BioPAX pathway converted from "RNA Polymerase I Promoter Clearance" in the Reactome database.RNA Polymerase I Promoter ClearanceRNA 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 OpeningRNA 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 00:00:00UBF-1 Binds rDNA PromoterUBF-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 00:00:00Reactome DB_ID: 736831nucleoplasmGO0005654UniProt:P17480 UBTFUBTFUBTFUBFUBF1FUNCTION 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.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtP17480Chain Coordinates1EQUAL764EQUALReactome DB_ID: 736821rDNA Promoter [nucleoplasm]rDNA PromoterReactome DB_ID: 736841UBF-1:rDNA Promoter [nucleoplasm]UBF-1:rDNA PromoterReactome DB_ID: 7368311EQUAL764EQUALReactome DB_ID: 736821Reactome Database ID Release 6973684Database 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 6973718Database 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 69427398Database 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-427398.111583633Pubmed2001Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene transcriptionSantoro, RGrummt, IMol Cell 8:719-2514610093Pubmed2004Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expressionGhoshal, KMajumder, SDatta, JMotiwala, TBai, SSharma, SMFrankel, WJacob, STJ Biol Chem 279:6783-93Reactome DB_ID: 427343Chromatin (H3K9me2, 5mC):MBD2 [nucleoplasm]Chromatin (H3K9me2, 5mC):MBD2Reactome DB_ID: 4273671UniProt:Q9UBB5 MBD2MBD2MBD2FUNCTION 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.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 DB_ID: 52268771Chromatin with H3K9me2, 5mC [nucleoplasm]Chromatin with H3K9me2, 5mCReactome DB_ID: 2121721DNA containing 5-mC [nucleoplasm]DNA containing 5-mCmethylated DNADouble-Stranded DNA containing 5-methylcytosineReactome DB_ID: 4273311Nucleosome with H3K9me2 [nucleoplasm]Nucleosome with H3K9me2Nucleosome with Deacetylated H4 and H3 Dimethylated at Lysine-9Converted from EntitySet in ReactomeReactome DB_ID: 1818992Histone H2A [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1819022UniProt:P62805 HIST1H4AHIST1H4AH4/DH4/CH4/EH4/HH4/GH4FAH4/JH4/IH4FCH4FBH4/KH4FEH4/NH4/MH4FDH4FGH4/OH4FIH4FHH4FKHIST2H4AH4FJH4FMHIST2H4BH4FOH4FNHIST1H4KHIST1H4LHIST1H4AHIST1H4BHIST4H4HIST2H4HIST1H4HH4F2HIST1H4IHIST1H4JHIST1H4CHIST1H4DH4/BHIST1H4EH4/AHIST1H4FFUNCTION 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). Monomethylation is performed by SET8. Trimethylation is performed by KMT5B and KMT5C and induces gene silencing.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 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.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.UniProtP628052EQUAL103EQUALConverted from EntitySet in ReactomeReactome DB_ID: 4274062Histone H3 dimethylated at lysine-9 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMe2K10-HIST1H3A [nucleoplasm]Me2K-10-H3F3A [nucleoplasm]Me2K-10-HIST2H3A [nucleoplasm]UniProtP68431UniProtP84243UniProtQ71DI3Converted from EntitySet in ReactomeReactome DB_ID: 1819112Histone H2B [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 69427331Database 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-427331.1Reactome Database ID Release 695226877Database 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-5226877.1Reactome Database ID Release 69427343Database 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 69427347Database 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-427347.1Reactome DB_ID: 427402Nucleosome [nucleoplasm]NucleosomeNucleosome (Deacetylated)Converted from EntitySet in ReactomeReactome DB_ID: 1818992Converted from EntitySet in ReactomeReactome DB_ID: 2122932Histone H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityHIST1H3A [nucleoplasm]HIST2H3A [nucleoplasm]H3F3A [nucleoplasm]Reactome DB_ID: 18190222EQUAL103EQUALConverted from EntitySet in ReactomeReactome DB_ID: 1819112Reactome Database ID Release 69427402Database 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-427402.12.7.11.24Phosphorylation of UBF-1:rDNA PromoterPhosphorylation 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 00:00:00Reactome DB_ID: 736841Reactome DB_ID: 293581ATP [ChEBI:15422]ATPAdenosine 5'-triphosphateChEBI15422Reactome