Q9Y4L5 · RN115_HUMAN
- ProteinE3 ubiquitin-protein ligase RNF115
- GeneRNF115
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids304 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Pathway
Protein modification; protein ubiquitination.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | Golgi apparatus | |
Cellular Component | nucleus | |
Molecular Function | metal ion binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin-protein transferase activity | |
Biological Process | negative regulation of epidermal growth factor receptor signaling pathway | |
Biological Process | negative regulation of toll-like receptor signaling pathway | |
Biological Process | protein autoubiquitination | |
Biological Process | protein K11-linked ubiquitination | |
Biological Process | protein K48-linked ubiquitination | |
Biological Process | protein K63-linked ubiquitination | |
Biological Process | protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RNF115
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y4L5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: The GTP-bound form of RAB7A recruits RNF115 from the cytosol onto late endosomes/lysosomes.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 26 | Loss of autoubiquitination; when associated with R-32. | ||||
Sequence: K → R | ||||||
Mutagenesis | 32 | Loss of autoubiquitination; when associated with R-26. | ||||
Sequence: K → R | ||||||
Mutagenesis | 132 | About 50% loss of phosphorylation; when associated with A-133. | ||||
Sequence: S → A | ||||||
Mutagenesis | 133 | About 50% loss of phosphorylation; when associated with A-132. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_052105 | 194 | in dbSNP:rs11577731 | |||
Sequence: G → R | ||||||
Mutagenesis | 228 | Loss of autoubiquitination. | ||||
Sequence: C → A | ||||||
Mutagenesis | 228 | Loss of E3 ligase activity. Maintains the ability to restrict viral particle production; when associated with A-232. | ||||
Sequence: C → A | ||||||
Mutagenesis | 231 | Loss of autoubiquitination. | ||||
Sequence: C → A | ||||||
Mutagenesis | 231 | Loss of E3 ligase activity. Maintains the ability to restrict viral particle production; when associated with A-228. | ||||
Sequence: C → A |
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.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000056314 | 2-304 | UniProt | E3 ubiquitin-protein ligase RNF115 | |||
Sequence: AEASAAGADSGAAVAAHRFFCHFCKGEVSPKLPEYICPRCESGFIEEVTDDSSFLGGGGSRIDNTTTTHFAELWGHLDHTMFFQDFRPFLSSSPLDQDNRANERGHQTHTDFWGARPPRLPLGRRYRSRGSSRPDRSPAIEGILQHIFAGFFANSAIPGSPHPFSWSGMLHSNPGDYAWGQTGLDAIVTQLLGQLENTGPPPADKEKITSLPTVTVTQEQVDMGLECPVCKEDYTVEEEVRQLPCNHFFHSSCIVPWLELHDTCPVCRKSLNGEDSTRQSQSTEASASNRFSNDSQLHDRWTF | |||||||
Modified residue | 132 | UniProt | Phosphoserine; by PKB/AKT1 | ||||
Sequence: S | |||||||
Modified residue | 133 | UniProt | Phosphoserine; by PKB/AKT1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 296 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 303 | PRIDE | Phosphothreonine | ||||
Sequence: T |
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
- PTM
Proteomic databases
PTM 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).
Interacts with STX17 (PubMed:32980859).
Interacts with YWHAE (PubMed:35343654).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y4L5 | DAZAP2 Q15038 | 5 | EBI-2129242, EBI-724310 | |
BINARY | Q9Y4L5 | MDM2 Q00987 | 2 | EBI-2129242, EBI-389668 | |
BINARY | Q9Y4L5 | MDM4 O15151 | 3 | EBI-2129242, EBI-398437 | |
BINARY | Q9Y4L5 | UBE2D1 P51668 | 12 | EBI-2129242, EBI-743540 | |
BINARY | Q9Y4L5 | UBE2D2 P62837 | 6 | EBI-2129242, EBI-347677 | |
BINARY | Q9Y4L5 | UBE2D3 P61077 | 11 | EBI-2129242, EBI-348268 | |
BINARY | Q9Y4L5 | UBE2D4 Q9Y2X8 | 12 | EBI-2129242, EBI-745527 | |
BINARY | Q9Y4L5 | UBE2E2 Q96LR5 | 6 | EBI-2129242, EBI-2129763 | |
BINARY | Q9Y4L5 | UBE2E3 Q969T4 | 4 | EBI-2129242, EBI-348496 | |
BINARY | Q9Y4L5 | VCP P55072 | 3 | EBI-2129242, EBI-355164 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 95-138 | Disordered | ||||
Sequence: PLDQDNRANERGHQTHTDFWGARPPRLPLGRRYRSRGSSRPDRS | ||||||
Zinc finger | 228-269 | RING-type | ||||
Sequence: CPVCKEDYTVEEEVRQLPCNHFFHSSCIVPWLELHDTCPVCR | ||||||
Region | 272-304 | Disordered | ||||
Sequence: LNGEDSTRQSQSTEASASNRFSNDSQLHDRWTF |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length304
- Mass (Da)33,703
- Last updated2004-12-07 v2
- Checksum22F0C8FCC0F55045
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 299 | in Ref. 7; CAB45280 | ||||
Sequence: H → N |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |