UniProtKB - B2RX14 (TUT4_MOUSE)
Protein
Terminal uridylyltransferase 4
Gene
Tut4
Organism
Mus musculus (Mouse)
Status
Functioni
Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:28792939). 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 (PubMed:28792939). 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 (By similarity). 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:28671666). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (By similarity). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (By similarity). Does not play a role in replication-dependent histone mRNA degradation (By similarity). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:28671666, PubMed:28792939, PubMed:22898984). 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 (By similarity).By similarity4 Publications
Catalytic activityi
- EC:2.7.7.521 Publication
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 326 | Zinc 1By similarity | 1 | |
Metal bindingi | 329 | Zinc 1By similarity | 1 | |
Metal bindingi | 342 | Zinc 1By similarity | 1 | |
Metal bindingi | 348 | Zinc 1By similarity | 1 | |
Metal bindingi | 1026 | Magnesium or manganese; catalyticBy similarity | 1 | |
Metal bindingi | 1028 | Magnesium or manganese; catalyticBy similarity | 1 | |
Binding sitei | 1098 | UTPBy similarity | 1 | |
Binding sitei | 1120 | UTPBy similarity | 1 | |
Binding sitei | 1254 | UTPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 324 – 354 | Matrin-typePROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 930 – 947 | CCHC-type 1PROSITE-ProRule annotationAdd BLAST | 18 | |
Zinc fingeri | 1310 – 1327 | CCHC-type 2PROSITE-ProRule annotationAdd BLAST | 18 | |
Zinc fingeri | 1358 – 1375 | CCHC-type 3PROSITE-ProRule annotationAdd BLAST | 18 |
GO - Molecular functioni
- miRNA binding Source: UniProtKB
- RNA uridylyltransferase activity Source: UniProtKB
- uridylyltransferase activity Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- cytokine production Source: MGI
- interleukin-6-mediated signaling pathway Source: UniProtKB
- miRNA catabolic process Source: UniProtKB
- miRNA metabolic process Source: UniProtKB
- negative regulation of NF-kappaB transcription factor activity Source: MGI
- negative regulation of transposition, RNA-mediated Source: UniProtKB
- oocyte maturation Source: UniProtKB
- polyuridylation-dependent mRNA catabolic process Source: UniProtKB
- positive regulation of interleukin-6 production Source: UniProtKB
- pre-miRNA processing Source: UniProtKB
- regulation of lipopolysaccharide-mediated signaling pathway Source: MGI
- RNA 3'-end processing Source: UniProtKB
- RNA 3' uridylation Source: UniProtKB
- stem cell population maintenance Source: UniProtKB
Keywordsi
Molecular function | Nucleotidyltransferase, Transferase |
Biological process | RNA-mediated gene silencing |
Ligand | Magnesium, Manganese, Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-429947 Deadenylation of mRNA |
Names & Taxonomyi
Protein namesi | Recommended name: Terminal uridylyltransferase 4Curated (EC:2.7.7.521 Publication)Short name: TUTase 4 Alternative name(s): Zinc finger CCHC domain-containing protein 11 |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2445126 Tut4 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm 1 Publication
- Cytoplasmic ribonucleoprotein granule By similarity
Note: Mainly cytoplasmic (PubMed:19703396). Translocates into the cytoplasm following treatment of the cell with LPS. Co-enriched in cytoplasmic foci with MOV10.By similarity1 Publication
Cytosol
- cytosol Source: MGI
Nucleus
Other locations
- cytoplasm Source: MGI
- cytoplasmic ribonucleoprotein granule Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Double conditional knockouts that have deleted both TUT4 and TUT7 at the secondary oocyte stage are infertile. Females ovulate normal numbers of oocytes with normal morphology of antral follicles but with a slight decrease in the frequency of surrounded nucleolus state oocytes. Mutant oocytes are unable to support early embryonic development, they fail to complete meiosis I properly.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 326 | C → A: No effect on basal uridylation activity, but loss of LIN28A-enhanced uridylation; when associated with A-329. 1 Publication | 1 | |
Mutagenesisi | 329 | C → A: No effect on basal uridylation activity, but loss of LIN28A-enhanced uridylation; when associated with A-326. 1 Publication | 1 | |
Mutagenesisi | 1026 | D → A: Loss of nucleotidyltransferase activity and oocytes are unable to support early embryonic development; when associated with A-1028. 2 Publications | 1 | |
Mutagenesisi | 1028 | D → A: Loss of nucleotidyltransferase activity and oocytes are unable to support early embryonic development; when associated with A-1026. 2 Publications | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000385330 | 1 – 1644 | Terminal uridylyltransferase 4Add BLAST | 1644 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 102 | PhosphoserineBy similarity | 1 | |
Modified residuei | 131 | PhosphoserineCombined sources | 1 | |
Modified residuei | 176 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1624 | Omega-N-methylarginineCombined sources | 1 |
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | B2RX14 |
jPOSTi | B2RX14 |
MaxQBi | B2RX14 |
PaxDbi | B2RX14 |
PRIDEi | B2RX14 |
PTM databases
iPTMneti | B2RX14 |
PhosphoSitePlusi | B2RX14 |
Expressioni
Tissue specificityi
Ubiquitously expressed.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000034610 Expressed in 240 organ(s), highest expression level in dorsal pancreas |
ExpressionAtlasi | B2RX14 baseline and differential |
Genevisiblei | B2RX14 MM |
Interactioni
Subunit structurei
Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:28671666).
