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    MARCHF8 membrane associated ring-CH-type finger 8 [ Homo sapiens (human) ]

    Gene ID: 220972, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MARCHF8provided by HGNC
    Official Full Name
    membrane associated ring-CH-type finger 8provided by HGNC
    Primary source
    HGNC:HGNC:23356
    See related
    Ensembl:ENSG00000165406 MIM:613335; AllianceGenome:HGNC:23356
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MIR; CMIR; c-MIR; MARCH8; RNF178; MARCH-VIII
    Summary
    MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]
    Expression
    Ubiquitous expression in testis (RPKM 18.4), bone marrow (RPKM 12.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MARCHF8 in Genome Data Viewer
    Location:
    10q11.21-q11.22
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (45454585..45594907, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (46335573..46475913, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (45950033..46090355, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene olfactory receptor family 13 subfamily A member 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:45839254-45839455 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45869432-45870042 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45870043-45870651 Neighboring gene arachidonate 5-lipoxygenase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45914387-45915080 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45915081-45915772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45915801-45916302 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45921315-45921815 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45923135-45923798 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45928754-45929292 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:45928214-45928753 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:45933181-45934380 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:45937030-45937261 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45937618-45938388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45938389-45939157 Neighboring gene uncharacterized LOC102724323 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:45958734-45959933 Neighboring gene uncharacterized LOC105378286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3321 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45970297-45970798 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45970799-45971298 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:45998823-45999323 Neighboring gene VISTA enhancer hs2065 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:46070300-46070960 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:46086550-46087050 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2344 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2345 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2346 Neighboring gene zinc finger AN1-type containing 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3322 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2347 Neighboring gene ArfGAP with GTPase domain, ankyrin repeat and PH domain 10, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Yersinia pestis acetyltransferase-mediated dual acetylation at the serine and lysine residues enhances the auto-ubiquitination of ubiquitin ligase MARCH8 in human cells. Li C, et al. Cell Cycle, 2017 Apr 3. PMID 28103160, Free PMC Article
    2. MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation. Yu C, et al. mBio, 2020 Sep 15. PMID 32934085, Free PMC Article
    3. MARCH8 inhibits viral infection by two different mechanisms. Zhang Y, et al. Elife, 2020 Aug 11. PMID 32778221, Free PMC Article
    4. MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells. Villalón-Letelier F, et al. mBio, 2021 Oct 26. PMID 34517760, Free PMC Article
    5. Sh-MARCH8 Inhibits Tumorigenesis via PI3K Pathway in Gastric Cancer. Yin J, et al. Cell Physiol Biochem, 2018. PMID 30138931

    See all (62) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.
      Title: MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.
    2. The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer.
      Title: The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer.
    3. Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.
      Title: Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.
    4. EGR1 functions as a new host restriction factor for SARS-CoV-2 to inhibit virus replication through the E3 ubiquitin ligase MARCH8.
      Title: EGR1 functions as a new host restriction factor for SARS-CoV-2 to inhibit virus replication through the E3 ubiquitin ligase MARCH8.
    5. E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
      Title: E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4.
    6. Ubiquitin ligase MARCH8 promotes the malignant progression of hepatocellular carcinoma through PTEN ubiquitination and degradation.
      Title: Ubiquitin ligase MARCH8 promotes the malignant progression of hepatocellular carcinoma through PTEN ubiquitination and degradation.
    7. HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer.
      Title: HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer.
    8. Membrane-associated RING-CH protein (MARCH8) is a novel glycolysis repressor targeted by miR-32 in colorectal cancer.
      Title: Membrane-associated RING-CH protein (MARCH8) is a novel glycolysis repressor targeted by miR-32 in colorectal cancer.
    9. Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors.
      Title: Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors.
    10. MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells.
      Title: MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells.
    Submit: New GeneRIF Correction See all GeneRIFs (32)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genome-wide association study of hematological and biochemical traits in a Japanese population.
    EBI GWAS Catalog
    Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
    EBI GWAS Catalog
    Seventy-five genetic loci influencing the human red blood cell.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 replication is inhibited by MARCH8 expression in monocyte derived macrophages as replication is recovered through MARCH8 knockdown by shRNA PubMed
    HIV-1 replication is inhibited by MARCH8 expression in 293T or MAGIC5 cells PubMed
    Knockdown of membrane-associated ring finger (C3HC4) 8, E3 ubiquitin protein ligase (MARCH8) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 Env (gp120) binds MARCH8 leading to Env (gp120) removal from the surface of cells PubMed
    env HIV-1 Env (gp120) incorporation into virions is inhibited by MARCH8 expression PubMed
    env HIV-1 Env (gp120) binds MARCH8 leading to Env (gp120) downregulation from the surface of cells PubMed
    Pr55(Gag) gag Expression of MARCH-8 inhibits HLA-DR-mediated enhancement of mature Gag products internalization by downregulating cell surface HLA-DR PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MHC protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in antigen processing and presentation of peptide antigen via MHC class II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein polyubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in early endosome membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in late endosome membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase MARCHF8
    Names
    E3 ubiquitin-protein ligase MARCH8
    RING finger protein 178
    RING-type E3 ubiquitin transferase MARCH8
    RING-type E3 ubiquitin transferase MARCHF8
    c-mir, cellular modulator of immune recognition
    cellular modulator of immune recognition (c-MIR)
    membrane associated ring finger 8
    membrane-associated RING finger protein 8
    membrane-associated RING-CH protein VIII
    membrane-associated ring finger (C3HC4) 8, E3 ubiquitin protein ligase
    NP_001002266.1
    NP_001269795.1
    NP_001388574.1
    NP_001388575.1
    NP_659458.2
    XP_011537794.1
    XP_011537797.1
    XP_047280719.1
    XP_047280720.1
    XP_047280721.1
    XP_047280722.1
    XP_047280723.1
    XP_047280724.1
    XP_047280725.1
    XP_054221068.1
    XP_054221069.1
    XP_054221070.1
    XP_054221071.1
    XP_054221072.1
    XP_054221073.1
    XP_054221074.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001002266.3 → NP_001002266.1  E3 ubiquitin-protein ligase MARCHF8 isoform a

