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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
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