BioPAX pathway converted from "RNA Polymerase II Transcription Pre-Initiation And Promoter Opening" in the Reactome database.RNA Polymerase II Transcription Pre-Initiation And Promoter OpeningRNA Polymerase II Transcription Pre-Initiation And Promoter OpeningFormation of the pre-initiation complex proceeds in five steps, recognition and binding of core promoter elements by TFIID, binding of TFIIA and TFIIB to the pol II promoter:TFIID complex, recruitment of RNA Polymerase II Holoenzyme by TFIIF to the pol II promoter:TFIID:TFIIA:TFIIB complex, binding of TFIIE to the growing preinitiation complex, and formation of the closed pre-initiation complex (Orphanides et al. 1997).Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Recognition and Binding of Core Promoter Elements by TFIIDRecognition and Binding of Core Promoter Elements by TFIIDAlthough TBP (TATA box binding factor) is necessary and sufficient for initiation of basal transcription, the other subunits of the general transcription factor TFIID, the TBP-associated factors, are required for response to transcriptional activators. TBP binds to the TATA box (a core promoter element), and bends the DNA 80 degrees toward the major groove. This conformation of TBP-TATA box provides the proper topology for the binding of the general transcription factor TFIIB.<p>Transcriptional activators function by affecting the kinetics of binding of TBP to the promoter DNA.Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Reactome DB_ID: 1096271nucleoplasmGO0005654DNA containing RNA Polymerase II promoter [nucleoplasm]DNA containing RNA Polymerase II promoterReactomehttp://www.reactome.orgReactome DB_ID: 1096261TFIID [nucleoplasm]TFIIDReactome DB_ID: 2124521UniProt:Q16594 TAF9TAF9TAF2GTAFII31TAF9FUNCTION Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.SUBUNIT Component of TFIID, the TATA-binding protein-free TAF complex (TFTC), the PCAF complex and the STAGA transcription coactivator-HAT complex. The PCAF complex consists at least of TADA2L/ADA2, SUPT3H/SPT3, TADA3L/ADA3, TAF5L/PAF65-beta, TAF6L/PAF65-alpha, TAF10/TAFII30, TAF12/TAFII20, TAF9/TAFII31 and TRRAP. The STAGA transcription coactivator-HAT complex consists at least of SUPT3H, GCN5L2, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Binds N-terminal domain of p53/TP53 which is essential for transcription. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Binds TFIIB and the Herpes simplex virus activator VP16. Forms a heterodimer with TAF6/TAFII80 in a complex with the TAF4B/TAFII105-TAF12/TAFII20 heterodimer. Also interacts with TAF5. Binds directly DNA. Increased DNA binding when complexed with TAF6/TAFII80.INDUCTION 6 to 8-fold by apoptotic signals.SIMILARITY Belongs to the TAF9 family.CAUTION AK6 and TAF9 were initially considered as products of the same gene since they share two exons. However, they are translated from different initiation codons and reading frames and encode unrelated proteins. This arrangement is conserved in some mammalian species.Homo sapiensNCBI Taxonomy9606UniProtQ16594Chain Coordinates1EQUAL264EQUALReactome DB_ID: 655431UniProt:Q15542 TAF5TAF5TAF2DTAF5FUNCTION TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription. TAF5/TAFII100 interacts strongly with the histone H4-related TAF6/TAFII80 and the histone H3-related TAF9/TAFII31, as well as a stable complex comprised of both TAF5/TAFII80 and TAF6/TAFII31. Apparently weaker interactions of TAF5/TAFII100 with TBP, TAF1/TAFII250, TAF11/TAFII28, and TAF12/TAFII20, but not TAF7/TAFII55, also have been observed.SUBUNIT Homodimer. TFIID and PCAF are composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TBP is not part of TFTC. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, GCN5L2/GCN5, TAF10 and TRRAP.SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen.DOMAIN Distinct domains of TAF5/TAFII100 are required for functional interaction with transcription factor TFIIFB (RAP30) and incorporation into the TFIID complex.SIMILARITY Belongs to the WD repeat TAF5 family.UniProtQ155421EQUAL800EQUALReactome DB_ID: 655411UniProt:O00268 TAF4TAF4TAF2CTAFII130TAF4ATAFII135TAF4TAF2C1FUNCTION Part of the TFIID complex, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone.SUBUNIT TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L, SUPT3H, TAF2, TAF4, TAF5, GCN5L2/GCN5, TAF10 and TRRAP. