Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
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Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
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Germline Genetics

RUVBL1 (Q9Y265) - Overview - Molecular Target Synopsis

Protein


RUVBL1, RuvB-like 1
Enzyme Classification 3.6.4.12
UniProt Q9Y265

Also Known as RUVB1_HUMAN, RUVBL1, INO80H, NMP238, TIP49, TIP49A

Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') 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/H2AFZ from the nucleosome., Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair., Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation., May be able to bind plasminogen at cell surface and enhance plasminogen activation. Forms homohexameric rings. Can form a dodecamer with RUVBL2 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. Interacts with the transcriptional activation domain of MYC. 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. RUVBL1 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. Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM, and TRRAP/PAF400. 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 BAP18, 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. Associates with alpha and gamma tubulins, particularly during metaphase and early anaphase. 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. Interacts with IGHMBP2. Interacts with OFD1. Interacts with HINT1. Component of a complex with USP49 and PSMC5. Component of a SWR1-like complex. Component of the R2TP complex composed at least of PIHD1, RUVBL1, RUVBL2 and RPAP3 (PubMed:20864032). Interacts with PIH1D1 (PubMed:17636026). Interacts with ITFG1 (PubMed:25437307). 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 (PubMed:26812014).

6QI9
TRUNCATED HUMAN R2TP COMPLEX, STRUCTURE 4 (ADP-EMPTY)
RCSB/PDB
Inspect Structure
See all 3D Structures for RUVBL1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RUVBL1 is active in the following subcellular-locations: centrosome, cytoplasm, cytoskeleton, membrane, microtubule organizing center, nucleoplasm, nucleus, nucleus matrix.
GO terms: RUVBL1 is active in the following subcellular-locations: cytosol, extracellular exosome, Ino80 complex, membrane, microtubule organizing center, MLL1 complex, NuA4 histone acetyltransferase complex, nuclear matrix, nucleoplasm, nucleus, R2TP complex, ribonucleoprotein complex, Swr1 complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RUVBL1 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: UACC_62, OVCAR_3, HOP_62

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NIH:OVCAR-3, NCI-H1581, NCI-H810

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, HMEC

(see details)

3D Structures


For RUVBL1 there are:
7 structures (21 chains) solved
7 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RUVBL1 has been screened with 6 compounds (10 bioactivities). (see details)