BioPAX pathway converted from "NSL acetylates histone H4" in the Reactome database.LEFT-TO-RIGHT2.3.1.48NSL acetylates histone H4KAT8 (MOF, MYST1) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). KAT8 is the catalytic component of the nine-subunit non-specific lethal (NSL) complex (Mendjan et al. 2006, Cai et al. 2010).<br><br>NSL acetylates histone H4 on lysines 17 (H4K16), 6 (H4K5) and 9 (H4K8) (Cai et al. 2010).<br><br>KAT8 is also the catalytic subunit of the male-specific lethal (MSL) complex, which acetylates almost exclusively H4K16 and is responsible for a large fraction of H4K16 acetylation in human cells (Smith et al. 2005).<br><br>N.B. Coordinates of post-translational modifications described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature. Authored: Jupe, S, 2013-03-12Reviewed: Karagiannis, Tom, 2013-11-18Edited: Jupe, S, 2013-11-18HIST1H4Histone H4HIST1H4AHIST1H4BHIST1H4CHIST1H4DHIST1H4EHIST1H4FHIST1H4HHIST1H4IHIST1H4JHIST1H4KHIST1H4LHIST2H4AHIST2H4BReactome DB_ID: 181902nucleoplasmGENE ONTOLOGYGO:0005654UniProt:P62805 H4C1H4C1H4/AH4FAHIST1H4AH4C2H4/IH4FIHIST1H4BH4C3H4/GH4FGHIST1H4CH4C4H4/BH4FBHIST1H4DH4C5H4/JH4FJHIST1H4EH4C6H4/CH4FCHIST1H4FH4C8H4/HH4FHHIST1H4HH4C9H4/MH4FMHIST1H4IH4C11H4/EH4FEHIST1H4JH4C12H4/DH4FDHIST1H4KH4C13H4/KH4FKHIST1H4LH4C14H4/NH4F2H4FNHIST2H4HIST2H4AH4C15H4/OH4FOHIST2H4BH4-16HIST4H4FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.PTM Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.PTM Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.PTM Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526).PTM Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4.PTM Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me).PTM Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.PTM Sumoylated, which is associated with transcriptional repression.PTM Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.PTM Butyrylation of histones marks active promoters and competes with histone acetylation.PTM Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.DISEASE Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6.SIMILARITY Belongs to the histone H4 family.Homo sapiensNCBI Taxonomy9606UniProtP628052EQUAL103EQUALReactome Database ID Release 75181902Database 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=181902ReactomeR-HSA-1819021Reactome 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-181902.1Reactomehttp://www.reactome.org3Ac-CoAAcetyl coenzyme Aacetyl-CoAReactome DB_ID: 113560acetyl-CoA [ChEBI:15351]acetyl-CoAChEBICHEBI:15351Reactome Database ID Release 75113560Database 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=113560ReactomeR-ALL-1135603Reactome 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-ALL-113560.3COMPOUNDC00024additional informationMIMI:0361Converted from EntitySet in ReactomeAcK-HIST1H4Reactome DB_ID: 4551305HIST1H4AAcK6-HIST1H4Histone H4HIST1H4BHIST1H4CHIST1H4DHIST1H4EHIST1H4FHIST1H4HHIST1H4IHIST1H4JHIST1H4KHIST1H4LHIST2H4AHIST2H4BReactome DB_ID: 45687486EQUALN6-acetyl-L-lysineMODMOD:000642EQUAL103EQUALReactome Database ID Release 754568748Database 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=4568748ReactomeR-HSA-45687481Reactome 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-4568748.1HIST1H4AAcK9-HIST1H4Histone H4HIST1H4BHIST1H4CHIST1H4DHIST1H4EHIST1H4FHIST1H4HHIST1H4IHIST1H4JHIST1H4KHIST1H4LHIST2H4AHIST2H4BReactome DB_ID: 45687589EQUAL2EQUAL103EQUALReactome Database ID Release 754568758Database 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=4568758ReactomeR-HSA-45687581Reactome 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-4568758.1AcK17-HIST1H4Histone H4 (acetylated at lysine-16)AcK17-HIST1H4AReactome DB_ID: 42746917EQUAL2EQUAL103EQUALReactome Database ID Release 75427469Database 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=427469ReactomeR-HSA-4274691Reactome 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-427469.1Reactome Database ID Release 754551305Database 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=4551305ReactomeR-HSA-45513051Reactome 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-4551305.1CoACoA-SHcoenzyme AReactome DB_ID: 2485002coenzyme A [ChEBI:15346]coenzyme AChEBICHEBI:15346Reactome Database ID Release 752485002Database 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=2485002ReactomeR-ALL-24850023Reactome 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-ALL-2485002.3COMPOUNDC00010ACTIVATIONNSLReactome DB_ID: 3321855WDR5WD repeat-containing protein 5BMP2-induced 3-kb gene proteinBIG3Reactome DB_ID: 1629838UniProt:P61964 WDR5WDR5BIG3FUNCTION Contributes to histone modification (PubMed:19131338, PubMed:19556245, PubMed:19103755, PubMed:20018852, PubMed:16600877, PubMed:16829960). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (PubMed:16829960). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:18840606). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:19103755, PubMed:20018852). May regulate osteoblasts differentiation (By similarity). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653).SUBUNIT Interacts with PAXBP1; the interaction is direct and links a WDR5-containing histone methyltransferase complex to PAX7 and PAX3 (By similarity). Interacts with HCFC1 (PubMed:12670868). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:19103755). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, PubMed:17355966, PubMed:17998332, PubMed:18838538). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122, PubMed:15960975, PubMed:17021013, PubMed:17500065). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:14992727, PubMed:18378692). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Interacts with KMT2A/MLL1 (via WIN motif) and RBBP5; the interaction is direct (PubMed:19556245, PubMed:21220120, PubMed:22665483, PubMed:22266653, PubMed:18840606, PubMed:18829459). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (PubMed:19103755). In the complex, it probably interacts directly with KAT2A, MBIP and KAT14 (PubMed:19103755). Interacts with histone H3 (PubMed:16946699, PubMed:16600877, PubMed:16829960, PubMed:16829959). Interacts with SETD1A (via WIN motif) (PubMed:17998332, PubMed:22665483, PubMed:22266653). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126). Components of this complex may associate with components of the ZNF335-CCAR2-EMSY nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Interacts with PER1 (By similarity). Interacts with KMT2B (via WIN motif), KMT2C (via WIN motif), KMT2D (via WIN motif) and SETD1B (via WIN motif) (PubMed:22665483, PubMed:22266653, PubMed:18840606).SIMILARITY Belongs to the WD repeat WDR5/wds family.UniProtP619642EQUAL334EQUALReactome Database ID Release 751629838Database 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=1629838ReactomeR-HSA-16298382Reactome 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-1629838.21HCF1HCFC1Host cell factor 1HCFC1_HUMANReactome DB_ID: 1592209UniProt:P51610 HCFC1HCFC1HCF1HFC1FUNCTION Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655).FUNCTION (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes.SUBUNIT Composed predominantly of six polypeptides ranging from 110 to 150 kDa and a minor 300 kDa polypeptide (PubMed:10920196). The majority of N- and C-terminal cleavage products remain tightly, albeit non-covalently, associated (PubMed:10920196). Interacts with POU2F1, CREB3, ZBTB17, EGR2, E2F4, CREBZF, SP1, GABP2, Sin3 HDAC complex (SIN3A, HDAC1, HDAC2, SUDS3), SAP30, SIN3B and FHL2 (PubMed:9271389, PubMed:9389645, PubMed:10675337, PubMed:10976766, PubMed:10629049, PubMed:10871379, PubMed:10984507, PubMed:12244100, PubMed:14532282, PubMed:12670868, PubMed:15705566, PubMed:16624878). Component of a MLL1 complex, composed of at least the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, DPY30, E2F6, HCFC2, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8, PELP1, PHF20, PRP31, RING2, RUVBL1, RUVBL2, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15199122, PubMed:15960975). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). Interacts directly with THAP3 (via its HBM) (PubMed:20200153). Interacts (via the Kelch-repeat domain) with THAP1 (via the HBM); the interaction recruits HCHC1 to the RRM1 (PubMed:20200153). Interacts directly with OGT; the interaction, which requires the HCFC1 cleavage site domain, glycosylates and promotes the proteolytic processing of HCFC1, retains OGT in the nucleus and impacts the expression of herpes simplex virus immediate early viral genes (PubMed:12670868, PubMed:21285374, PubMed:23353889). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L, CXXC1, HCFC1 and DPY30 (PubMed:17998332, PubMed:18838538). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (PubMed:19131338). Within the complex interacts with ZNF335 (PubMed:19131338). Interacts with TET2 and TET3 (PubMed:23353889). Interacts with HCFC1R1 (PubMed:12235138). Interacts with THAP11 (By similarity). Interacts (via Kelch domain) with KMT2E/MLL5 isoform 3 (via HBM motif) (PubMed:23629655). Interacts with E2F1 (PubMed:23629655).SUBUNIT (Microbial infection) Associates with the VP16-induced complex; binding to HCFC1 activates the viral transcriptional activator VP16 for association with POU2F1, to form a multiprotein-DNA complex responsible for activating transcription of the viral immediate early genes (PubMed:10629049). Interacts with the viral transactivator protein VP16 (PubMed:9271389, PubMed:9389645, PubMed:10629049).TISSUE SPECIFICITY Highly expressed in fetal tissues and the adult kidney. Present in all tissues tested.DOMAIN The HCF repeat is a highly specific proteolytic cleavage signal.DOMAIN The kelch repeats fold into a 6-bladed kelch beta-propeller called the beta-propeller domain which mediates interaction with HCFC1R1.PTM Proteolytically cleaved at one or several PPCE--THET sites within the HCF repeats. Further cleavage of the primary N- and C-terminal chains results in a 'trimming' and accumulation of the smaller chains. Cleavage is promoted by O-glycosylation.PTM O-glycosylated. GlcNAcylation by OGT promotes proteolytic processing.PTM Ubiquitinated. Lys-1807 and Lys-1808 are ubiquitinated both via 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. BAP1 mediated deubiquitination of 'Lys-48'-linked polyubiquitin chains; deubiquitination by BAP1 does not seem to stabilize the protein.CAUTION Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).UniProtP516102EQUAL2035EQUALReactome Database ID Release 751592209Database 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=1592209ReactomeR-HSA-15922091Reactome 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-1592209.11MCRS1Microspherule protein 1MCRS1_HUMANReactome DB_ID: 3321849UniProt:Q96EZ8 MCRS1MCRS1INO80QMSP58FUNCTION Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus (PubMed:11948183). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity (PubMed:15044100). Binds to G-quadruplex structures in mRNA (PubMed:16571602). Binds to RNA homopolymer poly(G) and poly(U) (PubMed:16571602).SUBUNIT Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80 (PubMed:16230350, PubMed:18922472, PubMed:21303910). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15960975). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Interacts with NOP2 (PubMed:9654073). Interacts with PINX1 (PubMed:15044100). Interacts with TERT (PubMed:15044100). Interacts with CCDC85B (PubMed:17014843). Interacts with DAXX (PubMed:11948183). Interacts (via N-terminus) with FMR1 (via phosphorylated form) (PubMed:16571602). Interacts with FXR1 AND FXR2 (PubMed:16571602).SUBUNIT (Microbial infection) Interacts with Herpes simplex virus ICP22.TISSUE SPECIFICITY Detected in testis, and at lower levels in spleen, thymus, prostate, uterus, small intestine, colon and leukocytes.DEVELOPMENTAL STAGE Cell-cycle regulated: levels are highest early in S phase; not detectable in G2.UniProtQ96EZ81EQUAL462EQUALReactome Database ID Release 753321849Database 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=3321849ReactomeR-HSA-33218491Reactome 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-3321849.11NZFPHF20PHD finger protein 20Glioma-expressed antigen 2Hepatocellular carcinoma-associated antigen 58Novel zinc finger proteinTranscription factor TZPC20orf104GLEA2HCA58TZPReactome DB_ID: 3222239UniProt:Q9BVI0 PHF20PHF20C20orf104GLEA2HCA58NZFTZPFUNCTION Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage.SUBUNIT Homodimer; disulfide-linked. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.TISSUE SPECIFICITY Expressed in heart, kidney, liver, lung, pancreas, placenta, spleen and testis. Not expressed in brain, skeletal muscle, colon, ovary, prostate, small intestine and thymus. Expressed in colon and ovary cancer cell lines while it is not expressed in the respective normal tissues.DOMAIN The Tudor domain 2 mediates reading of dimethyl-lysine residues.DOMAIN The Tudor domain 1 doesn't bind dimethyl-lysine residues, due to an atypical and occluded aromatic cage.MISCELLANEOUS Antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula.UniProtQ9BVI01EQUAL1012EQUALReactome Database ID Release 753222239Database 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=3222239ReactomeR-HSA-32222391Reactome 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-3222239.11MOFKAT8Histone acetyltransferase KAT8KAT8_HUMANMYST1Reactome DB_ID: 3321802UniProt:Q9H7Z6 KAT8KAT8MOFMYST1PP7073FUNCTION Histone acetyltransferase which may be involved in transcriptional activation (PubMed:12397079, PubMed:22020126). May influence the function of ATM (PubMed:15923642). As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac (PubMed:16227571, PubMed:16543150, PubMed:21217699, PubMed:22547026, PubMed:22020126). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852, PubMed:22547026). That activity is less specific than the one of the MSL complex (PubMed:20018852, PubMed:22547026). Can also acetylate TP53/p53 at 'Lys-120'.SUBUNIT Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the MOF/KAT8, MSL1/hampin, MSL2L1 and MSL3L1 (PubMed:16227571, PubMed:16543150). Interacts with MSL1; the interaction is direct (PubMed:21217699, PubMed:22547026). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:16543150, PubMed:20018852). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MOF/KAT8, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15960975). Interacts with the chromodomain of MORF4L1/MRG15 (PubMed:12397079). Interacts with ATM through the chromodomain (PubMed:15923642). Interacts with KANSL1; the interaction is direct (PubMed:16543150, PubMed:20620954, PubMed:21217699, PubMed:22547026). Interacts with MSL3 (PubMed:21217699, PubMed:22547026, PubMed:30224647). Interacts with NELFD (By similarity).PTM Autoacetylation at Lys-274 is required for binding histone H4 with high affinity and for proper function.SIMILARITY Belongs to the MYST (SAS/MOZ) family.UniProtQ9H7Z61EQUAL458EQUALReactome Database ID Release 753321802Database 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=3321802ReactomeR-HSA-33218021Reactome 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-3321802.11OGTUDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit ecNumber2.4.1.255/ecNumberOGT1_HUMANReactome DB_ID: 3321845UniProt:O15294 OGTOGTFUNCTION Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc) (PubMed:26678539, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:15361863). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539). Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3) (PubMed:22121020, PubMed:23353889). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins ARNTL/BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, PubMed:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863). O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). O-glycosylates FNIP1 (PubMed:30699359).ACTIVITY REGULATION Subject to product inhibition by UDP.PATHWAY Protein modification; protein glycosylation.SUBUNIT Monomer; may exist in different oligomerization states in cells (PubMed:21240259). Homotrimer, oligomerizes via TPR repeats 6 and 7. Trimerization is not necessary for activity in vitro, however it increases affinity for UDP-GlcNAc (By similarity). Component of a THAP1/THAP3-HCFC1-OGT complex (PubMed:20200153). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Interacts directly with HCFC1; the interaction O-glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus (PubMed:12670868, PubMed:20200153, PubMed:21285374, PubMed:23353889). Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase (PubMed:12150998). Interacts (via TPR 5-6) with TET1, TET2 and TET3 (PubMed:23353889, PubMed:23222540). Interacts (via TPR repeats 6 and 7) with ATXN10 (By similarity). Interacts with histone H2B (PubMed:22121020). Interacts with ARNTL/BMAL1. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with SINHCAF (By similarity). Component of a complex composed of KMT2E/MLL5 (isoform 3), OGT (isoform 1) and USP7; the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and proteosomal-mediated degradation (PubMed:26678539). Isoform 1 interacts (via TRP repeats) with isoform 3 KMT2E/MLL5 (via N-terminus) (PubMed:26678539, PubMed:23629655). Isoform 1 interacts with USP7 (PubMed:26678539). Interacts with TRAK1; this interaction is not required for glycosylation of TRAK1 by this protein. Found in a complex with KIF5B, RHOT1, RHOT2 and TRAK1 (PubMed:24995978). Interacts (via TPR repeats domain) with HOXA1; the interaction takes place mainly in the nucleus (By similarity).SUBUNIT (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein Tax; this interaction increases Tax interacting partner CREB1 O-GlcNAcylation.TISSUE SPECIFICITY Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver.INDUCTION Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux.DOMAIN The TPR repeat domain is required for substrate binding and oligomerization.PTM Ubiquitinated, leading to its proteasomal degradation.PTM Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity.DISEASE Regulation of OGT activity and altered O-GlcNAcylations are implicated in diabetes and Alzheimer disease. O-GlcNAcylation of AKT1 affects insulin signaling and, possibly diabetes. Reduced O-GlcNAcylations and resulting increased phosphorylations of MAPT/TAU are observed in Alzheimer disease (AD) brain cerebrum.SIMILARITY Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.CAUTION Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).UniProtO152942EQUAL1046EQUALReactome Database ID Release 753321845Database 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=3321845ReactomeR-HSA-33218451Reactome 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-3321845.11KANSL3KAT8 regulatory NSL complex subunit 3KANL3_HUMANReactome DB_ID: 3321882UniProt:Q9P2N6 KANSL3KANSL3KIAA1310NSL3PRTDSI1FUNCTION As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.SUBUNIT Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.UniProtQ9P2N61EQUAL904EQUALReactome Database ID Release 753321882Database 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=3321882ReactomeR-HSA-33218821Reactome 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-3321882.11KANSL1KAT8 regulatory NSL complex subunit 1KANL1_HUMANReactome DB_ID: 3321875UniProt:Q7Z3B3 KANSL1KANSL1CENP-36KIAA1267MSL1V1NSL1FUNCTION As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.SUBUNIT Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with KAT8; the interaction is direct.TISSUE SPECIFICITY Expressed in the brain.UniProtQ7Z3B31EQUAL1105EQUALReactome Database ID Release 753321875Database 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=3321875ReactomeR-HSA-33218751Reactome 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-3321875.11KANSL2KAT8 regulatory NSL complex subunit 2KANL2_HUMANReactome DB_ID: 3321796UniProt:Q9H9L4 KANSL2KANSL2C12orf41NSL2FUNCTION As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.SUBUNIT Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.UniProtQ9H9L41EQUAL492EQUALReactome Database ID Release 753321796Database 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=3321796ReactomeR-HSA-33217961Reactome 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-3321796.11Reactome Database ID Release 753321855Database 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=3321855ReactomeR-HSA-33218551Reactome 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-3321855.1ComplexPortalCPX-809GENE ONTOLOGYGO:0004402gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 753321793Database 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=3321793Reactome Database ID Release 753321805Database 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=3321805ReactomeR-HSA-33218052Reactome 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-3321805.216543150Pubmed2006Nuclear pore components are involved in the transcriptional regulation of dosage compensation in DrosophilaMendjan, SaschaTaipale, MikkoKind, JopHolz, HerbertGebhardt, PhilippSchelder, MalgorzataVermeulen, MichielBuscaino, AlessiaDuncan, KentMueller, JuergWilm, MatthiasStunnenberg, Henk GSaumweber, HaraldAkhtar, AsifaMol. Cell 21:811-2320018852Pubmed2010Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complexCai, YongJin, JingjiSwanson, Selene KCole, Michael DChoi, Seung HyukFlorens, Laurence AWashburn, Michael PConaway, Joan WConaway, Ronald CJ. Biol. Chem. 285:4268-7216227571Pubmed2005A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16Smith, Edwin RCayrou, ChristelleHuang, RongLane, William SCôté, JacquesLucchesi, John CMol. Cell. Biol. 25:9175-88