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with ATF7; the interaction inhibits ATF7-mediated tranactivation.SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen.SIMILARITY Belongs to the TAF4 family.UniProtO002681EQUAL1085EQUALReactome DB_ID: 655551UniProt:Q16514 TAF12TAF12TAF15TAF12TAFII20TAF2JFUNCTION TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TAFs components-TIIFD are essential for mediating regulation of RNA polymerase transcription.SUBUNIT TFIID and PCAF are composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TBP is not part of TFTC. Interacts directly with TBP; additional interactions between TAFII20 and TAFII28 or TAFII30 were detected. Component of the PCAF complex, at least composed of TADA2L/ADA2, TADA3L/ADA3, TAF5L/PAF65-beta, SUPT3H, TAF6L, TAF9, TAF10, TAF12 and TRRAP. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, STAF65-gamma/KIAA0764, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Interacts (isoform TAFII15 and isoform TAFII20) with ATF7 (via the transactivation domain); the interaction is prevented by sumoylation of ATF7 and promotes (isoform TAFII20 only) the transactivation of ATF7.TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the TAF12 family.UniProtQ165141EQUAL161EQUALReactome DB_ID: 2124081UniProt:Q6P1X5 TAF2TAF2CIF150TAF2BTAF2FUNCTION Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. It requires core promoter-specific cofactors for productive transcription stimulation. TAF2 stabilizes TFIID binding to core promoter.SUBUNIT Component of transcription factor TFIID which is composed of TBP and a number of TBP-associated factors. Interacts with TAF2C1. Component of the TFTC-HAT complex.TISSUE SPECIFICITY Expressed in all tissues tested.MISCELLANEOUS PubMed:9418870 was unable to show an association between TAF2 and TFIID.SIMILARITY Belongs to the TAF2 family.UniProtQ6P1X51EQUAL1199EQUALReactome DB_ID: 655531UniProt:Q15544 TAF11TAF11TAF11PRO2134TAF2IFUNCTION Core TAFII present in both of the previously described TFIID species which either lack or contain TAFII30 (TFIID alpha and TFIID beta respectively).SUBUNIT TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Interacts with TAF13 both in vitro and intracellularly; also interacts directly with TBP.DOMAIN TBP and TAFII18 bind to distinct domains of TAFII28.SIMILARITY Belongs to the TAF11 family.UniProtQ155441EQUAL211EQUALReactome DB_ID: 90206801UniProt:Q92804 TAF15TAF15TAF15RBP56TAF2NFUNCTION RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters. Can enter the preinitiation complex together with the RNA polymerase II (Pol II).SUBUNIT Belongs to the RNA polymerase II (Pol II) transcriptional multiprotein complex, together with the TATA-binding protein (TBP) and other TBP-associated factors (TAF(II)s). Binds SF1.TISSUE SPECIFICITY Ubiquitous. Observed in all fetal and adult tissues.PTM Dimethylated by PRMT1 at Arg-206 to asymmetric dimethylarginine. The methylation may favor nuclear localization and positive regulation of TAF15 transcriptional activity.PTM ADP-ribosylated during genotoxic stress.DISEASE A chromosomal aberration involving TAF15/TAF2N is found in a form of extraskeletal myxoid chondrosarcomas (EMC). Translocation t(9;17)(q22;q11) with NR4A3.SIMILARITY Belongs to the RRM TET family.UniProtQ928041EQUAL592EQUALReactome DB_ID: 2124041UniProt:Q9HBM6 TAF9BTAF9BTAF9LTAF9BFUNCTION Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.SUBUNIT Binds TAF5 and TAF6. Component of TFIID and the TATA-binding protein-free TAF complex (TFTC). TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Binds N-terminal domain of p53/TP53 which is essential for transcription.SIMILARITY Belongs to the TAF9 family.UniProtQ9HBM61EQUAL251EQUALReactome DB_ID: 655591UniProt:Q92750 TAF4BTAF4BTAF2C2TAF4BTAFII105FUNCTION Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. TAF4B is a transcriptional coactivator of the p65/RELA NF-kappa-B subunit. Involved in the activation of a subset of antiapoptotic genes including TNFAIP3. May be involved in regulating folliculogenesis. Through interaction with OCBA/POU2AF1, acts as a coactivator of B-cell-specific transcription. Plays a role in spermiogenesis and oogenesis.SUBUNIT TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Heterodimerizes with TAF12/TFII20 via the C-terminal H2A-like histone-fold domain. This heterodimer forms a histone-like octamer with the TAF6/TAFII70-TAF9/TAFII31 heterodimer. Interacts with P65/RELA homodimers and P65/RELA-REL heterodimers. Interaction with POU2AF1, via its C-terminal activation domain, is required for octamer-dependent transcription.TISSUE SPECIFICITY Preferentially expressed in ovarian granulosa cells (at protein level). Highly expressed in B-cells.PTM Under stimulation by forskolin, Isoform 1 is phosphorylated by protein kinase A (PKA).SIMILARITY Belongs to the TAF4 family.UniProtQ927501EQUAL862EQUALReactome