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FLASH GENE
Symbol MARCHF1 contributors: mct - updated : 01-02-2023
HGNC name membrane associated ring-CH-type finger 1
HGNC id 26077
Location 4q32.2      Physical location : -
Synonym name
  • membrane-associated ring finger (C3HC4)
  • RING finger protein 171
  • Synonym symbol(s) FLJ20668, MARCH-I, RNF171, DKFZp564M1682, MARCH1
    EC.number 6.3.2.-/ 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 858.96 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 5502 - 289 - 2022 35045264
    4 - 5389 - 272 - 2022 35045264
    10 - 6140 - 545 - 2022 35045264
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a short N terminus
  • a RING-CH domain
  • two transmembrane domains (a TM domain alone is sufficient to confer association with MARCH1)
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • MARCH family (family of transmembrane ubiquitin ligases)
  • membrane-associated RING-CH family of E3 ubiquitin ligases family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • recruits multiple substrates via transmembrane domain-mediated interactions to permit substrate ubiquitination in the face of diverse cytosolic domain sequences
  • affects the biogenesis of CD86 via ubiquitin-dependent lysosomal degradation
  • responsible for the intracellular sequestration of MHC class II molecules in dendritic cells and monocytes in response to IL10
  • capable of autoubiquitination
  • may regulate its own expression through dimerization and autoubiquitination
  • MARCHF1 impairs cellular insulin action by degrading cell surface INSR
  • MARCHF1 expression is increased in white adipose tissue of obese humans, suggesting that MARCH1 contributes to the pathophysiology of T2D
  • MARCHF1 is a regulator of lipid metabolism and glucose tolerance, whose function is modified by sex-specific factors
  • membrane-anchored E3 ubiquitin ligase that is involved in a variety of cellular processes
  • has an important role in the development and progression of hepatocellular carcinoma
  • ubiquitin ligase MARCHF1 limits the number of MHC II-C3 complexes displayed on conventional dendritic cells (cDCs) to prevent their elimination through excessive trogocytosis
  • MARCHF1 and MARCHF8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors
  • tissue-specific functions of MARCHF1 and MARCHF8 in regulation of immune receptor expression
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homodimerizes and also forms heterodimers with others family members
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • its expression is potentially regulated at a posttranscriptional level by trafficking within the endolysosomal pathway where MARCH1 is proteolyzed
  • associates with and ubiquitinates MHC-II
  • involved in CD86 ubiquitination in dendritic cells, and this ubiquitination plays a key role in CD86 regulation
  • CD86 is rapidly endocytosed in the presence of MARCH1 followed by lysosome-dependent degradation
  • can functionally interact with multiple diverse substrates
  • IL10 can have opposite effects on MARCH1 regulation in different cell types
  • SLC3A2 is transcriptionally regulated and ectopic expression of the membrane-associated RING-CH (MARCH) E3 ubiquitin ligases MARCHF1 or MARCHF8 leads to ubiquitylation and lysosomal degradation of SLC3A2
  • MARCHF1 is a negative regulator of INSR
  • MARCH1 likely undergoes lysine-independent ubiquitination by an as yet unidentified E3 ubiquitin ligase that, together with UBE2D1, regulates MARCH1 expression
  • cell & other
    REGULATION
    induced by IL10 and despite a strong increase in mRNA expression in human primary monocytes, the protein remains hardly detectable
    Other negatively regulated during dendritic cells maturation
    is ubiquitinated and this ubiquitination contributes to MARCHF1 turnover
    complex regulation of MARCHF1 trafficking in the endocytic pathway as well as the intricate interactions between its cytoplasmic tails
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in white adipose tissue of obese humans, suggesting that MARCHF1 contributes to the pathophysiology of T2D
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    may be used as a novel potential molecular therapeutic target in the future treatment of hepatocellular carcinoma
    diabetetype 2 
    could be a new therapeutic target in obesity with type 2 diabetes
    ANIMAL & CELL MODELS
    dendritic cells from March1-deficient mice are defective at antigen presentation and cytokine production