Tbio TUT4 Terminal uridylyltransferase 4

Protein Summary

Description

Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesis using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Adds oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (PubMed:16643855). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:25979828, PubMed:25480299, PubMed:16643855, PubMed:19703396, PubMed:18172165) (By similarity). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (PubMed:30122351). ZCCHC11 is an RNA uridyltransferase (EC 2.7.7.52) that uses UTP to add uridines to the 3-prime end of substrate RNA molecules (Jones et al., 2009 [PubMed 19701194]).[supplied by OMIM, Jan 2011]

Uniprot Accession IDs

• Q5TAX3
• A2RRP0
• B7Z8J5
• D3DQ35
• Q12764
• Q5TAX2
• Q5TAX4
• Q86XZ3
• TUTase 4

Gene Name

• TUT4

Ensembl ID

• ENST00000371544
• ENSP00000360599
• ENSG00000134744

Symbol

• KIAA0191
• ZCCHC11
• PAPD3
• TENT3A
• ZCCHC11

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.9
histone modification site profile	0.87
cell type or tissue	0.77
interacting protein	0.76
biological process	0.69

Protein Classes

PANTHER Classes

Protein / Transferase / Nucleotidyltransferase / Terminal Uridylyltransferase 4

DTO Classes

Protein / Enzyme / Transferase / Nucleotidyltransferase / Terminal Uridylyltransferase 4

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: 43.71   (req: < 5)

Gene RIFs: 21   (req: <= 3)

Antibodies: 188   (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: 43.71   (req: >= 5)

Gene RIFs: 21   (req: > 3)

Antibodies: 188   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

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