DB_ID: 655571UniProt:Q15543 TAF13TAF13TAFII18TAF13TAF2KFUNCTION Component of the DNA-binding general RNA polymerase II transcription factor IID complex (TFIID). TFIID plays a critical role in the regulation of gene transcription in eukaryotic cells.SUBUNIT TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Interacts with TBP, and more strongly with TAF10 and TAF11.DOMAIN The binding of TAF10 and TAF11 requires distinct domains of TAF13.SIMILARITY Belongs to the TAF13 family.UniProtQ155431EQUAL124EQUALConverted from EntitySet in ReactomeReactome DB_ID: 88667021TAF7,TAF7L [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityTAF7 [nucleoplasm]UniProtQ15545Converted from EntitySet in ReactomeReactome DB_ID: 54208801TAF1,TAF1L [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityTAF1 [nucleoplasm]TAF1L [nucleoplasm]UniProtP21675UniProtQ8IZX4Reactome DB_ID: 2124461UniProt:Q5VWG9 TAF3TAF3TAF3FUNCTION Transcription factor TFIID is one of the general factors required for accurate and regulated initiation by RNA polymerase II. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Required in complex with TBPL2 for the differentiation of myoblasts into myocytes. The complex replaces TFIID at specific promoters at an early stage in the differentiation process.SUBUNIT Belongs to the TFIID complex which is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Interacts with TAF10 via the histone fold. Interacts with TAF13, TBP, SAP130 and GCN5L2. Interacts with TBPL2.DOMAIN The PHD-type zinc finger mediates binding to histone H3 methyllysine at position 4 (H3K4me3).SIMILARITY Belongs to the TAF3 family.UniProtQ5VWG91EQUAL929EQUALReactome DB_ID: 655511UniProt:Q12962 TAF10TAF10TAF2HTAFII30TAF10TAF2AFUNCTION TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors.SUBUNIT TFIID and PCAF are composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TBP is not part of TFTC. Component of the PCAF complex, at least composed of TADA2L/ADA2, TADA3L/ADA3, SUPT3H, TAF5L TAF6L, TAF9, TAF10, TAF12 and TRRAP (PubMed:9885574). Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L, SUPT3H, TAF2, TAF4, TAF5, GCN5L2/GCN5, TAF10 and TRRAP (PubMed:10373431, PubMed:12601814). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (PubMed:11564863, PubMed:18206972). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22. Interacts with TAF3 (PubMed:11438666). Interacts with LOXL2 (PubMed:25959397).DOMAIN The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.PTM Monomethylated at Lys-189 by SETD7, leading to increased affinity for RNA polymerase II.PTM Lysine deamination at Lys-189 to form allysine is mediated by LOXL2. Allysine formation by LOXL2 results in release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription.SIMILARITY Belongs to the TAF10 family.UniProtQ129621EQUAL218EQUALReactome DB_ID: 655451UniProt:P49848 TAF6TAF6TAFII70TAF2ETAF6FUNCTION TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors.SUBUNIT TFIID and PCAF are composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TBP is not part of TFTC. Interacts directly with TBP, TAF1/TAFII250, TAF9/TAFII31 AND TAF12/TAFII20. The TAF6/TAFII70-TAF9/TAFII31 heterodimer forms an octamer complex with the TAF4B/TFII105-TAF12/TFIID20 heterodimer. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Also interacts with the GTFs, TFIIEalpha/GTF2E1 and TFIIFalpha/GTF2F1. Component of the TFTC-HAT complex. Isoform 1: Interacts with TP53/p53 (PubMed:20096117). Isoform 4: Part of a TFIID-like complex which lacks TAF9 (PubMed:11583621). Isoform 4: Not part of the TFTC (PubMed:11583621). Isoform 4: Interacts with TP53/p53 (PubMed:20096117).SIMILARITY Belongs to the TAF6 family.UniProtP498481EQUAL677EQUALReactome 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 Database ID Release 75109626Database 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=109626ReactomeR-HSA-1096263Reactome 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-109626.3Reactome DB_ID: 1096281pol II promoter:TFIID complex [nucleoplasm]pol II promoter:TFIID complexReactome DB_ID: 1096271Reactome DB_ID: 1096261Reactome Database ID Release 75109628Database 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=109628ReactomeR-HSA-1096281Reactome 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-109628.1Reactome Database ID Release 75109636Database 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=109636ReactomeR-HSA-1096362Reactome 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-109636.28946909Pubmed1997The general transcription factors of RNA polymerase II.Orphanides, GLagrange, TReinberg, DannyGenes Dev 