Q99M02 · MARH2_MOUSE
- ProteinE3 ubiquitin-protein ligase MARCHF2
- GeneMarchf2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids246 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
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
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 64 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 67 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 80 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 82 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 90 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 93 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 106 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 109 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic vesicle | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | endosome membrane | |
Cellular Component | Golgi membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | plasma membrane | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | antibacterial innate immune response | |
Biological Process | antiviral innate immune response | |
Biological Process | endocytosis | |
Biological Process | protein ubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase MARCHF2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ99M02
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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
Cell membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 138-158 | Helical | ||||
Sequence: LCCDMVCFVFITPLAAISGWL | ||||||
Transmembrane | 175-195 | Helical | ||||
Sequence: AVGLIALTIALFTIYVLWTLV |
Keywords
- Cellular component
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).
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.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000055926 | 1-246 | E3 ubiquitin-protein ligase MARCHF2 | |||
Sequence: MTTGDCCHLPGSLCDCSSSPAFSKVVEATGLGPPQYVAQVTSRDGRLLSTVIRALDSQSDCPFCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEFAVEKRPRPLTEWLKDPGPRTEKRTLCCDMVCFVFITPLAAISGWLCLRGAQDHLRLHSRLEAVGLIALTIALFTIYVLWTLVSFRYHCQLYSEWRKTNQKVRLKIREADGSEDPHHSLLATGLLKKVAEETPV |
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 56-116 | RING-CH-type | ||||
Sequence: DSQSDCPFCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEFAVE | ||||||
Region | 121-246 | Required for interaction with IKBKG | ||||
Sequence: PLTEWLKDPGPRTEKRTLCCDMVCFVFITPLAAISGWLCLRGAQDHLRLHSRLEAVGLIALTIALFTIYVLWTLVSFRYHCQLYSEWRKTNQKVRLKIREADGSEDPHHSLLATGLLKKVAEETPV |
Domain
The RING-CH-type zinc finger domain is required for E3 ligase activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length246
- Mass (Da)27,186
- Last updated2001-06-01 v1
- ChecksumDC4A6EE34B8AE897
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |