Q9BV68 · RN126_HUMAN
- ProteinE3 ubiquitin-protein ligase RNF126
- GeneRNF126
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids311 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins (PubMed:23277564, PubMed:24275455, PubMed:24981174, PubMed:36563124).
Depending on the associated E2 ligase, mediates 'Lys-27'-, 'Lys-29'-, 'Lys-48'- and/or 'Lys-63'-linked polyubiquitination of substrates (PubMed:36563124).
Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (PubMed:24981174, PubMed:29042515).
May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455).
May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353).
By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136).
May monoubiquitinate AICDA (PubMed:23277564).
Acts as a regulator of DNA repair by mediating 'Lys-27'- and 'Lys-29'-linked polyubiquitination of MRE11, thereby promoting the exonuclease activity of MRE11 (PubMed:36563124).
Depending on the associated E2 ligase, mediates 'Lys-27'-, 'Lys-29'-, 'Lys-48'- and/or 'Lys-63'-linked polyubiquitination of substrates (PubMed:36563124).
Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (PubMed:24981174, PubMed:29042515).
May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455).
May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353).
By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136).
May monoubiquitinate AICDA (PubMed:23277564).
Acts as a regulator of DNA repair by mediating 'Lys-27'- and 'Lys-29'-linked polyubiquitination of MRE11, thereby promoting the exonuclease activity of MRE11 (PubMed:36563124).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RNF126
- 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 accessionQ9BV68
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 14 | Impaired interaction with BAG6. | ||||
Sequence: H → A | ||||||
Mutagenesis | 36 | Impaired interaction with BAG6. | ||||
Sequence: F → A | ||||||
Mutagenesis | 38-39 | Impaired interaction with BAG6. | ||||
Sequence: EE → RR | ||||||
Natural variant | VAR_057217 | 68 | in dbSNP:rs2285751 | |||
Sequence: V → M | ||||||
Mutagenesis | 229-232 | Loss of E3 ligase activity. | ||||
Sequence: CPVC → APVA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 379 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_0000056093 | 2-311 | UniProt | E3 ubiquitin-protein ligase RNF126 | |||
Sequence: AEASPHPGRYFCHCCSVEIVPRLPDYICPRCESGFIEELPEETRSTENGSAPSTAPTDQSRPPLEHVDQHLFTLPQGYGQFAFGIFDDSFEIPTFPPGAQADDGRDPESRRERDHPSRHRYGARQPRARLTTRRATGRHEGVPTLEGIIQQLVNGIITPATIPSLGPWGVLHSNPMDYAWGANGLDAIITQLLNQFENTGPPPADKEKIQALPTVPVTEEHVGSGLECPVCKDDYALGERVRQLPCNHLFHDGCIVPWLEQHDSCPVCRKSLTGQNTATNPPGLTGVSFSSSSSSSSSSSPSNENATSNS | |||||||
Modified residue | 5 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 5 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 17 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated. May undergo autoubiquitination.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in liver and testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with CCDC50, EGFR, FLT3 and SCAMP3 (PubMed:23418353).
Interacts with BAG6 (via ubiquitin-like domain); required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol (PubMed:24981174, PubMed:27193484).
Interacts with CDKN1A (PubMed:23026136).
Interacts with AICDA (PubMed:23277564).
Interacts with BAG6 (via ubiquitin-like domain); required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol (PubMed:24981174, PubMed:27193484).
Interacts with CDKN1A (PubMed:23026136).
Interacts with AICDA (PubMed:23277564).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9BV68 | BAG6 P46379 | 8 | EBI-357322, EBI-347552 | |
BINARY | Q9BV68 | BAG6 P46379-2 | 4 | EBI-357322, EBI-10988864 | |
BINARY | Q9BV68 | UBE2D1 P51668 | 7 | EBI-357322, EBI-743540 | |
BINARY | Q9BV68 | UBE2D3 P61077 | 4 | EBI-357322, EBI-348268 | |
BINARY | Q9BV68 | UBE2D4 Q9Y2X8 | 3 | EBI-357322, EBI-745527 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 5-100 | Required for interaction with BAG6 | ||||
Sequence: SPHPGRYFCHCCSVEIVPRLPDYICPRCESGFIEELPEETRSTENGSAPSTAPTDQSRPPLEHVDQHLFTLPQGYGQFAFGIFDDSFEIPTFPPGA | ||||||
Zinc finger | 13-32 | C4-type | ||||
Sequence: CHCCSVEIVPRLPDYICPRC | ||||||
Region | 42-64 | Disordered | ||||
Sequence: EETRSTENGSAPSTAPTDQSRPP | ||||||
Compositional bias | 46-61 | Polar residues | ||||
Sequence: STENGSAPSTAPTDQS | ||||||
Region | 94-132 | Disordered | ||||
Sequence: PTFPPGAQADDGRDPESRRERDHPSRHRYGARQPRARLT | ||||||
Compositional bias | 104-122 | Basic and acidic residues | ||||
Sequence: DGRDPESRRERDHPSRHRY | ||||||
Region | 200-304 | Sufficient for interaction with AICDA | ||||
Sequence: TGPPPADKEKIQALPTVPVTEEHVGSGLECPVCKDDYALGERVRQLPCNHLFHDGCIVPWLEQHDSCPVCRKSLTGQNTATNPPGLTGVSFSSSSSSSSSSSPSN | ||||||
Zinc finger | 229-270 | RING-type | ||||
Sequence: CPVCKDDYALGERVRQLPCNHLFHDGCIVPWLEQHDSCPVCR | ||||||
Region | 277-311 | Disordered | ||||
Sequence: NTATNPPGLTGVSFSSSSSSSSSSSPSNENATSNS |
Domain
The C4-type zinc finger is required for interaction with BAG6.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length311
- Mass (Da)33,861
- Last updated2019-01-16 v2
- Checksum0C748E78E6719C3E
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 46-61 | Polar residues | ||||
Sequence: STENGSAPSTAPTDQS | ||||||
Compositional bias | 104-122 | Basic and acidic residues | ||||
Sequence: DGRDPESRRERDHPSRHRY |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK000559 EMBL· GenBank· DDBJ | BAA91254.1 EMBL· GenBank· DDBJ | mRNA | ||
BC001442 EMBL· GenBank· DDBJ | AAH01442.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC025374 EMBL· GenBank· DDBJ | AAH25374.1 EMBL· GenBank· DDBJ | mRNA |