Property Summary

NCBI Gene PubMed Count 78
PubMed Score 381.80
PubTator Score 623.83

Knowledge Summary


No data available


  Disease (4)


  Differential Expression (40)

Disease log2 FC p
gastric cancer 1.100 1.9e-03
hepatocellular carcinoma 1.100 1.3e-03
pancreatic cancer 1.900 1.6e-05
esophageal adenocarcinoma 1.800 3.0e-02
psoriasis 3.200 4.3e-55
cutaneous lupus erythematosus 2.000 2.6e-03
astrocytoma 1.700 5.8e-08
glioblastoma 5.000 2.0e-14
oligodendroglioma 2.100 2.5e-07
posterior fossa group A ependymoma 3.600 2.5e-11
group 3 medulloblastoma 6.300 3.5e-11
atypical teratoid/rhabdoid tumor 4.300 2.8e-13
medulloblastoma, large-cell 5.600 1.8e-08
primitive neuroectodermal tumor 4.900 8.0e-08
Atopic dermatitis 2.600 7.7e-05
adrenocortical carcinoma 3.756 5.2e-07
tuberculosis 3.000 1.1e-06
pancreatic ductal adenocarcinoma liver m... 1.447 3.7e-02
non-small cell lung cancer 4.024 7.1e-33
intraductal papillary-mucinous carcinoma... 4.100 1.5e-03
intraductal papillary-mucinous neoplasm ... 4.600 6.5e-03
colon cancer 2.200 2.2e-02
lung cancer 5.500 1.2e-04
active Crohn's disease 1.596 6.9e-03
breast carcinoma 3.000 7.0e-47
Breast cancer 4.900 2.2e-02
interstitial cystitis 3.100 8.8e-03
lung adenocarcinoma 2.100 3.4e-08
pediatric high grade glioma 4.900 2.1e-10
pilocytic astrocytoma 2.200 2.7e-05
primary Sjogren syndrome 2.200 2.0e-04
pancreatic carcinoma 1.600 1.6e-02
nasopharyngeal carcinoma 1.600 1.4e-04
Endometriosis 2.312 9.2e-03
ductal carcinoma in situ 4.800 1.3e-04
invasive ductal carcinoma 5.300 1.3e-04
ulcerative colitis 2.100 1.8e-07
ovarian cancer 2.900 2.7e-03
chronic rhinosinusitis 1.056 4.1e-02
cystic fibrosis and chronic rhinosinusit... 1.156 2.1e-02

Protein-protein Interaction (7)

Gene RIF (65)

