InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PAF1

Summary

InnateDB Protein

IDBP-50232.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PAF1

Protein Name

Paf1, RNA polymerase II associated factor, homolog (S. cerevisiae)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000221265

InnateDB Gene

IDBG-50230 (PAF1)

Protein Structure

UniProt Annotation

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 indepentently 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:0000269PubMed:16491129, ECO:0000269PubMed:19410543, ECO:0000269PubMed:19952111, ECO:0000269PubMed:20178742, ECO:0000269PubMed:20541477, ECO:0000269PubMed:21329879, ECO:0000269PubMed:22419161}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:16491129}. Note=Punctuate distribution throughout the nucleus except in nucleoli and the perinuclear chromatin.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 75 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	75 [view]
Protein-Protein	70 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000993	RNA polymerase II core binding
GO:0003682	chromatin binding
GO:0005515	protein binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001711	endodermal cell fate commitment
GO:0006351	transcription, DNA-templated
GO:0006378	mRNA polyadenylation
GO:0010390	histone monoubiquitination
GO:0016055	Wnt signaling pathway
GO:0019827	stem cell maintenance
GO:0031442	positive regulation of mRNA 3'-end processing
GO:0032968	positive regulation of transcription elongation from RNA polymerase II promoter
GO:0033523	histone H2B ubiquitination
GO:0045638	negative regulation of myeloid cell differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0071222	cellular response to lipopolysaccharide