Conserved Protein Domain Family
mRING-HC-C3HC5_MGRN1

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cd16816: mRING-HC-C3HC5_MGRN1 
Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) and similar proteins
MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. Furthermore, MGRN1 interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.
Statistics
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PSSM-Id: 319730
View PSSM: cd16816
Aligned: 6 rows
Threshold Bit Score: 86.6599
Threshold Setting Gi: 82209566
Created: 27-Mar-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
Zn binding sitemodified
Feature 1:Zn binding site [ion binding site]
Evidence:
  • Comment:Based on the structural evidence that Homo sapiens CGRF1 (2EA5) binds two Zn2+ ions through its modified C3HC5-type RING-HC finger.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
Feature 1         #  #           # #   #  #          #  # 
gi 110810435 277 ECVVCLSDLRDTLILPCRHLCLCTSCADTLRYQANNCPICR 317
gi 632979644 275 ECVVCLSDLRDTLILPCRHLCLCSTCADTLRYQANNCPICR 315
gi 676243923 259 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICR 299
gi 82209566  275 ECVVCLSDLRDTLILPCRHLCLCNACADTLRYQANNCPICR 315
gi 556960898 275 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICR 315
gi 147904702 237 ECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANNCPICR 277

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