TUT4_HUMAN
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 03-AUG-2022, entry version 152.
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}.
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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; 73.
DR IntAct; Q5TAX3; 16.
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; Q5TAX3; -.
DR PeptideAtlas; Q5TAX3; -.
DR PRIDE; Q5TAX3; -.
DR ProteomicsDB; 64876; -. [Q5TAX3-1]
DR ProteomicsDB; 64877; -. [Q5TAX3-2]
DR Antibodypedia; 19117; 214 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 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; 803033at2759; -.
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 SignaLink; Q5TAX3; -.
DR SIGNOR; Q5TAX3; -.
DR BioGRID-ORCS; 23318; 14 hits in 1083 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 189 other tissues.
DR ExpressionAtlas; Q5TAX3; baseline and differential.
DR Genevisible; Q5TAX3; HS.
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:0016779; F:nucleotidyltransferase activity; IBA:GO_Central.
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:0010526; P:negative regulation of transposition, RNA-mediated; IDA:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
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: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 Gene3D; 3.30.460.10; -; 2.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR002058; PAP_assoc.
DR InterPro; IPR045100; TUTase_dom.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF03828; PAP_assoc; 2.
DR Pfam; PF19088; TUTase; 2.
DR Pfam; PF00098; zf-CCHC; 2.
DR SMART; SM00343; ZnF_C2HC; 3.
DR SUPFAM; SSF57756; SSF57756; 2.
DR SUPFAM; SSF81301; SSF81301; 2.
DR PROSITE; PS50158; ZF_CCHC; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
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 pre-
FT 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
