Q99M02 · MARH2_MOUSE

  • Protein
    E3 ubiquitin-protein ligase MARCHF2
  • Gene
    Marchf2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Together with GOPC/CAL mediates the ubiquitination and lysosomal degradation of CFTR (By similarity).
Ubiquitinates and therefore mediates the degradation of DLG1 (By similarity).
Regulates the intracellular trafficking and secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and degradation of the cargo receptor ERGIC3 (By similarity).
Negatively regulates the antiviral and antibacterial immune response by repression of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated K48-linked polyubiquitination of IKBKG/NEMO, resulting in its proteasomal degradation (PubMed:32935379).
May be involved in endosomal trafficking through interaction with STX6

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site64Zn2+ 1 (UniProtKB | ChEBI)
Binding site67Zn2+ 1 (UniProtKB | ChEBI)
Binding site80Zn2+ 2 (UniProtKB | ChEBI)
Binding site82Zn2+ 2 (UniProtKB | ChEBI)
Binding site90Zn2+ 1 (UniProtKB | ChEBI)
Binding site93Zn2+ 1 (UniProtKB | ChEBI)
Binding site106Zn2+ 2 (UniProtKB | ChEBI)
Binding site109Zn2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytoplasmic vesicle
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Cellular Componentendosome membrane
Cellular ComponentGolgi membrane
Cellular Componentlysosomal membrane
Cellular Componentplasma membrane
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Molecular Functionzinc ion binding
Biological Processantibacterial innate immune response
Biological Processantiviral innate immune response
Biological Processendocytosis
Biological Processprotein ubiquitination

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase MARCHF2
  • EC number
  • Alternative names
    • Membrane-associated RING finger protein 2
    • Membrane-associated RING-CH protein II (MARCH-II)
    • RING finger protein 172
    • RING-type E3 ubiquitin transferase MARCHF2

Gene names

    • Name
      Marchf2
    • Synonyms
      March2, Rnf172

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q99M02
  • Secondary accessions
    • Q8C4Q5

Proteomes

Organism-specific databases

Subcellular Location

Endoplasmic reticulum membrane
; Multi-pass membrane protein
Lysosome membrane
; Multi-pass membrane protein
Endosome membrane
; Multi-pass membrane protein
Golgi apparatus membrane
; Multi-pass membrane protein
Cytoplasm
Cell membrane
; Multi-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane138-158Helical
Transmembrane175-195Helical

Keywords

Phenotypes & Variants

Disruption phenotype

Knockout mice are phenotypically normal (PubMed:32935379).
Increase in cytokine production following viral and bacterial challenge, including increases in Ifnb1, Il6, Il12, Ccl5, Cxcl10 and Tnf protein abundance (PubMed:32935379).
Increase in survival following exposure to a lethal dose of L.monocytogenes and decrease in bacterial load in the spleen and liver (PubMed:32935379).
Increase in susceptibility to endotoxin shock (PubMed:32935379).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000559261-246E3 ubiquitin-protein ligase MARCHF2

Proteomic databases

PTM databases

Expression

Induction

Induced in macrophages by viral or bacterial infection.

Gene expression databases

Interaction

Subunit

Interacts with STX6; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR (By similarity).
Interacts with MARCHF3 (By similarity).
Interacts with GOPC/CAL; the interaction leads to CFTR ubiquitination and degradation (By similarity).
Interacts with CFTR; the interaction leads to CFTR ubiqtuitination and degradation (By similarity).
Interacts (via PDZ domain) with DLG1 (via PDZ domains); the interaction leads to DLG1 ubiqtuitination and degradation (By similarity).
Interacts with ERGIC3 (By similarity).
Interacts with ADRB2 (By similarity).
Interacts with IKBKG/NEMO; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for zinc finger, region.

TypeIDPosition(s)Description
Zinc finger56-116RING-CH-type
Region121-246Required for interaction with IKBKG

Domain

The RING-CH-type zinc finger domain is required for E3 ligase activity.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    246
  • Mass (Da)
    27,186
  • Last updated
    2001-06-01 v1
  • Checksum
    DC4A6EE34B8AE897
MTTGDCCHLPGSLCDCSSSPAFSKVVEATGLGPPQYVAQVTSRDGRLLSTVIRALDSQSDCPFCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEFAVEKRPRPLTEWLKDPGPRTEKRTLCCDMVCFVFITPLAAISGWLCLRGAQDHLRLHSRLEAVGLIALTIALFTIYVLWTLVSFRYHCQLYSEWRKTNQKVRLKIREADGSEDPHHSLLATGLLKKVAEETPV

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q8CA25Q8CA25_MOUSEMarchf2287
G3UZC4G3UZC4_MOUSEMarchf2217
G3UYC2G3UYC2_MOUSEMarchf2242
G3UYX1G3UYX1_MOUSEMarchf282
G3UY44G3UY44_MOUSEMarchf2177
G3UXS1G3UXS1_MOUSEMarchf2232
G3UXU1G3UXU1_MOUSEMarchf2197

Sequence caution

The sequence BAC38235.1 differs from that shown. Reason: Frameshift

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK079234
EMBL· GenBank· DDBJ
BAC37584.1
EMBL· GenBank· DDBJ
mRNA
AK081495
EMBL· GenBank· DDBJ
BAC38235.1
EMBL· GenBank· DDBJ
mRNA Frameshift
BC002144
EMBL· GenBank· DDBJ
AAH02144.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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