RUVBL2

Summary

RUVBL2 (RuvB like AAA ATPase 2, HGNC:10475) is a protein-coding gene on chromosome 19q13.33, encoding RuvB-like 2 (Q9Y230). Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5’ to 3’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation.

Source: NCBI Gene 10856 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 92 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_006666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10475
Approved symbol	RUVBL2
Name	RuvB like AAA ATPase 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	RVB2, TIP48, TIP49b, Reptin52, ECP51, TIH2, INO80J, Rvb2
Ensembl gene	ENSG00000183207
Ensembl biotype	protein_coding
OMIM	604788
Entrez	10856

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000221413, ENST00000593570, ENST00000594017, ENST00000594338, ENST00000595002, ENST00000595090, ENST00000595811, ENST00000596247, ENST00000596837, ENST00000598768, ENST00000601968, ENST00000627972, ENST00000888165, ENST00000888166, ENST00000888167, ENST00000888168, ENST00000888169, ENST00000888170, ENST00000940725, ENST00000940726, ENST00000940727, ENST00000940728, ENST00000940729

RefSeq mRNA: 3 — MANE Select: NM_006666 NM_001321190, NM_001321191, NM_006666

CCDS: CCDS42588

Canonical transcript exons

ENST00000595090 — 15 exons

Exon	Start	End
ENSE00003105181	48993887	48993923
ENSE00003170821	49015817	49015970
ENSE00003474853	49007018	49007147
ENSE00003480770	48999319	48999373
ENSE00003509023	49010999	49011093
ENSE00003522509	49010488	49010611
ENSE00003522773	49004277	49004418
ENSE00003522933	49015021	49015150
ENSE00003572193	49014484	49014603
ENSE00003637730	49011192	49011310
ENSE00003668909	49009973	49010066
ENSE00003668969	49015572	49015686
ENSE00003683754	49003279	49003334
ENSE00003693640	49009776	49009882
ENSE00003789330	49007302	49007368

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.1116 / max 324.5243, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176914	42.1606	1811
176913	0.9510	537

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.14	gold quality
right testis	UBERON:0004534	99.03	gold quality
bronchial epithelial cell	CL:0002328	98.94	gold quality
epithelium of bronchus	UBERON:0002031	98.87	gold quality
bronchus	UBERON:0002185	98.64	gold quality
right uterine tube	UBERON:0001302	98.45	gold quality
adult organism	UBERON:0007023	98.36	gold quality
testis	UBERON:0000473	97.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.12	gold quality
ventricular zone	UBERON:0003053	95.84	gold quality
parotid gland	UBERON:0001831	95.80	gold quality
tendon of biceps brachii	UBERON:0008188	95.34	gold quality
embryo	UBERON:0000922	95.11	gold quality
mucosa of transverse colon	UBERON:0004991	95.10	gold quality
stromal cell of endometrium	CL:0002255	95.09	gold quality
gastrocnemius	UBERON:0001388	94.98	gold quality
prefrontal cortex	UBERON:0000451	94.82	gold quality
ganglionic eminence	UBERON:0004023	94.73	gold quality
lower esophagus mucosa	UBERON:0035834	94.72	gold quality
muscle of leg	UBERON:0001383	94.70	gold quality
nasal cavity mucosa	UBERON:0001826	94.22	gold quality
esophagus mucosa	UBERON:0002469	94.18	gold quality
apex of heart	UBERON:0002098	94.15	gold quality
adenohypophysis	UBERON:0002196	94.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.15	gold quality
cortical plate	UBERON:0005343	94.12	gold quality
gingiva	UBERON:0001828	94.08	gold quality
gingival epithelium	UBERON:0001949	94.07	gold quality
gluteal muscle	UBERON:0002000	94.04	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.93
E-MTAB-9067	yes	20.56
E-MTAB-10042	yes	14.49
E-CURD-114	yes	11.57
E-MTAB-7606	no	1961.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

7 targeting RUVBL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-7704	95.30	62.35	115