DB_ID: 736851Phosphorylated UBF-1:rDNA promoter [nucleoplasm]Phosphorylated UBF-1:rDNA promoterReactome DB_ID: 760391phosphorylated residue at unknown positionphosphorylated residue [MOD:00696]1EQUAL764EQUALReactome DB_ID: 736821Reactome Database ID Release 6973685Database 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-73685.1Reactome DB_ID: 1135821ADP [ChEBI:16761]ADPAdenosine 5'-diphosphateChEBI16761PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 109845p-T202, Y204 MAPK3 dimer [nucleoplasm]p-T202, Y204 MAPK3 dimerphospho-ERK-1 dimerReactome DB_ID: 1123592UniProt:P27361 MAPK3MAPK3PRKM3ERK1MAPK3FUNCTION 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.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.UniProtP27361O-phospho-L-threonine at 202202EQUALO-phospho-L-threonine [MOD:00047]O4'-phospho-L-tyrosine at 204204EQUALO4'-phospho-L-tyrosine [MOD:00048]2EQUAL379EQUALReactome Database ID Release 69109845Database 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-109845.1GO0004707GO molecular functionReactome Database ID Release 69164955Database 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 6973722Database 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 6973728Database 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-73728.2GO0006361GO biological processRNA Polymerase I Transcription InitiationRNA 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 00:00:00Formation of SL1Formation 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.Reactome DB_ID: 736891UniProt:Q15573 TAF1ATAF1ATAF1AFUNCTION 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 DB_ID: 51385331UniProt:Q9H5J8 TAF1DTAF1DTAF1DJOSD3FUNCTION 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 DB_ID: 736871UniProt:Q15572 TAF1CTAF1CTAF1CFUNCTION 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 DB_ID: 736911UniProt:Q53T94 TAF1BTAF1BTAF1BFUNCTION 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 DB_ID: 837181UniProt:P20226 TBPTBPTFIIDTBPTF2DGTF2D1FUNCTION 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 DB_ID: 736921SL1 [nucleoplasm]SL1Reactome DB_ID: 7368911EQUAL450EQUALReactome DB_ID: 513853311EQUAL278EQUALReactome DB_ID: 7368711EQUAL869EQUALReactome DB_ID: 7369111EQUAL588EQUALReactome DB_ID: 8371811EQUAL339EQUALReactome Database ID Release 6973692Database 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 6973729Database 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-73729.27801123Pubmed1995Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or TFIID subunits.Comai, LZomerdijk, JCBeckmann, HZhou, STjian, RScience 266:1966-7217318177Pubmed2007A novel TBP-associated factor of SL1 functions in RNA polymerase I transcriptionGorski, Julia JPathak, ShaliniPanov, KostyaKasciukovic, TacianaPanova, TanyaRussell, JackieZomerdijk, Joost C B MEMBO J. 26:1560-82805069Pubmed1989Molecular 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 68:965-762.3.1Acetylation of SL1Acetylation 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 00:00:00Reactome DB_ID: 736921Reactome DB_ID: 1135601acetyl-CoA [ChEBI:15351]acetyl-CoAChEBI15351Reactome DB_ID: 736931Acetylated SL1 [nucleoplasm]Acetylated SL1Reactome DB_ID: 7368911EQUAL450EQUALReactome DB_ID: 51385301N6-acetyl-L-lysine at unknown positionN6-acetyl-L-lysine [MOD:00064]1EQUAL588EQUALReactome DB_ID: 513853311EQUAL278EQUALReactome DB_ID: 7368711EQUAL869EQUALReactome DB_ID: 8371811EQUAL339EQUALReactome Database ID Release 6973693Database 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-73693.1Reactome DB_ID: 24850021coenzyme A [ChEBI:15346]coenzyme AChEBI15346PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 350078PCAF [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityKAT2B [nucleoplasm]UniProtQ92831GO0016407GO molecular functionReactome Database ID Release 69109690Database 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 6973736Database 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 20:1353-62Recruitment of Acetylated SL1 to phosUBF-1:rDNA PromoterRecruitment 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 00:00:00Reactome DB_ID: 736851Reactome DB_ID: 736931Reactome DB_ID: 736941Acetylayed SL1:PhosUBF-1:rDNA promoter [nucleoplasm]Acetylayed