UniProtKB - Q9NS91 (RAD18_HUMAN)
E3 ubiquitin-protein ligase RAD18
RAD18
Functioni
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.
2 PublicationsCatalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. EC:2.3.2.27
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 204 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 207 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 219 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 223 | ZincPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 25 – 64 | RING-typePROSITE-ProRule annotationAdd BLAST | 40 | |
Zinc fingeri | 201 – 228 | UBZ4-typePROSITE-ProRule annotationAdd BLAST | 28 |
GO - Molecular functioni
- damaged DNA binding Source: UniProtKB
- identical protein binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- protein-containing complex binding Source: UniProtKB
- single-stranded DNA binding Source: InterPro
- ubiquitin protein ligase activity Source: InterPro
- ubiquitin protein ligase binding Source: UniProtKB
- Y-form DNA binding Source: UniProtKB
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- DNA repair Source: UniProtKB
- negative regulation of cell death Source: UniProtKB
- positive regulation of chromosome segregation Source: UniProtKB
- postreplication repair Source: GO_Central
- protein autoubiquitination Source: MGI
- protein monoubiquitination Source: GO_Central
Keywordsi
Molecular function | DNA-binding, Transferase |
Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9NS91 |
Reactomei | R-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex R-HSA-8866654, E3 ubiquitin ligases ubiquitinate target proteins |
SignaLinki | Q9NS91 |
SIGNORi | Q9NS91 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase RAD18 (EC:2.3.2.27)Alternative name(s): Postreplication repair protein RAD18 Short name: hHR18 Short name: hRAD18 RING finger protein 73 RING-type E3 ubiquitin transferase RAD18Curated |
Gene namesi | Name:RAD18 Synonyms:RNF73 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18278, RAD18 |
MIMi | 605256, gene |
neXtProti | NX_Q9NS91 |
VEuPathDBi | HostDB:ENSG00000070950 |
Subcellular locationi
Cytoskeleton
- centrosome 1 Publication
Nucleus
- Nucleus 3 Publications
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).3 Publications
Cytoskeleton
- centrosome Source: UniProtKB
Nucleus
- nuclear body Source: HPA
- nuclear inclusion body Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-KW
- Rad6-Rad18 complex Source: GO_Central
- replication fork Source: UniProtKB
- site of double-strand break Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 27 | I → A: Lower activity toward PCNA monoubiquitination. 1 Publication | 1 | |
Mutagenesisi | 442 | S → A: Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-444. 2 Publications | 1 | |
Mutagenesisi | 444 | S → A: Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-442. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 56852 |
OpenTargetsi | ENSG00000070950 |
PharmGKBi | PA134912253 |
Miscellaneous databases
Pharosi | Q9NS91, Tbio |
Genetic variation databases
BioMutai | RAD18 |
DMDMi | 313104165 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000056149 | 1 – 495 | E3 ubiquitin-protein ligase RAD18Add BLAST | 495 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 99 | PhosphoserineCombined sources | 1 | |
Modified residuei | 103 | PhosphoserineCombined sources | 1 | |
Modified residuei | 118 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 122 | PhosphoserineCombined sources | 1 | |
Modified residuei | 125 | PhosphoserineCombined sources | 1 | |
Modified residuei | 142 | PhosphoserineCombined sources | 1 | |
Modified residuei | 158 | PhosphoserineCombined sources | 1 | |
Modified residuei | 164 | PhosphoserineCombined sources | 1 | |
Modified residuei | 322 | PhosphoserineCombined sources | 1 | |
Cross-linki | 376 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 471 | PhosphoserineCombined sources | 1 | |
Modified residuei | 483 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-3246 CPTAC-3247 CPTAC-3285 CPTAC-939 CPTAC-940 |
EPDi | Q9NS91 |
jPOSTi | Q9NS91 |
MassIVEi | Q9NS91 |
MaxQBi | Q9NS91 |
PaxDbi | Q9NS91 |
PeptideAtlasi | Q9NS91 |
PRIDEi | Q9NS91 |
ProteomicsDBi | 82515 |
PTM databases
GlyGeni | Q9NS91, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9NS91 |
MetOSitei | Q9NS91 |
PhosphoSitePlusi | Q9NS91 |
SwissPalmi | Q9NS91 |
Expressioni
Gene expression databases
Bgeei | ENSG00000070950, Expressed in lung and 179 other tissues |
ExpressionAtlasi | Q9NS91, baseline and differential |
Genevisiblei | Q9NS91, HS |
Organism-specific databases
HPAi | ENSG00000070950, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer (PubMed:21549715).
Interacts with UBE2A and UBE2B, one homodimer binding one molecule of UBE2B.
Interacts with SHPRH (PubMed:17130289, PubMed:17108083).
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).