Interacts with T2BP.
Interacts with MOV10; the interaction is RNA-dependent.
By similarityProtein-protein interaction databases
BioGridi | 230978, 1 interactor |
DIPi | DIP-48571N |
IntActi | B2RX14, 1 interactor |
STRINGi | 10090.ENSMUSP00000095538 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 649 – 698 | PAP-associated 1Add BLAST | 50 | |
Domaini | 1201 – 1254 | PAP-associated 2Add BLAST | 54 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 273 – 353 | Required for interaction with LIN28A and pre-let-7 RNABy similarityAdd BLAST | 81 | |
Regioni | 918 – 1634 | Sufficient for monouridylation activityBy similarityAdd BLAST | 717 | |
Regioni | 1015 – 1018 | UTP bindingBy similarity | 4 | |
Regioni | 1025 – 1028 | UTP bindingBy similarity | 4 | |
Regioni | 1138 – 1142 | UTP bindingBy similarity | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1425 – 1598 | Pro-richAdd BLAST | 174 |
Domaini
Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activites while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation.1 Publication
Sequence similaritiesi
Belongs to the DNA polymerase type-B-like family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 324 – 354 | Matrin-typePROSITE-ProRule annotationAdd BLAST | 31 | |
Zinc fingeri | 930 – 947 | CCHC-type 1PROSITE-ProRule annotationAdd BLAST | 18 | |
Zinc fingeri | 1310 – 1327 | CCHC-type 2PROSITE-ProRule annotationAdd BLAST | 18 | |
Zinc fingeri | 1358 – 1375 | CCHC-type 3PROSITE-ProRule annotationAdd BLAST | 18 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG2277 Eukaryota COG5260 LUCA |
GeneTreei | ENSGT00940000156988 |
HOGENOMi | HOG000231134 |
InParanoidi | B2RX14 |
KOi | K13291 |
OMAi | NWIEGFD |
OrthoDBi | 803033at2759 |
Family and domain databases
InterProi | View protein in InterPro IPR002058 PAP_assoc IPR002934 Polymerase_NTP_transf_dom IPR001878 Znf_CCHC IPR036875 Znf_CCHC_sf |
Pfami | View protein in Pfam PF01909 NTP_transf_2, 1 hit PF03828 PAP_assoc, 2 hits PF00098 zf-CCHC, 2 hits |
SMARTi | View protein in SMART SM00343 ZnF_C2HC, 3 hits |
SUPFAMi | SSF57756 SSF57756, 2 hits |
PROSITEi | View protein in PROSITE PS50158 ZF_CCHC, 3 hits PS00028 ZINC_FINGER_C2H2_1, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
B2RX14-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEEPKTSKNE NHEPKKNIIC EESKAVKIIS NQTLKPRNDK SEIGTSSLNR
60 70 80 90 100
NSSKKTKQND ICIEKTEAKS CKVNAASVPG PKDLGLVHRD QSHCKMKKLP
110 120 130 140 150
NSPMKAQKGS SQTKLEKTPS LQTKAEKVPK SPNLPVKAEK APCTTAEATT
160 170 180 190 200
EKALNSQRKE ENTPTSQMKL QKTPRSPLEP ENVPSLLLKE NVKQTESQQT
210 220 230 240 250
GKKLTSSFVS MDKRKSEALQ GEKSALENSS LSQKQQTQTD NIADSDDSAS
260 270 280 290 300
GIEDTADDLS KMKSEESNKE NSSEMDYLEN ATVIDESALT PEQRLGLKQA
310 320 330 340 350
EERLERDHIF RLEKRSPEYT NCRYLCKLCL IHIENIQGAH KHIKEKRHKK
360 370 380 390 400
NILEKQEESE LRSLPSPSSA HLAALSVAVV ELAKEQGITD DDLRIRQDIV
410 420 430 440 450