10:2657-838330735Pubmed1993TBP, a universal eukaryotic transcription factor?Hernandez, NouriaGenes Dev 7:1291-308Binding of TFIIA and TFIIB to the pol II promoter:TFIID complexBinding of TFIIA and TFIIB to the pol II promoter:TFIID complexThe general transcription factor TFIIB is a single polypeptide of approximately 35 kDa. There is a Zn-binding domain near the N terminus of TFIIB, and the C-terminal domain encompasses two imperfect repeats; between the N and C termini is a phylogenetically conserved region. The C terminus interacts with TBP and RNA Polymerase II, whereas the N terminus interacts with factor TFIIF and RNA polymerase II. TFIIB is a sequence-specific factor, and it interacts with the BRE element within the promoter.<p>TFIIB interacts with the Rpb1 subunit of RNA polymerase II to define transcription strat sites. Several activators directly bind TFIIB, and stimulate transcription. The N-terminus and the C-terminus can participate in intramolecular interactions, and this can be disrupted by specific activators by causing a conformational change in TFIIB.<p> TFIIA also binds the preinitiation complex along with TFIIB. However, TFIIA is not required for accurate initiation, but rather functions as a coactivator of transcription.Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Reactome DB_ID: 1096281Reactome DB_ID: 658881UniProt:Q00403 GTF2BGTF2BTFIIBTF2BGTF2BFUNCTION General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). Involved in the pre-initiation complex (PIC) formation and Pol II recruitment at promoter DNA (PubMed:1876184, PubMed:1946368, PubMed:1517211, PubMed:3818643, PubMed:3029109, PubMed:8413225, PubMed:8515820, PubMed:8516311, PubMed:8516312, PubMed:7601352, PubMed:9420329, PubMed:12931194, PubMed:27193682). Together with the TATA box-bound TBP forms the core initiation complex and provides a bridge between TBP and the Pol II-TFIIF complex (PubMed:8504927, PubMed:8413225, PubMed:8515820, PubMed:8516311, PubMed:8516312). Released from the PIC early following the onset of transcription during the initiation and elongation transition and reassociates with TBP during the next transcription cycle (PubMed:7601352). Associates with chromatin to core promoter-specific regions (PubMed:12931194, PubMed:24441171). Binds to two distinct DNA core promoter consensus sequence elements in a TBP-independent manner; these IIB-recognition elements (BREs) are localized immediately upstream (BREu), 5'-[GC][GC][GA]CGCC-3', and downstream (BREd), 5'-[GA]T[TGA][TG][GT][TG][TG]-3', of the TATA box element (PubMed:9420329, PubMed:16230532, PubMed:7675079, PubMed:10619841). Modulates transcription start site selection (PubMed:10318856). Exhibits also autoacetyltransferase activity that contributes to the activated transcription (PubMed:12931194).SUBUNIT Found in a ternary complex with TATA box-bound TBP (PubMed:8413225, PubMed:8515820, PubMed:8516311, PubMed:8516312, PubMed:10619841, PubMed:29158257). Part of a TFIID-containing RNA polymerase II pre-initiation complex (PIC) 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). Associates with TFIID-TFIIA (DA complex) to form TFIID-TFIIA-TFIIB (DAB complex), which is then recognized by RNA polymerase II (Pol II) (PubMed:1876184, PubMed:2247058). Found in a RNA polymerase II initiation complex (PubMed:3818643, PubMed:3029109, PubMed:8413225, PubMed:8516312, PubMed:7601352). Interacts (via C-terminus) with TBP; this interaction with TATA box-bound TBP guides Pol II into the PIC (PubMed:8504927, PubMed:10619841). Interacts (via N-terminus) with Pol II (PubMed:8504927, PubMed:8413225). Interacts (via C-terminus) with SSU72; this interaction is inhibited by SYMPK (PubMed:29158257). Interacts with NR2F1; this interaction is direct (PubMed:1517211). Interacts with PGR (PubMed:1517211). Interacts with ESR1 (PubMed:1517211). Interacts with GTF2F1 (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2 (PubMed:8662660, PubMed:12931194). Interacts with GTF2F2 (via N-terminus); this interaction is inhibited in presence of GTF2F1 (PubMed:8504927, PubMed:8662660). Interacts with the transcription elongation factor TCEA2 (PubMed:8566795). Interacts with HSF1 (via transactivation domain) (PubMed:11005381). Interacts with GPBP1 (By similarity).SUBUNIT (Microbial infection) Interacts with HIV-1 Vpr.