ID TUT4_HUMAN Reviewed; 1644 AA. AC Q5TAX3; A2RRP0; B7Z8J5; D3DQ35; Q12764; Q5TAX2; Q5TAX4; Q86XZ3; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 161. DE RecName: Full=Terminal uridylyltransferase 4 {ECO:0000305}; DE Short=TUTase 4; DE EC=2.7.7.52 {ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:31036859}; DE AltName: Full=Zinc finger CCHC domain-containing protein 11; GN Name=TUT4 {ECO:0000312|HGNC:HGNC:28981}; GN Synonyms=KIAA0191, ZCCHC11 {ECO:0000312|HGNC:HGNC:28981}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 129-1644. RC TISSUE=Bone marrow; RX PubMed=8724849; DOI=10.1093/dnares/3.1.17; RA Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. V. The RT coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 3:17-24(1996). RN [6] RP FUNCTION, INTERACTION WITH T2BP, AND SUBCELLULAR LOCATION. RX PubMed=16643855; DOI=10.1016/j.bbrc.2006.04.006; RA Minoda Y., Saeki K., Aki D., Takaki H., Sanada T., Koga K., Kobayashi T., RA Takaesu G., Yoshimura A.; RT "A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates RT TLR signaling."; RL Biochem. Biophys. Res. Commun. 344:1023-1030(2006). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [8] RP ABSENCE OF FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY. RX PubMed=18172165; DOI=10.1101/gad.1622708; RA Mullen T.E., Marzluff W.F.; RT "Degradation of histone mRNA requires oligouridylation followed by RT decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to RT 5'."; RL Genes Dev. 22:50-65(2008). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH RP LIN28A, AND MUTAGENESIS OF ASP-1011. RX PubMed=19703396; DOI=10.1016/j.cell.2009.08.002; RA Heo I., Joo C., Kim Y.-K., Ha M., Yoon M.-J., Cho J., Yeom K.-H., Han J., RA Kim V.N.; RT "TUT4 in concert with Lin28 suppresses MicroRNA biogenesis through pre- RT microRNA uridylation."; RL Cell 138:696-708(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP INTERACTION WITH LIN28A. RX PubMed=22118463; DOI=10.1016/j.cell.2011.10.039; RA Piskounova E., Polytarchou C., Thornton J.E., LaPierre R.J., RA Pothoulakis C., Hagan J.P., Iliopoulos D., Gregory R.I.; RT "Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct RT mechanisms."; RL Cell 147:1066-1079(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND SER-156, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-1011. RX PubMed=25480299; DOI=10.1016/j.cell.2014.10.055; RA Lim J., Ha M., Chang H., Kwon S.C., Simanshu D.K., Patel D.J., Kim V.N.; RT "Uridylation by TUT4 and TUT7 marks mRNA for degradation."; RL Cell 159:1365-1376(2014). RN [14] RP FUNCTION. RX PubMed=25979828; DOI=10.15252/embj.201590931; RA Kim B., Ha M., Loeff L., Chang H., Simanshu D.K., Li S., Fareh M., RA Patel D.J., Joo C., Kim V.N.; RT "TUT7 controls the fate of precursor microRNAs by using three different RT uridylation mechanisms."; RL EMBO J. 34:1801-1815(2015). RN [15] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MOV10, AND MUTAGENESIS OF RP ASP-1011. RX PubMed=30122351; DOI=10.1016/j.cell.2018.07.022; RA Warkocki Z., Krawczyk P.S., Adamska D., Bijata K., Garcia-Perez J.L., RA Dziembowski A.; RT "Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s."; RL Cell 0:0-0(2018). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 253-723 IN COMPLEX WITH ZINC RP IONS, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LIN28A AND PRE-LET-7 RP RNA, AND MUTAGENESIS OF 253-SER--LEU-333; CYS-306; CYS-309; LYS-321; RP LYS-324; 326-LYS-ARG-327; 329-LYS-LYS-330; HIS-450; LYS-452 AND RP 669-ARG-ARG-670. RX PubMed=31036859; DOI=10.1038/s41467-019-09966-5; RA Yamashita S., Nagaike T., Tomita K.; RT "Crystal structure of the Lin28-interacting module of human terminal RT uridylyltransferase that regulates let-7 expression."; RL Nat. Commun. 10:1960-1960(2019). CC -!- FUNCTION: Uridylyltransferase that mediates the terminal uridylation of CC mRNAs with short (less than 25 nucleotides) poly(A) tails, hence CC facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). CC Essential for both oocyte maturation and fertility. Through 3' terminal CC uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by CC eliminating transcripts during oocyte growth (By similarity). Involved CC in microRNA (miRNA)-induced gene silencing through uridylation of CC deadenylated miRNA targets. Also functions as an integral regulator of CC microRNA biogenesis using 3 different uridylation mechanisms CC (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by CC mediating the terminal uridylation of some miRNA precursors, including CC that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated CC miRNAs are not processed by Dicer and undergo degradation. Degradation CC of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell CC pluripotency (By similarity). Also catalyzes the 3' uridylation of miR- CC 26A, a miRNA that targets IL6 transcript. This abrogates the silencing CC of IL6 transcript, hence promoting cytokine expression CC (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 CC monouridylate group II pre-miRNAs, which includes most of pre-let7 CC members, that shapes an optimal 3' end overhang for efficient CC processing (PubMed:25979828). Adds oligo-U tails to truncated pre- CC miRNAS with a 5' overhang which may promote rapid degradation of non- CC functional pre-miRNA species (PubMed:25979828). May also suppress Toll- CC like receptor-induced NF-kappa-B activation via binding to T2BP CC (PubMed:16643855). Does not play a role in replication-dependent CC histone mRNA degradation (PubMed:18172165). Due to functional CC redundancy between TUT4 and TUT7, the identification of the specific CC role of each of these proteins is difficult (PubMed:25979828, CC PubMed:25480299, PubMed:16643855, PubMed:19703396, PubMed:18172165) (By CC similarity). TUT4 and TUT7 restrict retrotransposition of long CC interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting CC the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in CC the cytoplasm which inhibits initiation of reverse transcription once CC in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in CC cytoplasmic ribonucleoprotein granules (PubMed:30122351). CC {ECO:0000250|UniProtKB:B2RX14, ECO:0000269|PubMed:16643855, CC ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:19703396, CC ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:25979828, CC ECO:0000269|PubMed:30122351, ECO:0000269|PubMed:31036859}. CC -!- CATALYTIC ACTIVITY: CC Reaction=RNA(n) + UTP = diphosphate + RNA(n)-3'-uridine ribonucleotide; CC Xref=Rhea:RHEA:14785, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17348, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:46398, ChEBI:CHEBI:140395, CC ChEBI:CHEBI:173116; EC=2.7.7.52; CC Evidence={ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:31036859}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- SUBUNIT: Interacts with LIN28A in the presence of pre-let-7 RNA CC (PubMed:19703396, PubMed:22118463, PubMed:31036859). Interacts with CC T2BP (PubMed:16643855). Interacts with MOV10; the interaction is RNA- CC dependent (PubMed:30122351). {ECO:0000269|PubMed:16643855, CC ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:22118463, CC ECO:0000269|PubMed:30122351, ECO:0000269|PubMed:31036859}. CC -!