BioPAX pathway converted from "KAT6A, KAT6B-containing ING5 complexes acetylate replicative histone H3" in the Reactome database.2.3.1.48KAT6A, KAT6B-containing ING5 complexes acetylate replicative histone H3KAT6A, KAT6B-containing ING5 complexes acetylate replicative histone H3KAT6A (Monocytic leukemia zinc finger protein, MOZ) and KAT6B (Monocytic leukemia zinc finger protein-related factor, MORF) are member of the MYST family of histone acetyltransferases, named after the founding members MOZ, Ybf2/Sas3, Sas2 and TIP60 (Borrow et al. 1996, Reifsnyder et al. 1996). The presence of a MYST domain is the only common structural motif in this family. MOZ and MORF are highly homologous (overall amino-acid sequence identity, 60%; similarity, 66%) but distinct from other family members (Yang & Ullah 2007).<br><br>KAT6A and KAT6B have intrinsic histone acetyltransferase activity (Champagne et al. 1999, 2001). Both can form tetrameric 'ING5' complexes with BRPF1 (possibly BRPF2 and 3), EAF6 and ING5. BRPF1 and EAF6 drastically stimulate the acetyltransferase activities of KAT6A/B against nucleosomal histone H3 (Doyon et al. 2006, Ullah et al. 2008). ING5-MOZ/MORF complexes acetylate only histone H3 at lysine-14.<br><br>KAT6A homozygous mice die at birth, with reduced hematopoiesis and profound defects in the stem cell compartment. These mice have no long-term repopulating stem cells and display substantial reduction in the number of multipotent cells able to form spleen colonies (Thomas et al. 2006). Chromosomal rearrangements of the KAT6A gene are associated with acute myeloid leukemia (AML), uterine leiomyomata and therapy-related myelodysplastic syndromes (Yang & Ullah, 2007).<br><br><br>Mutations in KAT6B are the cause of the Say-Barber-Biesecker variant of Ohdo syndrome and Genitopatellar syndrome (Campeau et al. 2012, Szakszon et al. 2013).Authored: Jupe, S, 2013-03-12Reviewed: Karagiannis, Tom, 2013-11-18Edited: Jupe, S, 2013-11-18Reactome DB_ID: 1135601nucleoplasmGO0005654acetyl-CoA [ChEBI:15351]acetyl-CoAReactomehttp://www.reactome.orgChEBI15351Converted from EntitySet in ReactomeReactome DB_ID: 46570301Histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 46570311AcK15-histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 24850021coenzyme A [ChEBI:15346]coenzyme AChEBI15346PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 3318490KAT6:ING5:MEAF6:BRPF1,(2,3) [nucleoplasm]KAT6:ING5:MEAF6:BRPF1,(2,3)KAT6-ING5 complexKAT6A,KAT6B:ING5:MEAF6:BRPF1,(BRPF2,BRPF3)Converted from EntitySet in ReactomeReactome DB_ID: 33184731BRPF1, (BRPF2, 3) [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityBRPF1 [nucleoplasm]Homo sapiensNCBI Taxonomy9606UniProtP55201Converted from EntitySet in ReactomeReactome DB_ID: 33184291KAT6A,B [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityKAT6A [nucleoplasm]KAT6B [nucleoplasm]UniProtQ92794UniProtQ8WYB5Reactome DB_ID: 33184481UniProt:Q9HAF1 MEAF6MEAF6MEAF6EAF6C1orf149CENP-28FUNCTION Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone 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. Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.SUBUNIT Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5 and the subunits EP400, TRRAP, BRD8, EPC1, DMAP1, RUVBL1, RUVBL2, ING3, actin, ACTL6A, MORF4L1, MORF4L2, MRGBP, YEATS4, VPS72 and MEAF6. Component of the HBO1 complex composed at least of ING4 or ING5, KAT7/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3.DISEASE A chromosomal aberration involving MEAF6 may be a cause of endometrial stromal tumors. Translocation t(1;6)(p34;p21) with PHF1.SIMILARITY Belongs to the EAF6 family.UniProtQ9HAF1Chain Coordinates1EQUAL191EQUALReactome DB_ID: 32151691UniProt:Q8WYH8 