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA2.SUBUNIT (Microbial infection) Interacts with Herpes simplex virus 1 protein ICP4.SUBUNIT (Microbial infection) Interacts (via C-terminus) with the Herpes simplex virus activator VP16; this interaction stimulates RNA Pol II transcription by increasing the extent of pre-initiation complex assembly.TISSUE SPECIFICITY Expressed in the inner cell mass forming the embryoblast (PubMed:24441171). Not detected in cells from the outer thin layer trophoblast (at protein level) (PubMed:24441171).DOMAIN The TFIIB-type zinc-binding domain is necessary for the interaction and recruitment of RNA polymerase II to the core promoter, the formation of a fully competent pre-initiation complex (PIC) assembly and basal transcription initiation (PubMed:8515820, PubMed:8516311, PubMed:8516312, PubMed:8413225). The C-terminus is necessary and sufficient for interaction with the TATA box-bound TBP complex and for the formation of PIC (PubMed:8515820, PubMed:8516311, PubMed:8413225).PTM Acetylated (PubMed:24441171). Autoacetylated; autoacetylation at Lys-238 stimulates transcription activation (PubMed:12931194).SIMILARITY Belongs to the TFIIB family.UniProtQ004031EQUAL316EQUALReactome DB_ID: 1096291TFIIA [nucleoplasm]TFIIAReactome DB_ID: 655331UniProt:P52657 GTF2A2GTF2A2TF2A2GTF2A2FUNCTION TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity.SUBUNIT TFIIA is a heterodimer of the large unprocessed subunit 1 and a small subunit gamma (By similarity). It was originally believed to be a heterotrimer of an alpha (p35), a beta (p19) and a gamma subunit (p12) (By similarity). Interacts with NCOA6 general coactivator (PubMed:10567404). TFIIA forms a complex with TBP (PubMed:11030333). Interacts with HSF1 (via transactivation domain) (PubMed:11005381).SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen.SIMILARITY Belongs to the TFIIA subunit 2 family.UniProtP526571EQUAL109EQUALReactome DB_ID: 1097681UniProt:P52655 GTF2A1GTF2A1TF2A1GTF2A1FUNCTION TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity.SUBUNIT TFIIA is a heterodimer of the large unprocessed subunit 1 and a small subunit gamma. It was originally believed to be a heterotrimer of an alpha (p35), a beta (p19) and a gamma subunit (p12). TFIIA forms a complex with TBP.PTM The alpha and beta subunits are postranslationally produced from the precursor form by TASP1. The cleavage promotes proteasomal degradation.SIMILARITY Belongs to the TFIIA subunit 1 family.UniProtP52655275EQUAL376EQUALReactome DB_ID: 10976711EQUAL274EQUALReactome Database ID Release 75109629Database 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=109629ReactomeR-HSA-1096291Reactome 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-109629.1Reactome DB_ID: 1096301pol II promoter:TFIID:TFIIA:TFIIB complex [nucleoplasm]pol II promoter:TFIID:TFIIA:TFIIB complexReactome DB_ID: 1096281Reactome DB_ID: 6588811EQUAL316EQUALReactome DB_ID: 1096291Reactome Database ID Release 75109630Database 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=109630ReactomeR-HSA-1096301Reactome 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-109630.1Reactome Database ID Release 75109637Database 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=109637ReactomeR-HSA-1096372Reactome 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-109637.2Recruitment of RNA Polymerase II Holoenzyme by TFIIF to the pol II promoter:TFIID:TFIIA:TFIIB complexRecruitment of RNA Polymerase II Holoenzyme by TFIIF to the pol II promoter:TFIID:TFIIA:TFIIB complexThe general transcription factor TFIIF has a high affinity for the RNA Polymerase II holoenzyme. TFIIF stabilizes the preinitiation complex, and suppresses non-specific binding of RNA Pol II to DNA, and is thus critical for start site recognition.Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Reactome DB_ID: 713071RNA Polymerase II (unphosphorylated):TFIIF complex [nucleoplasm]RNA Polymerase II (unphosphorylated):TFIIF complexReactome DB_ID: 1134011RNA Polymerase II holoenzyme complex (unphosphorylated) [nucleoplasm]RNA Polymerase II holoenzyme complex (unphosphorylated)Reactome DB_ID: 635061UniProt:P19387 POLR2CPOLR2CA-152E5.7POLR2CFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB11/POLR2J and RPB3/POLR2C subunits interact with each other.SIMILARITY Belongs to the archaeal RpoD/eukaryotic RPB3 RNA polymerase subunit family.UniProtP193872EQUAL275EQUALReactome 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 (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoK/eukaryotic RPB6 RNA polymerase subunit family.UniProtP612182EQUAL127EQUALReactome 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: 635021UniProt:P24928 POLR2APOLR2APOLR2POLR2AFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II 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. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (PubMed:24207025). Methylation and dimethylation have a repressive effect on target genes expression (By similarity).FUNCTION (Microbial infection) Acts as an RNA-dependent RNA polymerase when associated with small delta antigen of Hepatitis delta virus, acting both as a replicate and transcriptase for the viral RNA circular genome.SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with ATF7IP. Interacts with DDX5. Interacts with WWP2. Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1. Interacts with CCNL1. Interacts with CCNL2, MYO1C, PAF1 and SFRS19. Interacts (via C-terminus) with CMTR1, CTDSP1 and SCAF8. Interacts (via the C-terminal domain (CTD)) with CCNT2 (PubMed:15563843). Interacts with FUS. Interacts with MCM3AP isoform GANP (PubMed:23652018). Interacts with kinase SRPK2; the interaction occurs during the co-transcriptional formation of inappropriate R-loops (PubMed:28076779).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein ICP22; this interaction causes loss of CTD 'Ser-2' phosphorylation from pol II engaged in transcription (PubMed:23029222).DOMAIN The C-terminal domain (CTD) serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing.PTM The tandem heptapeptide repeats in the C-terminal domain (CTD) can be highly phosphorylated (PubMed:28076779). The phosphorylation activates Pol II. Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' of the heptapeptide repeat and is mediated, at least, by CDK7 and CDK9. CDK7 phosphorylation of POLR2A associated with DNA promotes transcription initiation by triggering dissociation from DNA. Phosphorylation also takes place at 'Ser-7' of the heptapeptide repeat, which is required for efficient transcription of snRNA genes and processing of the transcripts. The phosphorylation state is believed to result from the balanced action of site-specific CTD kinases and phosphatases, and a 'CTD code' that specifies the position of Pol II within the transcription cycle has been proposed. Dephosphorylated by the protein phosphatase CTDSP1.PTM Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated and dimethylated. EP300 is one of the enzyme able to acetylate 'Lys-7'. Acetylation at 'Lys-7' of non-consensus heptapeptide repeats is associated with 'Ser-2' phosphorylation and active transcription. Regulates initiation or early elongation steps of transcription specially for inducible genes.PTM Methylated at Arg-1810 prior to transcription initiation when the CTD is hypophosphorylated, phosphorylation at Ser-1805 and Ser-1808 preventing this methylation. Symmetrically or asymmetrically dimethylated at Arg-1810 by PRMT5 and CARM1 respectively. Symmetric or asymmetric dimethylation modulates interactions with CTD-binding proteins like SMN1/SMN2 and TDRD3. SMN1/SMN2 interacts preferentially with the symmetrically dimethylated form while TDRD3 interacts with the asymmetric form. Through the recruitment of SMN1/SMN2, symmetric dimethylation is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. CTD dimethylation may also facilitate the expression of select RNAs. Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated, dimethylated and trimethylated. Methylation occurs in the earliest transcription stages and precedes or is concomitant to 'Ser-5' and 'Ser-7' phosphorylation. Dimethylation and trimehtylation at 'Lys-7' of non-consensus heptapeptide repeats are exclusively associated with phosphorylated CTD.PTM Ubiquitinated by WWP2 leading to proteasomal degradation (By similarity). Following UV treatment, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated on UV damage sites without leading to degradation: ubiquitination is facilitated by KIAA1530/UVSSA and promotes RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery.MISCELLANEOUS The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion temporarily coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits. The ribonucleoside triphosphate is transferred by a rotation to the nucleotide addition (A) site for pairing with the template DNA. The catalytic A site involves three conserved aspartate residues of the RNA Pol II largest subunit which permanently coordinate a second magnesium ion.SIMILARITY Belongs to the RNA polymerase beta' chain family.UniProtP249281EQUAL1970EQUALReactome DB_ID: 635311UniProt:P52435 POLR2JPOLR2JPOLR2J1POLR2JFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with AATF.TISSUE SPECIFICITY Ubiquitously expressed. High expression was found in heart and skeletal muscle.SIMILARITY Belongs to the archaeal RpoL/eukaryotic RPB11/RPC19 RNA polymerase subunit family.UniProtP524351EQUAL117EQUALReactome DB_ID: 635041UniProt:P30876 POLR2BPOLR2BPOLR2BFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB2 