27348973 our findings establish a signaling role for RRM2 in gastric cancer cells and identify that the RRM2/AKT/NF-kappaB signaling pathway is essential for tumor invasiveness in gastric cancer cells
26921499 We suggest that MNNG-stimulated ATR/CHK1 signaling stabilizes E2F3 by S124 phosphorylation, and then E2F3 together with NFY co-transactivate RRM2 expression for DNA repair.
26718430 A significant association has been found between RRM2 rs6759180 (located in the 5'UTR, 10126436G>A) and the risk for developing non-small cell lung cancer.
26663950 High expression level of RRM2 might be negative prognostic factor for resected NSCLC patients.
26333382 Data show that ribonucleotide reductase M2 (RRM2) is associated with increased nuclear factor kappa B (NF-kappaB) activity.
26093293 Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in colorectal cancer
26026873 HBV exploits the Chk1-E2F1 axis of the DNA damage response pathway to induce R2 expression in a cell cycle-independent manner.
26001082 In non-small cell lung cancer, RRM2 expression was predictive of disease-specific survival in women, non-smokers and former smokers. Higher expression was associated with worse survival. This was not the case for men, and current or recently quit smokers.
25980818 The SCYL1- BP1 affects the cell cycle through increasing steady state levels of Cyclin F and RRM2 proteins, thus constituting a dual regulatory circuit.
25878246 R2 and p53R2 small subunits are subject to caspase-dependent degradation
25738429 These results suggested that RRM2 supported the growth of human OSCC cells and that targeting of RRM2, e.g., via GEM treatment, may be a promising therapeutic strategy for OSCC.
25227663 concomitant low expression levels of ERCC1, RRM1, and RRM2 and the high expression level of BRCA1 were predictive of a better outcome.
25213022 Results showed that RRM2 overexpression impacted the survivability of breast cancer patients.[Meta-Analysis]
25016594 Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance
24756820 these findings suggest that RRM2 plays a crucial role in gastric tumorigenesis and may serve as a potential prognostic marker and therapeutic target in gastric cancer.
24637958 RRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival.
24423925 HPVE7 induces upregulation of RRM2, which then promotes cervical carcinogenesis via ROS-ERK1/2-HIF-1alpha-VEGF-induced angiogenesis.
24360663 Data indicate that the expression of ribonucleotide reductase small subunit M2 (RRM2) positively associated with biochemical recurrence of prostate cancer (PCa).
24253041 Data indicate that transfection of the wild-type M2 but not the K95E mutant rescued the G1/S phase cell cycle arrest and cell growth inhibition caused by the siRNA knockdown of M2.
24155212 low expression of RRM1 and RRM2 could be used to predict the treatment response to platinum-based chemotherapy and survival in non-small cell lung cancer
24082141 p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway.
24024897 These results suggest that SNPs within ribonucleotide reductase (RRM1 and RRM2) might be helpful predictive markers of response to nucleoside analogs and should be further validated in larger cohorts.
23719266 Our novel findings add to the knowledge of RRM2 in regulating expression of the antiapoptotic protein Bcl-2 and reveal a critical link between RRM2 and Bcl-2 in apoptosis signaling.
23519412 The crystal structure of RRM1/2 complexed with target mRNA has been solved; comparison of the two structures show that RNA-binding protein RRM1/2 undergoes conformational changes upon RNA binding.
23466567 RRM2 small interfering RNA-mediated treatment is an effective strategy to inverse chemosensitivity of tumor cells to cisplatin, enhance the efficacy of Gem-induced cytotoxicity and promote apoptosis of cisplatin-resistant ovarian cancer cells in vitro.
23335963 RRM2 was found to be a key determinant of both inherent and acquired gemcitabine with reduced let-7 expression likely to contribute to RRM2-mediated inherent chemoresistance in poorly differentiated pancreatic cancer cells.
23249808 Report essential roles for ribonucleotide reductase and thymidylate synthase in C-MYC-dependent suppression of senescence in melanoma cells.
23002339 RRM2 may be a facilitating factor in colorectal tumorigenesis and UV-induced DNA damage repair.
22884145 RRM2 expression closely correlates with the development of ovarian tumor and may serve as a novel predictive marker for diagnosis and prognosis of the disease.
22670179 RRM2 protein expression in pancreatic adenocarcinoma is neither prognostic nor predictive of adjuvant gemcitabine benefit in patients with resectable pancreatic adenocarcinoma.
