finger protein 19A (RNF19A) and similar proteins
RNF19A, also known as double ring-finger protein (Dorfin) or p38, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. RNF19A contains an RBR domain followed by three TMs. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.
Links
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Statistics
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PSSM-Id: 438431
Aligned: 9 rows
Threshold Bit Score: 104.182
Created: 22-Mar-2015
Updated: 17-Oct-2022
Structure
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Aligned Rows:
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Zn binding site
Feature 1: Zn binding site [ion binding site], 8 residue positions
Conserved feature residue pattern:C C C H C C C CClick to see conserved feature residue pattern help
Evidence:
  • Comment:based on the structures of other RING-HC fingers with bound zinc
  • Comment:C3HC4-type RING-HC finger consensus motif: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C, where X is any amino acid and the number of X residues varies in different fingers
  • Comment:A RING finger typically binds two zinc atoms, with its Cys and/or His side chains in a unique "cross-brace" arrangement.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1          #  #              # #  #  #                 #  #      
Q9NV58       130 IECPLCLLRHSKDRFPDIMTCHHRSCVDCLRQYLRIEISESRvNISCPECTERFNP 185  human
NP_001116899 101 MECPLCLLRYSKDKFPEIMTCHHRSCADCLRQYLRIEISESRvNISCPECSERFNP 156  western clawed frog
XP_418362    111 MECPLCLLRHSKDRFPEIMTCHHRSCVDCLRQYLRIEISESRvNISCPECSERFNP 166  chicken
XP_007899423 103 LECPLCLLRHPRDRFPAIMTCHHRSCADCLRQYLRIEISESRvNISCPECSERFNP 158  elephant shark
XP_005995435 104 MECPLCLLRHSKDRFPEIMTCHHRSCVDCLRQYLRIEISESRvNISCPECSERFNP 159  coelacanth
XP_006825454   1 MECPLCLMERPKDQFPDIMTCHHRSCQECLRQYLKIEITESRvNIACPECAEHFHP 56   Saccoglossus kowalevskii
CAG05017     132 LECPLCLLHHSRESFPDIMTCHHRSCIDCLRQYLRIEISESRvNISCPECSERFNP 187  spotted green pufferfish
XP_013390307  94 HECPLCLGEQPRENFPGISTCHHRSCRDCLRQYLRIEITESRvNIACPECSERYHP 149  Lingula anatina
NP_001313624 197 LECPLCLLRHTRDRFPDIMTCHHRSCADCLRQYLRIEISESRvNISCPECSERFNP 252  zebrafish

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