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with WDR82. Interacts with MEN1.MISCELLANEOUS The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits (By similarity).SIMILARITY Belongs to the RNA polymerase beta chain family.UniProtP308761EQUAL1174EQUALReactome DB_ID: 635171UniProt:P62487 POLR2GPOLR2GRPB7POLR2GFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity). Binds RNA.SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.SIMILARITY Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.UniProtP624871EQUAL172EQUALReactome 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: 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 (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively (By similarity). In RNA Pol II, this subunit is present in 2-fold molar excess over the other subunits. Interacts with URI1.SUBUNIT (Microbial infection) Interacts with HBV protein X.SIMILARITY Belongs to the archaeal RpoH/eukaryotic RPB5 RNA polymerase subunit family.UniProtP193881EQUAL210EQUALReactome DB_ID: 635251UniProt:P36954 POLR2IPOLR2IPOLR2IFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.SIMILARITY Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.UniProtP369541EQUAL125EQUALReactome DB_ID: 635081UniProt:O15514 POLR2DPOLR2DPOLR2DFUNCTION DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RBP4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).SUBUNIT Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.SIMILARITY Belongs to the eukaryotic RPB4 RNA polymerase subunit family.UniProtO155141EQUAL142EQUALReactome 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 (By similarity).SUBUNIT Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.SIMILARITY Belongs to the archaeal RpoN/eukaryotic RPB10 RNA polymerase subunit family.UniProtP628751EQUAL67EQUALReactome Database ID Release 75113401Database 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=113401ReactomeR-HSA-1134011Reactome 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-113401.1Reactome DB_ID: 1096311TFIIF [nucleoplasm]TFIIFReactome DB_ID: 655671UniProt:P13984 GTF2F2GTF2F2RAP30GTF2F2FUNCTION TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation. This subunit shows ATP-dependent DNA-helicase activity.SUBUNIT Heterodimer of an alpha and a beta subunit. Interacts with HTATSF1 and GPBP1 (By similarity). Interacts with URI1. Interacts with GTF2B (via N-terminus); this interaction is inhibited in presence of GTF2F1 (PubMed:8504927, PubMed:8662660).SIMILARITY Belongs to the TFIIF beta subunit family.UniProtP139842EQUAL249EQUALReactome DB_ID: 655651UniProt:P35269 GTF2F1GTF2F1GTF2F1RAP74FUNCTION TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.SUBUNIT Heterodimer of an alpha and a beta subunit. Interacts with GTF2F2, CTDP1, TAF6/TAFII80 and URI1. Interacts with GTF2B (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2 (PubMed:8662660, PubMed:12931194).INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection.PTM Phosphorylated on Ser and other residues by TAF1 and casein kinase II-like kinases.SIMILARITY Belongs to the TFIIF alpha subunit family.CAUTION Was reported to have a protein kinase activity and to autophosphorylates on Ser-385 and Thr-389.UniProtP352692EQUAL517EQUALReactome Database ID Release 75109631Database 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=109631ReactomeR-HSA-1096311Reactome 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-109631.1Reactome Database ID Release 7571307Database 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=71307ReactomeR-HSA-713071Reactome 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-71307.1Reactome DB_ID: 1096301Reactome DB_ID: 1096321pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF complex [nucleoplasm]pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF complexReactome DB_ID: 713071Reactome DB_ID: 1096301Reactome Database ID Release 75109632Database 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=109632ReactomeR-HSA-1096321Reactome 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-109632.1Reactome Database ID Release 75109638Database 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=109638ReactomeR-HSA-1096382Reactome 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-109638.2Binding of TFIIE to the growing preinitiation complexBinding of TFIIE to the growing preinitiation complexFactor TFIIE enters the preinitiation complex after TFIIF recruits RNA Polymerase II. TFIIE is composed of two subunits of 56 kDA and 34 kDa. TFIIE facilitates the recruitment of factor TFIIH to the preinitiation complex, and it also stimulates the phosphorylation of the RNA Polymerase II CTD by TFIIH.Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Reactome DB_ID: 1096331TFIIE [nucleoplasm]TFIIEReactome DB_ID: 655631UniProt:P29084 GTF2E2GTF2E2TF2E2GTF2E2FUNCTION Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.SUBUNIT Tetramer of two alpha and two beta chains (PubMed:1956398). Interacts with FACT subunit SUPT16H (PubMed:10792464). Interacts with ATF7IP (PubMed:19106100). Interacts with SND1 (PubMed:7651391).SIMILARITY Belongs to the TFIIE beta subunit family.UniProtP290841EQUAL291EQUALReactome DB_ID: 655611UniProt:P29083 GTF2E1GTF2E1TF2E1GTF2E1FUNCTION Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.SUBUNIT Tetramer of two alpha and two beta chains (PubMed:1956398). Interacts with TAF6/TAFII80 (PubMed:7667268). Interacts with ATF7IP (PubMed:19106100). Interacts with SND1 (PubMed:7651391).SUBUNIT (Microbial infection) Interacts with varicella-zoster virus IE63 protein.SIMILARITY Belongs to the TFIIE alpha subunit family.UniProtP290832EQUAL439EQUALReactome Database ID Release 75109633Database 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=109633ReactomeR-HSA-1096331Reactome 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-109633.1Reactome DB_ID: 1096321Reactome DB_ID: 758711pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF:TFIIE complex [nucleoplasm]pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF:TFIIE complexReactome DB_ID: 1096331Reactome DB_ID: 1096321Reactome Database ID Release 7575871Database 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=75871ReactomeR-HSA-758711Reactome 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-75871.1Reactome Database ID Release 7575095Database 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=75095ReactomeR-HSA-750952Reactome 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-75095.2Formation of the closed pre-initiation complexFormation of the closed pre-initiation complexThe binding of TFIIH completes the assembly of the preinitiation complex (PIC) for RNA Polymerase II transcription. Although RNA polymerase binds the TATA box on the promoter DNA, no initiation of transcription occurs until TFIIH is bound to the PIC. TFIIH is the only factor with known enzymatic activities.Authored: Reinberg, D, 2003-09-11 07:42:30Edited: Joshi-Tope, G, 0000-00-00 00:00:00Reactome DB_ID: 1096341TFIIH [nucleoplasm]TFIIHReactome 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 (PubMed:8157004, PubMed:30894545). When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape (PubMed:8157004). The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.SUBUNIT Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription (PubMed:9852112). Interacts with PUF60 (PubMed:10882074, PubMed:11239393). Interacts with ATF7IP (PubMed:19106100). Interacts with KAT2A; leading to KAT2A recruitment to promoters and acetylation of histones (PubMed:30894545).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA2.SIMILARITY Belongs to the helicase family. RAD25/XPB subfamily.UniProtP194471EQUAL782EQUALReactome 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 (By similarity).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: 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 7569221Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69221ReactomeR-HSA-692211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-69221.1Reactome 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 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: 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: 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 Database ID Release 75109634Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109634ReactomeR-HSA-1096341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109634.1Reactome DB_ID: 758711Reactome DB_ID: 1096351pol II closed pre-initiation complex [nucleoplasm]pol II closed pre-initiation complexReactome DB_ID: 1096331Reactome DB_ID: 1096341Reactome DB_ID: 1096321Reactome Database ID Release 75109635Database 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=109635ReactomeR-HSA-1096351Reactome 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-109635.1Reactome Database ID Release 75109639Database 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=109639ReactomeR-HSA-1096392Reactome 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-109639.2Reactome Database ID Release 7573779Database 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=73779ReactomeR-HSA-737792Reactome 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-73779.2GO0006367GO biological process