Q9D074 · MGRN1_MOUSE
- ProteinE3 ubiquitin-protein ligase MGRN1
- GeneMgrn1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids532 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase. Mediates TSG101 monoubiquitination at multiple sites. Plays a role in the regulation of endosome-to-lysosome trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-binding to MCRs and inhibiting agonist-induced cAMP production. Does not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination (By similarity).
Acts also as a negative regulator of hedgehog signaling (PubMed:29290584).
Acts also as a negative regulator of hedgehog signaling (PubMed:29290584).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
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 | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | metal ion binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | endosome to lysosome transport | |
Biological Process | negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway | |
Biological Process | negative regulation of cAMP-mediated signaling | |
Biological Process | negative regulation of G protein-coupled receptor signaling pathway | |
Biological Process | negative regulation of smoothened signaling pathway | |
Biological Process | protein monoubiquitination | |
Biological Process | protein polyubiquitination | |
Biological Process | protein ubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase MGRN1
- 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 accessionQ9D074
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: The endosomal localization is dependent on the interaction with TSG101.
Isoform 1
Isoform 5
Note: In the cytoplasm, predominantly localized to the perinuclear region and discrete vesicular structures. In the nucleus, broadly distributed, but excluded from nucleoli.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, curly hair and whiskers, abnormal craniofacial patterning, reduced embryonic viability due to mispatterning of the left-right body axis and age-dependent spongiform neurodegeneration. Many months before onset of vacuolation, mitochondrial complex IV expression and activity is significantly reduced in mutant brains and oxidative stress is increased. A global reduction of ubiquitinated proteins in the brain is observed. At 1 month of age, null mutant mouse brains have less ubiquitinated TSG101, while adult mutant brains contain more ubiquitinated and insoluble TSG101 than wild type. At 1 month of age, significant increase in EGFR levels in the brains of null mutant mice relative to wild-type mice, suggesting an impaired trafficking to the lysosome for degradation.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 278-281 | Loss of ubiquitin-protein ligase activity. Increase in TSG101-binding. | ||||
Sequence: CVVC → AVVA | ||||||
Mutagenesis | 384-387 | Loss of TSG101-binding. | ||||
Sequence: PSAP → ASAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 24 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine | ||||
Sequence: G | ||||||
Chain | PRO_0000246688 | 2-532 | E3 ubiquitin-protein ligase MGRN1 | |||
Sequence: GSILSRRIAGVEDIDIQANSAYRYPPKSGNYFASHFFMGGEKFDTPHPEGYLFGENMDLNFLGSRPVQFPYVTPAPHEPVKTLRSLVNIRKDSLRLVRYKEDADSPTEDGEKPRVLYSLEFTFDADARVAITIYCQAVEELVNGVAVYSCKNPSLQSETVHYKRGVSQQFSLPSFKIDFSEWKDDELNFDLDRGVFPVVIQAVVDEGDVVEVTGHAHVLLAAFEKHVDGSFSVKPLKQKQIVDRVSYLLQEIYGIENKNNQETKPSDDENSDNSSECVVCLSDLRDTLILPCRHLCLCTSCADTLRYQANNCPICRLPFRALLQIRAVRKKPGALSPISFSPVLAQSVDHDEHSSSDSIPPGYEPISLLEALNGLRAVSPAIPSAPLYEEITYSGISDGLSQASCPLAGLDRIMESGLQKGKTQSKSPDSTLRSPSFPIHEEDEEKLSEDSDAPLPPSGVELVLRESSSPESFGTEEGDEPSLKQGSRVPSIDDVLQDGSPQHHGCSQPVPPADIYLPALGPESCSVGIEE | ||||||
Modified residue | 389 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 428 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 449 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 452 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 501 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autoubiquitinated in vitro.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with highest levels in brain, heart, kidney and liver. In the CNS, especially prominent in the Purkinje cells of the cerebellum. In the skin, expressed in the basal layer of the epidermis and hair follicles, primarily in the outer root sheath. Isoforms 1, 3, 4 and 5 are equally expressed in the liver. Isoforms 1, 3 and 4 are most abundant in brain, kidney and heart, respectively.
