BioPAX pathway converted from "RNA Polymerase I Promoter Clearance" in the Reactome database.RNA Polymerase I Promoter ClearancePromoter clearance is one of the rate-limiting steps in Polymerase I transcription. This step is composed of three phases, promoter opening, transcription initiation and promoter escape.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00RNA Polymerase I Promoter OpeningThe activity of the upstream binding factor (UBF-1) plays an important role in the regulation of rRNA synthesis. Studies reveal that phosphorylation of UBF-1 is required for its interaction with the RNA polymerase I complex, suggesting that phosphorylation of UBF-1 bound to the rDNA promoter during promoter opening modulates the assembly of the transcription initiation complex.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00LEFT-TO-RIGHTUBF-1 Binds rDNA PromoterUBF-1 binds directly to the CORE and UCE elements of the ribosomal DNA promoter. This binding is mediated by the HMG boxes (primarily HMG box1). Phosphorylation may play a role in the modulation of UBF's DNA binding activity, as well as in subsequent steps. UBF is thought to bind DNA in a conformation specific manner (as opposed to a sequence specific manner). The binding of UBF to the minor groove of DNA induces strong DNA bending.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00UBFUBTFNucleolar transcription factor 1 (Upstream binding factor 1) (UBF-1) (Autoantigen NOR-90)Nucleolar transcription factor 1Upstream binding factor 1UBF-1Autoantigen NOR-90Reactome DB_ID: 73683nucleoplasmGENE ONTOLOGYGO:0005654UniProt:P17480 UBTFUBTFUBFUBF1FUNCTION Recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element.SUBUNIT Homodimer (By similarity). Interacts with TBP (PubMed:7982918). Interacts with TAF1A (PubMed:7491500). Interacts with RASL11A (By similarity). Binds to IRS1 and PIK3CA (By similarity). Interacts with DHX33 (PubMed:21930779). Interacts with PHF6 (PubMed:23229552). Interacts with CEBPA (isoform 1 and isoform 4) (PubMed:20075868). Interacts with DDX11 (PubMed:26089203). Interacts with NOP53 (PubMed:27729611).PTM Phosphorylated and activated by PIK3CA.Homo sapiensNCBI Taxonomy9606UniProtP174801EQUAL764EQUALReactome Database ID Release 7573683Database 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=73683ReactomeR-HSA-736831Reactome 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-73683.1Reactomehttp://www.reactome.orgrDNA PromoterReactome DB_ID: 73682Reactome Database ID Release 7573682Database 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=73682ReactomeR-ALL-736822Reactome 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-73682.2ChEBI61120additional informationMIMI:0361UBF-1:rDNA PromoterReactome DB_ID: 7368411Reactome Database ID Release 7573684Database 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=73684ReactomeR-HSA-736841Reactome 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-73684.1Reactome Database ID Release 7573718Database 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=73718ReactomeR-HSA-737184Reactome 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-73718.42330041Pubmed1990Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins.Jantzen, HMBell, SPTjian, RNature 344:830-6INHIBITIONMethylcytosine in the promoter of a rRNA gene binds MBD2 (and possibly other Methyl Domain Binding Proteins) and prevents the transcription factor UBF-1 from binding. In mouse, methylation of the cytosine 133 nucleotides upstream of the start of transcription is sufficient. In the human rRNA promoter methylation of cytosines 9, 102, and 347 nucleotides upstream inhibit transcription.Reactome Database ID Release 75427398Database 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=427398ReactomeR-HSA-4273981Reactome 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-427398.1Chromatin (H3K9me2, 5mC):MBD2Reactome DB_ID: 427343MBD2Methyl-CpG-binding domain protein 2MBD2_HUMANReactome DB_ID: 427367UniProt:Q9UBB5 MBD2MBD2FUNCTION Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.SUBUNIT Heterodimer with MBD3. Component of the MeCP1 complex that contains HDAC1 and HDAC2. Binds DNMT1, MIZF, GPN1, SIN3A, GATAD2A/p66-alpha and GATAD2B/p66-beta. Interacts with DHX9. Interacts with SPHK2 (PubMed:19729656).TISSUE SPECIFICITY Highly expressed in brain, heart, kidney, stomach, testis and placenta.CAUTION Functional studies (PubMed:10050851, PubMed:10950960 and PubMed:12665568) have used a C-terminal fragment of isoform 1 which has been described originally as isoform MBD2b but cannot however be proven by supporting cDNA sequences.UniProtQ9UBB51EQUAL411EQUALReactome Database ID Release 75427367Database 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=427367ReactomeR-HSA-4273671Reactome 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-427367.11Chromatin with H3K9me2, 5mCReactome DB_ID: 5226877methylated DNADNA containing 5-mCDouble-Stranded DNA containing 5-methylcytosineReactome DB_ID: 212172Reactome Database ID Release 75212172Database 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=212172ReactomeR-ALL-2121721Reactome 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-212172.1ChEBI4705COMPOUNDC02967ChEBI275511Nucleosome with H3K9me2Nucleosome with Deacetylated H4 and H3 Dimethylated at Lysine-9Reactome DB_ID: 427331Converted from EntitySet in ReactomeHistone H2AReactome DB_ID: 181899H2AFB1Histone H2A-BbdReactome DB_ID: 181887UniProt:P0C5Y9 H2AB1H2AB1H2AFB1FUNCTION Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing (PubMed:22795134). 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 (PubMed:15257289, PubMed:16287874, PubMed:16957777, PubMed:17591702, PubMed:17726088, PubMed:18329190, PubMed:22795134). Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo (PubMed:15257289, PubMed:16957777, PubMed:17591702, PubMed:24336483). They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase (PubMed:17591702, PubMed:24753410). They associate with spliceosome components and are required for mRNA splicing (PubMed:22795134).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. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules.TISSUE SPECIFICITY Present in mature sperm.DOMAIN The docking domain is responsible for the weaker heterodimerization with H2B.MISCELLANEOUS In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.SIMILARITY Belongs to the histone H2A family.CAUTION Although related to variant histone H2AB1 in mouse (AC Q9CQ70), it is unclear whether human and mouse H2AB1 proteins are involved in similar processes. In mouse, variant histone H2AB1 is specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells during spermatogenesis. It is however unclear whether human protein, which participates in mRNA processing and is associated with active transcription, is also involved in nucleosomes to protamine replacement (PubMed:22795134).UniProtP0C5Y91EQUAL115EQUALReactome Database ID Release 75181887Database 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=181887ReactomeR-HSA-1818871Reactome 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-181887.1HIST1H2ABReactome DB_ID: 181888UniProt:P04908 H2AC4H2AC4H2AFMHIST1H2ABH2AC8H2AFAHIST1H2AEFUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.UniProtP049082EQUAL130EQUALReactome Database ID Release 75181888Database 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=181888ReactomeR-HSA-1818881Reactome 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-181888.1HIST1H2AJHistone H2A.eReactome DB_ID: 181890UniProt:Q99878 H2AC14H2AC14H2AFEHIST1H2AJFUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.UniProtQ998782EQUAL128EQUALReactome Database ID Release 75181890Database 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=181890ReactomeR-HSA-1818901Reactome 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-181890.1HIST1H2ADHistone H2A.gReactome DB_ID: 181896UniProt:P20671 H2AC7H2AC7H2AFGHIST1H2ADFUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.CAUTION Was originally thought to originate from mouse.UniProtP206712EQUAL130EQUALReactome Database ID Release 75181896Database 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=181896ReactomeR-HSA-1818961Reactome 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-181896.1HIST1H2ACHistone H2A.lReactome DB_ID: 181895UniProt:Q93077 H2AC6H2AC6H2AFLHIST1H2ACFUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.UniProtQ930772EQUAL130EQUALReactome Database ID Release 75181895Database 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=181895ReactomeR-HSA-1818951Reactome 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-181895.1HIST2H2AA3Histone H2A.oReactome DB_ID: 181891UniProt:Q6FI13 H2AC18H2AC18H2AFOHIST2H2AAHIST2H2AA3H2AC19HIST2H2AA4FUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.UniProtQ6FI132EQUAL130EQUALReactome Database ID Release 75181891Database 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=181891ReactomeR-HSA-1818911Reactome 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-181891.1HIST2H2ACHistone H2A.qReactome DB_ID: 181892UniProt:Q16777 H2AC20H2AC20H2AFQHIST2H2ACFUNCTION 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 Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.PTM Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).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.MASS SPECTROMETRY Monoisotopic with N-acetylserine.SIMILARITY Belongs to the histone H2A family.UniProtQ167772EQUAL129EQUALReactome Database ID Release 75181892Database 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=181892ReactomeR-HSA-1818921Reactome 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-181892.1H2AFJHistone H2A.JH2AJ_HUMANReactome DB_ID: 8862432UniProt:Q9BTM1 H2AJH2AJH2AFJFUNCTION 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 Monoubiquitination of Lys-120 (H2AXK119ub) gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties (By similarity).PTM Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription (By similarity).PTM Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (By similarity).SIMILARITY Belongs to the histone H2A family.UniProtQ9BTM12EQUAL129EQUALReactome Database ID Release 758862432Database 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=8862432ReactomeR-HSA-88624322Reactome 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-8862432.2H2AFVHistone H2A.VH2AV_HUMANReactome DB_ID: 8862427UniProt:Q71UI9 H2AZ2H2AZ2H2AFVH2AVFUNCTION Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division (By similarity).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. H2A or its variant H2AZ2 forms a heterodimer with H2B (By similarity).PTM Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.PTM Acetylated on Lys-5, Lys-8 and Lys-12 during interphase. Acetylation disappears at mitosis (By similarity).MASS SPECTROMETRY Monoisotopic, not modified.SIMILARITY Belongs to the histone H2A family.UniProtQ71UI91EQUAL128EQUALReactome Database ID Release 758862427Database 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=8862427ReactomeR-HSA-88624272Reactome 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-8862427.2H2AFXHistone H2A.xH2a/xReactome DB_ID: 56151UniProt:P16104 H2AXH2AXH2AFXFUNCTION Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.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 (Probable). Interacts with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-140 (PubMed:12419185, PubMed:12607005, PubMed:15201865). These include MDC1, TP53BP1, BRCA1 and the MRN complex, composed of MRE11, RAD50, and NBN (PubMed:12419185, PubMed:12607005, PubMed:15201865). Interaction with the MRN complex is mediated at least in part by NBN (PubMed:12419185). Also interacts with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when phosphorylated at Ser-140 or Tyr-143 (PubMed:15613478). Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation (PubMed:16820410). Interacts with WRAP53/TCAB1 (PubMed:26734725, PubMed:27715493).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus protein EBNA6.DEVELOPMENTAL STAGE Synthesized in G1 as well as in S-phase.DOMAIN The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.PTM Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents and by stalled replication forks, and may also occur during meiotic recombination events and immunoglobulin class switching in lymphocytes. Phosphorylation can extend up to several thousand nucleosomes from the actual site of the DSB and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Widespread phosphorylation may also serve to amplify the damage signal or aid repair of persistent lesions. Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing radiation is mediated by both ATM and PRKDC while defects in DNA replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is required for DNA DSB repair. In meiosis, Ser-140 phosphorylation (H2AX139ph) may occur at synaptonemal complexes during leptotene as an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) may subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene, downstream of ATR and BRCA1 activation. Ser-140 phosphorylation (H2AX139ph) may also be required for transcriptional repression of unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI), whereby the X and Y chromosomes condense in pachytene to form the heterochromatic XY-body. During immunoglobulin class switch recombination in lymphocytes, Ser-140 phosphorylation (H2AX139ph) may occur at sites of DNA-recombination subsequent to activation of the activation-induced cytidine deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1, triggering apoptosis. In contrast, dephosphorylation of Tyr-143 by EYA proteins (EYA1, EYA2, EYA3 or EYA4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-140 (H2AX139ph).PTM Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression (By similarity). