RUVBL2 (RuvB-like 2 (E. coli))

2009-03-01   Aude Grigoletto , Valérie Haurie , Jean Rosenbaum 

INSERM U889, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France





15 exons, 14 introns (Parfait et al., 2000).


1518bp mRNA with 463aa open reading frame.



463 amino acids, 52 kDa.
RUVBL2 belongs to the AAA+ ATPase superfamily (ATPases associated with diverse cellular activities) sharing conserved Walker A and B motifs, arginine fingers, and sensor domains. The monomers contain two domains, which are involved in ATP binding and hydrolysis respectively. RUVBL2 assembles into an hexameric structure with a central channel.
RUVBL2 interacts with RUVBL1 to form a dodecamer (Puri et al., 2007). This RUVBL1/RUVBL2 complex displays a significant ATPase activity and is likely one of the functional forms of the proteins.
Sumoylation of RUVBL2 has been reported on Lys456 in invasive prostate cancer cells (Kim et al., 2006).
RUVBL2 is phosphorylated on an ATM/ATR consensus site following DNA damage (Matsuoka et al., 2007).


Expression of RUVBL2 is ubiquitous but especially abundant in thymus and testis (Salzer et al., 1999; Parfait et al., 2000).
RUVBL2 is overexpressed in hepatocellular carcinoma (Rousseau et al., 2007). Overexpression of RUVBL2 in several cancers and its possible role in human cancers has been reported (reviewed in Huber et al., 2008).


Cytoplasm and nucleus.


RUVBL2 interacts with c-myc (Wood et al., 2000) and also modulates transcriptional regulation by the beta-catenin/TCF-LEF complex (Bauer et al., 2000) and ATF2 (Cho et al., 2001).
RUVBL2 participates in the remodelling of chromatin as a member of several complexes such as TIP60 (Ikura et al., 2000), INO80 (Jin et al., 2005), SRCAP (Cai et al., 2005).
It is also involved in transcriptional regulation (reviewed in Gallant, 2007), DNA repair (Gospodinov et al., 2008), snoRNP biogenesis (Watkins et al., 2002), and telomerase activity (Venteicher et al., 2008).
RUVBL2 silencing in fibroblasts induces a senescent phenotype (Chan et al., 2005).

Implicated in

Entity name
Hepatocellular carcinoma (HCC)
RUVBL2 was found to be overexpressed in 75% of cases in a series of 96 human HCC studied with real-time RT-PCR (Rousseau et al., 2007). It was also increased in a smaller 15 cases series (Iizuka et al., 2006). No mutations in the coding sequence were identified (Rousseau et al., 2007).
Overexpression of RUVBL2 was an independent factor of poor prognosis (Rousseau et al., 2007).
RUVBL2 depletion with siRNAs led to HCC cell growth arrest and apoptosis, whereas overexpression in HCC cells allowed these cells to give rise to more progressive tumors in xenografts than control cells (Rousseau et al., 2007).
Entity name
Colon cancer
RUVBL2 was overexpressed in a series of 18 colon cancers (Graudens et al., 2006).
Entity name
RUVBL2 was overexpressed in a series of 45 melanomas (Talantov et al., 2005).
Entity name
Bladder carcinoma
RUVBL2 was overexpressed in a series of 108 bladder carcinomas (Sanchez-Carbayo et al., 2006).
Entity name
Prostate cancer
In conjunction with beta-catenin, RUVBL2 represses the expression of the anti-metastasis gene KAI-1 (Kim et al., 2005) and is involved in the invasive phenotype of cultured prostate cancer cells (Kim et al., 2006).


Pubmed IDLast YearTitleAuthors
110801582000Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity.Bauer A et al
156472802005The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes.Cai Y et al
156551092005The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.Chan HM et al
117132762001TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage.Cho SG et al
173203972007Control of transcription by Pontin and Reptin.Gallant P et al
188349512009RAD51 foci formation in response to DNA damage is modulated by TIP49.Gospodinov A et al
165425012006Deciphering cellular states of innate tumor drug responses.Graudens E et al
187573982008Pontin and reptin, two related ATPases with multiple roles in cancer.Huber O et al
167033982006Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus.Iizuka N et al
109661082000Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.Ikura T et al
162303502005A mammalian chromatin remodeling complex with similarities to the yeast INO80 complex.Jin J et al
166995032006Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis.Kim JH et al
158299682005Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes.Kim JH et al
175253322007ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.Matsuoka S et al
109984472000Human TIP49b/RUVBL2 gene: genomic structure, expression pattern, physical link to the human CGB/LHB gene cluster on chromosome 19q13.3.Parfait B et al
171578682007Dodecameric structure and ATPase activity of the human TIP48/TIP49 complex.Puri T et al
176577342007Overexpression and role of the ATPase and putative DNA helicase RuvB-like 2 in human hepatocellular carcinoma.Rousseau B et al
105242111999Isolation, molecular characterization, and tissue-specific expression of ECP-51 and ECP-54 (TIP49), two homologous, interacting erythroid cytosolic proteins.Salzer U et al
164320782006Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays.Sanchez-Carbayo M et al
162437932005Novel genes associated with malignant melanoma but not benign melanocytic lesions.Talantov D et al
183588082008Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly.Venteicher AS et al
124177352002Conserved stem II of the box C/D motif is essential for nucleolar localization and is required, along with the 15.5K protein, for the hierarchical assembly of the box C/D snoRNP.Watkins NJ et al
160143792005The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription.Weiske J et al
108820732000An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc.Wood MA et al

Other Information

Locus ID:

NCBI: 10856
MIM: 604788
HGNC: 10475
Ensembl: ENSG00000183207


dbSNP: 10856
ClinVar: 10856
TCGA: ENSG00000183207


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cell CycleREACTOMER-HSA-1640170
Chromosome MaintenanceREACTOMER-HSA-73886
Telomere MaintenanceREACTOMER-HSA-157579
Extension of TelomeresREACTOMER-HSA-180786
Telomere Extension By TelomeraseREACTOMER-HSA-171319
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
HATs acetylate histonesREACTOMER-HSA-3214847

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
183588082008Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly.115
162303502005A mammalian chromatin remodeling complex with similarities to the yeast INO80 complex.93
206030762010Negative regulation of hypoxic responses via induced Reptin methylation.81
195245332009RVB1/RVB2: running rings around molecular biology.76
166995032006Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis.51
203717702010AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay.51
194506872009High-resolution mapping of the protein interaction network for the human transcription machinery and affinity purification of RNA polymerase II-associated complexes.42
219337162011Structural and functional insights into a dodecameric molecular machine - the RuvBL1/RuvBL2 complex.38
176577342007Overexpression and role of the ATPase and putative DNA helicase RuvB-like 2 in human hepatocellular carcinoma.36
194031352009Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study.36


Aude Grigoletto ; Valérie Haurie ; Jean Rosenbaum

RUVBL2 (RuvB-like 2 (E. coli))

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version: