Terminal uridylyltransferase 4 (TUT4)
The protein contains 1644 amino acids for an estimated molecular weight of 185166 Da.
Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). 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 (updated: July 3, 2019)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs12127732 |
No binding partner found
Biological Process
MiRNA catabolic process
MiRNA metabolic process
MRNA polyadenylation
MRNA processing
Negative regulation of transposition, RNA-mediated
Nuclear-transcribed mRNA poly(A) tail shortening
Oocyte maturation
Polyuridylation-dependent mRNA catabolic process
Pre-miRNA processing
RNA 3' uridylation
RNA 3'-end processing
Stem cell population maintenance
The reference OMIM entry for this protein is 613692
Zinc finger cchc domain-containing protein 11; zcchc11
Kiaa0191
Terminal uridyltransferase 4; tut4
DESCRIPTION
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).CLONING
By sequencing clones obtained from a size-fractionated KG-1 immature myeloid leukemia cell line cDNA library, Nagase et al. (1996) obtained a partial ZCCHC11 clone, which they designated KIAA0191. Northern blot analysis detected highest expression in skeletal muscle and testis, with low to moderate expression in all other tissues and cell lines examined. By searching for proteins that interacted with TIFA (609028) in activated murine macrophages, followed by database analysis and RT-PCR of HEK293T cells, Minoda et al. (2006) obtained full-length ZCCHC11 and a variant encoding a short ZCCHC11 isoform, which they called ZCCHC11L and ZCCHC11S, respectively. The deduced 1,644-amino acid ZCCHC11L protein contains an N-terminal C2H2 zinc finger, followed by a poly(A) polymerase (PAP; see 605553)/2-prime,5-prime oligoadenylate synthetase (25A; see 164350) (PAP/25A)-associated domain, a CCHC-type zinc finger, a nucleotidyltransferase domain, a second PAP/25A-associated domain, and 2 C-terminal CCHC-type zinc fingers. Full-length mouse and human ZCCHC11L share 84% amino acid identity. Compared with ZCCHC11L, the 435-amino acid ZCCHC11S isoform contains N- and C-terminal truncations, but it retains the N-terminal C2H2 zinc finger and first PAP/25A domain. Western blot analysis detected ZCCHC11L at an apparent molecular mass of 200 kD and ZCCHC11S at an apparent molecular mass of 60 kD. Immunofluorescence analysis detected ZCCHC11 in the nucleus of HEK293T cells. Jones et al. (2009) cloned mouse Zcchc11. The deduced 1,644-amino acid protein has the same domain structure as human ZCCHC11, and the polymerase beta (POLB; 174760) nucleotidyltransferase domain is highly conserved in eukaryotes. Mouse Zcchc11 mRNA expression was ubiquitous, whereas Zcchc11 protein expression was tissue specific, with highest levels in thymus, spleen, testis, and lung.GENE FUNCTION
Minoda et al. (2006) showed that a substantial proportion of ZCCHC11 translocated from the nucleus to the cytoplasm following lipopolysaccharide (LPS) stimulation of HEK293T cells. ZCCHC11L coimmunoprecipitated with TIFA only following LPS treatment, and it specifically suppressed LPS-induced NF-kappa-B (see 164011) activation. Mutation analysis showed that the N-terminal half of ZCCHC11 was responsible for NF-kappa-B inhibitory activity, and ZCCHC11S was as potent as full-length ZCCHC11L at inhibiting NF-kappa-B. The basal protein level of ZCCHC11S was low, but it increased dramatically after treatment with LPS or other Toll-like receptor (TLR; see 603030) activators. Treatment with a proteasome inhibitor also led to ZCCHC11S protein accumulation, suggesting that ZCCHC11S was ubiquitinated and degraded by the proteasome at basal levels and accumulated in response to LPS stimulation. ZCCHC11S appeared to inhibit NF-kappa-B by suppressing phosphorylation of I-kappa-B (NFKBIA; 164008). Jones et al. (2009) found that recombinant mouse Zcchc11 and endogenous human ZCCHC11 showed nucleotidyltransferase activity, with greatest activity with UTP, followed by CTP, ATP, and GTP. ZCCHC11 did not show RNA substrate specificity and used all RNA substrates examined. Knockdown of ZCCHC11 via small interfering RNA in activated A549 human lung epithelial cells or HEK293T cells reduced the levels of several cyto ... More on the omim web site
July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 613692 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).