UniProt functional annotation for Q8N7H5

UniProt code: Q8N7H5.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: 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 RNF20/40 E3 ubiquitin-protein ligase complex. Involved in polyadenylation of mRNA precursors. Has oncogenic activity in vivo and in vitro. {ECO:0000269|PubMed:16491129, ECO:0000269|PubMed:19410543, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879, ECO:0000269|PubMed:22419161}.
 
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 (By similarity). Interacts with POLR2A, TCEA1, TTC37, KMT2A/MLL1, SUPT5H, RNF20 and RNF40 (PubMed:15923622, PubMed:16024656, PubMed:19952111, PubMed:20178742, PubMed:20541477, PubMed:16491129, PubMed:19410543). Interacts with UBE2E1 (PubMed:16307923). {ECO:0000250|UniProtKB:Q8K2T8, ECO:0000269|PubMed:15923622, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:16491129, ECO:0000269|PubMed:19410543, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477}.
Subunit: (Microbial infection) Interacts with influenza A strain H3N2 NS1 protein; the interaction interferes with host cell gene transcription, specifically with that of antiviral genes. {ECO:0000269|PubMed:22419161}.
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). {ECO:0000269|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). {ECO:0000269|PubMed:30550790}.
Subcellular location: Nucleus {ECO:0000269|PubMed:16491129}. Note=Punctuate distribution throughout the nucleus except in nucleoli and the perinuclear chromatin.
Similarity: Belongs to the PAF1 family. {ECO:0000305}.
Sequence caution: Sequence=AAC25503.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=EAW56880.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=EAW56881.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.