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.PTM Acetylation at Lys-37 increases in S and G2 phases. This modification has been proposed to play a role in DNA double-strand break repair (By similarity).SIMILARITY Belongs to the histone H2A family.UniProtP161042EQUAL143EQUALReactome Database ID Release 7556151Database 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=56151ReactomeR-HSA-561511Reactome 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-56151.1H2AFZHistone H2A.zReactome DB_ID: 181897UniProt:P0C0S5 H2AZ1H2AZ1H2AFZH2AZFUNCTION Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division.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. H2A or its variant H2AZ1 forms a heterodimer with H2B. H2AZ1 interacts with INCENP (By similarity). Interacts (via M6 cassette) with ANP32E; leading to removal of H2A.Z/H2AZ1 from the nucleosome. Heterodimer H2BC11 and H2AZ1 interacts with VPS72 (via N-terminal domain) (PubMed:26974126). Interacts with PWWP2A (PubMed:28645917). Interacts with FH (when phosphorylated by PRKDC) (PubMed:26237645).PTM Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.PTM Acetylated on Lys-5, Lys-8, Lys-12 and Lys-14 by KAT2A; KAT2A is recruited by the XPC complex in absence of DNA damage (PubMed:31527837). Acetylated on Lys-5, Lys-8 and Lys-12 during interphase; acetylation disappears at mitosis (By similarity).PTM Monomethylated on Lys-5 and Lys-8 by SETD6. SETD6 predominantly methylates Lys-8, lys-5 being a possible secondary site.PTM Not phosphorylated.MASS SPECTROMETRY Monoisotopic, not modified.SIMILARITY Belongs to the histone H2A family.UniProtP0C0S52EQUAL128EQUALReactome Database ID Release 75181897Database 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=181897ReactomeR-HSA-1818971Reactome 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-181897.1Reactome Database ID Release 75181899Database 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=181899ReactomeR-HSA-1818992Reactome 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-181899.22Converted from EntitySet in ReactomeHistone H2BReactome DB_ID: 181911HIST1H2BKHistone H2B KReactome DB_ID: 181898UniProt:O60814 H2BC12H2BC12H2BFTHIRIP1HIST1H2BKFUNCTION 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.FUNCTION Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtO608142EQUAL126EQUALReactome Database ID Release 75181898Database 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=181898ReactomeR-HSA-1818981Reactome 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-181898.1HIST3H2BBHistone H2B type 12Reactome DB_ID: 181923UniProt:Q8N257 H2BU1H2BU1HIST3H2BBFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtQ8N2572EQUAL126EQUALReactome Database ID Release 75181923Database 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=181923ReactomeR-HSA-1819231Reactome 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-181923.1HIST1H2BAHistone H2B, testisReactome DB_ID: 181916UniProt:Q96A08 H2BC1H2BC1HIST1H2BATSH2BFUNCTION Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells (By similarity). Entirely replaces classical histone H2B prior nucleosome to protamine transition and probably acts as a nucleosome dissociating factor that creates a more dynamic chromatin, facilitating the large-scale exchange of histones (By similarity). Core component of nucleosome (By similarity). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (By similarity). Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (By similarity). DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling (By similarity). Also found in fat cells, its function and the presence of post-translational modifications specific to such cells are still unclear (PubMed:21249133).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.TISSUE SPECIFICITY Mainly expressed in testis, and the corresponding protein is also present in mature sperm (at protein level). Also found in some fat cells.PTM Monoubiquitination at Lys-36 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-122 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.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 Acetylated during spermatogenesis. Acetylated form is most abundant in spermatogonia compared to spermatocytes and round spermatids (By similarity).PTM Phosphorylated at Thr-117 in spermatogonia, spermatocytes and round spermatids.PTM Methylated at Lys-118 in spermatogonia, spermatocytes and round spermatids.SIMILARITY Belongs to the histone H2B family.UniProtQ96A082EQUAL127EQUALReactome Database ID Release 75181916Database 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=181916ReactomeR-HSA-1819161Reactome 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-181916.1HIST1H2BCHistone H2B type 1-C/E/F/G/IReactome DB_ID: 181906UniProt:P62807 H2BC4H2BC4H2BFLHIST1H2BCH2BC6H2BFHHIST1H2BEH2BC7H2BFGHIST1H2BFH2BC8H2BFAHIST1H2BGH2BC10H2BFKHIST1H2BIFUNCTION 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.FUNCTION Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes.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.SIMILARITY Belongs to the histone H2B family.UniProtP628072EQUAL126EQUALReactome Database ID Release 75181906Database 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=181906ReactomeR-HSA-1819061Reactome 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-181906.1HIST1H2BDHistone H2B.bReactome DB_ID: 181912UniProt:P58876 H2BC5H2BC5H2BFBHIRIP2HIST1H2BDFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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 ADP-ribosylated on Ser-7 in response to DNA damage.MISCELLANEOUS The mouse orthologous protein seems not to exist.SIMILARITY Belongs to the histone H2B family.UniProtP588762EQUAL126EQUALReactome Database ID Release 75181912Database 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=181912ReactomeR-HSA-1819121Reactome 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-181912.1HIST1H2BLHistone H2B.cReactome DB_ID: 181920UniProt:Q99880 H2BC13H2BC13H2BFCHIST1H2BLFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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 ADP-ribosylated on Ser-7 in response to DNA damage.SIMILARITY Belongs to the histone H2B family.UniProtQ998802EQUAL126EQUALReactome Database ID Release 75181920Database 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=181920ReactomeR-HSA-1819201Reactome 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-181920.1HIST1H2BNHistone H2B.dReactome DB_ID: 181907UniProt:Q99877 H2BC15H2BC15H2BFDHIST1H2BNFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtQ998772EQUAL126EQUALReactome Database ID Release 75181907Database 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=181907ReactomeR-HSA-1819071Reactome 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-181907.1HIST1H2BMHistone H2B.eReactome DB_ID: 181917UniProt:Q99879 H2BC14H2BC14H2BFEHIST1H2BMFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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 ADP-ribosylated on Ser-7 in response to DNA damage.SIMILARITY Belongs to the histone H2B family.UniProtQ998792EQUAL126EQUALReactome Database ID Release 75181917Database 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=181917ReactomeR-HSA-1819171Reactome 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-181917.1HIST1H2BBHistone H2B.fReactome DB_ID: 181903UniProt:P33778 H2BC3H2BC3H2BFFHIST1H2BBFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtP337782EQUAL126EQUALReactome Database ID Release 75181903Database 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=181903ReactomeR-HSA-1819031Reactome 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-181903.1HIST1H2BHHistone H2B.jReactome DB_ID: 181915UniProt:Q93079 H2BC9H2BC9H2BFJHIST1H2BHFUNCTION 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 (Probable). The octamer wraps approximately 147 bp of DNA (Probable). Found in a complex with PPAR9; DTX3L AND STAT1; the interaction is likely to induce DTX3L-mediated ubiquitination of H2BC9/H2BJ (PubMed:26479788).PTM Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (PubMed:16627869). Monoubiquitinated by DTX3L upon encephalomyocarditis virus (EMCV)-mediated infection (PubMed:26479788).PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtQ930792EQUAL126EQUALReactome Database ID Release 75181915Database 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=181915ReactomeR-HSA-1819151Reactome 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-181915.1HIST1H2BOHistone H2B.nReactome DB_ID: 181910UniProt:P23527 H2BC17H2BC17H2BFHH2BFNHIST1H2BOFUNCTION 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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.MISCELLANEOUS The mouse orthologous protein seems not to exist.SIMILARITY Belongs to the histone H2B family.UniProtP235272EQUAL126EQUALReactome Database ID Release 75181910Database 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=181910ReactomeR-HSA-1819101Reactome 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-181910.1HIST2H2BEHistone H2B.qReactome DB_ID: 181908UniProt:Q16778 H2BC21H2BC21H2BFQHIST2H2BEFUNCTION 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.FUNCTION Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtQ167782EQUAL126EQUALReactome Database ID Release 75181908Database 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=181908ReactomeR-HSA-1819081Reactome 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-181908.1HIST1H2BJHistone H2B.rReactome DB_ID: 181900UniProt:P06899 H2BC11H2BC11H2BFRHIST1H2BJFUNCTION 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.FUNCTION Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.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. Heterodimer H2BC11 and H2AZ1 interacts with VPS72 (via N-terminal domain) (PubMed:26974126).PTM Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtP068992EQUAL126EQUALReactome Database ID Release 75181900Database 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=181900ReactomeR-HSA-1819001Reactome 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-181900.1H2BFSHistone H2B.sReactome DB_ID: 181904UniProt:P57053 H2BS1H2BS1H2BFSFUNCTION 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.FUNCTION Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.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 Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons.PTM Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (By similarity). Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination.PTM GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).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.SIMILARITY Belongs to the histone H2B family.UniProtP570532EQUAL126EQUALReactome Database ID Release 75181904Database 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=181904ReactomeR-HSA-1819041Reactome 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-181904.1Reactome Database ID Release 75181911Database 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=181911ReactomeR-HSA-1819111Reactome 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-181911.12Converted from EntitySet in ReactomeHistone H3 dimethylated at lysine-9Reactome DB_ID: 427406Me2K10-HIST1H3AHistone H3.1 with dimethylated lysine9 (H3K9)Reactome DB_ID: 427378UniProt:P68431 H3C1H3C1H3FAHIST1H3AH3C2H3FLHIST1H3BH3C3H3FCHIST1H3CH3C4H3FBHIST1H3DH3C6H3FDHIST1H3EH3C7H3FIHIST1H3FH3C8H3FHHIST1H3GH3C10H3FKHIST1H3HH3C11H3FFHIST1H3IH3C12H3FJHIST1H3JFUNCTION 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.DEVELOPMENTAL STAGE Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.PTM Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.PTM Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). 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.PTM Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene 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. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:30257210). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).DISEASE HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells.MISCELLANEOUS This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).UniProtP6843110EQUALN6,N6-dimethyl-L-lysineMODMOD:000842EQUAL136EQUALReactome Database ID Release 75427378Database 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=427378ReactomeR-HSA-4273781Reactome 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-427378.1Me2K-10-HIST2H3AHistone H3.2 with dimethylated lysine9 (H3K9)Reactome DB_ID: 427407UniProt:Q71DI3 H3C15H3C15HIST2H3AH3C14H3F2H3FMHIST2H3CH3C13HIST2H3DFUNCTION 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. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer.DEVELOPMENTAL STAGE Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.PTM Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.PTM Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. 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.PTM Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene 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. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).UniProtQ71DI310EQUAL2EQUAL136EQUALReactome Database ID Release 75427407Database 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=427407ReactomeR-HSA-4274071Reactome 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-427407.1Me2K-10-H3F3AHistone H3.3 with dimethylated lysine9 (H3K9)Reactome DB_ID: 427324UniProt:P84243 H3-3AH3-3AH3.3AH3F3H3F3APP781H3-3BH3.3BH3F3BFUNCTION Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. 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. Interacts with HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).DEVELOPMENTAL STAGE Expressed throughout the cell cycle independently of DNA synthesis.DOMAIN Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.PTM Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes.PTM Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity).PTM Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene 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. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).DISEASE H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).UniProtP8424310EQUAL2EQUAL136EQUALReactome Database ID Release 75427324Database 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=427324ReactomeR-HSA-4273241Reactome 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-427324.1Reactome Database ID Release 75427406Database 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=427406ReactomeR-HSA-4274061Reactome 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-427406.12HIST1H4Histone H4HIST1H4AHIST1H4BHIST1H4CHIST1H4DHIST1H4EHIST1H4FHIST1H4HHIST1H4IHIST1H4JHIST1H4KHIST1H4LHIST2H4AHIST2H4BReactome DB_ID: 181902UniProt: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.UniProtP628052EQUAL103EQUALReactome 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-181902.12Reactome Database ID Release 75427331Database 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=427331ReactomeR-HSA-4273311Reactome 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-427331.11Reactome Database ID Release 755226877Database 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=5226877ReactomeR-HSA-52268771Reactome 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-5226877.11Reactome Database ID Release 75427343Database 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=427343ReactomeR-HSA-4273431Reactome 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-427343.1INHIBITIONReactome Database ID Release 75427347Database 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=427347ReactomeR-HSA-4273471Reactome 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-427347.1NucleosomeNucleosome (Deacetylated)Reactome DB_ID: 42740222Converted from EntitySet in ReactomeHistone H3Reactome DB_ID: 212293HIST1H3AHistone H3.1Histone H3aHistone H3bHistone H3cHistone H3dHistone H3fHistone H3hHistone H3iHistone H3jHistone H3kHistone H3lReactome DB_ID: 2120702EQUAL136EQUALReactome Database ID Release 75212070Database 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=212070ReactomeR-HSA-2120701Reactome 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-212070.1HIST2H3AHistone H3.2HIST2H3CHIST2H3DReactome DB_ID: 2122812EQUAL136EQUALReactome Database ID Release 75212281Database 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=212281ReactomeR-HSA-2122811Reactome 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-212281.1H3F3AHistone H3.3Reactome DB_ID: 2122952EQUAL136EQUALReactome Database ID Release 75212295Database 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=212295ReactomeR-HSA-2122951Reactome 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-212295.1Reactome Database ID Release 75212293Database 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=212293ReactomeR-HSA-2122931Reactome 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-212293.122Reactome Database ID Release 75427402Database 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=427402ReactomeR-HSA-4274021Reactome 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-427402.1LEFT-TO-RIGHT2.7.11.24Phosphorylation of UBF-1:rDNA PromoterPhosphorylation of UBF-1, bound to the promoter, activates UBF-1 and recruits SL1, and eventually polymerase. This phosphorylation of UBF-1 by Erk1, has been shown to both weaken the binding of UBF-1 to DNA and to activate transcription (the authors of the paper showing these data suggest that loosening the binding of UBF-1 with the promoter may somehow promote transcription initiation). Though not definitively worked out phosphorylation of UBF-1 by Erk1 plays a role in the activation of the UBF-1:rDNA complex.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 29358ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 7529358Database 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=29358ReactomeR-ALL-293583Reactome 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-29358.3COMPOUNDC00002Phosphorylated UBF-1:rDNA promoterReactome DB_ID: 736851UBF-1p-UBTFphosphorylated UBF-1Nucleolar transcription factor 1Upstream binding factor 1Autoantigen NOR-90Reactome DB_ID: 76039phosphorylated residueMODMOD:006961EQUAL764EQUALReactome Database ID Release 7576039Database 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=76039ReactomeR-HSA-760391Reactome 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-76039.11Reactome Database ID Release 7573685Database 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=73685ReactomeR-HSA-736851Reactome 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-73685.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 75113582Database 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=113582ReactomeR-ALL-1135823Reactome 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-113582.3COMPOUNDC00008ACTIVATIONphospho-ERK-1 dimerp-T202, Y204 MAPK3 dimerReactome DB_ID: 109845p-T202,Y204-MAPK3p-T202,Y204-ERK-1Mitogen-activated protein kinase 3(phosphorylated)Extracellular signal-regulated kinase 1(phosphorylated)Insulin-stimulated MAP2 kinaseMAP kinase 1 phosphorylatedp-T202,Y204-MAPK 1p44-ERK1phosphorylatedERT2 phosphorylatedMAP kinase isoform p44(phosphorylated)Microtubule- associated protein-2 kinaseReactome DB_ID: 112359UniProt:P27361 MAPK3MAPK3ERK1PRKM3FUNCTION Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.ACTIVITY REGULATION Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with TPR. Interacts with CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs upon heat shock (PubMed:10747973). Interacts with CAVIN4 (By similarity).SUBUNIT (Microbial infection) Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity.DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.PTM Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-204.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.UniProtP27361202EQUALO-phospho-L-threonineMODMOD:00047204EQUALO4'-phospho-L-tyrosineMODMOD:000482EQUAL379EQUALReactome Database ID Release 75112359Database 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=112359ReactomeR-HSA-1123591Reactome 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-112359.12Reactome Database ID Release 75109845Database 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=109845ReactomeR-HSA-1098451Reactome 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-109845.1GENE ONTOLOGYGO:0004707gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 75164955Database 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=164955Reactome Database ID Release 7573722Database 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=73722ReactomeR-HSA-737223Reactome 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-73722.311741541Pubmed2001An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF.Stefanovsky, VYPelletier, GHannan, RGagnon-Kugler, TRothblum, LIMoss, TMol Cell 8:1063-73Reactome Database ID Release 7573728Database 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=73728ReactomeR-HSA-737282Reactome 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-73728.2GENE ONTOLOGYGO:0006361gene ontology term for cellular processMIMI:0359RNA Polymerase I Transcription InitiationDuring initiation the double-stranded DNA must be melted and transcription begins. SL1 forms and interacts with UBF-1 and the rDNA promoter. It is this platform that will recruit active RNA polymerase I to the SL1:phosphorlated UBF-1:rDNA promoter complex.<p>Mammalian rRNA genes are preceded by a terminator element that is recognized by the SL1 complex. This SL1 modulated acetylation of the basal Pol I transcription machinery has functional consequences suggesting that the reversible acetylation may be one way to regulate rDNA transcription.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00LEFT-TO-RIGHTFormation of SL1Human SL1 is a four subunit complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs): TAF(1)110, TAF(1)63, and TAF(1)48. Note that none of these three TAFs for Pol I show any homology to the Pol II or Pol III TAFs. TAFs SL1 is a species specific factor.TAF1BTAF(1)68Reactome DB_ID: 73691UniProt:Q53T94 TAF1BTAF1BFUNCTION Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment events in polymerase I (Pol I) transcription. Binds rDNA promoters and plays a role in Pol I recruitment as a component of the SL1/TIF-IB complex and, possibly, directly through its interaction with RRN3.SUBUNIT Interacts with FLNA (via N-terminus) (By similarity). Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1C. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with TBP and RRN3.DOMAIN Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (PubMed:21921198 and PubMed:21921199).SIMILARITY Belongs to the RRN7/TAF1B family.UniProtQ53T941EQUAL588EQUALReactome Database ID Release 7573691Database 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=73691ReactomeR-HSA-736911Reactome 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-73691.1TAF1DTATA box-binding protein-associated factor RNA polymerase I subunit DTAF1D_HUMANReactome DB_ID: 5138533UniProt:Q9H5J8 TAF1DTAF1DJOSD3FUNCTION Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.SUBUNIT Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Interacts with UBTF.UniProtQ9H5J81EQUAL278EQUALReactome Database ID Release 755138533Database 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=5138533ReactomeR-HSA-51385331Reactome 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-5138533.1TAF1CTAF(1)110TATA box binding proteinTBP-associated factor, RNA polymerase I, C, 110kDaReactome DB_ID: 73687UniProt:Q15572 TAF1CTAF1CFUNCTION Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits. Recruits RNA polymerase I to the rRNA gene promoter via interaction with RRN3.SUBUNIT Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with MYC and RRN3. Interacts with p53/TP53; the interaction prevents the association of SL1/TIF-IB with UBTF and represses RNA polymerase I transcription.UniProtQ155721EQUAL869EQUALReactome Database ID Release 7573687Database 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=73687ReactomeR-HSA-736871Reactome 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-73687.1TBPTATA box binding protein (Transcription initiation factor TFIID) (TATA-box factor) (TATA sequence-binding protein) (TBP)TATA-box binding proteinTATA-box factorTATA binding factorTATA sequence-binding proteinTranscription initiation factor TFIID TBP subunitReactome DB_ID: 83718UniProt:P20226 TBPTBPGTF2D1TF2DTFIIDFUNCTION General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID (PubMed:2374612, PubMed:2363050, PubMed:2194289, PubMed:9836642, PubMed:27193682). Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II (PubMed:2374612, PubMed:2363050, PubMed:2194289, PubMed:9836642, PubMed:27193682). Component of a BRF2-containing transcription factor complex that regulates transcription mediated by RNA polymerase III (PubMed:26638071). Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription (PubMed:15970593). The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.SUBUNIT Binds DNA as monomer (PubMed:2374612, PubMed:2194289). Belongs to the TFIID complex together with the TBP-associated factors (TAFs) (PubMed:9836642, PubMed:27007846). Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:27007846). Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D (PubMed:7801123). Association of TBP to form either TFIID or SL1/TIF-IB appears to be mutually exclusive (PubMed:7801123). Interacts with TAF1A, TAF1B and TAF1C (PubMed:7801123). Interacts with TFIIB, NCOA6, DRAP1, DR1 and ELF3 (PubMed:10567404, PubMed:10391676, PubMed:11461703). Interacts with SPIB, SNAPC1, SNAPC2 and SNAPC4 (PubMed:10196196, PubMed:12621023). Interacts with UTF1 (PubMed:9748258). Interacts with BRF2; this interaction promotes recruitment of BRF2 to TATA box-containing promoters (PubMed:11564744, PubMed:26638071). Interacts with UBTF (PubMed:7982918). Interacts with GPBP1 (By similarity). Interacts with CITED2 (By similarity). Interacts with ATF7IP (Probable). Interacts with LLPH (By similarity). Interacts with HSF1 (via transactivation domain) (PubMed:11005381). Interacts with GTF2B (via C-terminus); this interaction with promoter-bound TBP guides RNA polymerase II into the pre-initiation complex (PIC) (PubMed:8504927).SUBUNIT (Microbial infection) Interacts with HIV-1 Tat.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 ICP4.SUBUNIT (Microbial infection) Interacts with human adenovirus E1A protein; this interaction probably disrupts the TBP-TATA complex.TISSUE SPECIFICITY Widely expressed, with levels highest in the testis and ovary.POLYMORPHISM The poly-Gln region of TBP is highly polymorphic (25 to 42 repeats) in normal individuals and is expanded to about 47-63 repeats in spinocerebellar ataxia 17 (SCA17) patients.SIMILARITY Belongs to the TBP family.UniProtP202261EQUAL339EQUALReactome Database ID Release 7583718Database 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=83718ReactomeR-HSA-837181Reactome 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-83718.1TAF1ATAF(1)48TATA box binding proteinTBP-associated factor, RNA polymerase I, A, 48kDReactome DB_ID: 73689UniProt:Q15573 TAF1ATAF1AFUNCTION Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.SUBUNIT Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with UBFT. Interacts with CEBPA (isoform 1 and isoform 4) (PubMed:20075868).UniProtQ155731EQUAL450EQUALReactome Database ID Release 7573689Database 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=73689ReactomeR-HSA-736891Reactome 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-73689.1SL1Reactome DB_ID: 7369211111Reactome Database ID Release 7573692Database 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=73692ReactomeR-HSA-736921Reactome 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-73692.1Reactome Database ID Release 7573729Database 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=73729ReactomeR-HSA-737292Reactome 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-73729.22805069Pubmed1989Molecular mechanisms governing species-specific transcription of ribosomal RNA.Bell, SPPikaard, CSReeder, RHTjian, RCell 59:489-971547496Pubmed1992The TATA-binding protein and associated factors are integral components of the RNA polymerase I transcription factor, SL1.Comai, LTanese, NTjian, RCell 68:965-7617318177Pubmed2007A novel TBP-associated factor of SL1 functions in RNA polymerase I transcriptionGorski, Julia JPathak, ShaliniPanov, KostyaKasciukovic, TacianaPanova, TanyaRussell, JackieZomerdijk, Joost C B MEMBO J. 26:1560-87801123Pubmed1995Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or TFIID subunits.Comai, LZomerdijk, JCBeckmann, HZhou, STjian, RScience 266:1966-72LEFT-TO-RIGHT2.3.1Acetylation of SL1Acetylation of the TAFI63 subunit of SL1 by PCAF stimulates the association of TAFI63 with DNA and stimulates pol I transcription in vitro. Conversely, deacetylation by the NAD+-dependent deacetylase Sir2 represses pol I transcription.