Q9NS91 · RAD18_HUMAN
- ProteinE3 ubiquitin-protein ligase RAD18
- GeneRAD18
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids495 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity.
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centrosome | |
Cellular Component | cytoplasm | |
Cellular Component | nuclear body | |
Cellular Component | nuclear inclusion body | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | Rad6-Rad18 complex | |
Cellular Component | replication fork | |
Cellular Component | site of double-strand break | |
Molecular Function | damaged DNA binding | |
Molecular Function | identical protein binding | |
Molecular Function | metal ion binding | |
Molecular Function | polyubiquitin modification-dependent protein binding | |
Molecular Function | protein-containing complex binding | |
Molecular Function | single-stranded DNA binding | |
Molecular Function | ubiquitin protein ligase activity | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | Y-form DNA binding | |
Biological Process | DNA damage response | |
Biological Process | DNA repair | |
Biological Process | positive regulation of chromosome segregation | |
Biological Process | postreplication repair | |
Biological Process | protein autoubiquitination | |
Biological Process | protein monoubiquitination |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RAD18
- 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 accessionQ9NS91
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Associates with chromatin (PubMed:25931565).
Colocalizes with SLF1 in the nucleus and to centrosomes (PubMed:15632077).
Relocalizes with SLF1 to nuclear foci in response to DNA damage (PubMed:22036607).
Accumulates with the SLF1-SLF2 and SMC5-SMC6 complexes at replication-coupled DNA interstrand repair and DNA double-strand breaks (DSBs) sites on chromatin in a ubiquitin-dependent manner (PubMed:25931565).
Colocalizes with SLF1 in the nucleus and to centrosomes (PubMed:15632077).
Relocalizes with SLF1 to nuclear foci in response to DNA damage (PubMed:22036607).
Accumulates with the SLF1-SLF2 and SMC5-SMC6 complexes at replication-coupled DNA interstrand repair and DNA double-strand breaks (DSBs) sites on chromatin in a ubiquitin-dependent manner (PubMed:25931565).
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_023423 | 6 | in dbSNP:rs45520133 | |||
Sequence: E → A | ||||||
Mutagenesis | 27 | Lower activity toward PCNA monoubiquitination. | ||||
Sequence: I → A | ||||||
Natural variant | VAR_023424 | 302 | in dbSNP:rs373572 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_023425 | 307 | in dbSNP:rs45569933 | |||
Sequence: I → V | ||||||
Mutagenesis | 442 | Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-444. | ||||
Sequence: S → A | ||||||
Mutagenesis | 444 | Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-442. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 613 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 modified residue, chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000056149 | 1-495 | UniProt | E3 ubiquitin-protein ligase RAD18 | |||
Sequence: MDSLAESRWPPGLAVMKTIDDLLRCGICFEYFNIAMIIPQCSHNYCSLCIRKFLSYKTQCPTCCVTVTEPDLKNNRILDELVKSLNFARNHLLQFALESPAKSPASSSSKNLAVKVYTPVASRQSLKQGSRLMDNFLIREMSGSTSELLIKENKSKFSPQKEASPAAKTKETRSVEEIAPDPSEAKRPEPPSTSTLKQVTKVDCPVCGVNIPESHINKHLDSCLSREEKKESLRSSVHKRKPLPKTVYNLLSDRDLKKKLKEHGLSIQGNKQQLIKRHQEFVHMYNAQCDALHPKSAAEIVREIENIEKTRMRLEASKLNESVMVFTKDQTEKEIDEIHSKYRKKHKSEFQLLVDQARKGYKKIAGMSQKTVTITKEDESTEKLSSVCMGQEDNMTSVTNHFSQSKLDSPEELEPDREEDSSSCIDIQEVLSSSESDSCNSSSSDIIRDLLEEEEAWEASHKNDLQDTEISPRQNRRTRAAESAEIEPRNKRNRN | |||||||
Modified residue (large scale data) | 7 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 99 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 99 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 103 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 103 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 106 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 118 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 118 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 122 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 122 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 125 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 142 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 142 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 155 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 158 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 158 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 164 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 172 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 174 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 194 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 322 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 322 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 376 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 403 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 405 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 409 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 468 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 471 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 471 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 483 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 483 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:21549715).
Interacts with UBE2A and UBE2B, one homodimer binding one molecule of UBE2B. Interacts with SHPRH (PubMed:17108083, PubMed:17130289).
Interacts with HLTF (PubMed:18316726, PubMed:18719106).
Interacts with SPRTN; leading to enhance chromatin association of RAD18 and RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887).
Interacts (via C-terminus and phosphorylated form) with SLF1 (via BRCT domains); this interaction is required for efficient repair of UV-induced DNA damage (PubMed:15632077, PubMed:22036607, PubMed:25931565).
Interacts with SLF2 (PubMed:25931565).
Interacts with SMC5; this interaction is increased in a SLF1 or SLF2-dependent manner (PubMed:25931565).