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• 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 increase in cell nuclei during cell differentiation. (PMID:19444951)
• Is part of an RNA polymerase II-associated complex with possible chaperone activity. (PMID:19450687)
• RVB1 and RVB2 function within multiple protein complexes is reviewed. (PMID:19524533)
• snoRNP assembly factor NUFIP can regulate the interactions between TIP48 and TIP49 and the core box C/D proteins. (PMID:19620283)
• Reptin and Pontin protein levels are strictly controlled by a posttranslational mechanism involving proteasomal degradation of newly synthesized proteins. (PMID:19877184)
• In vivo Reptin depletion leads to tumor growth arrest and may prove a valuable target in hepatocellular carcinoma. (PMID:20346530)
• 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)
• 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)
• hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC (PMID:20509972)
• 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)
• Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. (PMID:20603076)
• The Reptin docking site was mapped to a divergent octapeptide loop in the AGR2 superfamily between amino acids 104 and 111. Mutations at codon Y104 or F111 in full-length AGR2 destabilized the binding of Reptin. (PMID:20888340)
• data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences (PMID:21763315)
• 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)
• 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)
• Data suggest that reptin may prove to be a valuable target for prevention and treatment of renal cell carcinoma. (PMID:22341977)
• 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)
• Two coexisting conformations, compact and stretched, are revealed by analysis of cryo-electron microscopy structures of the RuvBL1-RuvBL2 complex. (PMID:23002137)
• 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)
• 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)
• 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)
• 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)
• Reptin and Pontin oligomerization and activity are modulated through histone H3 N-terminal tail interaction. (PMID:25336637)
• The results suggests that a potential mechanism for the role of RuvBL1-RuvBL2 in maintaining genome integrity is through controlling the cellular abundance of Fanconi anaemia core complex. (PMID:25428364)
• Data suggest that overexpression of Reptin in hepatocellular carcinoma (HCC) could be a factor of resistance to treatment. (PMID:25875766)
• results reveal a novel mechanism for the control of NF-kappaB pathway by cytoplasmic Reptin (PMID:25957047)
• 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)
• RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. (PMID:26303906)
• 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 hexameric ring (PMID:26863765)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ruvbl2	ENSDARG00000055639
mus_musculus	Ruvbl2	ENSMUSG00000003868
rattus_norvegicus	Ruvbl2	ENSRNOG00000020793
drosophila_melanogaster	rept	FBGN0040075
caenorhabditis_elegans		WBGENE00020687

Paralogs (1): RUVBL1 (ENSG00000175792)

Protein

Protein identifiers

RuvB-like 2 — Q9Y230 (reviewed: Q9Y230)

Alternative names: 48 kDa TATA box-binding protein-interacting protein, 51 kDa erythrocyte cytosolic protein, INO80 complex subunit J, Repressing pontin 52, TIP49b, TIP60-associated protein 54-beta

All UniProt accessions (7): Q9Y230, M0QXI6, M0QXZ7, M0QYD8, M0R0Y3, M0R0Z0, X6R2L4

UniProt curated annotations — full annotation on UniProt →

Function. Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5’ to 3’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity. Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of 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 seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding. Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. May also inhibit the transcriptional activity of ATF2. Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes. May play a role in regulating the composition of the U5 snRNP complex.

Subunit / interactions. Forms homohexameric rings. Can form a dodecamer with RUVBL1 made of two stacked hexameric rings; however, even though RUVBL1 and RUVBL2 are present in equimolar ratio, the oligomeric status of each hexamer is not known. Oligomerization may regulate binding to nucleic acids and conversely, binding to nucleic acids may affect the dodecameric assembly. Interaction of the complex with DHX34 results in conformational changes of the N-terminus of the RUVBL2 subunits, resulting in loss of nucleotide binding ability and ATP hydrolysis of the complex. Interacts with the transcriptional activation domain of MYC. Interacts with ATF2. Component of the RNA polymerase II holoenzyme complex. May also act to bridge the LEF1/TCF1-CTNNB1 complex and TBP. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. RUVBL2 interacts with EP400. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Interacts with NPAT. Component of the chromatin-remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with IGHMBP2. Interacts with TELO2. Interacts with HINT1. Component of a SWR1-like complex. Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with ITFG1. Interacts with ZMYND10. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation. Forms a complex with APPL1 and APPL2. Interacts with ZNHIT2 (via HIT-type zinc finger) in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP. The RUVBL1/RUVBL2 complex interacts with ZNHIT1 (via HIT-type zinc finger), ZNHIT3 (via HIT-type zinc finger), ZNHIT6 (via HIT-type zinc finger) and DDX59/ZNHIT5 (via HIT-type zinc finger) in the presence of ADP. Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding. Interacts with SMG1. (Microbial infection) Interacts with Mumps L polymerase; this interaction regulates the viral transcription.