- INTERACTION: CC Q5TAX3-1; Q96CG3: TIFA; NbExp=2; IntAct=EBI-1606425, EBI-740711; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16643855}. Cytoplasm CC {ECO:0000269|PubMed:16643855, ECO:0000269|PubMed:19703396, CC ECO:0000269|PubMed:25480299}. Cytoplasm, Cytoplasmic ribonucleoprotein CC granule {ECO:0000269|PubMed:30122351}. Note=Mainly cytoplasmic CC (PubMed:19703396, PubMed:25480299). Translocates into the cytoplasm CC following treatment of the cell with LPS (PubMed:16643855). Co-enriched CC in cytoplasmic foci with MOV10 (PubMed:30122351). CC {ECO:0000269|PubMed:30122351}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5TAX3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5TAX3-2; Sequence=VSP_038135, VSP_038136; CC -!- DOMAIN: Utilizes two multidomain functional modules during the switch CC from monouridylation to oligouridylation. The catalytic module CC (containing the 3 CCHC-type Zinc finger domains) is essential for both CC activities while the Lin28-interacting module (LIM) at the N-termail CC part is indispensable for oligouridylation. CC {ECO:0000250|UniProtKB:B2RX14}. CC -!- SIMILARITY: Belongs to the DNA polymerase type-B-like family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK303532; BAH13981.1; -; mRNA. DR EMBL; AL138849; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06778.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06780.1; -; Genomic_DNA. DR EMBL; BC131734; AAI31735.1; -; mRNA. DR EMBL; D83776; BAA12105.1; -; mRNA. DR CCDS; CCDS30716.1; -. [Q5TAX3-1] DR RefSeq; NP_001009881.1; NM_001009881.2. DR RefSeq; NP_056084.1; NM_015269.2. [Q5TAX3-1] DR PDB; 6IW6; X-ray; 2.40 A; A/B=253-723. DR PDBsum; 6IW6; -. DR AlphaFoldDB; Q5TAX3; -. DR SMR; Q5TAX3; -. DR BioGRID; 116909; 85. DR IntAct; Q5TAX3; 17. DR MINT; Q5TAX3; -. DR STRING; 9606.ENSP00000257177; -. DR GlyGen; Q5TAX3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q5TAX3; -. DR PhosphoSitePlus; Q5TAX3; -. DR BioMuta; ZCCHC11; -. DR DMDM; 116242850; -. DR EPD; Q5TAX3; -. DR jPOST; Q5TAX3; -. DR MassIVE; Q5TAX3; -. DR MaxQB; Q5TAX3; -. DR PaxDb; 9606-ENSP00000257177; -. DR PeptideAtlas; Q5TAX3; -. DR ProteomicsDB; 64876; -. [Q5TAX3-1] DR ProteomicsDB; 64877; -. [Q5TAX3-2] DR Pumba; Q5TAX3; -. DR Antibodypedia; 19117; 241 antibodies from 32 providers. DR DNASU; 23318; -. DR Ensembl; ENST00000371544.7; ENSP00000360599.3; ENSG00000134744.14. [Q5TAX3-1] DR GeneID; 23318; -. DR KEGG; hsa:23318; -. DR UCSC; uc001ctx.3; human. [Q5TAX3-1] DR AGR; HGNC:28981; -. DR CTD; 23318; -. DR DisGeNET; 23318; -. DR GeneCards; TUT4; -. DR HGNC; HGNC:28981; TUT4. DR HPA; ENSG00000134744; Low tissue specificity. DR MIM; 613692; gene. DR neXtProt; NX_Q5TAX3; -. DR OpenTargets; ENSG00000134744; -. DR PharmGKB; PA134918178; -. DR VEuPathDB; HostDB:ENSG00000134744; -. DR eggNOG; KOG2277; Eukaryota. DR GeneTree; ENSGT00940000156988; -. DR InParanoid; Q5TAX3; -. DR OrthoDB; 170176at2759; -. DR PhylomeDB; Q5TAX3; -. DR TreeFam; TF315661; -. DR BRENDA; 2.7.7.52; 2681. DR PathwayCommons; Q5TAX3; -. DR Reactome; R-HSA-429947; Deadenylation of mRNA. DR Reactome; R-HSA-9819196; Zygotic genome activation (ZGA). DR Reactome; R-HSA-9820865; Z-decay: degradation of maternal mRNAs by zygotically expressed factors. DR SignaLink; Q5TAX3; -. DR SIGNOR; Q5TAX3; -. DR BioGRID-ORCS; 23318; 17 hits in 1161 CRISPR screens. DR ChiTaRS; ZCCHC11; human. DR GenomeRNAi; 23318; -. DR Pharos; Q5TAX3; Tbio. DR PRO; PR:Q5TAX3; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5TAX3; Protein. DR Bgee; ENSG00000134744; Expressed in right hemisphere of cerebellum and 191 other cell types or tissues. DR ExpressionAtlas; Q5TAX3; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0050265; F:RNA uridylyltransferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0010587; P:miRNA catabolic