9 PublicationsBinary interactionsi
Q9NS91
GO - Molecular functioni
- identical protein binding Source: MGI
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121212, 452 interactors |
DIPi | DIP-29831N |
IntActi | Q9NS91, 74 interactors |
MINTi | Q9NS91 |
STRINGi | 9606.ENSP00000264926 |
Miscellaneous databases
RNActi | Q9NS91, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9NS91 |
SMRi | Q9NS91 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 248 – 282 | SAPPROSITE-ProRule annotationAdd BLAST | 35 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 152 – 197 | DisorderedSequence analysisAdd BLAST | 46 | |
Regioni | 400 – 423 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 456 – 495 | DisorderedSequence analysisAdd BLAST | 40 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 232 – 240 | LR motif | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 166 – 184 | Basic and acidic residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 25 – 64 | RING-typePROSITE-ProRule annotationAdd BLAST | 40 | |
Zinc fingeri | 201 – 228 | UBZ4-typePROSITE-ProRule annotationAdd BLAST | 28 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG0287, Eukaryota |
GeneTreei | ENSGT00390000011230 |
InParanoidi | Q9NS91 |
OMAi | ERTQGGH |
OrthoDBi | 1013108at2759 |
PhylomeDBi | Q9NS91 |
TreeFami | TF101214 |
Family and domain databases
DisProti | DP01796 |
Gene3Di | 1.10.720.30, 1 hit 3.30.40.10, 1 hit |
IDEALi | IID00588 |
InterProi | View protein in InterPro IPR039577, Rad18 IPR006642, Rad18_UBZ4 IPR003034, SAP_dom IPR036361, SAP_dom_sf IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR14134, PTHR14134, 1 hit |
Pfami | View protein in Pfam PF02037, SAP, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 1 hit SM00513, SAP, 1 hit SM00734, ZnF_Rad18, 1 hit |
PROSITEi | View protein in PROSITE PS50800, SAP, 1 hit PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit PS51908, ZF_UBZ4, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MDSLAESRWP PGLAVMKTID DLLRCGICFE YFNIAMIIPQ CSHNYCSLCI
60 70 80 90 100
RKFLSYKTQC PTCCVTVTEP DLKNNRILDE LVKSLNFARN HLLQFALESP
110 120 130 140 150
AKSPASSSSK NLAVKVYTPV ASRQSLKQGS RLMDNFLIRE MSGSTSELLI
160 170 180 190 200
KENKSKFSPQ KEASPAAKTK ETRSVEEIAP DPSEAKRPEP PSTSTLKQVT
210 220 230 240 250
KVDCPVCGVN IPESHINKHL DSCLSREEKK ESLRSSVHKR KPLPKTVYNL
260 270 280 290 300
LSDRDLKKKL KEHGLSIQGN KQQLIKRHQE FVHMYNAQCD ALHPKSAAEI
310 320 330 340 350
VREIENIEKT RMRLEASKLN ESVMVFTKDQ TEKEIDEIHS KYRKKHKSEF
360 370 380 390 400
QLLVDQARKG YKKIAGMSQK TVTITKEDES TEKLSSVCMG QEDNMTSVTN
410 420 430 440 450
HFSQSKLDSP EELEPDREED SSSCIDIQEV LSSSESDSCN SSSSDIIRDL
460 470 480 490
LEEEEAWEAS HKNDLQDTEI SPRQNRRTRA AESAEIEPRN KRNRN
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8WE49 | F8WE49_HUMAN | RING-type E3 ubiquitin transferase | RAD18 | 310 | Annotation score: | ||
C9J0Q4 | C9J0Q4_HUMAN | E3 ubiquitin-protein ligase RAD18 | RAD18 | 91 | Annotation score: | ||
F8WFA6 | F8WFA6_HUMAN | E3 ubiquitin-protein ligase RAD18 | RAD18 | 126 | Annotation score: | ||
F8WAZ7 | F8WAZ7_HUMAN | E3 ubiquitin-protein ligase RAD18 | RAD18 | 53 | Annotation score: | ||
H7C0A5 | H7C0A5_HUMAN | E3 ubiquitin-protein ligase RAD18 | RAD18 | 79 | Annotation score: | ||
H7C3I2 | H7C3I2_HUMAN | E3 ubiquitin-protein ligase RAD18 | RAD18 | 131 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 191 | P → L in AAF80856 (PubMed:10908344).Curated | 1 | |
Sequence conflicti | 482 – 484 | ESA → GKC in AAF80856 (PubMed:10908344).Curated | 3 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023423 | 6 | E → A1 PublicationCorresponds to variant dbSNP:rs45520133Ensembl. | 1 | |
Natural variantiVAR_023424 | 302 | R → Q6 PublicationsCorresponds to variant dbSNP:rs373572Ensembl. | 1 | |
Natural variantiVAR_023425 | 307 | I → V1 PublicationCorresponds to variant dbSNP:rs45569933Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB035274 mRNA Translation: BAA99284.1 AF169796 mRNA Translation: AAF80856.1 AY004333 mRNA Translation: AAF86618.1 AK023075 mRNA Translation: BAB14392.1 AY961989 Genomic DNA Translation: AAX44049.1 AC008151 Genomic DNA No translation available. AC034186 Genomic DNA No translation available. BC001302 mRNA Translation: AAH01302.1 |
