Tbio LEO1 RNA polymerase-associated protein LEO1

Protein Summary

Description

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. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling. LEO1, parafibromin (CDC73; MIM 607393), CTR9 (MIM 609366), and PAF1 (MIM 610506) form the PAF protein complex that associates with the RNA polymerase II subunit POLR2A (MIM 180660) and with a histone methyltransferase complex (Rozenblatt-Rosen et al., 2005 [PubMed 15632063]).[supplied by OMIM, Mar 2008]

Uniprot Accession IDs

• Q8WVC0
• Q96N99

Gene Name

• LEO1

Ensembl ID

• ENST00000299601
• ENSP00000299601
• ENSG00000166477
• ENST00000315141
• ENSP00000314610

Symbol

• RDL
• RDL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	0.96
biological process	0.86
transcription factor binding site profile	0.85
ligand (protein) perturbation	0.83
histone modification site profile	0.81

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Dna-directed Rna Polymerase / Rna Polymerase-associated Protein Leo1

DTO Classes

Protein / Enzyme / Transferase / Nucleotidyltransferase / Polymerase / Dna-directed Rna Polymerase / Rna Polymerase-associated Protein Leo1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 152.33   (req: < 5)

Gene RIFs: 7   (req: <= 3)

Antibodies: 338   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 152.33   (req: >= 5)

Gene RIFs: 7   (req: > 3)

Antibodies: 338   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0