PAF1

Description

The PAF1 (PAF1 homolog, Paf1/RNA polymerase II complex component) is a protein-coding gene located on chromosome 19.

PAF1 is a human gene that encodes a protein known as PAF1. It is part of the PAF1 complex (PAF1C), which has multiple roles during transcription by RNA polymerase II. The complex is important for development, pluripotency of embryonic stem cells, and the regulation of various genes.

PAF1, also known as Pancreatic Differentiation Protein 2, is a key component of the PAF1 complex (PAF1C). This complex plays a crucial role in regulating gene transcription by RNA polymerase II, impacting a wide range of cellular processes. PAF1C associates with RNA polymerase II, interacting with its C-terminal domain (CTD) in both phosphorylated and non-phosphorylated states. This interaction enables PAF1C to participate in transcriptional elongation, both independently and in conjunction with other transcription factors such as TCEA1 and the DSIF complex. PAF1C is essential for the transcription of genes involved in development, including Hox and Wnt target genes. Furthermore, PAF1C is involved in hematopoiesis and stimulates the transcriptional activity of the KMT2A/MLL1 gene, a crucial regulator of hematopoietic development. However, PAF1C's association with rearranged oncoproteins, like KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL, has been implicated in leukemogenesis. PAF1C also plays a role in histone modifications, including ubiquitination of histone H2B and methylation of histone H3 Lys-4 (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin, facilitating the monoubiquitination of histone H2B at Lys-120 (H2BK120ub1). This process, mediated by UB2A/B, is believed to be linked to transcription. PAF1C is also involved in mRNA 3' end formation, likely through its association with cleavage and poly(A) factors. In the context of influenza A strain H3N2 infection, PAF1C interacts with the viral NS1 protein, impacting gene transcription. PAF1C connects the PAF1 complex to the RNF20/40 E3 ubiquitin-protein ligase complex and is involved in the polyadenylation of mRNA precursors. It has been shown to possess oncogenic activity both in vivo and in vitro.

PAF1 is also known as F23149_1, PD2.

Associated Diseases

WES Whole Exome Sequencing