Q9D074 · MGRN1_MOUSE

  • Protein
    E3 ubiquitin-protein ligase MGRN1
  • Gene
    Mgrn1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasm
Cellular Componentearly endosome
Cellular Componentendoplasmic reticulum
Cellular Componentnucleus
Cellular Componentplasma membrane
Molecular Functionmetal ion binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Biological Processendosome to lysosome transport
Biological Processnegative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
Biological Processnegative regulation of cAMP-mediated signaling
Biological Processnegative regulation of G protein-coupled receptor signaling pathway
Biological Processnegative regulation of smoothened signaling pathway
Biological Processprotein monoubiquitination
Biological Processprotein polyubiquitination
Biological Processprotein ubiquitination

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase MGRN1
  • EC number
  • Alternative names
    • Mahogunin RING finger protein 1
    • RING-type E3 ubiquitin transferase MGRN1

Gene names

    • Name
      Mgrn1
    • Synonyms
      Kiaa0544

Organism names

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

Accessions

  • Primary accession
    Q9D074
  • Secondary accessions
    • Q3U5V9
    • Q3UDA1
    • Q6ZQ97
    • Q8BZM9

Proteomes

Organism-specific databases

Subcellular Location

Early endosome
Note: The endosomal localization is dependent on the interaction with TSG101.

Isoform 1

Cell membrane

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

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.

TypeIDPosition(s)Description
Mutagenesis278-281Loss of ubiquitin-protein ligase activity. Increase in TSG101-binding.
Mutagenesis384-387Loss of TSG101-binding.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed
Lipidation2N-myristoyl glycine
ChainPRO_00002466882-532E3 ubiquitin-protein ligase MGRN1
Modified residue389Phosphotyrosine
Modified residue428Phosphoserine
Modified residue449Phosphoserine
Modified residue452Phosphoserine
Modified residue501Phosphoserine

Post-translational modification

Autoubiquitinated in vitro.

Keywords

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

Interaction

Subunit

Interacts with MC1R and MC4R (By similarity).
Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for zinc finger, motif, compositional bias, region.

TypeIDPosition(s)Description
Zinc finger277-316RING-type
Motif384-387Required for TSG101-binding
Compositional bias419-435Polar residues
Region419-518Disordered

Domain

The RING finger is required for ubiquitin ligase activity.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (5)
  • Sequence status
    Complete

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.

  • Name
    1
  • Synonyms
    I
  • Note
    Sufficient for normal development, pigmentation and neuronal integrity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    532
  • Mass (Da)
    58,477
  • Last updated
    2003-03-01 v2
  • Checksum
    89C2C1A28F9417EE
MGSILSRRIAGVEDIDIQANSAYRYPPKSGNYFASHFFMGGEKFDTPHPEGYLFGENMDLNFLGSRPVQFPYVTPAPHEPVKTLRSLVNIRKDSLRLVRYKEDADSPTEDGEKPRVLYSLEFTFDADARVAITIYCQAVEELVNGVAVYSCKNPSLQSETVHYKRGVSQQFSLPSFKIDFSEWKDDELNFDLDRGVFPVVIQAVVDEGDVVEVTGHAHVLLAAFEKHVDGSFSVKPLKQKQIVDRVSYLLQEIYGIENKNNQETKPSDDENSDNSSECVVCLSDLRDTLILPCRHLCLCTSCADTLRYQANNCPICRLPFRALLQIRAVRKKPGALSPISFSPVLAQSVDHDEHSSSDSIPPGYEPISLLEALNGLRAVSPAIPSAPLYEEITYSGISDGLSQASCPLAGLDRIMESGLQKGKTQSKSPDSTLRSPSFPIHEEDEEKLSEDSDAPLPPSGVELVLRESSSPESFGTEEGDEPSLKQGSRVPSIDDVLQDGSPQHHGCSQPVPPADIYLPALGPESCSVGIEE

Q9D074-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q9D074-3

  • Name
    3
  • Synonyms
    III
  • Note
    Sufficient for normal development, pigmentation and neuronal integrity.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 520-532: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF

Q9D074-4

  • Name
    4
  • Synonyms
    II
  • Note
    Partial rescue of the phenotype of mutant null mice.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 355-355: S → SCPFKKSKSHPASLASKKPKRET

Q9D074-5

  • Name
    5
  • Synonyms
    IV
  • Note
    Unable to rescue the phenotype of mutant null mice. This sequence has been deduced from the description in PubMed:19422019.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 355-355: S → SCPFKKSKSHPASLASKKPKRET
    • 520-532: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF

Features

Showing features for sequence conflict, alternative sequence, compositional bias.

TypeIDPosition(s)Description
Sequence conflict15in Ref. 1; BAE29360
Alternative sequenceVSP_01985429in isoform 2
Sequence conflict31in Ref. 1; BAE29360
Sequence conflict36in Ref. 1; BAE29360
Alternative sequenceVSP_019855355in isoform 4 and isoform 5
Compositional bias419-435Polar residues
Alternative sequenceVSP_019856520-532in isoform 3 and isoform 5

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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