process; IMP:UniProtKB. DR GO; GO:0010586; P:miRNA metabolic process; IDA:UniProtKB. DR GO; GO:0001556; P:oocyte maturation; ISS:UniProtKB. DR GO; GO:1990074; P:polyuridylation-dependent mRNA catabolic process; ISS:UniProtKB. DR GO; GO:0031054; P:pre-miRNA processing; IDA:UniProtKB. DR GO; GO:0141008; P:retrotransposon silencing by mRNA destabilization; IDA:UniProtKB. DR GO; GO:0071076; P:RNA 3' uridylation; ISS:UniProtKB. DR GO; GO:0031123; P:RNA 3'-end processing; IDA:UniProtKB. DR GO; GO:0019827; P:stem cell population maintenance; IMP:UniProtKB. DR CDD; cd05402; NT_PAP_TUTase; 2. DR Gene3D; 1.10.1410.10; -; 2. DR Gene3D; 3.30.460.10; Beta Polymerase, domain 2; 2. DR Gene3D; 4.10.60.10; Zinc finger, CCHC-type; 1. DR InterPro; IPR043519; NT_sf. DR InterPro; IPR002058; PAP_assoc. DR InterPro; IPR002934; Polymerase_NTP_transf_dom. DR InterPro; IPR045100; TUTase_dom. DR InterPro; IPR001878; Znf_CCHC. DR InterPro; IPR036875; Znf_CCHC_sf. DR PANTHER; PTHR12271; POLY A POLYMERASE CID PAP -RELATED; 1. DR PANTHER; PTHR12271:SF49; TERMINAL URIDYLYLTRANSFERASE 4; 1. DR Pfam; PF01909; NTP_transf_2; 1. DR Pfam; PF03828; PAP_assoc; 2. DR Pfam; PF19088; TUTase; 1. DR Pfam; PF00098; zf-CCHC; 2. DR SMART; SM00343; ZnF_C2HC; 3. DR SUPFAM; SSF81301; Nucleotidyltransferase; 2. DR SUPFAM; SSF81631; PAP/OAS1 substrate-binding domain; 2. DR SUPFAM; SSF57756; Retrovirus zinc finger-like domains; 2. DR PROSITE; PS50158; ZF_CCHC; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1. DR Genevisible; Q5TAX3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Magnesium; Manganese; KW Metal-binding; Methylation; Nucleotidyltransferase; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; RNA-mediated gene silencing; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1..1644 FT /note="Terminal uridylyltransferase 4" FT /id="PRO_0000150970" FT DOMAIN 628..678 FT /note="PAP-associated 1" FT DOMAIN 1184..1237 FT /note="PAP-associated 2" FT ZN_FING 304..334 FT /note="Matrin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00130" FT ZN_FING 913..930 FT /note="CCHC-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047" FT ZN_FING 1293..1310 FT /note="CCHC-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047" FT ZN_FING 1357..1374 FT /note="CCHC-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047" FT REGION 31..63 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 96..168 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 205..257 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 253..333 FT /note="Required for interaction with LIN28A and pre-let-7 FT RNA" FT /evidence="ECO:0000269|PubMed:31036859" FT REGION 579..617 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 794..816 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 901..1634 FT /note="Sufficient for monouridylation activity" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT REGION 1321..1348 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1401..1482 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 108..152 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 206..229 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 234..253 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 583..617 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 306 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:31036859" FT BINDING 309 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:31036859" FT BINDING 322 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:31036859" FT BINDING 328 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:31036859" FT BINDING 998..1001 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT BINDING 1008..1011 