SL1:PhosUBF-1:rDNA promoterReactome DB_ID: 736851Reactome DB_ID: 736931Reactome Database ID Release 6973694Database 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 6973739Database 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-73739.37491500Pubmed1996Coactivator 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 19:4988-9910913176Pubmed2000Repression of RNA polymerase I transcription by the tumor suppressor p53.Zhai, WComai, LMol Cell Biol 20:5930-810082553Pubmed1999Recruitment 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 19:2872-911486020Pubmed2001Overlapping 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 69427325Database 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-427325.1Reactome DB_ID: 427352TTF-I:Sal Box:CSB:G9a:NuRD [nucleoplasm]TTF-I:Sal Box:CSB:G9a:NuRDReactome DB_ID: 46570181NuRD complex [nucleoplasm]NuRD complexReactome DB_ID: 2122231UniProt:Q09028 RBBP4RBBP4RBBP4RBAP48FUNCTION 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.SIMILARITY Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.UniProtQ090282EQUAL425EQUALConverted from EntitySet in ReactomeReactome DB_ID: 46570141(GATAD2A, GATAD2B) [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 46570041HDAC1:HDAC2 [nucleoplasm]HDAC1:HDAC2Reactome DB_ID: 2050211UniProt:Q13547 HDAC1HDAC1HDAC1RPD3L1FUNCTION 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 H2AFY. 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 ELMSAN1; 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).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 DB_ID: 2051351UniProt:Q92769 HDAC2HDAC2HDAC2FUNCTION 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 H2AFY (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).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 694657004Database 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-4657004.1Converted from EntitySet in ReactomeReactome DB_ID: 46570191MTA1, MTA2, MTA3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMTA3 [nucleoplasm]MTA1 [nucleoplasm]MTA2 [nucleoplasm]UniProtQ9BTC8UniProtQ13330UniProtO94776Converted from EntitySet in ReactomeReactome DB_ID: 46570211Mi-2 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityCHD3 [nucleoplasm]CHD4 [nucleoplasm]UniProtQ12873UniProtQ14839Reactome DB_ID: 46570101UniProt:O95983 MBD3MBD3MBD3FUNCTION 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 DB_ID: 2122271UniProt:Q16576 RBBP7RBBP7RBBP7RBAP46FUNCTION 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. 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 694657018Database 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-4657018.2Reactome DB_ID: 749771TTF-I:Sal Box [nucleoplasm]TTF-I:Sal BoxReactome DB_ID: 749751NCBI Nucleotide:U13369 45S pre-rRNA geneHuman ribosomal DNA45S pre-rRNA geneNCBI NucleotideU13369Reactome DB_ID: 749741UniProt:Q15361 TTF1TTF1TTF1FUNCTION 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 6974977Database 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-74977.1Reactome DB_ID: 2121511UniProt:Q96KQ7 EHMT2EHMT2KMT1CC6orf30EHMT2NG36BAT8G9AFUNCTION 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.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 DB_ID: 53658641ERCC6 dimer [nucleoplasm]ERCC6 dimerCSB dimerReactome DB_ID: 544292UniProt:Q03468 ERCC6ERCC6CSBERCC6FUNCTION 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. 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. It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the at sites of RNA polymerase II-blocking lesions.SUBUNIT Homodimer. Binds DNA. Interacts with ERCC8. Interacts with a subunit of RNA polymerase II TFIIH. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts with KIAA1530/UVSSA.DOMAIN A C-terminal ubiquitin-binding domain (UBD) is essential for transcription-coupled nucleotide excision repair to proceed.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.SIMILARITY Belongs to the SNF2/RAD54 helicase family.UniProtQ034681EQUAL1493EQUALReactome Database ID Release 695365864Database 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-5365864.1Reactome Database ID Release 69427352Database 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-427352.1Assembly of RNA Polymerase I Holoenzyme (human)Assembly 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>Reactome DB_ID: 54192921UniProt:Q9P1U0 ZNRD1ZNRD1ZNRD1RPA12FUNCTION 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 DB_ID: 634961UniProt:Q9H9Y6 POLR1BPOLR1BPOLR1BFUNCTION 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.