ING5ING5ING5FUNCTION Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Through chromatin acetylation it may regulate DNA replication and may function as a transcriptional coactivator (PubMed:12750254, PubMed:16387653). Inhibits cell growth, induces a delay in S-phase progression and enhances Fas-induced apoptosis in an INCA1-dependent manner (PubMed:21750715).SUBUNIT Interacts with H3K 4me3 and to a lesser extent with H3K4me2. Component of the HBO1 complex composed at least of ING4 or ING5, KAT7/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with EP300 and TP53. Interacts with INCA1 (PubMed:21750715).TISSUE SPECIFICITY Down-regulated in bone marrow cells in acute myeloid leukemia patients as compared with normal bone marrow cells.DOMAIN The PHD-type zinc finger mediates the binding to H3K4me3.SIMILARITY Belongs to the ING family.UniProtQ8WYH81EQUAL240EQUALReactome Database ID Release 703318490Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3318490ReactomeR-HSA-33184901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3318490.1GO0004402GO molecular functionReactome Database ID Release 703318394Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3318394Reactome Database ID Release 703318486Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3318486ReactomeR-HSA-33184861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3318486.116387653Pubmed2006ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuationDoyon, YannickCayrou, ChristelleUllah, MuktaLandry, Anne-JulieCôté, ValérieSelleck, WilliamLane, William STan, SongYang, Xiang-JiaoCôté, JacquesMol. Cell 21:51-648782818Pubmed1996Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferasesReifsnyder, CLowell, JClarke, APillus, LNat. Genet. 14:42-922265014Pubmed2012Mutations in KAT6B, encoding a histone acetyltransferase, cause Genitopatellar syndromeCampeau, Philippe MKim, Jaeseung CLu, James TSchwartzentruber, Jeremy AAbdul-Rahman, Omar ASchlaubitz, SilkeMurdock, David MJiang, Ming-MingLammer, Edward JEnns, Gregory MRhead, WJRowland, JonRobertson, Stephen PCormier-Daire, ValerieBainbridge, Matthew NYang, Xiang-JiaoGingras, Marie-ClaudeGibbs, Richard ARosenblatt, DSMajewski, JacekLee, Brendan HAm. J. Hum. Genet. 90:282-916651658Pubmed2006Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cellsThomas, TimCorcoran, Lynn MGugasyan, RaffiDixon, Mathew PBrodnicki, ThomasNutt, Stephen LMetcalf, DonaldVoss, Anne KGenes Dev. 20:1175-868782817Pubmed1996The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding proteinBorrow, JStanton, V PAndresen, J MBecher, RBehm, F GChaganti, R SCivin, C IDisteche, CDubé, IFrischauf, A MHorsman, DMitelman, FVolinia, SWatmore, A EHousman, D ENat. Genet. 14:33-4117694082Pubmed2007MOZ and MORF, two large MYSTic HATs in normal and cancer stem cellsYang, X-JUllah, MOncogene 26:5408-1910497217Pubmed1999Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger proteinChampagne, NBertos, N RPelletier, NWang, A HVezmar, MYang, YHeng, H HYang, X JJ. Biol. Chem. 274:28528-3611313971Pubmed2001The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferaseChampagne, NPelletier, NYang, XJOncogene 20:404-923436491Pubmed2013De novo mutations of the gene encoding the histone acetyltransferase KAT6B in two patients with Say-Barber/Biesecker/Young-Simpson syndromeSzakszon, KatalinSalpietro, CarmeloKakar, NaseebullahKnegt, Alida COláh, EvaDallapiccola, BrunoBorck, GuntramAm. J. Med. Genet. A 161:884-818794358Pubmed2008Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexesUllah, MuktaPelletier, NadineXiao, LinZhao, Song PingWang, KainanDegerny, CindyTahmasebi, SoroushCayrou, ChristelleDoyon, YannickGoh, Siew-LeeChampagne, NathalieCôté, JacquesYang, Xiang-JiaoMol. Cell. Biol. 28:6828-43