Interacts with DNA damage up-regulated protein DDUP (PubMed:35849344).
Forms a complex with DDUP and H2AX following DDUP phosphorylation (PubMed:35849344).
Interacts with UBE2A and UBE2B, one homodimer binding one molecule of UBE2B. Interacts with SHPRH (PubMed:17108083, PubMed:17130289).
Interacts with HLTF (PubMed:18316726, PubMed:18719106).
Interacts with SPRTN; leading to enhance chromatin association of RAD18 and RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887).
Interacts (via C-terminus and phosphorylated form) with SLF1 (via BRCT domains); this interaction is required for efficient repair of UV-induced DNA damage (PubMed:15632077, PubMed:22036607, PubMed:25931565).
Interacts with SLF2 (PubMed:25931565).
Interacts with SMC5; this interaction is increased in a SLF1 or SLF2-dependent manner (PubMed:25931565).
Interacts with DNA damage up-regulated protein DDUP (PubMed:35849344).
Forms a complex with DDUP and H2AX following DDUP phosphorylation (PubMed:35849344).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NS91 | ARRDC3 Q96B67 | 3 | EBI-2339393, EBI-2875665 | |
BINARY | Q9NS91 | ATXN1 P54253 | 6 | EBI-2339393, EBI-930964 | |
BINARY | Q9NS91 | DAZAP2 Q15038 | 3 | EBI-2339393, EBI-724310 | |
BINARY | Q9NS91 | GOLGA2 Q08379 | 3 | EBI-2339393, EBI-618309 | |
BINARY | Q9NS91 | HLTF Q14527 | 3 | EBI-2339393, EBI-1045161 | |
BINARY | Q9NS91 | MAGEA4 P43358 | 6 | EBI-2339393, EBI-743122 | |
BINARY | Q9NS91 | ORC2 Q13416 | 3 | EBI-2339393, EBI-374957 | |
BINARY | Q9NS91 | PDCD5 O14737 | 3 | EBI-2339393, EBI-712290 | |
BINARY | Q9NS91 | TARDBP Q13148 | 3 | EBI-2339393, EBI-372899 | |
BINARY | Q9NS91 | TAX1BP1 Q86VP1 | 6 | EBI-2339393, EBI-529518 | |
BINARY | Q9NS91 | UBE2A P49459 | 4 | EBI-2339393, EBI-2339348 | |
BINARY | Q9NS91 | UBE2B P63146 | 7 | EBI-2339393, EBI-712629 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger, region, compositional bias, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 25-64 | RING-type | ||||
Sequence: CGICFEYFNIAMIIPQCSHNYCSLCIRKFLSYKTQCPTCC | ||||||
Region | 152-197 | Disordered | ||||
Sequence: ENKSKFSPQKEASPAAKTKETRSVEEIAPDPSEAKRPEPPSTSTLK | ||||||
Compositional bias | 166-184 | Basic and acidic residues | ||||
Sequence: AAKTKETRSVEEIAPDPSE | ||||||
Zinc finger | 201-228 | UBZ4-type | ||||
Sequence: KVDCPVCGVNIPESHINKHLDSCLSREE | ||||||
Motif | 232-240 | LR motif | ||||
Sequence: SLRSSVHKR | ||||||
Domain | 248-282 | SAP | ||||
Sequence: YNLLSDRDLKKKLKEHGLSIQGNKQQLIKRHQEFV | ||||||
Region | 400-423 | Disordered | ||||
Sequence: NHFSQSKLDSPEELEPDREEDSSS | ||||||
Region | 456-495 | Disordered | ||||
Sequence: AWEASHKNDLQDTEISPRQNRRTRAAESAEIEPRNKRNRN |
Sequence similarities
Belongs to the RAD18 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length495
- Mass (Da)56,223
- Last updated2010-11-30 v2
- Checksum744A053A50C65DD7
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 166-184 | Basic and acidic residues | ||||
Sequence: AAKTKETRSVEEIAPDPSE | ||||||
Sequence conflict | 191 | in Ref. 2; AAF80856 | ||||
Sequence: P → L | ||||||
Sequence conflict | 482-484 | in Ref. 2; AAF80856 | ||||
Sequence: ESA → GKC |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB035274 EMBL· GenBank· DDBJ | BAA99284.1 EMBL· GenBank· DDBJ | mRNA | ||
AF169796 EMBL· GenBank· DDBJ | AAF80856.1 EMBL· GenBank· DDBJ | mRNA | ||
AY004333 EMBL· GenBank· DDBJ | AAF86618.1 EMBL· GenBank· DDBJ | mRNA | ||
AK023075 EMBL· GenBank· DDBJ | BAB14392.1 EMBL· GenBank· DDBJ | mRNA | ||
AY961989 EMBL· GenBank· DDBJ | AAX44049.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC008151 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC034186 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC001302 EMBL· GenBank· DDBJ | AAH01302.1 EMBL· GenBank· DDBJ | mRNA |