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00Ac-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-113560.3COMPOUNDC00024Acetylated SL1Reactome DB_ID: 7369311Ac-TAF1Bacetylated TAF(1)68Reactome DB_ID: 5138530N6-acetyl-L-lysineMODMOD:000641EQUAL588EQUALReactome Database ID Release 755138530Database 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=5138530ReactomeR-HSA-51385301Reactome 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-5138530.1111Reactome Database ID Release 7573693Database 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=73693ReactomeR-HSA-736931Reactome 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-73693.1CoACoA-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-2485002.3COMPOUNDC00010ACTIVATIONConverted from EntitySet in ReactomePCAFReactome DB_ID: 350078PCAFKAT2BPCAF_HUMANHistone acetyltransferase PCAFReactome DB_ID: 352430UniProt:Q92831 KAT2BKAT2BPCAFFUNCTION Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Also acetylates non-histone proteins, such as ACLY, PLK4, RRP9/U3-55K and TBX5 (PubMed:9707565, PubMed:10675335, PubMed:27796307, PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (PubMed:14645221). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Also acetylates spermidine (PubMed:27389534).FUNCTION (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.ACTIVITY REGULATION Activated in vitro by very low concentrations of spermidine, but inhibited at spermidine concentrations higher than 4 uM. The activating effect of low spermidine concentrations may be mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting as a positive feedback loop.SUBUNIT Interacts with SIRT1. Interacts (unsumoylated form) with NR2C1; the interaction promotes transactivation activity (By similarity). Interacts with EP300, CREBBP and DDX17. Interacts with NCOA1 and NCOA3. Component of a large chromatin remodeling complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and unsumoylated form); the interaction promotes the transactivation activity of NR2C2. Interacts with KLF1; the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4. Interacts with MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting its DNA-binding and transcriptional activity. Interacts with NPAS2, ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts with CEBPB (PubMed:17301242). Interacts with NR4A3 (By similarity). Interacts with NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768). Interacts with PLK4 (PubMed:27796307). Interacts with RB1; this interaction leads to RB1 acetylation (By similarity).SUBUNIT (Microbial infection) Interacts with and acetylates HIV-1 Tat.SUBUNIT (Microbial infection) Interacts with HTLV-1 Tax.TISSUE SPECIFICITY Ubiquitously expressed but most abundant in heart and skeletal muscle. Also expressed in the skin, in keratinocytes (at protein level) (PubMed:20940255).DEVELOPMENTAL STAGE Up-regulated during keratinocyte differentiation (at protein level).DOMAIN (Microbial infection) The bromodomain mediates binding to HIV-1 Tat.DISEASE Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.SIMILARITY Belongs to the acetyltransferase family. GCN5 subfamily.UniProtQ928311EQUAL832EQUALReactome Database ID Release 75352430Database 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=352430ReactomeR-HSA-3524301Reactome 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-352430.1GCN5KAT2AHistone acetyltransferase KAT2AKAT2A_HUMANReactome DB_ID: 3006516UniProt:Q92830 KAT2AKAT2AGCN5GCN5L2FUNCTION Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase or succinyltransferase, depending on the context (PubMed:29211711). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, PLK4 and TBX5 (PubMed:17301242, PubMed:27796307, PubMed:29174768). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed:31542297).FUNCTION (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.SUBUNIT Homooligomer; may form a tetramer of homodimers (PubMed:30109122). Interacts with EP300, CREBBP and ADA2. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2, TAF10 and TRRAP (PubMed:10373431, PubMed:10611234, PubMed:11438666). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (PubMed:18206972). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (PubMed:18206972). 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 KAT14, MBIP and WDR5 (PubMed:19103755). Interacts with PML (By similarity). Interacts with CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3 (PubMed:14767476). Interacts with RELA (By similarity). Interacts with NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768). Interacts with PLK4 (PubMed:27796307). Associates with the 2-oxoglutarate dehydrogenase complex (PubMed:29211711). Interacts with XPC; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:29973595, PubMed:31527837). Interacts with ERCC3/XPB; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (PubMed:30894545).SUBUNIT (Microbial infection) Interacts with and acetylates HIV-1 Tat.TISSUE SPECIFICITY Expressed in all tissues tested, with most abundant expression in ovary.DOMAIN Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-645 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.SIMILARITY Belongs to the acetyltransferase family. GCN5 subfamily.CAUTION According to a report, has weak protein acyltransferase activity compared to protein acetyltransferase activity (PubMed:27377381). These conclusions are however not supported by subsequent studies (PubMed:29211711, PubMed:31542297).UniProtQ928301EQUAL837EQUALReactome Database ID Release 753006516Database 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=3006516ReactomeR-HSA-30065161Reactome 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-3006516.1Reactome Database ID Release 75350078Database 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=350078ReactomeR-HSA-3500781Reactome 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-350078.1GENE ONTOLOGYGO:0016407Reactome Database ID Release 75109690Database 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=109690Reactome Database ID Release 7573736Database 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=73736ReactomeR-HSA-737362Reactome 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-73736.211250901Pubmed2001Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription.Muth, VNadaud, SGrummt, IVoit, RenateEMBO J 20:1353-62LEFT-TO-RIGHTRecruitment of Acetylated SL1 to phosUBF-1:rDNA PromoterHuman SL1 does not bind to DNA itself, rather it is recruited to the rDNA promoter through a physical interaction with UBF-1. Phosphorylation of UBF-1 within the carboxy-terminal region is required for SL1 binding. SL1 consists of TATA-binding protein (TBP) and three associated factors (TAFIs). SL1 has no sequence-specific DNA binding activity its recruitment to the promoter being mediated by specific interactions with UBF. Once bound the SL1 complex makes direct contact with the DNA promoter and guides promoter-specific initiation. <p>Studies to identify the mechanistic relationship between SL1 and UBF-1 have indicated that the interaction between UBF-1 and SL1 is regulated by tumor suppressor proteins such as Rb and P53, although it has also been proposed that Rb prevents UBF-1 from binding to DNA itself.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00Acetylayed SL1:PhosUBF-1:rDNA promoterReactome DB_ID: 7369411Reactome Database ID Release 7573694Database 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=73694ReactomeR-HSA-736941Reactome 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-73694.1Reactome Database ID Release 7573739Database 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=73739ReactomeR-HSA-737393Reactome 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-73739.310082553Pubmed1999Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA promoter is mediated by the carboxy-terminal activation domain of upstream binding factor (UBF) and is regulated by UBF phosphorylation.Tuan, JCZhai, WComai, LMol Cell Biol 19:2872-910913176Pubmed2000Repression of RNA polymerase I transcription by the tumor suppressor p53.Zhai, WComai, LMol Cell Biol 20:5930-87491500Pubmed1996Coactivator and promoter-selective properties of RNA polymerase I TAFs.Beckmann, HChen, JLO'Brien, TTjian, RScience 270:1506-911042686Pubmed2000Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1.Hannan, KMHannan, RDSmith, SDJefferson, LSLun, MRothblum, LIOncogene 19:4988-9911486020Pubmed2001Overlapping functions of the pRb family in the regulation of rRNA synthesis.Ciarmatori, SScott, PHSutcliffe, JEMcLees, AAlzuherri, HMDannenberg, JHte Riele, HGrummt, IVoit, RenateWhite, RJMol Cell Biol 21:5806-14ACTIVATIONKnockdown of CSB reduces recruitment of SL1 and RNA Polymerase I to active rRNA genes.Reactome Database ID Release 75427325Database 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=427325ReactomeR-HSA-4273251Reactome 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-427325.1TTF-I:Sal Box:CSB:G9a:NuRDReactome DB_ID: 427352CSB dimerERCC6 dimerReactome DB_ID: 5365864ERCC6CSB proteinExcision repair protein ERCC-6 (Cockayne syndrome protein CSB)DNA excision repair protein ERCC-6Cockayne syndrome protein CSBReactome DB_ID: 54429UniProt:Q03468 ERCC6ERCC6CSBFUNCTION Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:20541997, PubMed:26620705). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (PubMed:15548521). It is required for transcription-coupled repair complex formation (PubMed:16916636). It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the sites of RNA polymerase II-blocking lesions (PubMed:16916636). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function. Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740).SUBUNIT Homodimer (PubMed:16128801, PubMed:15548521). Binds DNA (PubMed:15548521). Interacts with ERCC8 (PubMed:16751180). Interacts with RNA polymerase II; interaction is enhanced by UV irradiation (PubMed:26620705). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (PubMed:16603771). Interacts with KIAA1530/UVSSA (PubMed:22466612). Interacts with ELOA and CUL5; the interaction is induced by DNA damaging agents or by inhibitors of RNA polymerase II elongation (PubMed:28292928). Interacts (via WHD region) with RIF1 (PubMed:29203878). Interacts with SMARCC2/BAF170, SMARCB1/BAF47 and the neuron-specific chromatin remodeling complex (nBAF complex)(PubMed:24874740). Interacts with CAND1, CSTF1, DDX3X, DDX5, DDX17, DDX23, DHX36, HDAC1, HNRNPU, MTA2, PRPF3, PSMD3, RBBP4, SFPQ, SMARCA1, SMARCA2, TOP1, USP7, XRCC5, COPS3, COPS4, COPS6, DDX1, DDX41, GATAD2A, GATAD2B, PRPF4, PSMC5, SF3B2, CTR9, NONO, PSMD12 and TOP2A (PubMed:26030138).DOMAIN A C-terminal ubiquitin-binding domain (UBD) is essential for transcription-coupled nucleotide excision repair activity, interaction with RNA polymerase II, association with chromatin after UV irradiation and for mediating the UV-induced translocation of ERRC8 to the nuclear matrix.DOMAIN The N-terminal domain exerts an inhibitory effect on the helicase ATP-binding domain in such a manner that its ATPase activity is restricted (PubMed:29203878). Phosphorylation at Ser-10 and Ser-158 promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (PubMed:29203878).PTM Phosphorylated in a cell cycle-dependent manner at Ser-158 by cyclin A-CDK2 and at Ser-10 by ATM in response to DNA damage (PubMed:29203878). Phosphorylation at these two sites promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (PubMed:29203878). Phosphorylation is essential for its chromatin remodeling activity (PubMed:29203878).PTM Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner. Stabilized following interaction with KIAA1530/UVSSA, which promotes recruitment of deubiquitinating enzyme USP7, leading to deubiquitination of ERCC6 thereby preventing UV-induced degradation of ERCC6 by the proteasome.PTM Sumoylation at Lys-205 in an UV-radiation-dependent manner is essential for its transcription-coupled nucleotide excision repair activity.SIMILARITY Belongs to the SNF2/RAD54 helicase family.UniProtQ034681EQUAL1493EQUALReactome Database ID Release 7554429Database 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=54429ReactomeR-HSA-544291Reactome 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-54429.12Reactome Database ID Release 755365864Database 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=5365864ReactomeR-HSA-53658641Reactome 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-5365864.11G9aEHMT2Histone Methyltransferase G9aHistone-lysine N-methyltransferase, H3 lysine-9 specific 3KMT1CReactome DB_ID: 212151UniProt:Q96KQ7 EHMT2EHMT2BAT8C6orf30G9AKMT1CNG36FUNCTION Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.SUBUNIT Heterodimer; heterodimerizes with EHMT1/GLP. Interacts with GFI1B and WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with UHRF1. Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. Interacts with PRDM9 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA (By similarity).TISSUE SPECIFICITY Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.DOMAIN The SET domain mediates interaction with WIZ.DOMAIN The ANK repeats bind H3K9me1 and H3K9me2.DOMAIN In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.PTM Methylated at Lys-185; automethylated.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.CAUTION While NG36 and G9a were originally thought to derive from 2 separate genes, all G9A transcripts also contain the in frame coding sequence of NG36.CAUTION It is uncertain whether Met-1 or Met-21 is the initiator methionine.UniProtQ96KQ71EQUAL1210EQUALReactome Database ID Release 75212151Database 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=212151ReactomeR-HSA-2121511Reactome 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-212151.11NuRD complexReactome DB_ID: 4657018Converted from EntitySet in Reactome(GATAD2A, GATAD2B)Reactome DB_ID: 4657014GATAD2ATranscriptional repressor p66-alphaP66A_HUMANReactome DB_ID: 3702077UniProt:Q86YP4 GATAD2AGATAD2AFUNCTION Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B.SUBUNIT Interacts with MBD2 and MBD3 (PubMed:12183469, PubMed:16415179, PubMed:21490301). Interaction with MBD2 is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin (PubMed:12183469, PubMed:16415179, PubMed:21490301). Component of the MeCP1 histone deacetylase complex (PubMed:21490301). Interacts with histone tails, including that of histones H2A, H2B, H3 and H4 (PubMed:16415179). This interaction is reduced by histone acetylation (PubMed:16415179). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Ubiquitous, both in fetal and adult tissues.DOMAIN Both CR1 and CR2 regions are required for speckled nuclear localization.UniProtQ86YP41EQUAL633EQUALReactome Database ID Release 753702077Database 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=3702077ReactomeR-HSA-37020771Reactome 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-3702077.1GATAD2BTranscriptional repressor p66-betaP66B_HUMANReactome DB_ID: 3702079UniProt:Q8WXI9 GATAD2BGATAD2BKIAA1150FUNCTION Transcriptional repressor. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2A. Targets MBD3 to discrete loci in the nucleus. May play a role in synapse development.SUBUNIT Interacts with MBD2 and MBD3 (PubMed:11756549, PubMed:12183469, PubMed:16415179). Interaction with MBD2 is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin (PubMed:11756549, PubMed:12183469, PubMed:16415179). Component of the MeCP1 histone deacetylase complex (PubMed:11756549). Interacts with histone tails, including that of histones H2A, H2B, H3 and H4 (PubMed:16415179). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Widely expressed.DOMAIN Both CR1 and CR2 regions are required for speckled nuclear localization.UniProtQ8WXI91EQUAL593EQUALReactome Database ID Release 753702079Database 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=3702079ReactomeR-HSA-37020791Reactome 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-3702079.1Reactome Database ID Release 754657014Database 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=4657014ReactomeR-HSA-46570141Reactome 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-4657014.11RBBP4RbAp48CAF1CReactome DB_ID: 212223UniProt:Q09028 RBBP4RBBP4RBAP48FUNCTION Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.SUBUNIT Interacts with SUV39H1 and HDAC7 (By similarity). Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin. Subunit of the chromatin assembly factor 1 (CAF-1) complex, which is composed of RBBP4, CHAF1B and CHAF1A. Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex. The core HDAC complex may also associate with MTA2, MBD3, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylase complex (the NuRD complex). The NuRD complex may also interact with MBD3L1 and MBD3L2. Interacts with MTA1. Subunit of the PRC2/EED-EZH2 complex, which is composed of at least EED, EZH2, RBBP4, RBBP7 and SUZ12. The PRC2/EED-EZH2 complex may also associate with HDAC1. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. Part of the nucleosome remodeling factor (NURF) complex which consists of SMARCA1; BPTF; RBBP4 and RBBP7. Interacts with the viral protein-binding domain of the retinoblastoma protein (RB1). Interacts with SPEN/MINT. Interacts with BRCA1. Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with PHF6 (By similarity). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (By similarity). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.UniProtQ090282EQUAL425EQUALReactome Database ID Release 75212223Database 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=212223ReactomeR-HSA-2122231Reactome 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-212223.11Converted from EntitySet in ReactomeMi-2Reactome DB_ID: 4657021CHD4Chromodomain-helicase-DNA-binding protein 4CHD4_HUMANReactome DB_ID: 3702078UniProt:Q14839 CHD4CHD4FUNCTION Component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin by deacetylating histones.SUBUNIT Interacts with KLF1; the interaction depends on sumoylation of KLF1, and leads to its transcriptional repression (By similarity). Interacts directly with IKFZ1 in the NuRD complex. Central component of the nucleosome remodeling and histone deacetylase (NuRD) repressor complex (PubMed:9804427, PubMed:10204490, PubMed:15454082). Part of a complex containing ATR and HDAC2 (PubMed:10545197). Interacts with TRIM27 (PubMed:14530259). Interacts with ZGPAT; the interaction is direct (PubMed:19644445). Interacts with BCL6 (PubMed:15454082). Interacts with BRD4 (PubMed:21555454). Interacts with PCNT (PubMed:17626165). Interacts with SETX (PubMed:23149945). Interacts with HDAC1 (PubMed:27616479).MISCELLANEOUS One of the main antigens reacting with anti-MI-2 positive sera of dermatomyositis.SIMILARITY Belongs to the SNF2/RAD54 helicase family.UniProtQ148391EQUAL1912EQUALReactome Database ID Release 753702078Database 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=3702078ReactomeR-HSA-37020781Reactome 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-3702078.1CHD3Chromodomain-helicase-DNA-binding protein 3CHD3_HUMANReactome DB_ID: 4657012UniProt:Q12873 CHD3CHD3FUNCTION Component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin by deacetylating histones (PubMed:9804427, PubMed:30397230). Involved in transcriptional repressiobn as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165).SUBUNIT Central component of the nucleosome remodeling and histone deacetylase (NuRD) repressive complex (PubMed:9804427, PubMed:27068747). Interacts with TRIM28 (PubMed:11230151). Interacts with SERBP1 (PubMed:12505151). Interacts (via its C-terminal) with HABP4 (PubMed:12505151). Interacts with PCNT; the interaction regulates centrosome integrity (PubMed:17626165). Interacts with ZBED1/hDREF (PubMed:27068747).TISSUE SPECIFICITY Widely expressed.PTM Sumoylation at Lys-1971 results in dissociation from chromatin and suppression of transcriptional repression.MISCELLANEOUS One of the main antigens reacting with anti-MI-2 positive sera of dermatomyositis.SIMILARITY Belongs to the SNF2/RAD54 helicase family.UniProtQ128731EQUAL2000EQUALReactome Database ID Release 754657012Database 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=4657012ReactomeR-HSA-46570121Reactome 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-4657012.1Reactome Database ID Release 754657021Database 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=4657021ReactomeR-HSA-46570211Reactome 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-4657021.11Converted from EntitySet in ReactomeMTA1, MTA2, MTA3Reactome DB_ID: 4657019MTA1Metastasis-associated protein MTA1MTA1_HUMANReactome DB_ID: 3465550UniProt:Q13330 MTA1MTA1FUNCTION Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. As a part of the histone-deacetylase multiprotein complex (NuRD), regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA. In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3, PAX5 and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Regulates p53-dependent and -independent DNA repair processes following genotoxic stress. Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair. Plays an important role in tumorigenesis, tumor invasion, and metastasis. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles. Positively regulates the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. Isoform Short binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity).SUBUNIT Component of the nucleosome-remodeling and histone-deacetylase multiprotein complex (NuRD). Interacts with HDAC1 and ITGB3BP/CENPR. Binds to CSNK1G2 in the cytoplasm. Interacts with NACC2. Interacts with ARNTL/BMAL1 and CLOCK. Interacts with EP300, TFAP2C, IFI16, TPR, HDAC2, UBE2I/UBC9, PIAS1, PIAS3, PIAS4, p53/TP53, MDM2, COP1, SUMO1, SUMO2, SENP1 and SENP2. Interacts with SIX3; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter (By similarity). Interacts with TFCP2L1; which is indispensable for TFCP2L1-mediated self-renewal-promoting effect and endoderm-inhibiting action (By similarity).TISSUE SPECIFICITY Widely expressed. High expression in brain, liver, kidney, and cardiac muscle, ovaries, adrenal glands and virgin mammary glands. Higher in tumors than in adjacent normal tissue from the same individual. Up-regulated in a wide variety of cancers including breast, liver, ovarian, and colorectal cancer and its expression levels are closely correlated with tumor aggressiveness and metastasis.DEVELOPMENTAL STAGE Highly expressed in metastatic cells.DOMAIN Isoform Short contains a Leu-Arg-Ile-Leu-Leu motif (ER binding motif).PTM Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER).PTM Acetylation is essential for its transcriptional coactivator activity.PTM Sumoylation positively regulates its transcriptional corepressor activity but does not affect the protein stability. Sumoylated preferentially by SUMO2 or SUMO3 than SUMO1. Sumoylation is enhanced by PIAS1/3/4 and preferentially sumoylated by SUMO2 in the presence of PIAS1/3/4. Desumoylated by SENP1.PTM Ubiquitinated by COP1, which leads to proteasomal degradation.UniProtQ133301EQUAL715EQUALReactome Database ID Release 753465550Database 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=3465550ReactomeR-HSA-34655501Reactome 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-3465550.1MTA2Metastasis-associated protein MTA2MTA2_HUMANReactome DB_ID: 4657009UniProt:O94776 MTA2MTA2MTA1L1PIDFUNCTION May be involved in the regulation of gene expression as repressor and activator. The repression might be related to covalent modification of histone proteins.SUBUNIT Component of the nucleosome-remodeling and histone-deacetylase multiprotein complex (NuRD) (By similarity). Interacts with HDAC7 and MBD3 (By similarity). Interacts with p53/TP53 (PubMed:11099047). Interacts with MINT (PubMed:11331609). Interacts with PIMREG (PubMed:18757745). Interacts with NACC2 (PubMed:22926524). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Widely expressed.UniProtO947761EQUAL668EQUALReactome Database ID Release 754657009Database 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=4657009ReactomeR-HSA-46570091Reactome 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-4657009.1MTA3Metastasis-associated protein MTA3MTA3_HUMANReactome DB_ID: 4657013UniProt:Q9BTC8 MTA3MTA3KIAA1266FUNCTION Plays a role in maintenance of the normal epithelial architecture through the repression of SNAI1 transcription in a histone deacetylase-dependent manner, and thus the regulation of E-cadherin levels. Contributes to transcriptional repression by BCL6.SUBUNIT Component of the nucleosome-remodeling and histone-deacetylase multiprotein complex (NuRD). Interacts with BCL6. Interacts with NACC2.TISSUE SPECIFICITY Expressed in germinal centers of lymphoid tissues. No expression in nonepithelial cells.INDUCTION By estrogen.UniProtQ9BTC81EQUAL594EQUALReactome Database ID Release 754657013Database 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=4657013ReactomeR-HSA-46570131Reactome 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-4657013.1Reactome Database ID Release 754657019Database 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=4657019ReactomeR-HSA-46570191Reactome 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-4657019.11HDAC1:HDAC2Reactome DB_ID: 4657004HDAC2HDA2_HUMANHistone deacetylase 2Reactome DB_ID: 205135UniProt:Q92769 HDAC2HDAC2FUNCTION Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.SUBUNIT Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex associates with MTA2, MBD3, MTA1L1, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylation (NuRD) complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B. Interacts with SNW1, HDAC7, PRDM6, SAP30, SETDB1 and SUV39H1. Interacts with the MACROH2A1 (via the non-histone region). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX. Part of a complex containing ATR and CHD4. Forms a heterologous complex at least with YY1. Interacts with ATR, CBFA2T3, DNMT1, MINT, HDAC10, HCFC1, NRIP1, KDM4A and PELP1. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts with CHFR and SAP30L. Interacts (CK2 phosphorylated form) with SP3. Interacts with TSHZ3 (via its N-terminus). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with PIMREG. Interacts with BCL6 (non-acetylated form). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. Interacts with CRY1, INSM1 and ZNF431. Interacts with NACC2. Interacts with MTA1, with a preference for sumoylated MTA1. Interacts with SIX3 (By similarity). Interacts with BEND3. Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (PubMed:21573134). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC1 (PubMed:19433865). Interacts with SPHK2 (PubMed:19729656).TISSUE SPECIFICITY Widely expressed; lower levels in brain and lung.PTM S-nitrosylated by GAPDH. In neurons, S-Nitrosylation at Cys-262 and Cys-274 does not affect the enzyme activity but abolishes chromatin-binding, leading to increases acetylation of histones and activate genes that are associated with neuronal development. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily.UniProtQ927691EQUAL488EQUALReactome Database ID Release 75205135Database 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=205135ReactomeR-HSA-2051351Reactome 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-205135.11HDAC1HDA1_HUMANHistone deacetylase 1Reactome DB_ID: 205021UniProt:Q13547 HDAC1HDAC1RPD3L1FUNCTION Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.SUBUNIT Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex associates with MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylation (NuRD) complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2. Found in a trimeric complex with APBB1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3. Component of a RCOR/GFI/KDM1A/HDAC complex. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A. Associates with the 9-1-1 complex; interacts with HUS1. Found in a complex with DNMT3A and HDAC7. Interacts with the non-histone region of MACROH2A1. Interacts with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits its acetylation. Interacts with SP1; the interaction deacetylates SP1 and regulates its transcriptional activity. Interacts with SP3; the interaction deacetylates SP3 and regulates its transcriptional activity. In vitro, C(18) ceramides increase this interaction and the subsequent SP3 deacetylation and SP3-mediated repression of the TERT promoter. Interacts with TSHZ3 (via N-terminus); the interaction is direct. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with C10orf90/FATS (via its N-terminal); the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21. Interacts with CDKN1A/p21. Interacts with CDK5 complexed to CDK5R1 (p25). Interacts directly with GFI1 and GFI1B. Interacts with NR1D2 (via C-terminus). Interacts with TSC22D3 isoform 1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity. Interacts with BAZ2A/TIP5, BANP, BCL6, BCOR, BHLHE40/DEC1, BRMS1, BRMS1L, CBFA2T3, CHFR, CIART, CRY1, DAXX, DDIT3/CHOP, DDX5, DNMT1, E4F1, EP300, HCFC1, HDAC9, INSM1, NFE4, NR4A2/NURR1, MIER1, KDM4A, KDM5B, KLF1, MINT, NRIP1, PCAF, PHB2, PRDM6, PRDM16, RB1, RERE, SAMSN1, SAP30L, SETDB1, SMAD3, SMARCA4/BRG1, SMYD2, SUV39H1, TGIF, TGIF2, TRAF6, UHRF1, UHRF2, ZMYND15, ZNF431 and ZNF541. Interacts with KDM5A (By similarity). Interacts with DNTTIP1 (PubMed:25653165). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (PubMed:25653165). Interacts with CCAR2 (PubMed:21030595). Interacts with PPHLN1 (PubMed:17963697). Found in a complex with YY1, SIN3A and GON4L (By similarity). Interacts with CHD4 (PubMed:27616479). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with SIN3A (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with ZBTB7A (PubMed:25514493). Interacts with SMAD4; positively regulated by ZBTB7A (PubMed:25514493). Interacts with PACS2 (PubMed:29656858). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC2 (PubMed:19433865). Interacts with ZNF638 (PubMed:30487602). Interacts with SPHK2 (PubMed:19729656). Interacts with ERCC6 (PubMed:26030138).TISSUE SPECIFICITY Ubiquitous, with higher levels in heart, pancreas and testis, and lower levels in kidney and brain.PTM Sumoylated on Lys-444 and Lys-476; which promotes enzymatic activity. Desumoylated by SENP1.PTM Phosphorylation on Ser-421 and Ser-423 promotes enzymatic activity and interactions with NuRD and SIN3 complexes. Phosphorylated by CDK5.PTM Ubiquitinated by CHFR, leading to its degradation by the proteasome. Ubiquitinated by KCTD11, leading to proteasomal degradation.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily.UniProtQ135471EQUAL482EQUALReactome Database ID Release 75205021Database 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=205021ReactomeR-HSA-2050211Reactome 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-205021.11Reactome Database ID Release 754657004Database 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=4657004ReactomeR-HSA-46570041Reactome 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-4657004.11RBBP7RbAp46Reactome DB_ID: 212227UniProt:Q16576 RBBP7RBBP7RBAP46FUNCTION Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.SUBUNIT Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin (PubMed:18571423). Subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1. Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex. The core HDAC complex may also associate with MTA2, MBD3, CHD3 and CHD4 to form the nucleosome remodeling and histone deacetylase complex (the NuRD complex). The NuRD complex may also interact with MBD3L1 and MBD3L2. Interacts with MTA1. Subunit of the PRC2/EED-EZH2 complex, which is composed of at least EED, EZH2, RBBP4, RBBP7 and SUZ12 (PubMed:12435631). The PRC2/EED-EZH2 complex may also associate with HDAC1. Part of the nucleosome remodeling factor (NURF) complex which consists of SMARCA1; BPTF; RBBP4 and RBBP7. Interacts with the viral protein-binding domain of the retinoblastoma protein (RB1) (PubMed:7503932, PubMed:10220405). Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP. Interacts with BRCA1, HDAC7 and SUV39H1. Interacts with CENPA (PubMed:25556658).SIMILARITY Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.UniProtQ165762EQUAL425EQUALReactome Database ID Release 75212227Database 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=212227ReactomeR-HSA-2122271Reactome 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-212227.11MBD3Methyl-CpG-binding domain protein 3MBD3_HUMANReactome DB_ID: 4657010UniProt:O95983 MBD3MBD3FUNCTION Acts as transcriptional repressor and plays a role in gene silencing. Does not bind to DNA by itself (PubMed:12124384). Binds to DNA with a preference for sites containing methylated CpG dinucleotides (in vitro). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (PubMed:24307175). Recruits histone deacetylases and DNA methyltransferases.SUBUNIT Heterodimer with MBD2. Part of the NuRD and the MeCP1 complex. Interacts with BCL6, HDAC1, MTA2, DNMT1, p66-alpha and p66-beta.UniProtO959831EQUAL291EQUALReactome Database ID Release 754657010Database 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=4657010ReactomeR-HSA-46570101Reactome 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-4657010.11Reactome Database ID Release 754657018Database 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=4657018ReactomeR-HSA-46570182Reactome 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-4657018.2ComplexPortalCPX-880ComplexPortalCPX-9221TTF-I:Sal BoxReactome DB_ID: 74977Sal BoxReactome DB_ID: 74975NCBI Nucleotide:U13369 45S pre-rRNA geneHuman ribosomal DNA45S pre-rRNA geneNCBI NucleotideU13369Reactome Database ID Release 7574975Database 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=74975ReactomeR-HSA-749751Reactome 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-74975.11TTF1TTF-1Reactome DB_ID: 74974UniProt:Q15361 TTF1TTF1FUNCTION Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity.SUBUNIT Oligomer. The oligomeric structure enables to interact simultaneously with two separate DNA fragments. Interacts with BAZ2A/TIP5. Interacts with CAVIN1.DOMAIN The N-terminal region (NRD) inhibits DNA-binding via its interaction with the C-terminal region.UniProtQ153611EQUAL905EQUALReactome Database ID Release 7574974Database 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=74974ReactomeR-HSA-749741Reactome 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-74974.11Reactome Database ID Release 7574977Database 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=74977ReactomeR-HSA-749771Reactome 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-74977.11Reactome Database ID Release 75427352Database 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=427352ReactomeR-HSA-4273521Reactome 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-427352.1LEFT-TO-RIGHTAssembly of RNA Polymerase I Holoenzyme (human)At the beginning of this reaction, 1 molecule of each of POLR1A (RPA190, A194), POLR1B (RPA135), POLR1C (RPA40), POLR1D (RPA19), POLR1E (PAF53, RPA49), POLR2E (RPB5), POLR2F (RPB6), POLR2H (RPB8), POLR2K (RPABC4, RPB12), POLR2L (RPB10), TWISTNB (RPA43), CD3EAP (CAST, PAF49), and ZNRD1 (RPA12) are present. At the end of this reaction, 1 molecule of 'RNA Polymerase I Holoenzyme (Human)' is present.<br> This reaction takes place in the 'nucleolus'.<br>RPB6POLR2FHsRPABC2DNA-directed RNA polymerase II 14.4 kDa polypeptide (EC 2.7.7.6) (RPB6) (RPB14.4)DNA-directed RNA polymerase II 14.4 kDa polypeptide RPB14.4RPABC2Reactome DB_ID: 83714UniProt:P61218 POLR2FPOLR2FPOLRFFUNCTION DNA-dependent RNA polymerases catalyze the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II, and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2F/RPB6 is part of the clamp element and together with parts of RPB1 and RPB2 forms a pocket to which the RPB4-RPB7 subcomplex binds (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoK/eukaryotic RPB6 RNA polymerase subunit family.UniProtP612182EQUAL127EQUALReactome Database ID Release 7583714Database 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=83714ReactomeR-HSA-837141Reactome 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-83714.1ZNRD1DNA-directed RNA polymerase I subunit RPA12RPA12_HUMANReactome DB_ID: 5419292UniProt:Q9P1U0 POLR1HPOLR1HRPA12ZNRD1FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors.SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits.SIMILARITY Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.UniProtQ9P1U01EQUAL126EQUALReactome Database ID Release 755419292Database 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=5419292ReactomeR-HSA-54192921Reactome 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-5419292.1CD3EAPDNA-directed RNA polymerase I subunit RPA34RPA34_HUMANReactome DB_ID: 5419289UniProt:O15446 POLR1GPOLR1GASE1CASTCD3EAPPAF49FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors. Isoform 1 is involved in UBTF-activated transcription, presumably at a step following PIC formation.FUNCTION Isoform 2 has been described as a component of preformed T-cell receptor (TCR) complex.SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits. Interacts with TAF1A thereby associates with the SL1 complex. Interacts with UBTF. Interacts with POLR1E/PRAF1 through its N-terminal region (By similarity). Isoform 2 interacts with CD3E.PTM Isoform 2 undergoes tyrosine phosphorylation upon T-cell receptor (TCR) stimulation. This phosphorylation has not been confirmed by other groups.PTM Isoform 1 is phosphorylated on tyrosine residues in initiation-competent Pol I-beta complexes but not in Pol I-alpha complexes.MISCELLANEOUS It is in an antisense orientation to and overlaps the gene of the DNA repair enzyme ERCC1. This gene overlap is conserved in mouse, suggesting an important biological function.SIMILARITY Belongs to the eukaryotic RPA34 RNA polymerase subunit family.CAUTION It is not known whether the so-called human ASE1 and human CAST proteins represent two sides of a single gene product with sharply different functional characteristics. Experiments done with the mouse homolog protein are in favor of an implication of this gene in rRNA transcription instead of T-cell receptor signaling.UniProtO154461EQUAL510EQUALReactome Database ID Release 755419289Database 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=5419289ReactomeR-HSA-54192891Reactome 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-5419289.1RPB8POLR2HDNA-directed RNA polymerases I, II, and III 17.1 kDa polypeptide RPB17RPABC3Reactome DB_ID: 63523UniProt:P52434 POLR2HPOLR2HFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively.SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively. Directly interacts with POLR2A.SIMILARITY Belongs to the eukaryotic RPB8 RNA polymerase subunit family.UniProtP524342EQUAL150EQUALReactome Database ID Release 7563523Database 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=63523ReactomeR-HSA-635231Reactome 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-63523.1POLR1ADNA-directed RNA polymerase I largest subunit RNA polymerase I 194 kDa subunitRPA194Reactome DB_ID: 63494UniProt:O95602 POLR1APOLR1AFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase I which synthesizes ribosomal RNA precursors. Forms the polymerase active center together with the second largest subunit. A single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol I. A bridging helix emanates from RPA1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol I by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (PubMed:16809778). Interacts with MYO1C (By similarity). Interacts with ERBB2 (PubMed:21555369). Interacts with DDX11 (PubMed:26089203).SIMILARITY Belongs to the RNA polymerase beta' chain family.UniProtO956021EQUAL1720EQUALReactome Database ID Release 7563494Database 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=63494ReactomeR-HSA-634941Reactome 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-63494.1RPA40POLR1CHsRPAC1DNA-directed RNA polymerases I and III subunit RPAC1DNA-directed RNA polymerase I and III 40 kDa polypeptide RPA39Reactome DB_ID: 63498UniProt:O15160 POLR1CPOLR1CPOLR1EFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I