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FLASH GENE
Symbol MARCHF8 contributors: mct - updated : 08-02-2023
HGNC name membrane-associated ring finger (C3HC4) 8
HGNC id 23356
Location 10q11.21      Physical location : -
Synonym name
  • c-mir, cellular modulator of immune recognition
  • E3 ubiquitin-protein ligase MARCH8
  • RING finger protein 178
  • membrane-associated RING-CH protein VIII
  • E3 ubiquitin ligase membrane-associated RING-CH
  • Synonym symbol(s) c-MIR, MIR, MARCH-VIII, RNF178, RP11-67C2.1, MARCH8, CMIR
    EC.number 6.3.2.-/ 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 140.32 kb     8 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text Variants 1, 2, and 3 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 6220 - 573 - 2021 34517760
    8 - 4769 32 291 - 2021 34517760
    7 - 5281 32 291 - 2021 34517760
    8 - 6127 - 573 - 2021 34517760
    8 - 5615 - 573 - 2021 34517760
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Nervousspinal cord    
    Reproductivemale systemtestis   
    Respiratorylung    
    Visualeyeanterior segment   
     eyeuveachoroid  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningretinal pigment epithelium (RPE)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunedendritic cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one N terminal zinc finger motif of the PHD subfamily
  • two TM domains
  • one C terminal conserved region
  • HOMOLOGY
    interspecies homolog to murine 1300017E09Rik
    Homologene
    FAMILY
  • RING zinc finger protein family
  • MARCH proteins family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    basic FUNCTION
  • functioning as an E3 ubiquitin ligase for immune recognition-related molecules (e.g. major histocompatibility complex class I, B7-2, and ICAM-1)
  • inducing specific down-regulation of B7-2 surface expression through ubiquitination (molecular interaction is necessary), rapid endocytosis, and lysosomal degradation of the target molecule
  • role of MARCH8 and MARCH4 in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins
  • involved direct ubiquitination of SLC3A2 and routing of SLC3A2 to late endosomes/lysosomes
  • MARCH E3 ligases play a key role in controlling MHC class II surface expression by regulated ubiquitination of a lysine residue in the beta-chain
  • MARCHF8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection
  • MARCHF8 reduces viral infectivity by downregulating envelope glycoproteins through two different mechanisms mediated by a ubiquitination-dependent or tyrosine motif-dependent pathway
  • 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 protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • BCAP31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins, and of MARCH8
  • its expression completely shifted the trafficking of CD44 and CD98 proteins away from recycling tubules to early endosome antigen 1 compartments and late endosomes, resulting in reduced surface levels
  • multiple features of HLA-DR are involved in substrate recognition by MARCH8
  • suppressor of IL1B-induced NFKB- and MAPK-activation pathways
  • MARCHF8-mediated polyubiquitination and degradation of IL1RAP is an important mechanism for negative regulation of IL1B-induced signaling pathways
  • endogenous MARCHF8 regulates the steady-state cell surface expression of TNFRS10A
  • ubiquitylation of clathrin-independent endocytosis (CIE) cargo proteins by MARCH8 was reversed by USP6, suggesting that USP6 leads to deubiquitylation of CIE cargo proteins
  • 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
  • E3 ubiquitin ligases NEDD4 and MARCH8 are regulators of BST2 constitutive ubiquitylation and sorting to the lysosomes
  • MARCHF8 is a negative regulator of CGAS-mediated signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in non-small cell lung cancer NSCLC tissues compared to adjacent normal lung tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    might be a predictive factor and an attractive therapeutic target for NSCLC patients
    ANIMAL & CELL MODELS
  • March8-deficient mice were less susceptible than their wild-type counterparts to herpes simplex virus 1 (HSV-1) infection