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RUVBL2 exhibits single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity. Hexamerization is believed to be essential for ATP hydrolysis, and adjacent subunits within the ring-like structure contribute to the ATPase activity. RUVBL2 is a component of the NuA4 histone acetyltransferase complex, which plays a role in the transcriptional activation of specific genes, primarily through acetylation of nucleosomal histones H4 and H2A. This modification can alter nucleosome-DNA interactions and promote interactions with other proteins that positively regulate transcription. The NuA4 complex may be necessary for activating transcriptional programs associated with oncogene and proto-oncogene-mediated growth induction, tumor suppressor-mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities appear to be, at least partially, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 might also directly participate in DNA repair when recruited to sites of DNA damage. RUVBL2 is a component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. It is a proposed core component of the chromatin remodeling INO80 complex, which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding. RUVBL2 plays a crucial role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. It may also inhibit the transcriptional activity of ATF2. RUVBL2 is involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates the expression of ER stress response genes. It may play a role in regulating the composition of the U5 snRNP complex.
Gene References Into Functions
The interaction between RUVBL1/RUVBL2 and the U5 small nuclear ribonucleoprotein is primarily mediated by the previously uncharacterized factor ZNHIT2. PMID: 28561026
Mep1A is overexpressed in most hepatocellular carcinomas and induces tumor cell migration and invasion. Mep1A expression is regulated by Reptin, and Mep1A mediates Reptin-induced migration. PMID: 27999200
Reptin silencing did not affect the tyrosine phosphorylation of the insulin receptor nor of IRS1, but it enhanced the tyrosine phosphorylation of the p85 subunit of PI3K. PMID: 28833338
Overall, POLG interactome mapping identifies novel proteins which support mitochondrial biogenesis and a potential novel mitochondrial isoform of RuvbL2. PMID: 27845271
The authors report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative expression of Gag and Env for efficient production of infectious virions. PMID: 26211835
By means of molecular docking approaches, we first modeled the structures of hetero-hexameric TIP49 ( TIP49a and TIP49b )complexes with short ds-DNA fragments (20 base pairs with different GC content) within the central channel of the hexameric ring. PMID: 26863765
Data suggest that overexpression of Reptin in hepatocellular carcinoma (HCC) could be a factor of resistance to treatment. PMID: 25875766
RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. PMID: 26303906
Results reveal a novel mechanism for the control of the NF-kappaB pathway by cytoplasmic Reptin. PMID: 25957047
The results suggest that a potential mechanism for the role of RuvBL1-RuvBL2 in maintaining genome integrity is through controlling the cellular abundance of the Fanconi anemia core complex. PMID: 25428364
Reptin and Pontin oligomerization and activity are modulated through histone H3 N-terminal tail interaction. PMID: 25336637
These findings suggest that YY1-RuvBL1-RuvBL2 complexes could contribute to functions beyond transcription, and we show that YY1 and the ATPase activity of RuvBL2 are required for RAD51 foci formation during homologous recombination. PMID: 24990942
The Reptin is unable to bind with membrane-associated APPL proteins. PMID: 23891720
Anti-RuvBL1/2 antibody is a novel systemic scleroderma-related autoantibody associated with a unique combination of clinical features, including myositis overlap and diffuse cutaneous involvement. PMID: 24023044
Data suggest that reptin may prove to be a valuable target for prevention and treatment of renal cell carcinoma. PMID: 22341977
Data indicate that the RVB1/2 chromatin-remodeling complex is required for efficient Pol II recruitment and initiation at IFN-alpha-stimulated genes (ISGs) promoters and is recruited through interaction with the STAT2 transactivation domain. PMID: 23878400
We demonstrate that leukemogenic activity of MLL-AF9 requires RUVBL2 (RuvB-like 2), an AAA+ ATPase family member that functions in a wide range of cellular processes, including chromatin remodeling and transcriptional regulation. PMID: 23403462
Two coexisting conformations, compact and stretched, are revealed by analysis of cryo-electron microscopy structures of the RuvBL1-RuvBL2 complex. PMID: 23002137
The hexameric crystal structure of TIP49b confirms the validity of molecular models. PMID: 22748767
First insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes. PMID: 22923768
Ectopic expression of RUVBL2 decreases the levels of ARF, whereas knockdown of RUVBL2 results in a marked increase in ARF levels. In addition, RUVBL2 down-regulates the levels of p53 in an ARF-dependent manner. PMID: 22285491
Truncation of domain II led to a substantial increase in ATP consumption of RuvBL1, RuvBL2, and their complex. In addition, we present evidence that DNA unwinding of the human RuvBL proteins can be auto-inhibited by domain II. PMID: 21933716
Data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer, which has functional and clinical consequences. PMID: 21763315
RUVBL1 and RUVBL2 control the abundance of Phosphatidylinositol 3-kinase (PI3K)-related protein kinases (PIKKs) and stimulate the formation of PIKK-containing molecular complexes, such as those involved in nonsense-mediated mRNA decay. PMID: 20371770
In vivo Reptin depletion leads to tumor growth arrest and may prove a valuable target in hepatocellular carcinoma. PMID: 20346530
hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC. PMID: 20509972
Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. PMID: 20603076
TIP49b hexamers were found to be inactive for ATP hydrolysis and DNA unwinding, suggesting that, in cells, protein factors that remain unknown might be required to recycle these into an active form. PMID: 20553504
Several experimental approaches were used to investigate the molecular architecture of the RuvBL1-RuvBL2 complex and the role of the ATPase-insert domain (domain II) for its assembly and stability. PMID: 20412048
The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis. PMID: 16157330
Similar to the yeast INO80 complex, the hINO80 complex of Tip49a and Tip49b exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding. PMID: 16230350
Sumoylation status of reptin modulates the invasive activity of cancer cells with metastatic potential. PMID: 16699503
The results point to biochemical differences between TIP48 and TIP49, which may explain the structural differences between the two hexameric rings and could be significant for specialised functions that the proteins perform individually. PMID: 17157868
RUVBL2 is overexpressed in a large majority of HCCs. RUVBL2 overexpression enhances tumorigenicity, and RUVBL2 is required for tumor cell viability. These results argue for a major role of RUVBL2 in liver carcinogenesis. PMID: 17657734
Study identifies the ATPases pontin and reptin as telomerase components through affinity purification of TERT from human cells. PMID: 18358808
Crystal structure has been solved and the solutions obtained show that the RuvBL1-RuvBL2 complex forms a dodecamer. PMID: 18765919
RPAP3 interacts with Reptin to modulate UV-induced DNA damage by regulating H2AX phosphorylation. PMID: 19180575
RBL2 inhibits influenza virus replication by suppressing influenza A virus polymerases. PMID: 19369355
In human embryonic stem cells, the Reptin52 expression increases in cell nuclei during cell differentiation. PMID: 19444951
RVB1 and RVB2 function within multiple protein complexes is reviewed. PMID: 19524533
Reptin and Pontin protein levels are strictly controlled by a posttranslational mechanism involving proteasomal degradation of newly synthesized proteins. PMID: 19877184
Nucleus matrix. Nucleus, nucleoplasm. Cytoplasm. Membrane. Dynein axonemal particle. Note=Mainly localized in the nucleus, associated with nuclear matrix or in the nuclear cytosol. Although it is also present in the cytoplasm and associated with the cell membranes.
Tissue Specificity
Ubiquitously expressed. Highly expressed in testis and thymus.
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