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 DB_ID: 837151UniProt:P62875 POLR2LPOLR2LPOLR2LFUNCTION 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.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 DB_ID: 54192941UniProt:Q9GZS1 POLR1EPOLR1EPAF53PRAF1POLR1EFUNCTION 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. Appears to be involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBTF/UBF.SUBUNIT Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (PubMed:16809778, PubMed:29065309). Interacts with PAF49/CD3EAP (By similarity). Also binds UBTF/UBF (By similarity). Interacts with PWP1 (PubMed:29065309).SIMILARITY Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.UniProtQ9GZS11EQUAL481EQUALReactome DB_ID: 837131UniProt:P19388 POLR2EPOLR2EPOLR2EFUNCTION 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.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 DB_ID: 635371UniProt:P53803 POLR2KPOLR2KPOLR2KFUNCTION 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 DB_ID: 635001UniProt:P0DPB5 POLR1DPOLR1DPOLR1DCAUTION POLR1D isoform 2 lacks an RNA polymerase domain and therefore cannot have DNA-dependent RNA polymerase function.UniProtP0DPB51EQUAL133EQUALReactome DB_ID: 837141UniProt:P61218 POLR2FPOLR2FPOLR2FPOLRFFUNCTION 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.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 DB_ID: 634981UniProt:O15160 POLR1CPOLR1CPOLR1CPOLR1EFUNCTION 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.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 DB_ID: 54192891UniProt:O15446 CD3EAPCD3EAPASE1CASTCD3EAPPAF49FUNCTION 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 DB_ID: 635231UniProt:P52434 POLR2HPOLR2HPOLR2HFUNCTION 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 DB_ID: 54192901UniProt:Q3B726 TWISTNBTWISTNBTWISTNBFUNCTION 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 DB_ID: 634941UniProt:O95602 POLR1APOLR1APOLR1AFUNCTION 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.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 DB_ID: 738591RNA Polymerase I Holoenzyme [nucleoplasm]RNA Polymerase I HoloenzymeReactome DB_ID: 541929211EQUAL126EQUALReactome DB_ID: 6349611EQUAL1135EQUALReactome DB_ID: 8371511EQUAL67EQUALReactome DB_ID: 541929411EQUAL481EQUALReactome DB_ID: 8371311EQUAL210EQUALReactome DB_ID: 6353711EQUAL58EQUALReactome DB_ID: 6350011EQUAL133EQUALReactome DB_ID: 8371412EQUAL127EQUALReactome DB_ID: 6349812EQUAL346EQUALReactome DB_ID: 541928911EQUAL510EQUALReactome DB_ID: 6352312EQUAL150EQUALReactome DB_ID: 541929011EQUAL338EQUALReactome DB_ID: 6349411EQUAL1720EQUALReactome Database ID Release 6973859Database 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 6973865Database 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-73865.2Binding of RRN3 to RNA Polymerase IBinding 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 00:00:00Reactome DB_ID: 738591Reactome DB_ID: 737141UniProt:Q9NYV6 RRN3RRN3RRN3TIFIAFUNCTION 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.SUBUNIT Interacts with TWISTNB, 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 DB_ID: 737151Active RNA Polymerase I [nucleoplasm]Active RNA Polymerase IReactome DB_ID: 738591Reactome DB_ID: 7371411EQUAL651EQUALReactome Database ID Release 6973715Database 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 6973757Database 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 7:12126Recruitment of Active RNA Polymerase I to SL1:phos.UBF-1:rDNA PromoterRecruitment 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 00:00:00Reactome DB_ID: 1096341TFIIH [nucleoplasm]TFIIHReactome DB_ID: 674431UniProt:P18074 ERCC2ERCC2ERCC2XPDXPDCFUNCTION 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 DB_ID: 674391UniProt:P19447 ERCC3ERCC3XPBCERCC3XPBFUNCTION 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. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. 