CCDSi | CCDS2571.1 |
RefSeqi | NP_064550.3, NM_020165.3 |
Genome annotation databases
Ensembli | ENST00000264926.7; ENSP00000264926.2; ENSG00000070950.10 |
GeneIDi | 56852 |
KEGGi | hsa:56852 |
MANE-Selecti | ENST00000264926.7; ENSP00000264926.2; NM_020165.4; NP_064550.3 |
UCSCi | uc003brd.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB035274 mRNA Translation: BAA99284.1 AF169796 mRNA Translation: AAF80856.1 AY004333 mRNA Translation: AAF86618.1 AK023075 mRNA Translation: BAB14392.1 AY961989 Genomic DNA Translation: AAX44049.1 AC008151 Genomic DNA No translation available. AC034186 Genomic DNA No translation available. BC001302 mRNA Translation: AAH01302.1 |
CCDSi | CCDS2571.1 |
RefSeqi | NP_064550.3, NM_020165.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2MRE | NMR | - | B | 198-227 | [»] | |
2MRF | NMR | - | A | 198-227 | [»] | |
2Y43 | X-ray | 1.80 | A/B | 1-99 | [»] | |
2YBF | X-ray | 2.00 | B | 340-366 | [»] | |
5VF0 | NMR | - | B | 198-240 | [»] | |
AlphaFoldDBi | Q9NS91 | |||||
SMRi | Q9NS91 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121212, 452 interactors |
DIPi | DIP-29831N |
IntActi | Q9NS91, 74 interactors |
MINTi | Q9NS91 |
STRINGi | 9606.ENSP00000264926 |
PTM databases
GlyGeni | Q9NS91, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9NS91 |
MetOSitei | Q9NS91 |
PhosphoSitePlusi | Q9NS91 |
SwissPalmi | Q9NS91 |
Genetic variation databases
BioMutai | RAD18 |
DMDMi | 313104165 |
Proteomic databases
CPTACi | CPTAC-3246 CPTAC-3247 CPTAC-3285 CPTAC-939 CPTAC-940 |
EPDi | Q9NS91 |
jPOSTi | Q9NS91 |
MassIVEi | Q9NS91 |
MaxQBi | Q9NS91 |
PaxDbi | Q9NS91 |
PeptideAtlasi | Q9NS91 |
PRIDEi | Q9NS91 |
ProteomicsDBi | 82515 |
Protocols and materials databases
Antibodypediai | 10148, 417 antibodies from 40 providers |
CPTCi | Q9NS91, 5 antibodies |
DNASUi | 56852 |
Genome annotation databases
Ensembli | ENST00000264926.7; ENSP00000264926.2; ENSG00000070950.10 |
GeneIDi | 56852 |
KEGGi | hsa:56852 |
MANE-Selecti | ENST00000264926.7; ENSP00000264926.2; NM_020165.4; NP_064550.3 |
UCSCi | uc003brd.4, human |
Organism-specific databases
CTDi | 56852 |
DisGeNETi | 56852 |
GeneCardsi | RAD18 |
HGNCi | HGNC:18278, RAD18 |
HPAi | ENSG00000070950, Low tissue specificity |
MIMi | 605256, gene |
neXtProti | NX_Q9NS91 |
OpenTargetsi | ENSG00000070950 |
PharmGKBi | PA134912253 |
VEuPathDBi | HostDB:ENSG00000070950 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0287, Eukaryota |
GeneTreei | ENSGT00390000011230 |
InParanoidi | Q9NS91 |
OMAi | ERTQGGH |
OrthoDBi | 1013108at2759 |
PhylomeDBi | Q9NS91 |
TreeFami | TF101214 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | Q9NS91 |
Reactomei | R-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex R-HSA-8866654, E3 ubiquitin ligases ubiquitinate target proteins |
SignaLinki | Q9NS91 |
SIGNORi | Q9NS91 |
Miscellaneous databases
BioGRID-ORCSi | 56852, 52 hits in 1121 CRISPR screens |
ChiTaRSi | RAD18, human |
GeneWikii | RAD18 |
GenomeRNAii | 56852 |
Pharosi | Q9NS91, Tbio |
PROi | PR:Q9NS91 |
RNActi | Q9NS91, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000070950, Expressed in lung and 179 other tissues |
ExpressionAtlasi | Q9NS91, baseline and differential |
Genevisiblei | Q9NS91, HS |
Family and domain databases
DisProti | DP01796 |
Gene3Di | 1.10.720.30, 1 hit 3.30.40.10, 1 hit |
IDEALi | IID00588 |
InterProi | View protein in InterPro IPR039577, Rad18 IPR006642, Rad18_UBZ4 IPR003034, SAP_dom IPR036361, SAP_dom_sf IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR14134, PTHR14134, 1 hit |
Pfami | View protein in Pfam PF02037, SAP, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 1 hit SM00513, SAP, 1 hit SM00734, ZnF_Rad18, 1 hit |
PROSITEi | View protein in PROSITE PS50800, SAP, 1 hit PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit PS51908, ZF_UBZ4, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RAD18_HUMAN | |
Accessioni | Q9NS91Primary (citable) accession number: Q9NS91 Secondary accession number(s): Q58F55, Q9NRT6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 6, 2002 |
Last sequence update: | November 30, 2010 | |
Last modified: | May 25, 2022 | |
This is version 188 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families