Subcellular location. Nucleus matrix. Nucleus. Nucleoplasm. Cytoplasm. Membrane. Dynein axonemal particle.

Tissue specificity. Ubiquitously expressed. Highly expressed in testis and thymus.

Domain organisation. The C-terminal domain is required for association with ATF2.

Similarity. Belongs to the RuvB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y230-1	1	yes
Q9Y230-2	2

RefSeq proteins (3): NP_001308119, NP_001308120, NP_006657* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR010339	TIP49_P-loop	Domain
IPR027238	RuvB-like	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041048	RuvB-like_C	Domain
IPR042487	RuvBL1/2_DNA/RNA_bd_dom	Homologous_superfamily

Pfam: PF06068, PF17856

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (65 total): strand 28, helix 16, turn 7, mutagenesis site 3, cross-link 3, sequence conflict 2, modified residue 2, initiator methionine 1, chain 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

38 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8QR1	ELECTRON MICROSCOPY	2.4
9EMA	ELECTRON MICROSCOPY	2.4
6K0R	X-RAY DIFFRACTION	2.5
9C57	ELECTRON MICROSCOPY	2.75
6H7X	X-RAY DIFFRACTION	2.89
3UK6	X-RAY DIFFRACTION	2.95
2XSZ	X-RAY DIFFRACTION	3
9CAE	ELECTRON MICROSCOPY	3.07
7ZI4	ELECTRON MICROSCOPY	3.2
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
8XVT	ELECTRON MICROSCOPY	3.2
9EMC	ELECTRON MICROSCOPY	3.26
9CA7	ELECTRON MICROSCOPY	3.35
9GE5	ELECTRON MICROSCOPY	3.35
7OLE	ELECTRON MICROSCOPY	3.41
9CAC	ELECTRON MICROSCOPY	3.43
9GCG	ELECTRON MICROSCOPY	3.43
9GEV	ELECTRON MICROSCOPY	3.47
9HPO	ELECTRON MICROSCOPY	3.5
9GFB	ELECTRON MICROSCOPY	3.55
9CA9	ELECTRON MICROSCOPY	3.56
9HB4	ELECTRON MICROSCOPY	3.56
6FO1	ELECTRON MICROSCOPY	3.57
6QI8	ELECTRON MICROSCOPY	3.75
9CA8	ELECTRON MICROSCOPY	3.92
9CAB	ELECTRON MICROSCOPY	3.94
6IGM	ELECTRON MICROSCOPY	4
9CAA	ELECTRON MICROSCOPY	4.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y230-F1	84.26	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 77–84

Post-translational modifications (5): 2, 437, 9, 444, 456

Mutagenesis-validated functional residues (3):

Position	Phenotype
299	abolishes atpase activity.
300	reduces atpase activity. decreases interaction with nopchap1. no effect on formation of ruvbl1-ruvbl2 heteromeric comple
83	no effect on interaction with nopchap1.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-3214847	HATs acetylate histones
R-HSA-157579	Telomere Maintenance
R-HSA-1640170	Cell Cycle
R-HSA-180786	Extension of Telomeres
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73886	Chromosome Maintenance

MSigDB gene sets: 351 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELLULAR_RESPONSE_TO_UV, BASSO_B_LYMPHOCYTE_NETWORK, GOBP_CELLULAR_RESPONSE_TO_LIPID, CMYB_01, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, MORF_RRM1, MORF_CDK2, GOBP_TELOMERE_ORGANIZATION

