UniProt functional annotation for Q9Y230



	UniProt functional annotation for Q9Y230

UniProt code: Q9Y230.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (PubMed:10428817, PubMed:17157868). 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 (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). 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 (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP- dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25652260, ECO:0000269|PubMed:28561026}.

Catalytic activity: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:17157868}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; Evidence={ECO:0000305|PubMed:10428817};

Subunit: Forms homohexameric rings (Probable). 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. 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 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. Interacts with IGHMBP2. Interacts with TELO2. Interacts with HINT1. Component of a SWR1-like complex. Component of the R2TP complex composed at least of PIHD1, RUVBL1, RUVBL2 and RPAP3 (PubMed:20864032). Interacts with ITFG1 (PubMed:25437307). Interacts with ZMYND10 (PubMed:29601588). 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). Forms a complex with APPL1 and APPL2 (PubMed:19433865). Interacts with ZNHIT2 (via HIT-type zinc finger) in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP (PubMed:28561026). 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 (PubMed:28561026). Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding (PubMed:33367824). {ECO:0000269|PubMed:10428817, ECO:0000269|PubMed:10882073, ECO:0000269|PubMed:10966108, ECO:0000269|PubMed:11713276, ECO:0000269|PubMed:12963728, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16230350, ECO:0000269|PubMed:17157868, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:18026119, ECO:0000269|PubMed:19299493, ECO:0000269|PubMed:19433865, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20864032, ECO:0000269|PubMed:21303910, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:25437307, ECO:0000269|PubMed:26812014, ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:29601588, ECO:0000269|PubMed:33367824, ECO:0000305}.

Subcellular location: Nucleus matrix. Nucleus, nucleoplasm. Cytoplasm. Membrane. Dynein axonemal particle {ECO:0000250|UniProtKB:Q9DE27}. 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. {ECO:0000269|PubMed:10428817}.

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

Similarity: Belongs to the RuvB family. {ECO:0000305}.

Sequence caution: Sequence=AAD34041.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAH08355.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (PubMed:10428817, PubMed:17157868). 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 (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). 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 (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP- dependent nucleosome sliding (PubMed:16230350, PubMed:21303910). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (PubMed:10882073, PubMed:16014379). May also inhibit the transcriptional activity of ATF2 (PubMed:11713276). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (PubMed:25652260). May play a role in regulating the composition of the U5 snRNP complex (PubMed:28561026). {ECO:0000269\|PubMed:10428817, ECO:0000269\|PubMed:10882073, ECO:0000269\|PubMed:11713276, ECO:0000269\|PubMed:14966270, ECO:0000269\|PubMed:16014379, ECO:0000269\|PubMed:16230350, ECO:0000269\|PubMed:17157868, ECO:0000269\|PubMed:21303910, ECO:0000269\|PubMed:24463511, ECO:0000269\|PubMed:25652260, ECO:0000269\|PubMed:28561026}.


Catalytic activity:		Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000269\|PubMed:10428817, ECO:0000269\|PubMed:17157868}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; Evidence={ECO:0000305\|PubMed:10428817};
Subunit:		Forms homohexameric rings (Probable). 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. 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 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. Interacts with IGHMBP2. Interacts with TELO2. Interacts with HINT1. Component of a SWR1-like complex. Component of the R2TP complex composed at least of PIHD1, RUVBL1, RUVBL2 and RPAP3 (PubMed:20864032). Interacts with ITFG1 (PubMed:25437307). Interacts with ZMYND10 (PubMed:29601588). 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). Forms a complex with APPL1 and APPL2 (PubMed:19433865). Interacts with ZNHIT2 (via HIT-type zinc finger) in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP (PubMed:28561026). 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 (PubMed:28561026). Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding (PubMed:33367824). {ECO:0000269\|PubMed:10428817, ECO:0000269\|PubMed:10882073, ECO:0000269\|PubMed:10966108, ECO:0000269\|PubMed:11713276, ECO:0000269\|PubMed:12963728, ECO:0000269\|PubMed:14966270, ECO:0000269\|PubMed:15960975, ECO:0000269\|PubMed:16014379, ECO:0000269\|PubMed:16230350, ECO:0000269\|PubMed:17157868, ECO:0000269\|PubMed:17967892, ECO:0000269\|PubMed:18026119, ECO:0000269\|PubMed:19299493, ECO:0000269\|PubMed:19433865, ECO:0000269\|PubMed:20801936, ECO:0000269\|PubMed:20864032, ECO:0000269\|PubMed:21303910, ECO:0000269\|PubMed:24463511, ECO:0000269\|PubMed:25437307, ECO:0000269\|PubMed:26812014, ECO:0000269\|PubMed:28561026, ECO:0000269\|PubMed:29601588, ECO:0000269\|PubMed:33367824, ECO:0000305}.
Subcellular location:		Nucleus matrix. Nucleus, nucleoplasm. Cytoplasm. Membrane. Dynein axonemal particle {ECO:0000250\|UniProtKB:Q9DE27}. 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. {ECO:0000269\|PubMed:10428817}.
Domain:		The C-terminal domain is required for association with ATF2.
Similarity:		Belongs to the RuvB family. {ECO:0000305}.
Sequence caution:		Sequence=AAD34041.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAH08355.1; Type=Frameshift; Evidence={ECO:0000305};