      See identical proteins and their annotated locations for NP_001002266.1

      Status: VALIDATED

      Source sequence(s)
      AK023636, AK025472, AL833316, BC025394, BM151615
      Consensus CDS
      CCDS7213.1
      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72
      Related
      ENSP00000379116.2, ENST00000395769.6
      Conserved Domains (1) summary
      smart00744
      Location:79 → 127
      RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

    2. NM_001282866.2 → NP_001269795.1  E3 ubiquitin-protein ligase MARCHF8 isoform b

      See identical proteins and their annotated locations for NP_001269795.1

      Status: VALIDATED

      Source sequence(s)
      AK023636, AK025472, AK307667, AL833316, BM151615
      Consensus CDS
      CCDS60519.1
      UniProtKB/Swiss-Prot
      Q5T0T0
      Related
      ENSP00000411848.2, ENST00000453424.7
      Conserved Domains (1) summary
      smart00744
      Location:361 → 409
      RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

    3. NM_001401645.1 → NP_001388574.1  E3 ubiquitin-protein ligase MARCHF8 isoform b

      Status: VALIDATED

      Source sequence(s)
      AL445201, AL512595, AL731567
      Consensus CDS
      CCDS60519.1

    4. NM_001401646.1 → NP_001388575.1  E3 ubiquitin-protein ligase MARCHF8 isoform b

      Status: VALIDATED

      Source sequence(s)
      AL445201, AL512595, AL731567
      Consensus CDS
      CCDS60519.1

    5. NM_145021.6 → NP_659458.2  E3 ubiquitin-protein ligase MARCHF8 isoform a

      See identical proteins and their annotated locations for NP_659458.2

      Status: VALIDATED

      Source sequence(s)
      AK023636, AK025472, AL445201, AL833316, BC066988, BM151615, HY047787
      Consensus CDS
      CCDS7213.1
      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72
      Related
      ENSP00000317087.3, ENST00000319836.7
      Conserved Domains (1) summary
      smart00744
      Location:79 → 127
      RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      45454585..45594907 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047424768.1 → XP_047280724.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72

    2. XM_011539492.4 → XP_011537794.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

      See identical proteins and their annotated locations for XP_011537794.1

      UniProtKB/Swiss-Prot
      Q5T0T0
      Conserved Domains (1) summary
      smart00744
      Location:361 → 409
      RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

    3. XM_047424765.1 → XP_047280721.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    4. XM_047424769.1 → XP_047280725.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72

    5. XM_047424764.1 → XP_047280720.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    6. XM_047424766.1 → XP_047280722.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    7. XM_047424767.1 → XP_047280723.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72

    8. XM_047424763.1 → XP_047280719.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    9. XM_011539495.2 → XP_011537797.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

      See identical proteins and their annotated locations for XP_011537797.1

      UniProtKB/Swiss-Prot
      B2R8E7, H0Y7C6, Q5T0S8, Q5T0T0, Q8TC72
      Conserved Domains (1) summary
      smart00744
      Location:79 → 127
      RINGv; The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins

    RNA

    1. XR_007061947.1 RNA Sequence

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NW_003315935.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      295416..305254 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      46335573..46475913 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054365098.1 → XP_054221073.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

    2. XM_054365093.1 → XP_054221068.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    3. XM_054365095.1 → XP_054221070.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    4. XM_054365099.1 → XP_054221074.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

    5. XM_054365094.1 → XP_054221069.1  E3 ubiquitin-protein ligase MARCHF8 isoform X1

    6. XM_054365096.1 → XP_054221071.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

    7. XM_054365097.1 → XP_054221072.1  E3 ubiquitin-protein ligase MARCHF8 isoform X2

    RNA

    1. XR_008488176.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001002265.1: Suppressed sequence

      Description
      NM_001002265.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5T0T0.1 GenPept UniProtKB/Swiss-Prot:Q5T0T0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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