22632967 After DNA damage, cyclin F is downregulated in an ATR-dependent manner to allow accumulation of RRM2. Defective elimination of cyclin F delays DNA repair and sensitizes cells to DNA damage, a phenotype that is reverted by expressing a nondegradable RRM2 mutant.
22569992 High tumor expression of RRM2 and ERCC1 are associated with reduced recurrence free survival and overall survival after resection of pancreas cancer.
22190034 HIV-1 Pol is identified to have a physical interaction with ribonucleotide reductase M2 (RRM2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses
22166006 Recombinant RRM2 translocates from the cytoplasm to the nucleus in a time-dependent manner, leading to stabilization of urokinase mRNA. Overexpression of RRM2 inhibits urokinase protein and mRNA expression through destabilization of uPA mRNA.
21965764 p53R2 expression seems more important than that of hRRM2 in prognosis of early-stage lung cancer.
21875941 Knockdown of the ribonucleotide RR2 subunit leads to decreased cisplatin-induced gap-filling synthesis in nucleotide excision repair and a reduced 2'-deoxyadenosine triphosphate (dATP) level in the G2/M phase of the cell cycle.
21873171 Under serum-starved conditions, the expression level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116 cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3 cells induced the expression of RRM2.
21844567 HDM-2 inhibition suppresses expression of ribonucleotide reductase subunit M2, and synergistically enhances gemcitabine-induced cytotoxicity in mantle cell lymphoma.
21628579 Data suggest ribonucleotide reductase A site binding with inhibitor.
21166702 We have shown frequent overexpression of RRM2 protein and its possible role in bladder cancer.
20927319 High RRM2 is associated with gemcitabine resistance in pancreatic cancer.
20825972 Ribonucleotide reductase M2 subunit overexpression could be associated with the gastric cancer progression.
20587610 Observational study of gene-disease association. (HuGE Navigator)
20484015 This study correlates the distinct catalytic mechanisms of the small subunits hp53R2 and hRRM2 with a hydrogen-bonding network.
20155784 we provide molecular evidence for a new mechanism of HBV-host cell interaction where RNR-R2, a critical cell-cycle gene, is selectively activated in nonproliferating cells.
20056645 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19639316 Data show that cases with high RRM2 expression had a shorter OS than cases with low RRM2 levels.
19568409 thymidylate synthase/ribonucleotide reductase gene silencing and deoxycytidine kinase::uridine monophosphate kinase fusion gene gene overexpression markedly improved gemcitabine's therapeutic activity
19416980 Up-regulation in RRM2 expression levels coupled with its nuclear recruitment suggests an active role for ribonucleotide reductase in the cellular response to camptothecin-mediated DNA damage
19250552 These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.
19082948 The redox property, structure, and function of hRRM2 and p53R2, are studied.
19002265 RRM2 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival
18941749 Esophageal and gastric cancers overexpressed RRM2 protein when compared to prostate cancer. Esophageal and gastric cancers also overexpressed RRM2 mRNA when compared to prostate cancer
18414411 Ribonucleotide reductase subunit RRM2 mRNA expression in lung adenocarcinoma is associated with clinical outcome of docetaxel/gemcitabine therapy.
18278438 RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer
17222798 NF-kappaB is a key mediator of the invasive phenotypic changes induced by RRM2 overexpression.
16376858 RRM2 and p53R2 subunits share the same binding site on RRM1
15096505 R2 subunitof RNR can substuitute for the function of p53R2 in providing dNTPs for DNA repair in cells lacking functional p53R2.
14729598 Susceptibility differences to RR inhibitors between hRRM1 and hRRM2 may lead to a new direction in drug design for human cancer treatment.
14661056 RRM2 overexpression is associated with gemcitabine chemoresistance in pancreatic adenocarcinoma cells. Suppression of RRM2 expression using RNA interference mediated by siRNA enhances the drug-induced cytotoxicity.
14583450 Expression of antisense hRRM2 in PC3 cells led to decreased hRRM2 expression and resulted in greater sensitivity to UV than observed in wild-type PC3 cells.
12694192 Sequences downstream of the transcription initiation site are important for proper initiation and regulation of this gene's transcription.
12615712 Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits.
11978970 Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses
11978967 Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance

AA Sequence

ENISLEGKTNFFEKRVGEYQRMGVMSSPTENSFTLDADF                                   351 - 389

Text Mined References (88)

PMID Year Title
27348973 2016 Overexpression of RRM2 in gastric cancer cell promotes their invasiveness via AKT/NF-?B signaling pathway.
26921499 2016 ATR-CHK1-E2F3 signaling transactivates human ribonucleotide reductase small subunit M2 for DNA repair induced by the chemical carcinogen MNNG.
26718430 2015 Investigation of some DNA repair genes association in non small cell lung cancer.
26663950 2015 Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I-III Non-Small Cell Lung Cancer.
26333382 2015 Targeting Ribonucleotide Reductase M2 and NF-?B Activation with Didox to Circumvent Tamoxifen Resistance in Breast Cancer.
26093293 2015 E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2.
26026873 2015 Hepatitis B virus induces RNR-R2 expression via DNA damage response activation.
26001082 2015 Ribonucleotide reductase subunit M2 predicts survival in subgroups of patients with non-small cell lung carcinoma: effects of gender and smoking status.
25980818 2016 SCYL1-BP1 affects cell cycle arrest in human hepatocellular carcinoma cells via Cyclin F and RRM2.
25878246 2015 Caspase-dependent Proteolysis of Human Ribonucleotide Reductase Small Subunits R2 and p53R2 during Apoptosis.
25738429 2015 Ribonucleotide reductase M2 is a promising molecular target for the treatment of oral squamous cell carcinoma.
25227663 2014 Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy.
25213022 2014 Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers.
25016594 2014 Pathway-centric integrative analysis identifies RRM2 as a prognostic marker in breast cancer associated with poor survival and tamoxifen resistance.
24756820 2014 Targeting ribonucleotide reductase M2 subunit by small interfering RNA exerts anti-oncogenic effects in gastric adenocarcinoma.
24637958 2014 The expression of ribonucleotide reductase M2 in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients.
24423925 2014 Increased expression of RRM2 by human papillomavirus E7 oncoprotein promotes angiogenesis in cervical cancer.
24360663 2014 The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers.
24253041 2014 The conserved Lys-95 charged residue cluster is critical for the homodimerization and enzyme activity of human ribonucleotide reductase small subunit M2.
24155212 2014 Expression of RRM1 and RRM2 as a novel prognostic marker in advanced non-small cell lung cancer receiving chemotherapy.
24082141 2013 p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway.
24024897 2013 RRM1 and RRM2 pharmacogenetics: association with phenotypes in HapMap cell lines and acute myeloid leukemia patients.
23719266 2013 RRM2 regulates Bcl-2 in head and neck and lung cancers: a potential target for cancer therapy.
23535732 2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
23519412 2013 The structure of the ARE-binding domains of Hu antigen R (HuR) undergoes conformational changes during RNA binding.
23466567 2013 Small interfering RNA (siRNA)-mediated silencing of the M2 subunit of ribonucleotide reductase: a novel therapeutic strategy in ovarian cancer.
23335963 2013 Differential processing of let-7a precursors influences RRM2 expression and chemosensitivity in pancreatic cancer: role of LIN-28 and SET oncoprotein.
23249808 2012 Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23002339 2012 Emerging roles of the ribonucleotide reductase M2 in colorectal cancer and ultraviolet-induced DNA damage repair.
22884145 2012 Overexpression of catalytic subunit M2 in patients with ovarian cancer.
22670179 2012 Ribonucleotide reductase M2 does not predict survival in patients with resectable pancreatic adenocarcinoma.
22632967 2012 Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair.
22569992 2013 An analysis of human equilibrative nucleoside transporter-1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross-complementing gene-1 expression in patients with resected pancreas adenocarcinoma: implications for adjuvant treatment.
22166006 2012 Regulation of urokinase expression at the posttranscription level by lung epithelial cells.
21965764 2011 Expression status of ribonucleotide reductase small subunits hRRM2/p53R2 as prognostic biomarkers in stage I and II non-small cell lung cancer.
21875941 2011 Reduced level of ribonucleotide reductase R2 subunits increases dependence on homologous recombination repair of cisplatin-induced DNA damage.
21873171 2011 KRAS-mediated up-regulation of RRM2 expression is essential for the proliferation of colorectal cancer cell lines.
21844567 2011 HDM-2 inhibition suppresses expression of ribonucleotide reductase subunit M2, and synergistically enhances gemcitabine-induced cytotoxicity in mantle cell lymphoma.
21628579 2011 Clofarabine 5'-di and -triphosphates inhibit human ribonucleotide reductase by altering the quaternary structure of its large subunit.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
21166702 2010 Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer.
20927319 2010 Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.
20825972 2010 Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro.
20587610 2010 Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection.
20484015 2010 Structural basis on the dityrosyl-diiron radical cluster and the functional differences of human ribonucleotide reductase small subunits hp53R2 and hRRM2.
20155784 2010 Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20056645 2010 Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19639316 2010 Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer.
19568409 2009 Gemcitabine-based chemogene therapy for pancreatic cancer using Ad-dCK::UMK GDEPT and TS/RR siRNA strategies.
19416980 2009 Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19250552 2009 Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis.
19082948 2008 Redox property of ribonucleotide reductase small subunit M2 and p53R2.
19002265 2008 Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
18941749 2009 Evaluation of mRNA by Q-RTPCR and protein expression by AQUA of the M2 subunit of ribonucleotide reductase (RRM2) in human tumors.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18414411 2008 Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine.
18278438 2008 A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.
17924679 2007 Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.
17693683 2007 Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction.
17486094 2007 Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion.
17222798 2007 RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16376858 2006 Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15096505 2004 Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interference RNA sensitizes p53(-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitors.
14729598 2004 In vitro characterization of enzymatic properties and inhibition of the p53R2 subunit of human ribonucleotide reductase.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14661056 2004 RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine.
14583450 2003 The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53.
12694192 2003 Sequences downstream of the transcription initiation site are important for proper initiation and regulation of mouse ribonucleotide reductase R2 gene transcription.
12655059 2003 Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis.
12615712 2003 Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11978970 2001 Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses.
11781084 2002 A comprehensive model for the allosteric regulation of mammalian ribonucleotide reductase. Functional consequences of ATP- and dATP-induced oligomerization of the large subunit.
11517226 2001 Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells.
10631117 2000 Characterization of the promoter of the human ribonucleotide reductase R2 gene.
7937751 1994 Identification of genes expressed in premalignant breast disease by microscopy-directed cloning.
3311968 1987 Ribonucleotide reductase M2 subunit sequences mapped to four different chromosomal sites in humans and mice: functional locus identified by its amplification in hydroxyurea-resistant cell lines.
1627826 1992 Sequence analysis of the large and small subunits of human ribonucleotide reductase.