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT BINDING 1009 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 1011 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 1081 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT BINDING 1103 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT BINDING 1121..1125 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT BINDING 1237 FT /ligand="UTP" FT /ligand_id="ChEBI:CHEBI:46398" FT /evidence="ECO:0000250|UniProtKB:Q5VYS8" FT MOD_RES 104 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:B2RX14" FT MOD_RES 156 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1624 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:B2RX14" FT VAR_SEQ 685..719 FT /note="RSLNSQLVYEYVVERFRAAYRYFACPQTKGGNKST -> LQPGRQEWKLCLK FT KKKKNSVKYTFIYEIQVSLFVI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038135" FT VAR_SEQ 720..1644 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038136" FT VARIANT 796 FT /note="D -> Y (in dbSNP:rs12127732)" FT /id="VAR_028402" FT MUTAGEN 253..333 FT /note="Missing: Loss of interaction with LIN28A and FT pre-let-7 RNA." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 306 FT /note="C->A: Loss of LIN28A and pre-let-7 RNA binding and FT loss of pre-let-7 RNA uridylylation; when associated with FT A-309." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 309 FT /note="C->A: Loss of LIN28A and pre-let-7 RNA binding and FT loss of pre-let-7 RNA uridylylation; when associated with FT A-306." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 321 FT /note="K->A: Strongly decreased LIN28A and pre-let-7 RNA FT binding and pre-let-7 RNA uridylylation; when associated FT with A-324." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 324 FT /note="K->A: Strongly decreased LIN28A and pre-let-7 RNA FT binding and pre-let-7 RNA uridylylation; when associated FT with A-321." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 326..327 FT /note="KR->AA: Strongly decreased LIN28A and pre-let-7 RNA FT binding and pre-let-7 RNA uridylylation." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 329..330 FT /note="KK->AA: Decreased LIN28A and pre-let-7 RNA binding FT and pre-let-7 RNA uridylylation." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 450 FT /note="H->A: Decreased LIN28A and pre-let-7 RNA binding and FT pre-let-7 RNA uridylylation; when associated with A-452." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 452 FT /note="K->A: Decreased LIN28A and pre-let-7 RNA binding and FT pre-let-7 RNA uridylylation; when associated with A-450." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 669..670 FT /note="RR->AA: Decreased LIN28A and pre-let-7 RNA binding FT and pre-let-7 RNA uridylylation." FT /evidence="ECO:0000269|PubMed:31036859" FT MUTAGEN 1011 FT /note="D->A: Loss of nucleotidyltransferase activity and FT stabilization of pre-let-7 miRNAs. Abolishes inhibition of FT LIRE1 retrotransposition." FT /evidence="ECO:0000269|PubMed:19703396, FT ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:30122351" FT CONFLICT 1313 FT /note="S -> SS (in Ref. 4; AAI31735)" FT /evidence="ECO:0000305" FT HELIX 255..260 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 266..268 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 271..285 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 286..288 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 307..310 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 316..323 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 326..342 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 349..366 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 370..388 