O60291 · MGRN1_HUMAN

  • 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 monoubiquitination at multiple sites of TSG101 in the presence of UBE2D1, but not of UBE2G1, nor UBE2H. 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. Acts also as a negative regulator of hedgehog signaling (By similarity).

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 Componentcytosol
Cellular Componentearly endosome
Cellular Componentendoplasmic reticulum
Cellular Componentextracellular exosome
Cellular Componentintracellular membrane-bounded organelle
Cellular Componentmembrane
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 finger protein 156
    • RING-type E3 ubiquitin transferase MGRN1

Gene names

    • Name
      MGRN1
    • Synonyms
      KIAA0544, RNF156

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O60291
  • Secondary accessions
    • A4URL3
    • A4URL4
    • Q86W76

Proteomes

Organism-specific databases

Subcellular Location

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

Isoform 1

Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.

Isoform 2

Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.

Isoform 3

Isoform 4

Keywords

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis406-409Loss of TSG101-binding and drastic reduction of TSG101-ubiquitination.

Variants

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

The viewer provides 895 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Lipidation2UniProtN-myristoyl glycine
ChainPRO_00002466872-552UniProtE3 ubiquitin-protein ligase MGRN1
Modified residue (large scale data)106PRIDEPhosphoserine
Modified residue (large scale data)153PRIDEPhosphoserine
Modified residue (large scale data)155PRIDEPhosphoserine
Modified residue (large scale data)337PRIDEPhosphoserine
Modified residue (large scale data)342PRIDEPhosphoserine
Modified residue (large scale data)402PRIDEPhosphoserine
Modified residue411UniProtPhosphotyrosine
Modified residue (large scale data)457PRIDEPhosphoserine
Modified residue (large scale data)459PRIDEPhosphoserine
Modified residue (large scale data)460PRIDEPhosphoserine
Modified residue471UniProtPhosphoserine
Modified residue (large scale data)471PRIDEPhosphoserine
Modified residue (large scale data)506PRIDEPhosphoserine
Modified residue (large scale data)515PRIDEPhosphoserine
Modified residue (large scale data)523PRIDEPhosphoserine
Modified residue524UniProtPhosphoserine
Modified residue (large scale data)524PRIDEPhosphoserine

Post-translational modification

Autoubiquitinated in vitro.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with MC1R and MC4R, but not with TBXA2R. Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY O60291TSG101 Q998165EBI-2129851, EBI-346882

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

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

TypeIDPosition(s)Description
Zinc finger278-317RING-type
Region355-384Disordered
Motif406-409Required for TSG101-binding
Region439-552Disordered
Compositional bias443-458Polar residues
Compositional bias491-522Polar residues

Domain

The RING finger is required for ubiquitin ligase activity.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete

This entry describes 4 isoforms produced by Alternative splicing.

O60291-1

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
    (+)S
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    552
  • Mass (Da)
    60,753
  • Last updated
    2006-07-25 v2
  • Checksum
    1F923D25FB49DB4D
MGSILSRRIAGVEDIDIQANSAYRYPPKSGNYFASHFFMGGEKFDTPHPEGYLFGENMDLNFLGSRPVQFPYVTPAPHEPVKTLRSLVNIRKDSLRLVRYKDDADSPTEDGDKPRVLYSLEFTFDADARVAITIYCQASEEFLNGRAVYSPKSPSLQSETVHYKRGVSQQFSLPSFKIDFSEWKDDELNFDLDRGVFPVVIQAVVDEGDVVEVTGHAHVLLAAFEKHMDGSFSVKPLKQKQIVDRVSYLLQEIYGIENKNNQETKPSDDENSDNSNECVVCLSDLRDTLILPCRHLCLCTSCADTLRYQANNCPICRLPFRALLQIRAVRKKPGALSPVSFSPVLAQSLEHDEHSCPFKKSKPHPASLASKKPKRETNSDSVPPGYEPISLLEALNGLRAVSPAIPSAPLYEEITYSGISDGLSQASCPLAAIDHILDSSRQKGRPQSKAPDSTLRSPSSPIHEEDEEKLSEDVDAPPPLGGAELALRESSSPESFITEEVDESSSPQQGTRAASIENVLQDSSPEHCGRGPPADIYLPALGPDSCSVGIDE

O60291-2

  • Name
    2
  • Synonyms
    (+)L
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

O60291-3

  • Name
    3
  • Synonyms
    (-)L
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 356-377: Missing
    • 540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

O60291-4

  • Name
    4
  • Synonyms
    (-)S
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
K7EIM7K7EIM7_HUMANMGRN1332
B4DR12B4DR12_HUMANMGRN1320
K7EJN3K7EJN3_HUMANMGRN1166
K7EPJ5K7EPJ5_HUMANMGRN1594
K7ERA1K7ERA1_HUMANMGRN1149

Sequence caution

The sequence BAA25470.1 differs from that shown. Reason: Erroneous initiation

Features

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

TypeIDPosition(s)Description
Sequence conflict248in Ref. 1; ABO69623/ABO69624
Alternative sequenceVSP_036462356-377in isoform 3 and isoform 4
Compositional bias443-458Polar residues
Compositional bias491-522Polar residues
Sequence conflict537in Ref. 1; ABO69623/ABO69624
Alternative sequenceVSP_019853540-552in isoform 2 and isoform 3

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
EF471397
EMBL· GenBank· DDBJ
ABO69623.2
EMBL· GenBank· DDBJ
mRNA
EF471398
EMBL· GenBank· DDBJ
ABO69624.2
EMBL· GenBank· DDBJ
mRNA
AB011116
EMBL· GenBank· DDBJ
BAA25470.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AC023830
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC050389
EMBL· GenBank· DDBJ
AAH50389.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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