Developmental stage
In presomite and early somite stage embryos, most strongly expressed in the node and more weakly in the neuroepithelium. In 6- to 12-somite embryos, strongest expression in the node, symmetrically in the floor plate of the neural tube and in the developing heart; weaker expression in paraxial mesoderm, somites, neuroepithelium, as well as in hind- and foregut pockets. By 9.5 dpc, virtually ubiquitous.
Gene expression databases
Structure
Family & Domains
Features
Showing features for zinc finger, motif, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 277-316 | RING-type | ||||
Sequence: ECVVCLSDLRDTLILPCRHLCLCTSCADTLRYQANNCPIC | ||||||
Motif | 384-387 | Required for TSG101-binding | ||||
Sequence: PSAP | ||||||
Compositional bias | 419-435 | Polar residues | ||||
Sequence: LQKGKTQSKSPDSTLRS | ||||||
Region | 419-518 | Disordered | ||||
Sequence: LQKGKTQSKSPDSTLRSPSFPIHEEDEEKLSEDSDAPLPPSGVELVLRESSSPESFGTEEGDEPSLKQGSRVPSIDDVLQDGSPQHHGCSQPVPPADIYL |
Domain
The RING finger is required for ubiquitin ligase activity.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q9D074-1
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
- SynonymsI
- NoteSufficient for normal development, pigmentation and neuronal integrity.
- Length532
- Mass (Da)58,477
- Last updated2003-03-01 v2
- Checksum89C2C1A28F9417EE
Q9D074-2
- Name2
- Differences from canonical
- 29-29: S → SA
Q9D074-3
- Name3
- SynonymsIII
- NoteSufficient for normal development, pigmentation and neuronal integrity.
- Differences from canonical
- 520-532: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF
Q9D074-4
- Name4
- SynonymsII
- NotePartial rescue of the phenotype of mutant null mice.
- Differences from canonical
- 355-355: S → SCPFKKSKSHPASLASKKPKRET
Q9D074-5
- Name5
- SynonymsIV
- NoteUnable to rescue the phenotype of mutant null mice. This sequence has been deduced from the description in PubMed:19422019.
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 15 | in Ref. 1; BAE29360 | ||||
Sequence: I → F | ||||||
Alternative sequence | VSP_019854 | 29 | in isoform 2 | |||
Sequence: S → SA | ||||||
Sequence conflict | 31 | in Ref. 1; BAE29360 | ||||
Sequence: N → D | ||||||
Sequence conflict | 36 | in Ref. 1; BAE29360 | ||||
Sequence: H → R | ||||||
Alternative sequence | VSP_019855 | 355 | in isoform 4 and isoform 5 | |||
Sequence: S → SCPFKKSKSHPASLASKKPKRET | ||||||
Compositional bias | 419-435 | Polar residues | ||||
Sequence: LQKGKTQSKSPDSTLRS | ||||||
Alternative sequence | VSP_019856 | 520-532 | in isoform 3 and isoform 5 | |||
Sequence: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK011747 EMBL· GenBank· DDBJ | BAB27816.2 EMBL· GenBank· DDBJ | mRNA | ||
AK034100 EMBL· GenBank· DDBJ | BAC28587.1 EMBL· GenBank· DDBJ | mRNA | ||
AK088533 EMBL· GenBank· DDBJ | BAC40408.1 EMBL· GenBank· DDBJ | mRNA | ||
AK150176 EMBL· GenBank· DDBJ | BAE29360.1 EMBL· GenBank· DDBJ | mRNA | ||
AK153407 EMBL· GenBank· DDBJ | BAE31967.1 EMBL· GenBank· DDBJ | mRNA | ||
BC046830 EMBL· GenBank· DDBJ | AAH46830.1 EMBL· GenBank· DDBJ | mRNA | ||
AK129161 EMBL· GenBank· DDBJ | BAC97971.1 EMBL· GenBank· DDBJ | mRNA |