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Protein

E3 ubiquitin-protein ligase RAD18

Gene

RAD18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri25 – 64RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri201 – 224UBZ-typeAdd BLAST24

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-dependent ATPase activity Source: GO_Central
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB
  • Y-form DNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Transferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
SIGNORiQ9NS91
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000070950.9
HGNCiHGNC:18278 RAD18
MIMi605256 gene
neXtProtiNX_Q9NS91

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27I → A: Lower activity toward PCNA monoubiquitination. 1 Publication1
Mutagenesisi442S → A: Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-444. 2 Publications1
Mutagenesisi444S → A: Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-442. 2 Publications1

Organism-specific databases

DisGeNETi56852
OpenTargetsiENSG00000070950
PharmGKBiPA134912253

Polymorphism and mutation databases

BioMutaiRAD18
DMDMi313104165

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561491 – 495E3 ubiquitin-protein ligase RAD18Add BLAST495

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei99PhosphoserineCombined sources1
Modified residuei103PhosphoserineCombined sources1
Modified residuei118PhosphothreonineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Modified residuei125PhosphoserineCombined sources1
Modified residuei142PhosphoserineCombined sources1
Modified residuei158PhosphoserineCombined sources1
Modified residuei164PhosphoserineCombined sources1
Modified residuei322PhosphoserineCombined sources1
Cross-linki376Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei471PhosphoserineCombined sources1
Modified residuei483PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NS91
MaxQBiQ9NS91
PaxDbiQ9NS91
PeptideAtlasiQ9NS91
PRIDEiQ9NS91
ProteomicsDBi82515

PTM databases

iPTMnetiQ9NS91
PhosphoSitePlusiQ9NS91

Expressioni

Gene expression databases

BgeeiENSG00000070950 Expressed in 162 organ(s), highest expression level in lung
CleanExiHS_RAD18
ExpressionAtlasiQ9NS91 baseline and differential
GenevisibleiQ9NS91 HS

Organism-specific databases

HPAiHPA006716
HPA006724
HPA008752

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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121212, 88 interactors
DIPiDIP-29831N
IntActiQ9NS91, 43 interactors
MINTiQ9NS91
STRINGi9606.ENSP00000264926

Structurei

Secondary structure

1495
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NS91
SMRiQ9NS91
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini248 – 282SAPPROSITE-ProRule annotationAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi232 – 240LR motif9

Sequence similaritiesi

Belongs to the RAD18 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri25 – 64RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri201 – 224UBZ-typeAdd BLAST24

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0287 Eukaryota
COG5432 LUCA
GeneTreeiENSGT00390000011230
HOGENOMiHOG000234845
HOVERGENiHBG054721
InParanoidiQ9NS91
KOiK10627
OMAiNFLIREM
OrthoDBiEOG091G047P
PhylomeDBiQ9NS91
TreeFamiTF101214

Family and domain databases

Gene3Di1.10.720.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR039577 Rad18
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR006642 Znf_Rad18_put
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR14134 PTHR14134, 1 hit
PfamiView protein in Pfam
PF02037 SAP, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00513 SAP, 1 hit
SM00734 ZnF_Rad18, 1 hit
PROSITEiView protein in PROSITE
PS50800 SAP, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All

Q9NS91-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:495
Mass (Da):56,223
Last modified:November 30, 2010 - v2
Checksum:i744A053A50C65DD7
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WE49F8WE49_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
310Annotation score:
C9J0Q4C9J0Q4_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
91Annotation score:
F8WFA6F8WFA6_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
126Annotation score:
F8WAZ7F8WAZ7_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
53Annotation score:
H7C3I2H7C3I2_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
131Annotation score:
H7C0A5H7C0A5_HUMAN
E3 ubiquitin-protein ligase RAD18
RAD18
79Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti191P → L in AAF80856 (PubMed:10908344).Curated1
Sequence conflicti482 – 484ESA → GKC in AAF80856 (PubMed:10908344).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0234236E → A1 PublicationCorresponds to variant dbSNP:rs45520133Ensembl.1
Natural variantiVAR_023424302R → Q6 PublicationsCorresponds to variant dbSNP:rs373572Ensembl.1
Natural variantiVAR_023425307I → 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
CCDSiCCDS2571.1
RefSeqiNP_064550.3, NM_020165.3
UniGeneiHs.375684

Genome annotation databases

EnsembliENST00000264926; ENSP00000264926; ENSG00000070950
GeneIDi56852
KEGGihsa:56852
UCSCiuc003brd.4 human

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS2571.1
RefSeqiNP_064550.3, NM_020165.3
UniGeneiHs.375684

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MRENMR-B198-227[»]
2MRFNMR-A198-227[»]
2Y43X-ray1.80A/B1-99[»]
2YBFX-ray2.00B340-366[»]
5VF0NMR-B198-240[»]
ProteinModelPortaliQ9NS91
SMRiQ9NS91
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121212, 88 interactors
DIPiDIP-29831N
IntActiQ9NS91, 43 interactors
MINTiQ9NS91
STRINGi9606.ENSP00000264926

PTM databases

iPTMnetiQ9NS91
PhosphoSitePlusiQ9NS91

Polymorphism and mutation databases

BioMutaiRAD18
DMDMi313104165

Proteomic databases

EPDiQ9NS91
MaxQBiQ9NS91
PaxDbiQ9NS91
PeptideAtlasiQ9NS91
PRIDEiQ9NS91
ProteomicsDBi82515

Protocols and materials databases

DNASUi56852
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264926; ENSP00000264926; ENSG00000070950
GeneIDi56852
KEGGihsa:56852
UCSCiuc003brd.4 human

Organism-specific databases

CTDi56852
DisGeNETi56852
EuPathDBiHostDB:ENSG00000070950.9
GeneCardsiRAD18
H-InvDBiHIX0003022
HGNCiHGNC:18278 RAD18
HPAiHPA006716
HPA006724
HPA008752
MIMi605256 gene
neXtProtiNX_Q9NS91
OpenTargetsiENSG00000070950
PharmGKBiPA134912253
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0287 Eukaryota
COG5432 LUCA
GeneTreeiENSGT00390000011230
HOGENOMiHOG000234845
HOVERGENiHBG054721
InParanoidiQ9NS91
KOiK10627
OMAiNFLIREM
OrthoDBiEOG091G047P
PhylomeDBiQ9NS91
TreeFamiTF101214

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
SIGNORiQ9NS91

Miscellaneous databases

ChiTaRSiRAD18 human
GeneWikiiRAD18
GenomeRNAii56852
PROiPR:Q9NS91
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070950 Expressed in 162 organ(s), highest expression level in lung
CleanExiHS_RAD18
ExpressionAtlasiQ9NS91 baseline and differential
GenevisibleiQ9NS91 HS

Family and domain databases

Gene3Di1.10.720.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR039577 Rad18
IPR003034 SAP_dom
IPR036361 SAP_dom_sf
IPR006642 Znf_Rad18_put
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR14134 PTHR14134, 1 hit
PfamiView protein in Pfam
PF02037 SAP, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00513 SAP, 1 hit
SM00734 ZnF_Rad18, 1 hit
PROSITEiView protein in PROSITE
PS50800 SAP, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRAD18_HUMAN
AccessioniPrimary (citable) accession number: Q9NS91
Secondary accession number(s): Q58F55, Q9NRT6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: November 30, 2010
Last modified: November 7, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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