GO Biological Process (30): box C/D snoRNP assembly (GO:0000492), telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), protein folding (GO:0006457), regulation of chromosome organization (GO:0033044), cellular response to UV (GO:0034644), regulation of apoptotic process (GO:0042981), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), establishment of protein localization to chromatin (GO:0071169), cellular response to estradiol stimulus (GO:0071392), negative regulation of canonical Wnt signaling pathway (GO:0090090), telomerase RNA localization to Cajal body (GO:0090671), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), chromatin organization (GO:0006325), DNA damage response (GO:0006974), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (21): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), TFIID-class transcription factor complex binding (GO:0001094), DNA helicase activity (GO:0003678), transcription corepressor activity (GO:0003714), ATP binding (GO:0005524), beta-catenin binding (GO:0008013), ATP hydrolysis activity (GO:0016887), TBP-class protein binding (GO:0017025), chromatin DNA binding (GO:0031490), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), ADP binding (GO:0043531), obsolete unfolded protein binding (GO:0051082), ATPase binding (GO:0051117), promoter-enhancer loop anchoring activity (GO:0140585), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), hydrolase activity (GO:0016787)

GO Cellular Component (20): nucleosome (GO:0000786), euchromatin (GO:0000791), Swr1 complex (GO:0000812), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), nuclear matrix (GO:0016363), Ino80 complex (GO:0031011), NuA4 histone acetyltransferase complex (GO:0035267), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), MLL1 complex (GO:0071339), R2TP complex (GO:0097255), protein folding chaperone complex (GO:0101031), dynein axonemal particle (GO:0120293), RPAP3/R2TP/prefoldin-like complex (GO:1990062), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Extension of Telomeres	1
Chromatin modifying enzymes	1
Chromosome Maintenance	1
Telomere Maintenance	1
Chromatin organization	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
DNA metabolic process	3
regulation of DNA metabolic process	3
ATP-dependent activity	3
protein-containing complex	3
DNA repair	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
adenyl ribonucleotide binding	2
protein binding	2
chromatin	2
nuclear chromosome	2
INO80-type complex	2
nuclear lumen	2
microtubule organizing center	2
cytoplasm	2
small nucleolar ribonucleoprotein complex assembly	1
telomere organization	1
DNA replication	1
DNA damage response	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
protein maturation	1
regulation of organelle organization	1
chromosome organization	1
response to UV	1
cellular response to light stimulus	1
apoptotic process	1
regulation of programmed cell death	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

4766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RUVBL2	RPAP3	Q9H6T3	999
RUVBL2	PIH1D1	Q9NWS0	997
RUVBL2	TRRAP	Q9Y4A5	995
RUVBL2	EP400	Q96L91	993
RUVBL2	RUVBL1	P82276	988
RUVBL2	ACTL6A	O96019	988
RUVBL2	CTNNB1	P35222	988
RUVBL2	TERT	O14746	981
RUVBL2	KAT5	Q92993	981
RUVBL2	DMAP1	Q9NPF5	980
RUVBL2	INO80C	Q6PI98	967
RUVBL2	K7ENP7	K7ENP7	967
RUVBL2	NOP10	Q9NPE3	959
RUVBL2	DKC1	O60832	949
RUVBL2	YEATS4	O95619	941

IntAct

492 interactions, top by confidence:

A	B	Type	Score
RUVBL2	RUVBL1	psi-mi:“MI:0915”(physical association)	0.970
RUVBL1	RUVBL2	psi-mi:“MI:0915”(physical association)	0.970
RUVBL2	DPCD	psi-mi:“MI:0915”(physical association)	0.940
DPCD	RUVBL2	psi-mi:“MI:0915”(physical association)	0.940
PIH1D1	RUVBL2	psi-mi:“MI:0914”(association)	0.860
RUVBL1	DKC1	psi-mi:“MI:0914”(association)	0.820
ACTR6	ZNHIT1	psi-mi:“MI:0914”(association)	0.820
RUVBL2	DKC1	psi-mi:“MI:0914”(association)	0.810
RUVBL2	RUVBL2	psi-mi:“MI:0407”(direct interaction)	0.780
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
ANP32E	H2AZ1	psi-mi:“MI:0915”(physical association)	0.770
DKC1	TERT	psi-mi:“MI:0914”(association)	0.750
PIH1D1	ECD	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730

