CTR9

Description

The CTR9 (CTR9 homolog, Paf1/RNA polymerase II complex component) is a protein-coding gene located on chromosome 11.

CTR9 is an enzyme that in humans is encoded by the CTR9 gene. CTR9 is part 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. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity). Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (PubMed:16024656, PubMed:19952111, PubMed:20178742). The PAF1 complex interacts with PHF5A (By similarity). Interacts with KMT2A/MLL1 (PubMed:20541477). Interacts with STAT3 (By similarity). Interacts with SETD5 (By similarity). Interacts with ERCC6 (PubMed:26030138). (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). (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).

CTR9 is a component of the PAF1 complex (PAF1C), which plays a crucial role in transcription by RNA polymerase II. PAF1C is involved in various aspects of transcription, including elongation, regulation of gene expression, and histone modifications. It interacts with RNA polymerase II through its C-terminal domain (CTD) and collaborates with other transcription factors, such as TCEA1 and the DSIF complex, to regulate gene expression. PAF1C is essential for the transcription of Hox and Wnt target genes and is implicated in hematopoiesis and the regulation of stem cell pluripotency. It promotes leukemogenesis by interacting with KMT2A/MLL1-rearranged oncoproteins. PAF1C is involved in histone modifications, including ubiquitination of histone H2B and methylation of histone H3, which contribute to transcriptional regulation. It also plays a role in mRNA 3' end formation and interacts with viral proteins, such as NS1 from influenza A, to influence gene transcription. PAF1C is required for the trimethylation of histone H3 lysine 4 (H3K4me3), a crucial mark associated with active transcription, on genes involved in stem cell pluripotency. Additionally, it is implicated in the transcriptional regulation of IL6-responsive genes and in the JAK-STAT pathway, potentially regulating the DNA association of STAT3. The PAF1 complex interacts with various other proteins, including PHF5A, KMT2A/MLL1, STAT3, SETD5, ERCC6, and NS5 proteins from Zika, Dengue 2, and Dengue 4 viruses.

CTR9 is also known as SH2BP1, TSBP, p150, p150TSP.

Associated Diseases

WES Whole Exome Sequencing