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. Interacts with PUF60. Interacts with ATF7IP.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA2.SIMILARITY Belongs to the helicase family. RAD25/XPB subfamily.UniProtP194471EQUAL782EQUALReactome DB_ID: 659141UniProt:Q13888 GTF2H2GTF2H2BTF2P44GTF2H2FUNCTION 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 DB_ID: 692211CAK [nucleoplasm]CAKReactome DB_ID: 692181UniProt:P50613 CDK7CDK7STK1CDK7MO15CDKN7CAK1CAKFUNCTION 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 DB_ID: 590121UniProt:P51948 MNAT1MNAT1MAT1RNF66CAP35MNAT1FUNCTION 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 DB_ID: 692201UniProt:P51946 CCNHCCNHCCNHFUNCTION 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 6969221Database 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-69221.1Reactome DB_ID: 659181UniProt:Q92759 GTF2H4GTF2H4GTF2H4FUNCTION 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 DB_ID: 659161UniProt:Q13889 GTF2H3GTF2H3GTF2H3FUNCTION 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.SIMILARITY Belongs to the TFB4 family.UniProtQ138891EQUAL308EQUALReactome DB_ID: 659121UniProt:P32780 GTF2H1GTF2H1BTF2GTF2H1FUNCTION 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 DB_ID: 56884461UniProt:Q6ZYL4 GTF2H5GTF2H5C6orf175TTDAGTF2H5FUNCTION 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 69109634Database 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-109634.1Reactome DB_ID: 737151Reactome DB_ID: 736941Reactome DB_ID: 737161RNA Polymerase I Transcription Initiation complex [nucleoplasm]RNA Polymerase I Transcription Initiation complexReactome DB_ID: 1096341Reactome DB_ID: 737151Reactome DB_ID: 736941Reactome Database ID Release 6973716Database 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 6973758Database 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 6973762Database 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 EscapeRNA 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 00:00:00Loss of Rrn3 from RNA Polymerase I promoter escape complexLoss 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 00:00:00Reactome DB_ID: 737161Reactome DB_ID: 737171RNA Polymerase I promoter escape complex [nucleoplasm]RNA Polymerase I promoter escape complexReactome DB_ID: 1096341Reactome DB_ID: 738591Reactome DB_ID: 7368311EQUAL764EQUALReactome DB_ID: 736931Reactome Database ID Release 6973717Database 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 DB_ID: 7371411EQUAL651EQUALReactome Database ID Release 6973769Database 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 278:18953-92.7.7.6Elongation of pre-rRNA transcriptElongation 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>Reactome DB_ID: 749851elongating pre-rRNA transcript [nucleoplasm]elongating pre-rRNA transcriptConverted from EntitySet in ReactomeReactome DB_ID: 305951NTP [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGTP [nucleoplasm]UTP [nucleoplasm]CTP [nucleoplasm]ATP [nucleoplasm]ChEBI15996ChEBI15713ChEBI17677Reactome DB_ID: 749851PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 73717GO0003899GO molecular functionReactome Database ID Release 69164035Database 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 6974986Database 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 69427361Database 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-427361.1Reactome DB_ID: 427344Chromatin (H3K9me2):CBX3 [nucleoplasm]Chromatin (H3K9me2):CBX3Chromatin with H3K9me2: HP1gammaReactome DB_ID: 32116831Chromatin (H3K9me2) [nucleoplasm]Chromatin (H3K9me2)Reactome DB_ID: 294281DNA [nucleoplasm]DNADeoxyribonucleic AcidReactome DB_ID: 4273311Reactome Database ID Release 693211683Database 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-3211683.1Reactome DB_ID: 4273861UniProt:Q13185 CBX3CBX3CBX3FUNCTION 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 recruitement 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).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 69427344Database 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 6973772Database 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 6973854Database 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