BioGRID (1128): RUVBL2 (Affinity Capture-MS), RUVBL2 (Two-hybrid), DPCD (Two-hybrid), LNX1 (Two-hybrid), CCDC103 (Two-hybrid), RUVBL2 (Affinity Capture-RNA), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A061AE05, A1JT88, A6V3E8, A7SG48, B1I024, B2T4A8, B2VET7, B6LS00, B7V2Z1, C3K5J5, O28974, P0C920, P0C921, P16638, P20627, P27368, P46015, P53396, P83571, Q02PB3, Q08BN1, Q0V6P9, Q12464, Q12555, Q13YR8, Q1H0P3, Q2TBU9, Q32PF2, Q3KNL4, Q43883, Q4P6N7, Q5AGZ9, Q5BBV9, Q5KXD3, Q5WGC5, Q6BSB8, Q6C3X6, Q6CFD2, Q6CQA9, Q6FSF1

Diamond homologs: O17607, O94692, P0CR26, P0CR27, P0CR28, P0CR29, P60122, P60123, P83571, Q03940, Q0IFL2, Q12464, Q16TA2, Q29AK9, Q29DI0, Q2TBU9, Q4I948, Q4ICA8, Q4P112, Q4P6N7, Q4WKH9, Q4WPW8, Q54UW5, Q5A0W7, Q5AGZ9, Q5BBV9, Q5BGK3, Q6BI60, Q6BSB8, Q6C3X6, Q6CB52, Q6CQA9, Q6CT29, Q6FSF1, Q6FU78, Q750R1, Q755G5, Q873C7, Q8AWW7, Q8STP2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RUVBL2	“form complex”	“NuA4 complex”	binding
RUVBL2	“form complex”	“INO80 complex”	binding
RUVBL2	“form complex”	“R2TP core co-chaperone”	binding
RUVBL2	“form complex”	“R2SP co-chaperone”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of AMPK downstream of NMDARs	6	18.6×	2e-04
RHO GTPases activate IQGAPs	5	14.1×	3e-03
Selective autophagy	5	11.3×	3e-03
Transcriptional Regulation by VENTX	5	10.8×	3e-03
Assembly and cell surface presentation of NMDA receptors	5	10.3×	3e-03
Aggrephagy	5	10.1×	3e-03
Post NMDA receptor activation events	6	9.9×	3e-03
Activation of NF-kappaB in B cells	6	9.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	10	40.1×	2e-11
regulation of chromosome organization	5	32.3×	6e-05
positive regulation of double-strand break repair via homologous recombination	12	31.7×	2e-12
regulation of DNA replication	5	12.6×	3e-03
positive regulation of DNA repair	5	12.4×	3e-03
DNA recombination	5	11.6×	5e-03
tumor necrosis factor-mediated signaling pathway	5	11.4×	5e-03
telomere maintenance	6	11.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

92 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2410 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49003346:G:GT	donor_gain	1.0000
19:49004271:CCACA:C	acceptor_loss	1.0000
19:49004272:CACA:C	acceptor_loss	1.0000
19:49004274:CA:C	acceptor_loss	1.0000
19:49004275:A:AC	acceptor_loss	1.0000
19:49004275:A:AG	acceptor_gain	1.0000
19:49004276:G:GG	acceptor_gain	1.0000
19:49004416:TGGG:T	donor_loss	1.0000
19:49004417:GG:G	donor_gain	1.0000
19:49004417:GGGTA:G	donor_loss	1.0000
19:49004418:GG:G	donor_gain	1.0000
19:49004418:GGTA:G	donor_loss	1.0000
19:49004419:G:GG	donor_gain	1.0000
19:49004420:T:A	donor_loss	1.0000
19:49007013:CCCA:C	acceptor_loss	1.0000
19:49007014:CCA:C	acceptor_loss	1.0000
19:49007015:CAG:C	acceptor_loss	1.0000
19:49007016:A:AT	acceptor_loss	1.0000
19:49007148:G:GG	donor_gain	1.0000
19:49009968:TGTAG:T	acceptor_loss	1.0000
19:49009969:GTAG:G	acceptor_loss	1.0000
19:49009970:TAGGG:T	acceptor_loss	1.0000
19:49009971:A:AG	acceptor_gain	1.0000
19:49009971:AG:A	acceptor_gain	1.0000
19:49009971:AGG:A	acceptor_gain	1.0000
19:49009971:AGGGA:A	acceptor_loss	1.0000
19:49009972:G:GG	acceptor_gain	1.0000
19:49009972:GG:G	acceptor_gain	1.0000
19:49009972:GGG:G	acceptor_gain	1.0000
19:49009972:GGGA:G	acceptor_gain	1.0000