EEMSKVIMTF LPECSLRLYG SSLTKFALKS SDVNIDIKFP PKMNHPDLLI
460 470 480 490 500
QVLGILKKSA LYIDVESDFH AKVPVVVCKD RKSALLCRVS AGNDMACLTT
510 520 530 540 550
DLLAALGKVE PVFTPLVLAF RYWAKLCYID SQTDGGIPSY CFALMVMFFL
560 570 580 590 600
QQRKPPLLPC LLGSWIEGFD PKRMDDFQLK GIVEEKFVKW EYNSSSATEK
610 620 630 640 650
NLIADENKAK ADEPKDDTKK TETDNQSNAA KAKHGKSPLT LEAPNQVPLG
660 670 680 690 700
QLWLELLKFY TLDFALEEYV ICVRIQDILT RENKNWPKRR IAIEDPFSVK
710 720 730 740 750
RNVARSLNSQ LVYEYVVERF RAAYRYFACP QKKGGNKSTM DPKKKEKGKL
760 770 780 790 800
SSKKPVKSDC SATNCCILGE SAEKIHMERG QPAKHDETEF TSQRCIVDND
810 820 830 840 850
SLLVNELGLA NHGQDSSSLS TASGGSDLKQ KSAEKQGDLT PSETSLKKEL
860 870 880 890 900
SQCICIGTPD GAESAGTDCR SNLEMDSSHQ IVCNNVSATS CNCKATEVTS
910 920 930 940 950
DLVDEDNLPS QELYYVFDKF ILTSGKPPTI VCSICKKDGH SKNDCPEDFR
960 970 980 990 1000
KIDLKPLPPM TNRFREILDL VCKRCFDELS PPCSEQHNRE QILIGLEKFI
1010 1020 1030 1040 1050
QKEYDEKARL CLFGSSKNGF GFRDSDLDIC MTLEGHENAE KLNCKEIIEN
1060 1070 1080 1090 1100
LAKILKRHPG LRNILPITTA KVPIVKFEHR RSGLEGDISL YNTLAQHNTR
1110 1120 1130 1140 1150
MLATYAAIDP RVQYLGYTMK VFAKRCDIGD ASRGSLSSYA YILMVLYFLQ
1160 1170 1180 1190 1200
QRKPPVIPVL QEIFDGKQIP QRMVDGWNAF FFDKTEELKK RLPSLGKNTE
1210 1220 1230 1240 1250
SLGELWLGLL RFYTEEFDFK EYVISIRQKK LLTTFEKQWT SKCIAIEDPF
1260 1270 1280 1290 1300
DLNHNLGAGV SRKMTNFIMK AFINGRKLFG TPFYPLIGRE AEYFFDSRVL
1310 1320 1330 1340 1350
TDGELAPNDR CCRVCGKIGH YMKDCPKRKR LKKKDSEEEK EGNEEEKDSR
1360 1370 1380 1390 1400
DLLDSRDLRC FICGDAGHVR RECPEVKMAR QRNSSVAAAQ LVRNLVNAQQ
1410 1420 1430 1440 1450
VAGSAQQQSD QSIRTRQSSE CSDSPSYSPQ PQPFPQNSPQ PSALPPPPSQ
1460 1470 1480 1490 1500
PGSQPKLGPP QQGGQPPHQV QMPLYNFPQS PPAHYSPMHS MGLLPMHPLQ
1510 1520 1530 1540 1550
IPAPSWPIHG PMLHSAPGST PSNIGLNDPS IIFAQPAARP MAIPSPSHDG
1560 1570 1580 1590 1600
HWPRTVAPNS LVNNGAVGNS EPRFRGLNPP IPWEHAPRHF PLVPASWPYG
1610 1620 1630 1640
LHQNFMHQGN PRFQPKPFYA QADRCATRRC RERCPHPPRG NVSE
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA2A8R7 | A2A8R7_MOUSE | Terminal uridylyltransferase 4 | Tut4 Zcchc11 | 1,648 | Annotation score: | ||
A0A0A0MQJ6 | A0A0A0MQJ6_MOUSE | Terminal uridylyltransferase 4 | Tut4 Zcchc11 | 1,006 | Annotation score: | ||
A2A8R1 | A2A8R1_MOUSE | Terminal uridylyltransferase 4 | Tut4 Zcchc11 | 105 | Annotation score: | ||
A2A9H0 | A2A9H0_MOUSE | Terminal uridylyltransferase 4 | Tut4 Zcchc11 | 63 | Annotation score: |
Sequence cautioni
The sequence CAM23506 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAM25329 differs from that shown. Reason: Erroneous gene model prediction.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 815 | D → A in AAI50792 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 815 | D → A in BAD90397 (Ref. 3) Curated | 1 | |
Sequence conflicti | 1336 | S → R in BAE22125 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 1422 | S → C in BAE22125 (PubMed:16141072).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL626783, AL627238 Genomic DNA Translation: CAM23506.1 Sequence problems. AL627238, AL626783 Genomic DNA Translation: CAM25329.1 Sequence problems. BC150791 mRNA Translation: AAI50792.1 AK220327 mRNA Translation: BAD90397.1 AK134388 mRNA Translation: BAE22125.1 |
CCDSi | CCDS18451.1 |
RefSeqi | NP_780681.2, NM_175472.3 |
Genome annotation databases
Ensembli | ENSMUST00000043368; ENSMUSP00000044836; ENSMUSG00000034610 |
GeneIDi | 230594 |
KEGGi | mmu:230594 |
UCSCi | uc008ubd.1 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL626783, AL627238 Genomic DNA Translation: CAM23506.1 Sequence problems. AL627238, AL626783 Genomic DNA Translation: CAM25329.1 Sequence problems. BC150791 mRNA Translation: AAI50792.1 AK220327 mRNA Translation: BAD90397.1 AK134388 mRNA Translation: BAE22125.1 |
CCDSi | CCDS18451.1 |
RefSeqi | NP_780681.2, NM_175472.3 |
3D structure databases
SMRi | B2RX14 |
ModBasei | Search... |
Protein-protein interaction databases
BioGridi | 230978, 1 interactor |
DIPi | DIP-48571N |
IntActi | B2RX14, 1 interactor |
STRINGi | 10090.ENSMUSP00000095538 |
PTM databases
iPTMneti | B2RX14 |
PhosphoSitePlusi | B2RX14 |
Proteomic databases
EPDi | B2RX14 |
jPOSTi | B2RX14 |
MaxQBi | B2RX14 |
PaxDbi | B2RX14 |
PRIDEi | B2RX14 |
Genome annotation databases
Ensembli | ENSMUST00000043368; ENSMUSP00000044836; ENSMUSG00000034610 |
GeneIDi | 230594 |
KEGGi | mmu:230594 |
UCSCi | uc008ubd.1 mouse |
Organism-specific databases
CTDi | 23318 |
MGIi | MGI:2445126 Tut4 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG2277 Eukaryota COG5260 LUCA |
GeneTreei | ENSGT00940000156988 |
HOGENOMi | HOG000231134 |
InParanoidi | B2RX14 |
KOi | K13291 |
OMAi | NWIEGFD |
OrthoDBi | 803033at2759 |
Enzyme and pathway databases
Reactomei | R-MMU-429947 Deadenylation of mRNA |
Miscellaneous databases
ChiTaRSi | Zcchc11 mouse |
PROi | PR:B2RX14 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000034610 Expressed in 240 organ(s), highest expression level in dorsal pancreas |
ExpressionAtlasi | B2RX14 baseline and differential |
Genevisiblei | B2RX14 MM |
Family and domain databases
InterProi | View protein in InterPro IPR002058 PAP_assoc IPR002934 Polymerase_NTP_transf_dom IPR001878 Znf_CCHC IPR036875 Znf_CCHC_sf |
Pfami | View protein in Pfam PF01909 NTP_transf_2, 1 hit PF03828 PAP_assoc, 2 hits PF00098 zf-CCHC, 2 hits |
SMARTi | View protein in SMART SM00343 ZnF_C2HC, 3 hits |
SUPFAMi | SSF57756 SSF57756, 2 hits |
PROSITEi | View protein in PROSITE PS50158 ZF_CCHC, 3 hits PS00028 ZINC_FINGER_C2H2_1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TUT4_MOUSE | |
Accessioni | B2RX14Primary (citable) accession number: B2RX14 Secondary accession number(s): A2A8R8, Q3UYT6, Q5DU43 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 22, 2009 |
Last sequence update: | September 22, 2009 | |
Last modified: | October 16, 2019 | |
This is version 91 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot