Q6NZQ8 · MARH1_MOUSE
- ProteinE3 ubiquitin-protein ligase MARCHF1
- GeneMarchf1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids289 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, down-regulates their cell surface localization thus sequestering them in the intracellular endosomal system.
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 80 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 83 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 97 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 99 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 107 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 110 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 123 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 126 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | early endosome membrane | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | late endosome membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | lysosome | |
Cellular Component | plasma membrane | |
Cellular Component | trans-Golgi network membrane | |
Molecular Function | MHC protein binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | antigen processing and presentation of peptide antigen via MHC class II | |
Biological Process | immune response | |
Biological Process | protein polyubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase MARCHF1
- 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 accessionQ6NZQ8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytoplasmic vesicle membrane ; Multi-pass membrane protein
Late endosome membrane ; Multi-pass membrane protein
Early endosome membrane ; Multi-pass membrane protein
Golgi apparatus, trans-Golgi network membrane ; Multi-pass membrane protein
Lysosome membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 155-175 | Helical | ||||
Sequence: IFCSVTFHVIAVTCVVWSLYV | ||||||
Transmembrane | 197-217 | Helical | ||||
Sequence: FWTKLVVVAIGFTGGLVFMYV |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Shows increase in the cell surface expression or half-life of MHC class II. Null cells have accumulated MHC class II and CD86 at the cell surface and a low antigen-presenting ability for exogenous antigens, in conventional dendritic cells (PubMed:19917682).
Null cells have high antigen-presenting ability for exogenous antigens in B-cells (PubMed:17255932).
Null cells have high antigen-presenting ability for exogenous antigens in B-cells (PubMed:17255932).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 114 | Loss of ubiquitin ligase activity and loss of down-regulation of CD86 cell surface expression. | ||||
Sequence: W → A | ||||||
Mutagenesis | 225 | Partial loss of down-regulation of CD86 cell surface expression. Almost complete loss of down-regulation of CD86 cell surface expression; when associated with F-232. | ||||
Sequence: L → S | ||||||
Mutagenesis | 232 | Almost complete loss of down-regulation of CD86 cell surface expression; when associated with S-225. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 7 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_0000274366 | 1-289 | E3 ubiquitin-protein ligase MARCHF1 | |||
Sequence: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISKASSPTTGTAPRSQSRLSVCPSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWEKLQMTTSERRKIFCSVTFHVIAVTCVVWSLYVLIDRTAEEIKQGNDNGVLEWPFWTKLVVVAIGFTGGLVFMYVQCKVYVQLWRRLKAYNRVIFVQNCPDTANKLEKNFPCNVNTEIKDAVVVPVPQTGSNTLPTAEGAPPEVIPV |
Post-translational modification
Has a short half-life. Instability/short half-life permits rapid changes that allow efficient induction of antigen presentation once antigen presenting cells, APCs, receive maturation signals. Small changes in protein levels significantly alter the cell surface display of MHC class II proteins.
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-66 | Responsible for low stability | ||||
Sequence: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISKASSPTTGTAPRS | ||||||
Region | 13-69 | Disordered | ||||
Sequence: HRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISKASSPTTGTAPRSQSR | ||||||
Compositional bias | 14-69 | Polar residues | ||||
Sequence: RIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISKASSPTTGTAPRSQSR | ||||||
Zinc finger | 72-133 | RING-CH-type | ||||
Sequence: VCPSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIME | ||||||
Region | 222-279 | Responsible for down-regulation of CD86 and MHC class II cell surface expression | ||||
Sequence: YVQLWRRLKAYNRVIFVQNCPDTANKLEKNFPCNVNTEIKDAVVVPVPQTGSNTLPTA |
Domain
The RING-CH-type zinc finger domain is required for E3 ligase activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q6NZQ8-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length289
- Mass (Da)32,347
- Last updated2007-02-06 v2
- Checksum0DBE9A308D5ED0CE
Q6NZQ8-2
- Name2
- Differences from canonical
- 1-54: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISK → MNLTMSNMTSSHICCNFLNMWKKSKISTMYYLNQDAKLSNLFLQ
Q6NZQ8-3
- Name3
- Differences from canonical
- 1-37: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTL → MPLHQISVIPARETASNGRSSMGRNKEKNKEVE
Q6NZQ8-4
- Name4
Q6NZQ8-5
- Name5
- Differences from canonical
- 187-190: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D3YVY0 | D3YVY0_MOUSE | Marchf1 | 540 |
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_022727 | 1-37 | in isoform 3 | |||
Sequence: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTL → MPLHQISVIPARETASNGRSSMGRNKEKNKEVE | ||||||
Alternative sequence | VSP_022726 | 1-54 | in isoform 2 and isoform 4 | |||
Sequence: MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISK → MNLTMSNMTSSHICCNFLNMWKKSKISTMYYLNQDAKLSNLFLQ | ||||||
Compositional bias | 14-69 | Polar residues | ||||
Sequence: RIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNISKASSPTTGTAPRSQSR | ||||||
Sequence conflict | 85 | in Ref. 1; BAE31341 | ||||
Sequence: C → Y | ||||||
Alternative sequence | VSP_022728 | 187-190 | in isoform 4 and isoform 5 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK036489 EMBL· GenBank· DDBJ | BAC29449.1 EMBL· GenBank· DDBJ | mRNA | ||
AK089040 EMBL· GenBank· DDBJ | BAC40715.1 EMBL· GenBank· DDBJ | mRNA | ||
AK137337 EMBL· GenBank· DDBJ | BAE23311.1 EMBL· GenBank· DDBJ | mRNA | ||
AK152592 EMBL· GenBank· DDBJ | BAE31341.1 EMBL· GenBank· DDBJ | mRNA | ||
AK163081 EMBL· GenBank· DDBJ | BAE37183.1 EMBL· GenBank· DDBJ | mRNA | ||
BC066008 EMBL· GenBank· DDBJ | AAH66008.1 EMBL· GenBank· DDBJ | mRNA |