AlphaMissense

3013 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49003284:C:G	H25D	1.000
19:49003287:T:C	S26P	1.000
19:49003290:C:G	H27D	1.000
19:49003292:C:A	H27Q	1.000
19:49003292:C:G	H27Q	1.000
19:49003294:T:A	I28N	1.000
19:49003305:G:A	G32R	1.000
19:49003305:G:C	G32R	1.000
19:49003305:G:T	G32W	1.000
19:49003306:G:A	G32E	1.000
19:49004382:G:C	G77R	1.000
19:49004383:G:A	G77D	1.000
19:49004383:G:T	G77V	1.000
19:49004397:G:A	G82R	1.000
19:49004397:G:C	G82R	1.000
19:49004397:G:T	G82W	1.000
19:49004398:G:A	G82E	1.000
19:49004398:G:T	G82V	1.000
19:49004400:A:C	K83Q	1.000
19:49004401:A:T	K83M	1.000
19:49004402:G:C	K83N	1.000
19:49004402:G:T	K83N	1.000
19:49004407:C:A	A85D	1.000
19:49004413:C:A	A87D	1.000
19:49007138:T:A	V129D	1.000
19:49007324:G:A	G140R	1.000
19:49007324:G:C	G140R	1.000
19:49007324:G:T	G140W	1.000
19:49007325:G:A	G140E	1.000
19:49007325:G:T	G140V	1.000

dbSNP variants (sampled 300 via entrez): RS1000073972 (19:49013775 G>A), RS1000079755 (19:49008422 A>C), RS1000105029 (19:49001515 C>T), RS1000257583 (19:48993805 G>A,C), RS1000278924 (19:48999855 T>C), RS1000606628 (19:48999686 T>A,C), RS1000792957 (19:49013899 C>A,G,T), RS1000869733 (19:48995987 A>AG), RS1000983933 (19:48996219 G>A), RS1001013460 (19:48998650 A>C), RS1001193721 (19:49000401 A>G), RS1001221409 (19:48993769 A>C,G), RS1001678020 (19:49006437 GTGCCTGCC>G,GTGCC,GTGCCTGCCTGCC,GTGCCTGCCTGCCTGCC), RS1001826677 (19:48993545 C>G,T), RS1001890743 (19:49003866 A>G)

Disease associations

OMIM: gene MIM:604788 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062349 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 86,060 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1336	SORAFENIB	4	86,060

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 5 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.32	Kd	47.77	nM	CHEMBL5653589
7.32	ED50	47.77	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 51 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149330: Binding affinity to human RUVBL2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0478	uM

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Smoke	increases abundance, increases expression, decreases expression	3
Valproic Acid	increases expression, increases methylation, affects expression	3
bisphenol A	decreases expression	2
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment	2
Tretinoin	decreases expression, increases reaction	2
TAK-243	increases sumoylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
linalool	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
quinocetone	increases expression	1
NSC 689534	decreases expression, affects binding	1
excavatolide B	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2065197	Binding	Binding affinity to RUVBL2 in human Jurkat cells at 150 uM followed by UV irradiation for 30 mins with Wood’s glass filtered medium pressure mercury arc light after cell lysis measured after denaturing wash by SDS-PAGE based pull down assay	Biotinylated quercetin as an intrinsic photoaffinity proteomics probe for the identification of quercetin target proteins. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5Z1	SEES3-1V human RUVBL2, clone1	Embryonic stem cell	Male
CVCL_A5Z2	SEES3-1V human RUVBL2, clone2	Embryonic stem cell	Male
CVCL_A5Z3	SEES3-1V human RUVBL2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.