and III which synthesize ribosomal RNA precursors and small RNAs, such as 5S rRNA and tRNAs, respectively. RPAC1 is part of the Pol core element with the central large cleft and probably a clamp element that moves to open and close the cleft (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I) and RNA polymerase III (Pol III) complexes consisting of at least 13 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoD/eukaryotic RPB3 RNA polymerase subunit family.UniProtO151602EQUAL346EQUALReactome Database ID Release 7563498Database 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=63498ReactomeR-HSA-634981Reactome 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-63498.1POLR1EDNA-directed RNA polymerase I subunit RPA49RPA49_HUMANReactome DB_ID: 5419294UniProt:Q9GZS1 POLR1EPOLR1EPAF53PRAF1FUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors (PubMed:24207024). Appears to be involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBTF/UBF (PubMed:24207024).SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (PubMed:16809778, PubMed:29065309). Interacts with POLR1G (By similarity). Also binds UBTF/UBF (By similarity). Interacts with PWP1 (PubMed:29065309).PTM Acetylated at Lys-373 by CREBBP/CBP, leading to decreased RNA polymerase I transcription (PubMed:24207024). In normal conditions, deacetylated by SIRT7, promoting the association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). In response to stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased association of RNA polymerase I with the rDNA promoter region (PubMed:24207024).SIMILARITY Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.UniProtQ9GZS11EQUAL481EQUALReactome Database ID Release 755419294Database 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=5419294ReactomeR-HSA-54192941Reactome 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-5419294.1AC19POLR1DHsRPAC2DNA-directed RNA polymerases I and III subunit RPAC2RPA16DNA-directed RNA polymerase I and III 16 kDa polypeptide Reactome DB_ID: 63500UniProt:P0DPB5 POLR1DPOLR1DCAUTION POLR1D isoform 2 lacks an RNA polymerase domain and therefore cannot have DNA-dependent RNA polymerase function.UniProtP0DPB51EQUAL133EQUALReactome Database ID Release 7563500Database 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=63500ReactomeR-HSA-635002Reactome 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-63500.2XAP4POLR2EHsRPABC1DNA-directed RNA polymerase II 23 kDa polypeptide (EC 2.7.7.6) (RPB25) (XAP4) (RPB5)DNA-directed RNA polymerase II 23 kDa polypeptide RPB25RPB5RPABC1Reactome DB_ID: 83713UniProt:P19388 POLR2EPOLR2EFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively (By similarity). In RNA Pol II, this subunit is present in 2-fold molar excess over the other subunits. Interacts with URI1.SUBUNIT (Microbial infection) Interacts with HBV protein X.SIMILARITY Belongs to the archaeal RpoH/eukaryotic RPB5 RNA polymerase subunit family.UniProtP193881EQUAL210EQUALReactome Database ID Release 7583713Database 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=83713ReactomeR-HSA-837131Reactome 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-83713.1POLR2KDNA-directed RNA polymerases I, II, and III 7.0 kDa polypeptide ABC10-alphaRPB7.0RPB10alphaRPABC4Reactome DB_ID: 63537UniProt:P53803 POLR2KPOLR2KFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively.SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoP/eukaryotic RPC10 RNA polymerase subunit family.UniProtP538031EQUAL58EQUALReactome Database ID Release 7563537Database 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=63537ReactomeR-HSA-635371Reactome 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-63537.1TWISTNBDNA-directed RNA polymerase I subunit RPA43RPA43_HUMANReactome DB_ID: 5419290UniProt:Q3B726 POLR1FPOLR1FTWISTNBFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors. Through its association with RRN3/TIF-IA may be involved in recruitment of Pol I to rDNA promoters.SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (By similarity). Interacts with RRN3/TIF-IA.TISSUE SPECIFICITY Widely expressed. Expressed in all fetal and adult tissues tested, with highest expression in fetal lung, liver, and kidney, and low expression in all adult tissues.SIMILARITY Belongs to the eukaryotic RPA43 RNA polymerase subunit family.UniProtQ3B7261EQUAL338EQUALReactome Database ID Release 755419290Database 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=5419290ReactomeR-HSA-54192901Reactome 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-5419290.1POLR1BDNA-directed RNA polymerase I 135 kDa polypeptide RNA polymerase I subunit 2RPA135Reactome DB_ID: 63496UniProt:Q9H9Y6 POLR1BPOLR1BFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest core component of RNA polymerase I which synthesizes ribosomal RNA precursors. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol I is composed of mobile elements and RPA2 is part of the core element with the central large cleft and probably a clamp element that moves to open and close the cleft (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits.SIMILARITY Belongs to the RNA polymerase beta chain family.UniProtQ9H9Y61EQUAL1135EQUALReactome Database ID Release 7563496Database 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=63496ReactomeR-HSA-634961Reactome 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-63496.1RPB10POLR2LHsRPABC5DNA-directed RNA polymerase II 7.6 kDa polypeptide (EC 2.7.7.6) (RPB10) (RPB7.6)DNA-directed RNA polymerase II 7.6 kDa polypeptide RPB7.6RPABC5Reactome DB_ID: 83715UniProt:P62875 POLR2LPOLR2LFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2L/RBP10 is part of the core element with the central large cleft (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoN/eukaryotic RPB10 RNA polymerase subunit family.UniProtP628751EQUAL67EQUALReactome Database ID Release 7583715Database 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=83715ReactomeR-HSA-837151Reactome 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-83715.1RNA Polymerase I HoloenzymeReactome DB_ID: 738591111111111111Reactome Database ID Release 7573859Database 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=73859ReactomeR-HSA-738591Reactome 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-73859.1Reactome Database ID Release 7573865Database 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=73865ReactomeR-HSA-738652Reactome 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-73865.2LEFT-TO-RIGHTBinding of RRN3 to RNA Polymerase IAfter the assembly of the RNA Polymerase I Holoenzyme, Rrn3 binding occurs (Engel et al. 2016, Pilsl et al. 2016).Authored: Gillespie, ME, 2003-09-02 00:00:00Edited: Gillespie, ME, 0000-00-00 00:00:00RRN3Rrn3Reactome DB_ID: 73714UniProt:Q9NYV6 RRN3RRN3TIFIAFUNCTION Required for efficient transcription initiation by RNA polymerase I. Required for the formation of the competent preinitiation complex (PIC). Dissociates from pol I as a consequence of transcription. In vitro, cannot activate transcription in a subsequent transcription reaction (By similarity).SUBUNIT Interacts with POLR1F, EIF3L, TAF1B and TAF1C.PTM Phosphorylation is required for participation in rDNA transcription (By similarity). Phosphorylated at Thr-200 by MAPK9/JNK2, which abrogates initiation complex formation.SIMILARITY Belongs to the RRN3 family.UniProtQ9NYV61EQUAL651EQUALReactome Database ID Release 7573714Database 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=73714ReactomeR-HSA-737141Reactome 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-73714.1Active RNA Polymerase IReactome DB_ID: 7371511Reactome Database ID Release 7573715Database 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=73715ReactomeR-HSA-737151Reactome 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-73715.1Reactome Database ID Release 7573757Database 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=73757ReactomeR-HSA-737573Reactome 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-73757.327418309Pubmed2016RNA polymerase I-Rrn3 complex at 4.8 Å resolutionEngel, ChristophPlitzko, JürgenCramer, PNat Commun 7:1212927418187Pubmed2016Structure of the initiation-competent RNA polymerase I and its implication for transcriptionPilsl, MichaelCrucifix, CorinnePapai, GaborKrupp, FerdinandSteinbauer, RobertGriesenbeck, JoachimMilkereit, PhilippTschochner, HerbertSchultz, PatrickNat Commun 7:12126LEFT-TO-RIGHTRecruitment of Active RNA Polymerase I to SL1:phos.UBF-1:rDNA PromoterComposed of Acetylated SL1, phosphorylated UBF-1 bound the rDNA promoter as well as the active RNA polymerase holoenzyme, rrn3 and TFIIH the transcription initiation complex is complete. The assembly picture is incomplete, as the point at which TFIIH joins the complex is unknown, though by the time that this complex is formed TFIIH is present (it has been included at this step for completeness). This forms the transcriptionally active enzyme, that is capable of initiating transcription from the rDNA promoter.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00TFIIHReactome DB_ID: 109634ERCC3XPB protein ERCC-3TFIIH basal transcription factor complex helicase XPB subunit (EC 3.6.1.-) (Basic transcription factor 2 89 kDa subunit) (BTF2-p89) (TFIIH 89 kDa subunit) (DNA-repair protein complementing XP-B cells) (Xeroderma pigmentosum group B complementing protein) (DNA excision repair protein ERCC-3)TFIIH basal transcription factor complex helicase XPB subunit Basic transcription factor 2 89 kDa subunitBTF2-p89TFIIH 89 kDa subunitDNA-repair protein complementing XP-B cellsXeroderma pigmentosum group B complementing proteinDNA excision repair protein ERCC-3Reactome DB_ID: 67439UniProt:P19447 ERCC3ERCC3XPBXPBCFUNCTION ATP-dependent 3'-5' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation (PubMed:8157004, PubMed:30894545). When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape (PubMed:8157004). The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription (PubMed:9852112). Interacts with PUF60 (PubMed:10882074, PubMed:11239393). Interacts with ATF7IP (PubMed:19106100). Interacts with KAT2A; leading to KAT2A recruitment to promoters and acetylation of histones (PubMed:30894545).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA2.SIMILARITY Belongs to the helicase family. RAD25/XPB subfamily.UniProtP194471EQUAL782EQUALReactome Database ID Release 7567439Database 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=67439ReactomeR-HSA-674391Reactome 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-67439.11GTF2H3BTF2-p34 (TFIIH component)TFIIH basal transcription factor complex p34 subunit (Basic transcription factor 2 34 kDa subunit) (BTF2-p34) (General transcription factor IIH polypeptide 3)TFIIH basal transcription factor complex p34 subunitBasic transcription factor 2 34 kDa subunitBTF2-p34General transcription factor IIH polypeptide 3Reactome DB_ID: 65916UniProt:Q13889 GTF2H3GTF2H3FUNCTION Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.SUBUNIT Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:27193682). Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription (PubMed:9852112). Interacts with RARA; the interaction requires prior phosphorylation of RARA on 'Ser-369' which then enhances interaction of RARA with CDK7 (By similarity).SIMILARITY Belongs to the TFB4 family.UniProtQ138891EQUAL308EQUALReactome Database ID Release 7565916Database 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=65916ReactomeR-HSA-659161Reactome 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-65916.11GTF2H1TFIIH basal transcription factor complex p62 subunitBasic transcription factor 62 kDa subunitBTF2-p62General transcription factor IIH polypeptide 1Reactome DB_ID: 65912UniProt:P32780 GTF2H1GTF2H1BTF2FUNCTION Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60.SIMILARITY Belongs to the TFB1 family.UniProtP327801EQUAL548EQUALReactome Database ID Release 7565912Database 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=65912ReactomeR-HSA-659121Reactome 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-65912.11CAKReactome DB_ID: 69221CAKCDK7Cdk7Cell division protein kinase 7 (EC 2.7.1.-) (CDK-activating kinase) (CAK)(TFIIH) (basal transcription factor complex kinase subunit) (39 kDa protein kinase) (P39 Mo15)(STK1)(CAK1)Cell division protein kinase 7 CDK-activating kinaseTFIIH basal transcription factor complex kinase subunit39 kDa protein kinaseP39 Mo15STK1CAK1Reactome DB_ID: 69218UniProt:P50613 CDK7CDK7CAKCAK1CDKN7MO15STK1FUNCTION Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.ACTIVITY REGULATION Inactivated by phosphorylation. Repressed by roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-387032). The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression. The inactivation by roscovitine promotes caspase-mediated apoptosis in leukemic cells.SUBUNIT Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI.TISSUE SPECIFICITY Ubiquitous.INDUCTION Repressed by DNA-bound peptides.PTM Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity. Phosphorylated at Ser-164 and Thr-170 by CDK2.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.UniProtP506131EQUAL346EQUALReactome Database ID Release 7569218Database 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=69218ReactomeR-HSA-692182Reactome 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-69218.21p36MNAT1MAT1CDK-activating kinase assembly factor MAT1 (RING finger protein MAT1) (Menage a trois) (CDK7/cyclin H assembly factor) (p36) (p35) (Cyclin G1 interacting protein)CDK-activating kinase assembly factor MAT1RING finger protein MAT1Menage a troisCDK7/cyclin H assembly factorp35Cyclin G1 interacting proteinReactome DB_ID: 59012UniProt:P51948 MNAT1MNAT1CAP35MAT1RNF66FUNCTION Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II.SUBUNIT Associates primarily with CDK7 and cyclin H to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.TISSUE SPECIFICITY Highest levels in colon and testis. Moderate levels are present thymus, prostate, ovary, and small intestine. The lowest levels are found in spleen and leukocytes.UniProtP519481EQUAL309EQUALReactome Database ID Release 7559012Database 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=59012ReactomeR-HSA-590121Reactome 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-59012.11p37CCNHCyclin HMO15-associated proteinp34Reactome DB_ID: 69220UniProt:P51946 CCNHCCNHFUNCTION Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle.SUBUNIT Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.SIMILARITY Belongs to the cyclin family. Cyclin C subfamily.UniProtP519461EQUAL323EQUALReactome Database ID Release 7569220Database 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=69220ReactomeR-HSA-692202Reactome 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-69220.21Reactome Database ID Release 7569221Database 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=69221ReactomeR-HSA-692211Reactome 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-69221.1ComplexPortalCPX-5781TTDAGTF2H5General transcription factor IIH subunit 5TFB5 orthologGeneral transcription factor IIH polypeptide 5TFIIH basal transcription factor complex TTD-A subunitReactome DB_ID: 5688446UniProt:Q6ZYL4 GTF2H5GTF2H5C6orf175TTDAFUNCTION Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription.SIMILARITY Belongs to the TFB5 family.UniProtQ6ZYL41EQUAL71EQUALReactome Database ID Release 755688446Database 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=5688446ReactomeR-HSA-56884461Reactome 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-5688446.11GTF2H4BTF2-p52 (TFIIH component)TFIIH basal transcription factor complex p52 subunit (Basic transcription factor 52 kDa subunit) (BTF2-p52) (General transcription factor IIH polypeptide 4)TFIIH basal transcription factor complex p52 subunitBasic transcription factor 52 kDa subunitBTF2-p52General transcription factor IIH polypeptide 4Reactome DB_ID: 65918UniProt:Q92759 GTF2H4GTF2H4FUNCTION Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription.SIMILARITY Belongs to the TFB2 family.UniProtQ927591EQUAL462EQUALReactome Database ID Release 7565918Database 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=65918ReactomeR-HSA-659181Reactome 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-65918.11GTF2H2BTF2-p44 (TFIIH component)TFIIH basal transcription factor complex p44 subunit (Basic transcription factor 2 44 kDa subunit) (BTF2-p44) (General transcription factor IIH polypeptide 2)TFIIH basal transcription factor complex p44 subunitBasic transcription factor 2 44 kDa subunitBTF2-p44General transcription factor IIH polypeptide 2Reactome DB_ID: 65914UniProt:Q13888 GTF2H2GTF2H2BTF2P44FUNCTION Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. The N-terminus of GTF2H2 interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter.SUBUNIT Component of the TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2 and ERCC3 (PubMed:27193682). Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription (PubMed:9852112, PubMed:11319235). Interacts with XPB, XPD, GTF2H1 and GTF2H3 (PubMed:11319235).SUBUNIT (Microbial infection) Interacts with varicella-zoster virus IE63 protein.TISSUE SPECIFICITY Widely expressed, with higher expression in skeletal muscle.SIMILARITY Belongs to the GTF2H2 family.UniProtQ138881EQUAL395EQUALReactome Database ID Release 7565914Database 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=65914ReactomeR-HSA-659141Reactome 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-65914.11CXPDERCC2XPD proteinERCC2/CXPDTFIIH basal transcription factor complex helicase subunit (EC 3.6.1.-) (DNA-repair protein complementing XP-D cells) (Xeroderma pigmentosum group D complementing protein) (CXPD) (DNA excision repair protein ERCC-2)TFIIH basal transcription factor complex helicase subunit DNA-repair protein complementing XP-D cellsXeroderma pigmentosum group D complementing proteinDNA excision repair protein ERCC-2Reactome DB_ID: 67443UniProt:P18074 ERCC2ERCC2XPDXPDCFUNCTION ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. The interaction with GTF2H2 results in the stimulation of the 5'--&gt;3' helicase activity (PubMed:9771713, PubMed:9852112). Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5 (PubMed:20797633). Interacts with CIAO1 and CIAO2B; the interaction WITH CIAO2B is direct (PubMed:23891004). Interacts with ATF7IP (PubMed:19106100). Interacts directly with MMS19 (PubMed:23585563).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA2.PTM ISGylated.SIMILARITY Belongs to the helicase family. RAD3/XPD subfamily.UniProtP180741EQUAL760EQUALReactome Database ID Release 7567443Database 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=67443ReactomeR-HSA-674431Reactome 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-67443.11Reactome Database ID Release 75109634Database 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=109634ReactomeR-HSA-1096341Reactome 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-109634.1RNA Polymerase I Transcription Initiation complexReactome DB_ID: 73716111Reactome Database ID Release 7573716Database 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=73716ReactomeR-HSA-737161Reactome 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-73716.1Reactome Database ID Release 7573758Database 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=73758ReactomeR-HSA-737582Reactome 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-73758.212393749Pubmed2002Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter.Yuan, XZhao, JZentgraf, HHoffmann-Rohrer, UGrummt, IEMBO Rep 3:1082-7Reactome Database ID Release 7573762Database 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=73762ReactomeR-HSA-737623Reactome 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-73762.3RNA Polymerase I Promoter EscapeAs the active RNA Polymerase I complex leaves the promoter Rrn3 dissociates from the complex. RNA polymerase I Promoter Clearance is complete and Chain Elongation begins (Milkereit and Tschochner, 1998). The assembly of the initiation complex on the promoter and the transition from a closed to an open complex is then followed by promoter clearance and transcription elongation by RNA Pol I. Unlike the RNA polymerase II system, RNA polymerase I transcription does not require a form of energy such as ATP for initiation and elongation. Regulatory mechanisms operating at both the level of transcription initiation and elongation probably concurrently to adjust the level of rRNA synthesis to the need of the cell.Authored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00LEFT-TO-RIGHTLoss of Rrn3 from RNA Polymerase I promoter escape complexUpon transcription initiation it is thought that RRN3 is inactivated and dissociates from the Loss of Rrn3 from the RNA Polymerase I promoter escape complex. SL1 and UBF are thought to remain bound to the promoter for multiple rounds of transcription initiationAuthored: Comai, L, 2003-07-03 17:13:29Edited: Gillespie, ME, 0000-00-00 00:00:00RNA Polymerase I promoter escape complexReactome DB_ID: 737171111Reactome Database ID Release 7573717Database 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=73717ReactomeR-HSA-737171Reactome 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-73717.1Reactome Database ID Release 7573769Database 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=73769ReactomeR-HSA-737692Reactome 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-73769.212646563Pubmed2003Rrn3 becomes inactivated in the process of ribosomal DNA transcription.Hirschler-Laszkiewicz, ICavanaugh, AHMirza, ALun, MHu, QSmink, TRothblum, LIJ Biol Chem 278:18953-9LEFT-TO-RIGHT2.7.7.6Elongation of pre-rRNA transcriptAt the beginning of this reaction, 1 molecule of 'elongating pre-rRNA transcript', and 1 molecule of 'NTP' are present. At the end of this reaction, 1 molecule of 'elongating pre-rRNA transcript' is present.<br><br> This reaction takes place in the 'nucleolus' and is mediated by the 'DNA-directed RNA polymerase activity' of 'RNA Polymerase I promoter escape complex'.<br>Converted from EntitySet in ReactomeNTPReactome DB_ID: 30595CTPcytidine 5'-triphosphateCytidine triphosphateReactome DB_ID: 29470CTP [ChEBI:17677]CTPcytidine 5'-triphosphateCytidine triphosphateChEBICHEBI:17677Reactome Database ID Release 7529470Database 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=29470ReactomeR-ALL-294702Reactome 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-29470.2COMPOUNDC00063GTPGuanosine 5'-triphosphateReactome DB_ID: 113571GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBICHEBI:15996Reactome Database ID Release 75113571Database 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=113571ReactomeR-ALL-1135712Reactome 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-113571.2COMPOUNDC00044UTPuridine 5'-triphosphateUridine triphosphateReactome DB_ID: 113562UTP [ChEBI:15713]UTPuridine 5'-triphosphateUridine triphosphateChEBICHEBI:15713Reactome Database ID Release 75113562Database 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=113562ReactomeR-ALL-1135622Reactome 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-113562.2COMPOUNDC00075Reactome Database ID Release 7530595Database 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=30595ReactomeR-ALL-305951Reactome 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-30595.1COMPOUNDC00699elongating pre-rRNA transcriptReactome DB_ID: 74985Reactome Database ID Release 7574985Database 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=74985ReactomeR-ALL-749852Reactome 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-74985.2ChEBI33697ACTIVATIONGENE ONTOLOGYGO:0003899Reactome Database ID Release 75164035Database 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=164035Reactome Database ID Release 7574986Database 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=74986ReactomeR-HSA-749865Reactome 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-74986.514969726Pubmed2004Mechanism of RNA polymerase I transcriptionComai, LucioAdv. Protein Chem. 67:123-55ACTIVATIONReactome Database ID Release 75427361Database 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=427361ReactomeR-HSA-4273611Reactome 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-427361.1Chromatin (H3K9me2):CBX3Chromatin with H3K9me2: HP1gammaReactome DB_ID: 427344Chromatin (H3K9me2)Reactome DB_ID: 3211683DNADeoxyribonucleic AcidReactome DB_ID: 29428Reactome Database ID Release 7529428Database 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=29428ReactomeR-ALL-294281Reactome 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-29428.1ChEBI470511Reactome Database ID Release 753211683Database 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=3211683ReactomeR-HSA-32116831Reactome 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-3211683.11CBX3HP1gammaChromobox protein homolog 3CBX3_HUMANReactome DB_ID: 427386UniProt:Q13185 CBX3CBX3FUNCTION Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with lamin B receptor (LBR). Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins. Contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation, mediates the recruitment of the methyltransferases SUV39H1 and/or SUV39H2 by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1. Mediates the recruitment of NIPBL to sites of DNA damage at double-strand breaks (DSBs) (PubMed:28167679).SUBUNIT Binds directly to CHAF1A. Interacts with histone H3 methylated at 'Lys-9' (PubMed:11242053). Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts with INCENP, TRIM28/TIF1B, KMT5B, KMT5C and SP100 (PubMed:10330177, PubMed:12004135, PubMed:9636146). Interacts with TIF1A (By similarity). Interacts with MIS12 and DSN1 (PubMed:15502821). Can interact directly with CBX5 via the chromoshadow domain (PubMed:9169472). Interacts with POGZ (PubMed:20850016, PubMed:20562864). Interacts with CHAMP1 (PubMed:20850016). The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with INCENP (PubMed:9864353, PubMed:21346195). Interacts with NIPBL (via PxVxL motif) (PubMed:28167679). Interacts with LRIF1 (via PxVxL motif) (PubMed:23542155). Interacts with TTLL12 (PubMed:23251473).PTM Phosphorylated by PIM1. Phosphorylated during interphase and possibly hyper-phosphorylated during mitosis.CAUTION Was previously reported to interact with ASXL1. However, this publication has been retracted.UniProtQ131851EQUAL183EQUALReactome Database ID Release 75427386Database 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=427386ReactomeR-HSA-4273861Reactome 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-427386.11Reactome Database ID Release 75427344Database 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=427344ReactomeR-HSA-4273441Reactome 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-427344.1Reactome Database ID Release 7573772Database 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=73772ReactomeR-HSA-737725Reactome 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-73772.59649439Pubmed1998A specialized form of RNA polymerase I, essential for initiation and growth-dependent regulation of rRNA synthesis, is disrupted during transcriptionMilkereit, PTschochner, HEMBO J. 17:3692-70311032814Pubmed2000The recruitment of RNA polymerase I on rDNA is mediated by the interaction of the A43 subunit with Rrn3Peyroche, GMilkereit, PBischler, NTschochner, HSchultz, PSentenac, ACarles, CRiva, MEMBO J. 19:5473-82Reactome Database ID Release 7573854Database 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=73854ReactomeR-HSA-738543Reactome 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-73854.3