BioPAX pathway converted from "GLI proteins bind CDC73" in the Reactome database. GLI proteins bind CDC73 GLI proteins bind CDC73 Each of the GLI proteins can form a complex in the nucleus with CDC73, also known as Parafibromin, a component of the PAF complex (Mosimann et al, 2009). PAF1 is a conserved protein complex that affects aspects of RNA polymerase II transcription including histone modification, transcription elongation and RNA 3' end formation, among others. In humans, the PAF1 complex consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61 (reviewed in Tomson and Arndt, 2013). Knockdown of CDC73 in mammalian cell culture compromises GLI1- and GLI2-dependent transcriptional activation and has been shown to abrogate expression of endogenous targets in Drosophila. CDC73 interacts with the GLI proteins through the SUFU-interacting domain in region 1 of the N-terminal (Mosimann et al, 2009). Direct binding of a CDC73:GLI complex on an endogenous human target gene has not yet been demonstrated. Authored: Rothfels, Karen, 2014-10-30 Reviewed: Liu, Yulu Cherry, 2014-11-09 Edited: Gillespie, Marc E, 2014-10-30 Reactome DB_ID: 3322360 1 nucleoplasm GO 0005654 UniProt:Q6P1J9 CDC73 CDC73 HRPT2 C1orf28 CDC73 FUNCTION Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors.SUBUNIT Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61 (PubMed:19952111, PubMed:20178742). The PAF1 complex interacts with PHF5A. Within the PAF1 complex interacts directly with PHF5A (By similarity). Interacts with POLR2A, CPSF1, CPSF4, CSTF2, KMT2A/MLL1 and CTNNB1 (PubMed:15632063, PubMed:15923622, PubMed:16630820, PubMed:19136632, PubMed:20541477). Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3 (PubMed:15632063). Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex (PubMed:17113272). Interacts with PTPN11 (PubMed:26742426). Interacts with SETD5 (By similarity).SUBUNIT (Microbial infection) The PAF1 complex interacts with Zika virus French Polynesia 10087PF/2013 non-structural protein 5/NS5 (PubMed:30550790). The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).SUBUNIT (Microbial infection) The PAF1 complex interacts with Dengue virus DENV2 16681 non-structural protein 5/NS5 (PubMed:30550790). The PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981 non-structural protein 5/NS5 (PubMed:30550790). The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).TISSUE SPECIFICITY Found in adrenal and parathyroid glands, kidney and heart.PTM Phosphorylated. Dephosphorylated by PTPN11.SIMILARITY Belongs to the CDC73 family. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt Q6P1J9 Chain Coordinates 2 EQUAL 531 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 5635077 1 2p-GLI1,2,3 [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 2p-GLI1 [nucleoplasm] 2p-GLI3 [nucleoplasm] 2p-GLI2 [nucleoplasm] UniProt P08151 UniProt P10071 UniProt P10070 Reactome DB_ID: 5635076 1 CDC73:2p-GLI [nucleoplasm] CDC73:2p-GLI Reactome DB_ID: 3322360 1 2 EQUAL 531 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 5635077 1 Reactome Database ID Release 78 5635076 Database 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=5635076 Reactome R-HSA-5635076 1 Reactome 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-5635076.1 Reactome Database ID Release 78 5635845 Database 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=5635845 Reactome R-HSA-5635845 1 Reactome 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-5635845.1 19368795 Pubmed 2009 The role of Parafibromin/Hyrax as a nuclear Gli/Ci-interacting protein in Hedgehog target gene control Mosimann, Christian Hausmann, George Basler, Konrad Mech. Dev. 126:394-405 22982193 Pubmed 2013 The many roles of the conserved eukaryotic Paf1 complex in regulating transcription, histone modifications, and disease states Tomson, Brett N Arndt, KM Biochim. Biophys. Acta 1829:116-26