Selected-GenAtlas references SOURCE GeneCards NCBI Gene Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MARCHF6 contributors: mct - updated : 24-01-2020
HGNC name membrane associated ring-CH-type finger 6 [Homo sapiens
HGNC id 30550
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
Reproductivefemale systemovary  moderately
 female systemuteruscervix highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscular    
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticprogenitor cell Homo sapiens
cell lineage
cell lines
fluid/secretion blood
at STAGE
physiological period fetal
Text pancreas predominantly
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminus RING (really interesting new gene) finger, located in the cytosol, and having the unconventional C4HC3 configuration
  • 13 predicted transmembrane domains
  • conserved C-terminal element (CTE) involved in the recognition and/or ubiquitylation of specific protein substrate
  • mono polymer complex
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • C4HC3 RING finger-containing ubiquitin ligase, ER degradation substrate itself, promoting its own degradation in a RING finger- and proteasome-dependent manner
  • mediates degradation of type 2 iodothyronine deiodinase
  • regulator of cholesterol biosynthesis, owing to its ability to promote degradation of the rate-limiting enzymes 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) and squalene epoxidase (SQLE)
  • MARCHF6-dependent mechanism to direct cellular cholesterol accretion that relies on uncoupling of cholesterol synthesis from lipoprotein uptake
  • MARCHF6 and RNF139 facilitate the quality control of cytosolic and tail-anchored proteins
  • is a polytopic enzyme bound to the membranes of the endoplasmic reticulum
  • MARCHF6 is the first example of an E3 ubiquitin ligase which targets multiple steps in a biochemical pathway
  • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    protein ubiquitination
    a component
  • ubiquitin ligase complex
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interacting with DIO2 (Zavacki 2009)
  • MARCHF6 controls abundance of both SQLE and HMGCR, establishing it as a major regulator of flux through the cholesterol synthesis pathway
  • USP19 is involved in the regulation of ERAD by controlling the stability of MARCHF6 via deubiquitination
  • cholesterol-mediated MARCHF6 stabilization increases its activity
  • cholesterol accelerates the ubiquitination of SQLE by MARCHF6, a key E3 ubiquitin ligase involved in ER-associated degradation
  • MARCHF6, known to control earlier rate-limiting steps in cholesterol synthesis, also controls levels of lanosterol 14alpha-demethylase (LDM) and the terminal cholesterol synthesis enzyme, 24-dehydrocholesterol reductase (DHCR24)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BAFME3
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS