RAD18 (RAD18 E3 ubiquitin protein ligase)

symbol:
RAD18
locus group:
protein-coding gene
location:
3p25.3
gene_family:
Ring finger proteins
alias symbol:
RNF73
alias name:
None
entrez id:
56852
ensembl gene id:
ENSG00000070950
ucsc gene id:
uc003brd.4
refseq accession:
NM_020165
hgnc_id:
HGNC:18278
approved reserved:
2003-07-01
3p25.3

RAD18是RAD基因家族的重要成员,属于E3泛素连接酶家族,在DNA损伤修复和基因组稳定性维持中发挥关键作用。它的主要功能是通过泛素化修饰调控DNA损伤应答,特别是针对复制压力或紫外线等诱发的DNA损伤。RAD18与RAD6形成复合物,共同参与复制后修复(PRR)途径,通过单泛素化修饰PCNA(增殖细胞核抗原)来启动跨损伤DNA合成(TLS),允许DNA聚合酶绕过损伤位点继续复制。该基因在细胞核内活跃表达,尤其在快速增殖的细胞中表达较高。RAD18突变会导致DNA修复缺陷,增加基因组不稳定性,与多种癌症(如乳腺癌、卵巢癌和结直肠癌)的发生发展密切相关。突变可能削弱其与RAD6或PCNA的相互作用,损害TLS功能,导致突变积累和肿瘤易感性增加。RAD18过表达可能异常激活DNA损伤修复通路,促进癌细胞存活和化疗耐药;而表达降低则会导致DNA损伤修复能力下降,加剧基因组不稳定性。RAD18还参与调控同源重组(HR)和非同源末端连接(NHEJ)等其他修复途径,影响细胞周期检查点激活。RAD基因家族成员多参与DNA损伤应答,具有保守的锌指结构域或环指结构域,介导蛋白质相互作用和泛素化修饰。该家族在维持基因组完整性方面具有共性,但各成员在具体修复通路中的作用存在分工。

ChineseEnglish

None

Nucleotide sequence of RAD18:[NCBI]
Loading Gene Browser...
Protein Sequence
1MDSLAESRWP PGLAVMKTID DLLRCGICFE YFNIAMIIPQ
41CSHNYCSLCI RKFLSYKTQC PTCCVTVTEP DLKNNRILDE
81 LVKSLNFAR NHLLQFALES PAKSPASSSS KNLAVKVYTP
121VASRQSLKQG SRLMDNFLIR EMSGSTSELL IKENKSKFSP
161Q KEASPAAK TKETRSVEEI APDPSEAKRP EPPSTSTLKQ
201VTKVDCPVCG VNIPESHINK HLDSCLSREE KKESLRSSVH
241KR KPLPKTV YNLLSDRDLK KKLKEHGLSI QGNKQQLIKR
281HQEFVHMYNA QCDALHPKSA AEIVREIENI EKTRMRLEAS
321KLN ESVMVF TKDQTEKEID EIHSKYRKKH KSEFQLLVDQ
361ARKGYKKIAG MSQKTVTITK EDESTEKLSS VCMGQEDNMT
401SVTN HFSQS KLDSPEELEP DREEDSSSCI DIQEVLSSSE
441SDSCNSSSSD IIRDLLEEEE AWEASHKNDL QDTEISPRQN
481RRTRA AESA EIEPRNKRNR N
结构预测来自 AlphaFold DB(UniProt: Q9NS91),颜色表示 pLDDT 置信度(深蓝高、黄橙低)。
SNP variants of RAD18:           Showing partial SNPs
rs83626       rs124847       rs166094       rs166095       rs168186       rs171029       rs180498       rs193920       rs193921       rs193922       rs250400       rs250401       rs250402       rs250403       rs250404       rs250405       rs250406      

Tissue expression of RAD18:    [UniProt]

Gene expression across tissues
Forward Primer
Forward Tm
Reverse Primer
Reverse Tm
Score
CAGATTCATGCAATAGTTCCAG
58
TCACTTATGTGATGCTTCCC
58
AGAGAAGAGGATTCTTCTAGCT
58
GTCTGAACTGGAACTATTGCA
58
ATGAACTGGAATCATCTGCTG
59
ACAGCAAGATTCTTTGAAGAGG
59
AATAGATGATTTGCTGCGGTG
60
GAGAGCAGTAGTTATGTGAACAC
59
GAGAAGAGGATTCTTCTAGCTG
58
AGAAGTAGAGCTTATGTGATGC
58
AATAGATGATTTGCTGCGGTG
60
GAGAGCAGTAGTTATGTGAACAC
59
GGTTAACATTCCAGAAAGTCAC
58
TTGTGAACAGAACTTCTGAGG
58
TTGCATCCTAAATCAGCTGC
59
GTTTACTAGCTTCAAGACGCA
59
TAGATGATTTGCTGCGGTG
58
GCTCTGTGACAGTAGTTATGTG
59
GCAGTCATGAAGACTGCTC
59
CCAGTTCATCTAATATGCGGT
58
      No data available

Subcellular localization of RAD18 (and its protein):

[UniProt]     [GenomeNet]

" d="M482.414,245.296c3.539,4.293,4.455,10.009,0.202,11 c-4.244,0.996-4.983-10.983-8.293-8.438c-5.271,4.08,9.834,12.271,5.144,17.287c-3.717,3.607-6.172-5.75-10.839-1.976 c-4.673,3.776,6.781,7.299,2.831,11.326c-4.354,4.045-6.979-1.449-9.837-5.517c-1.193-1.742-2.059-3.851-3.595-2.748 c-1.516,1.078-1.854,1.795-0.938,3.666c2.374,4.854,9.235,10.119,5.156,12.535c-5.636,3.346-5.044-8.871-9.426-7.574 c-4.388,1.291,2.557,10.66-1.245,11.141c-4.089,0.545-3.483-10.239-6.979-8.575c-2.522,1.206-0.929,3.071-0.938,4.899 c0.004,1.32-0.964,3.6-2.372,4.062c-3.593,1.171-8.544-1.065-10.251-3.59c-6.04-8.93,0.396-15.997,4.639-7.015 c3.023,4.642,5.182,0.834,2.839-2.219c-1.032-1.354-4.309-5.901-0.781-7.252c2.904-1.113,4.271,1.941,5.985,4.592 c2.61,4.016,5.485,0.117,3.031-3.414c-1.828-2.633-2.74-3.803,3.156-7.42c6.405-4.369,6.52,3.869,10.077,0.646 c2.309-1.832-4.783-5.149,0.06-8.995c2.896-2.293,5.18,6.207,7.961,3.516c3.523-2.737-7.717-7.369,0.117-11.736 C473.413,240.77,480.519,242.891,482.414,245.296z"/> Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
  • plasma membrane
  • cytoplasm
  • extracellular
  • golgi
  • vesicle
  • cytoskeleton
  • endoplasmic reticulum
  • nucleus
  • endosome
  • lysosome
  • mitochondrion

Gene Ontology (GO) terms for RAD18:

GO ID
Protein
Source DB
GO:0008270
C9J0Q4 (UniProtKB)
IEA
GO:0003677
F8WE49 (UniProtKB)
IEA
GO:0006281
F8WE49 (UniProtKB)
IEA
GO:0008270
F8WE49 (UniProtKB)
IEA
GO:0008270
F8WFA6 (UniProtKB)
IEA
GO:0000403
Q9NS91 (UniProtKB)
IDA
GO:0003684
Q9NS91 (UniProtKB)
NAS
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005515
Q9NS91 (UniProtKB)
IPI
GO:0005634
Q9NS91 (UniProtKB)
NAS
GO:0005634
Q9NS91 (UniProtKB)
IDA
GO:0005634
Q9NS91 (UniProtKB)
IDA
GO:0005634
Q9NS91 (UniProtKB)
IDA
GO:0005654
Q9NS91 (UniProtKB)
IDA
GO:0005654
Q9NS91 (UniProtKB)
TAS
GO:0005654
Q9NS91 (UniProtKB)
TAS
GO:0005657
Q9NS91 (UniProtKB)
IDA
GO:0005737
Q9NS91 (UniProtKB)
IEA
GO:0005813
Q9NS91 (UniProtKB)
IDA
GO:0006281
Q9NS91 (UniProtKB)
NAS
GO:0006301
Q9NS91 (UniProtKB)
IBA
GO:0006513
Q9NS91 (UniProtKB)
IBA
GO:0006974
Q9NS91 (UniProtKB)
IDA
GO:0006974
Q9NS91 (UniProtKB)
IDA
GO:0006974
Q9NS91 (UniProtKB)
IDA
GO:0008270
Q9NS91 (UniProtKB)
IEA
GO:0009411
Q9NS91 (UniProtKB)
IBA
GO:0016874
Q9NS91 (UniProtKB)
IEA
GO:0031593
Q9NS91 (UniProtKB)
IDA
GO:0031625
Q9NS91 (UniProtKB)
IPI
GO:0031625
Q9NS91 (UniProtKB)
IPI
GO:0031625
Q9NS91 (UniProtKB)
IPI
GO:0032403
Q9NS91 (UniProtKB)
IPI
GO:0032403
Q9NS91 (UniProtKB)
IPI
GO:0035861
Q9NS91 (UniProtKB)
IDA
GO:0042405
Q9NS91 (UniProtKB)
IDA
GO:0042769
Q9NS91 (UniProtKB)
TAS
GO:0042802
Q9NS91 (UniProtKB)
IDA
GO:0043142
Q9NS91 (UniProtKB)
IBA
GO:0051865
Q9NS91 (UniProtKB)
IDA
GO:0051984
Q9NS91 (UniProtKB)
IMP
GO:0060548
Q9NS91 (UniProtKB)
IDA
GO:0061630
Q9NS91 (UniProtKB)
IBA
GO:0097505
Q9NS91 (UniProtKB)
IBA

microRNAs potentially regulating RAD18:     

String
BioGrid
IntAct
mentha
MINT
Loading…
Interacting Gene Interaction Source/Score
Disease Score NofPmids NofSnps Source
Disease Score NofPmids NofSnps Source
Colorectal Cancer 0.002909916 2 0 BeFree_GAD
Colorectal Neoplasms 0.00272435 1 0 LHGDN
Lung Neoplasms 0.00272435 1 0 LHGDN
Malignant neoplasm of breast 0.002367032 1 0 GAD
Malignant neoplasm of lung 0.002367032 1 0 GAD
FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder) 0.000814326 3 0 BeFree
Fanconi Anemia 0.000814326 3 0 BeFree
Colorectal Carcinoma 0.000542884 2 0 BeFree
Non-Small Cell Lung Carcinoma 0.000542884 2 2 BeFree
Adenocarcinoma 0.000271442 1 0 BeFree
The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins.
Woodward TJ, Ripley BM, Ling JA, Washington MT Biomolecules 2026-08-12
Differential roles of Rad18 in repressing carcinogen- and oncogene-driven mutagenesis in vivo.
Anand JR, Brown BW, Lou J, Gu Q, Yang Y, Droby G, Wu D, Jena A, Xie J, Fedoriw Y, Weissman B, Williams S, Vaziri C NAR Cancer IF: 4.6 2026-03-00
The backside β-turn is a key structural element of Rad6-family E2 ubiquitin-conjugating enzymes.
Shukla PK, Leng AM, Chen HH, Ganguly R, Newell N, Chandrasekharan MB Biochem J IF: 3.9 2026-06-03
Advancing inducible gene-inactivation systems to explore synthetic lethality.
Sánta ÁT, Gráf A, Vincze-Kontár K, Kovács K, Bóna B, Mórocz M, Kiss E, Haracska L NAR Cancer IF: 4.6 2026-03-00
USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.
Ashton NW, Ravindranathan R, Korchak EJ, Somuncu OS, Zambrano GA, Mukkavalli SV, Asada S, Korzhnev D, Bezsonova I, D'Andrea AD bioRxiv 2026-05-10
Neuronal Injury and Regeneration-Linked Gene Expression Dynamics in the Hypothalamic-Pituitary-Adrenal Axis Following Experimental Traumatic Brain Injury.
Ulutabanca H, Albayrak S, Yilmaz Şükranli Z, Er B, Abat E, Taheri S Int J Mol Sci IF: 3.226 2026-06-07

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