Q9Y4L5 · RN115_HUMAN

  • Protein
    E3 ubiquitin-protein ligase RNF115
  • Gene
    RNF115
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

E3 ubiquitin-protein ligase that catalyzes the 'Lys-48'- and/or 'Lys-63'-linked polyubiquitination of various substrates and thereby plays a role in a number of signaling pathways including autophagy, innate immunity, cell proliferation and cell death (PubMed:20019814, PubMed:30689267).
Plays a role in the endosomal trafficking and degradation of membrane receptors including EGFR, FLT3, MET and CXCR4 through their polyubiquitination. Participates together with BST2 in antiviral immunity by facilitating the internalization of HIV-1 virions into intracellular vesicles leading to their lysosomal degradation (PubMed:20019814).
Possesses also an antiviral activity independently of BST2 by promoting retroviral GAG proteins ubiquitination, redistribution to endo-lysosomal compartments and, ultimately, lysosomal degradation (PubMed:24852021).
Catalyzes distinct types of ubiquitination on MAVS and STING1 at different phases of viral infection to promote innate antiviral response (PubMed:33139700).
Mediates the 'Lys-48'-linked ubiquitination of MAVS leading to its proteasomal degradation and ubiquitinates STING1 via 'Lys-63'-linked polyubiquitination, critical for its oligomerization and the subsequent recruitment of TBK1 (PubMed:33139700).
Plays a positive role in the autophagosome-lysosome fusion by interacting with STX17 and enhancing its stability without affecting 'Lys-48'- or 'Lys-63'-linked polyubiquitination levels, which in turn promotes autophagosome maturation (PubMed:32980859).
Negatively regulates TLR-induced expression of proinflammatory cytokines by catalyzing 'Lys-11'-linked ubiquitination of RAB1A and RAB13 to inhibit post-ER trafficking of TLRs to the Golgi by RAB1A and subsequently from the Golgi apparatus to the cell surface by RAB13 (PubMed:35343654).

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

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentendoplasmic reticulum
Cellular ComponentGolgi apparatus
Cellular Componentnucleus
Molecular Functionmetal ion binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Biological Processnegative regulation of epidermal growth factor receptor signaling pathway
Biological Processnegative regulation of toll-like receptor signaling pathway
Biological Processprotein autoubiquitination
Biological Processprotein K11-linked ubiquitination
Biological Processprotein K48-linked ubiquitination
Biological Processprotein K63-linked ubiquitination
Biological Processprotein ubiquitination
Biological Processubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase RNF115
  • EC number
  • Alternative names
    • RING finger protein 115
    • RING-type E3 ubiquitin transferase RNF115
    • Rab7-interacting RING finger protein
      (Rabring 7
      )
    • Zinc finger protein 364

Gene names

    • Name
      RNF115
    • Synonyms
      ZNF364

Organism names

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

Accessions

  • Primary accession
    Q9Y4L5
  • Secondary accessions
    • A8K3Y4
    • Q5T2V9
    • Q7Z2J2

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Endoplasmic reticulum
Golgi apparatus
Note: The GTP-bound form of RAB7A recruits RNF115 from the cytosol onto late endosomes/lysosomes.

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis26Loss of autoubiquitination; when associated with R-32.
Mutagenesis32Loss of autoubiquitination; when associated with R-26.
Mutagenesis132About 50% loss of phosphorylation; when associated with A-133.
Mutagenesis133About 50% loss of phosphorylation; when associated with A-132.
Natural variantVAR_052105194in dbSNP:rs11577731
Mutagenesis228Loss of autoubiquitination.
Mutagenesis228Loss of E3 ligase activity. Maintains the ability to restrict viral particle production; when associated with A-232.
Mutagenesis231Loss of autoubiquitination.
Mutagenesis231Loss of E3 ligase activity. Maintains the ability to restrict viral particle production; when associated with A-228.

Variants

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

The viewer provides 370 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, modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Modified residue2UniProtN-acetylalanine
ChainPRO_00000563142-304UniProtE3 ubiquitin-protein ligase RNF115
Modified residue132UniProtPhosphoserine; by PKB/AKT1
Modified residue133UniProtPhosphoserine; by PKB/AKT1
Modified residue (large scale data)296PRIDEPhosphoserine
Modified residue (large scale data)303PRIDEPhosphothreonine

Post-translational modification

Phosphorylated by AKT1, allowing association with the 14-3-3 chaperones that facilitates associating with TLRs.
RING-type zinc finger-dependent and E2-dependent autoubiquitination.
Deubiquitinated by USP9X; antogonizing its autoubiquitination and subsequent proteasomal degradation.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed at extremely low levels in normal breast, prostate, lung, colon. Higher levels of expression are detected in heart, skeletal muscle, testis as well as in breast and prostate cancer cells.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with RAB7A. Interacts with EGFR and FLT3. Interacts with BST2 (PubMed:20019814).
Interacts with STX17 (PubMed:32980859).
Interacts with YWHAE (PubMed:35343654).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, zinc finger.

TypeIDPosition(s)Description
Region95-138Disordered
Zinc finger228-269RING-type
Region272-304Disordered

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    304
  • Mass (Da)
    33,703
  • Last updated
    2004-12-07 v2
  • Checksum
    22F0C8FCC0F55045
MAEASAAGADSGAAVAAHRFFCHFCKGEVSPKLPEYICPRCESGFIEEVTDDSSFLGGGGSRIDNTTTTHFAELWGHLDHTMFFQDFRPFLSSSPLDQDNRANERGHQTHTDFWGARPPRLPLGRRYRSRGSSRPDRSPAIEGILQHIFAGFFANSAIPGSPHPFSWSGMLHSNPGDYAWGQTGLDAIVTQLLGQLENTGPPPADKEKITSLPTVTVTQEQVDMGLECPVCKEDYTVEEEVRQLPCNHFFHSSCIVPWLELHDTCPVCRKSLNGEDSTRQSQSTEASASNRFSNDSQLHDRWTF

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict299in Ref. 7; CAB45280

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF542552
EMBL· GenBank· DDBJ
AAQ09535.1
EMBL· GenBank· DDBJ
mRNA
AF419857
EMBL· GenBank· DDBJ
AAP97292.1
EMBL· GenBank· DDBJ
mRNA
AK290749
EMBL· GenBank· DDBJ
BAF83438.1
EMBL· GenBank· DDBJ
mRNA
AL390725
EMBL· GenBank· DDBJ
CAI13717.1
EMBL· GenBank· DDBJ
Genomic DNA
AL160282
EMBL· GenBank· DDBJ
CAI13717.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471244
EMBL· GenBank· DDBJ
EAW71437.1
EMBL· GenBank· DDBJ
Genomic DNA
BC054049
EMBL· GenBank· DDBJ
AAH54049.1
EMBL· GenBank· DDBJ
mRNA
BC064903
EMBL· GenBank· DDBJ
AAH64903.1
EMBL· GenBank· DDBJ
mRNA
AL079314
EMBL· GenBank· DDBJ
CAB45280.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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