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    MARCHF2 membrane associated ring-CH-type finger 2 [ Homo sapiens (human) ]

    Gene ID: 51257, updated on 16-Apr-2024

    Summary

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    Official Symbol
    MARCHF2provided by HGNC
    Official Full Name
    membrane associated ring-CH-type finger 2provided by HGNC
    Primary source
    HGNC:HGNC:28038
    See related
    Ensembl:ENSG00000099785 MIM:613332; AllianceGenome:HGNC:28038
    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
    MARCH2; RNF172; HSPC240; MARCH-II
    Summary
    MARCH2 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. MARCH2 reduces surface accumulation of several glycoproteins and appears to regulate early endosome-to-trans-Golgi network (TGN) trafficking (Bartee et al., 2004 [PubMed 14722266]; Nakamura et al., 2005 [PubMed 15689499]).[supplied by OMIM, Mar 2010]
    Expression
    Ubiquitous expression in fat (RPKM 20.9), heart (RPKM 12.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    19p13.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (8413305..8439017)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (8399779..8426935)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (8478189..8503901)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene RAB11B antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:8454876-8455157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10020 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10021 Neighboring gene microRNA 4999 Neighboring gene RAB11B, member RAS oncogene family Neighboring gene Sharpr-MPRA regulatory region 2878 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:8477814-8478314 Neighboring gene Sharpr-MPRA regulatory region 12836 Neighboring gene GATA motif-containing MPRA enhancer 154 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:8488918-8489781 Neighboring gene Sharpr-MPRA regulatory region 689 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10024 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10025 Neighboring gene heterogeneous nuclear ribonucleoprotein M Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10026 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13916 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13917 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:8563393-8564079 Neighboring gene PML-RARA regulated adaptor molecule 1

    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. Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection. Zhang Y, et al. J Biol Chem, 2019 Mar 8. PMID 30630952, Free PMC Article
    2. MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through envelope protein translocation or degradation. Zhang Y, et al. Virology, 2018 May. PMID 29573664
    3. DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell-cell contact. Cao Z, et al. Cell Signal, 2008 Jan. PMID 17980554, Free PMC Article
    4. MARCH2 regulates autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling. Xia D, et al. Autophagy, 2016 Sep. PMID 27308891, Free PMC Article
    5. Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2 through its association with adaptor proteins CAL and STX6. Cheng J, et al. PLoS One, 2013. PMID 23818989, Free PMC Article

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.
      Title: MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.
    2. 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.
    3. MARCH2 reduced secretion of alpha1-antitrypsin and haptoglobin, and coexpression of the ubiquitination-resistant ERGIC3 variant largely restored their secretion, suggesting that MARCH2-mediated ERGIC3 ubiquitination is the major cause of the decrease in trafficking of ERGIC3-binding secretory proteins.
      Title: The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent trafficking of secretory proteins.
    4. Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection
      Title: Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection.
    5. In this study, the authors found the expression of MARCH2 to be upregulated upon HIV-1 infection. MARCH2 inhibits the production and infection of HIV-1 through ligase activity-dependent envelope protein degradation and/or intracellular retention.
      Title: MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through envelope protein translocation or degradation.
    6. MARCH2 has a role in regulating autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling
      Title: MARCH2 regulates autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling.
    7. Data indicate that E3 ubiquitin ligase MARCH2 co-immunoprecipitated and co-localized with CAL and syntaxin 6 (STX6), and show the ubiquitination of CFTR by MARCH2.
      Title: Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2 through its association with adaptor proteins CAL and STX6.
    8. The MARCH2 E3 ligase activity regulates cell surface beta(2)AR expression and, consequently, its signaling.
      Title: MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.
    9. MARCH2 is co-localized with DLG1 at sites of cell-cell contact.
      Title: DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell-cell contact.
    10. Depletion of MARCH-II by small interfering RNA perturbed the trans-Golgi network (TGN) localization of syntaxin 6 and TGN38/46
      Title: MARCH-II is a syntaxin-6-binding protein involved in endosomal trafficking.
    Submit: New GeneRIF Correction

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in antibacterial innate immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in antiviral innate immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in endocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of lysosomal protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in suppression of viral release by host IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lysosomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase MARCHF2
    Names
    E3 ubiquitin-protein ligase MARCH2
    RING finger protein 172
    RING-type E3 ubiquitin transferase MARCH2
    RING-type E3 ubiquitin transferase MARCHF2
    membrane associated ring finger 2
    membrane-associated RING finger protein 2
    membrane-associated RING-CH protein II
    membrane-associated ring finger (C3HC4) 2, E3 ubiquitin protein ligase
    NP_001005415.1
    NP_001005416.1
    NP_001356705.1
    NP_001356706.1
    NP_001356707.1
    NP_001356708.1
    NP_057580.3

    NCBI Reference Sequences (RefSeq)

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    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_001005415.2 → NP_001005415.1  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      See identical proteins and their annotated locations for NP_001005415.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 4. Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AF151074, BC015910, BC032624, BI546028, CN363445
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Related
      ENSP00000215555.2, ENST00000215555.7
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    2. NM_001005416.2 → NP_001005416.1  E3 ubiquitin-protein ligase MARCHF2 isoform 2

      See identical proteins and their annotated locations for NP_001005416.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) has multiple differences in the coding region but maintains the reading frame, compared to variant 4. This variant encodes isoform 2, which is shorter than isoform 1.
      Source sequence(s)
      AF151074, BC015910, BC032624, BI546028, CN363445
      Consensus CDS
      CCDS32894.1
      UniProtKB/Swiss-Prot
      Q9P0N8
      Related
      ENSP00000370423.3, ENST00000381035.8
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    3. NM_001369776.1 → NP_001356705.1  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longer isoform (1). Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AC136469
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    4. NM_001369777.1 → NP_001356706.1  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 4. Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AC136469
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    5. NM_001369778.1 → NP_001356707.1  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 4. Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AC136469
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    6. NM_001369779.1 → NP_001356708.1  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 4. Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AC136469, BC032624
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Related
      ENSP00000471536.1, ENST00000602117.1
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    7. NM_016496.5 → NP_057580.3  E3 ubiquitin-protein ligase MARCHF2 isoform 1

      See identical proteins and their annotated locations for NP_057580.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 4. Variants 1, 2, and 4-7 all encode the longer isoform (1).
      Source sequence(s)
      AF151074, BC015910, BC032624, BI546028, CN363445
      Consensus CDS
      CCDS12202.1
      UniProtKB/Swiss-Prot
      A6NP10, Q5H785, Q8N5A3, Q96B78, Q9P0N8
      Conserved Domains (1) summary
      cd16808
      Location:62 → 113
      RING_CH-C4HC3_MARCH2; RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2)

    RNA

    1. NR_163145.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC136469

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      8413305..8439017
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      8399779..8426935
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9P0N8.1 GenPept UniProtKB/Swiss-Prot:Q9P0N8

    Gene LinkOut

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

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