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 395..399 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 401..404 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 413..418 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 421..423 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 425..438 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 442..448 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 450..453 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 455..460 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 461..463 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 466..472 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 474..489 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 493..502 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 503..505 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 506..509 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 517..532 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 533..535 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 541..543 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 558..563 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 564..566 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 567..571 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 613..619 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 629..641 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 646..648 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 649..651 FT /evidence="ECO:0007829|PDB:6IW6" FT TURN 661..665 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 673..675 FT /evidence="ECO:0007829|PDB:6IW6" FT STRAND 678..682 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 683..687 FT /evidence="ECO:0007829|PDB:6IW6" FT HELIX 690..707 FT /evidence="ECO:0007829|PDB:6IW6" SQ SEQUENCE 1644 AA; 185166 MW; B7C88D7DCF0F3356 CRC64; MEESKTLKSE NHEPKKNVIC EESKAVQVIG NQTLKARNDK SVKEIENSSP NRNSSKKNKQ NDICIEKTEV KSCKVNAANL PGPKDLGLVL RDQSHCKAKK FPNSPVKAEK ATISQAKSEK ATSLQAKAEK SPKSPNSVKA EKASSYQMKS EKVPSSPAEA EKGPSLLLKD MRQKTELQQI GKKIPSSFTS VDKVNIEAVG GEKCALQNSP RSQKQQTCTD NTGDSDDSAS GIEDVSDDLS KMKNDESNKE NSSEMDYLEN ATVIDESALT PEQRLGLKQA EERLERDHIF RLEKRSPEYT NCRYLCKLCL IHIENIQGAH KHIKEKRHKK NILEKQEESE LRSLPPPSPA HLAALSVAVI ELAKEHGITD DDLRVRQEIV EEMSKVITTF LPECSLRLYG SSLTRFALKS SDVNIDIKFP PKMNHPDLLI KVLGILKKNV LYVDVESDFH AKVPVVVCRD RKSGLLCRVS AGNDMACLTT DLLTALGKIE PVFIPLVLAF RYWAKLCYID SQTDGGIPSY CFALMVMFFL QQRKPPLLPC LLGSWIEGFD PKRMDDFQLK GIVEEKFVKW ECNSSSATEK NSIAEENKAK ADQPKDDTKK TETDNQSNAM KEKHGKSPLA LETPNRVSLG QLWLELLKFY TLDFALEEYV ICVRIQDILT RENKNWPKRR IAIEDPFSVK RNVARSLNSQ LVYEYVVERF RAAYRYFACP QTKGGNKSTV DFKKREKGKI SNKKPVKSNN MATNGCILLG ETTEKINAER EQPVQCDEMD CTSQRCIIDN NNLLVNELDF ADHGQDSSSL STSKSSEIEP KLDKKQDDLA PSETCLKKEL SQCNCIDLSK SPDPDKSTGT DCRSNLETES SHQSVCTDTS ATSCNCKATE DASDLNDDDN LPTQELYYVF DKFILTSGKP PTIVCSICKK DGHSKNDCPE DFRKIDLKPL PPMTNRFREI LDLVCKRCFD ELSPPCSEQH NREQILIGLE KFIQKEYDEK ARLCLFGSSK NGFGFRDSDL DICMTLEGHE NAEKLNCKEI IENLAKILKR HPGLRNILPI TTAKVPIVKF EHRRSGLEGD ISLYNTLAQH NTRMLATYAA IDPRVQYLGY TMKVFAKRCD IGDASRGSLS SYAYILMVLY FLQQRKPPVI PVLQEIFDGK QIPQRMVDGW NAFFFDKTEE LKKRLPSLGK NTESLGELWL GLLRFYTEEF DFKEYVISIR QKKLLTTFEK QWTSKCIAIE DPFDLNHNLG AGVSRKMTNF IMKAFINGRK LFGTPFYPLI GREAEYFFDS RVLTDGELAP NDRCCRVCGK IGHYMKDCPK RKSLLFRLKK KDSEEEKEGN EEEKDSRDVL DPRDLHDTRD FRDPRDLRCF ICGDAGHVRR ECPEVKLARQ RNSSVAAAQL VRNLVNAQQV AGSAQQQGDQ SIRTRQSSEC SESPSYSPQP QPFPQNSSQS AAITQPSSQP GSQPKLGPPQ QGAQPPHQVQ MPLYNFPQSP PAQYSPMHNM GLLPMHPLQI PAPSWPIHGP VIHSAPGSAP SNIGLNDPSI IFAQPAARPV AIPNTSHDGH WPRTVAPNSL VNSGAVGNSE PGFRGLTPPI PWEHAPRPHF PLVPASWPYG LHQNFMHQGN ARFQPNKPFY TQDRCATRRC RERCPHPPRG NVSE //