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Protein

Terminal uridylyltransferase 4

Gene

TUT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-fnctional 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).By similarity5 Publications

Catalytic activityi

UTP + RNA(n) = diphosphate + RNA(n+1).1 Publication

Cofactori

Mg2+By similarity, Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1009Magnesium or manganese; catalyticBy similarity1
Metal bindingi1011Magnesium or manganese; catalyticBy similarity1
Binding sitei1081UTPBy similarity1
Binding sitei1103UTPBy similarity1
Binding sitei1237UTPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri304 – 334Matrin-typePROSITE-ProRule annotationAdd BLAST31
Zinc fingeri913 – 930CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1293 – 1310CCHC-type 2PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1357 – 1374CCHC-type 3PROSITE-ProRule annotationAdd BLAST18

GO - Molecular functioni

  • RNA binding Source: UniProtKB
  • RNA uridylyltransferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • miRNA catabolic process Source: UniProtKB
  • miRNA metabolic process Source: UniProtKB
  • nuclear-transcribed mRNA poly(A) tail shortening Source: Reactome
  • pre-miRNA processing Source: UniProtKB
  • RNA 3'-end processing Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB

Keywordsi

Molecular functionNucleotidyltransferase, Transferase
Biological processRNA-mediated gene silencing
LigandMagnesium, Manganese, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.7.52 2681
ReactomeiR-HSA-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
Name:TUT4Imported
Synonyms:KIAA0191, ZCCHC11Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000134744.13
HGNCiHGNC:28981 TUT4
MIMi613692 gene
neXtProtiNX_Q5TAX3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1011D → A: Loss of nucleotidyltransferase activity and stabilization of pre-let-7 miRNAs. 2 Publications1

Organism-specific databases

DisGeNETi23318
OpenTargetsiENSG00000134744
PharmGKBiPA134918178

Polymorphism and mutation databases

BioMutaiZCCHC11
DMDMi116242850

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001509701 – 1644Terminal uridylyltransferase 4Add BLAST1644

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei104PhosphoserineCombined sources1
Modified residuei134PhosphoserineBy similarity1
Modified residuei156PhosphoserineCombined sources1
Modified residuei1624Omega-N-methylarginineBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ5TAX3
MaxQBiQ5TAX3
PaxDbiQ5TAX3
PeptideAtlasiQ5TAX3
PRIDEiQ5TAX3
ProteomicsDBi64876
64877 [Q5TAX3-2]

PTM databases

iPTMnetiQ5TAX3
PhosphoSitePlusiQ5TAX3

Expressioni

Gene expression databases

BgeeiENSG00000134744
CleanExiHS_ZCCHC11
ExpressionAtlasiQ5TAX3 baseline and differential
GenevisibleiQ5TAX3 HS

Organism-specific databases

HPAiHPA027412
HPA027973

Interactioni

Subunit structurei

Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:19703396, PubMed:22118463). Interacts with T2BP (PubMed:16643855).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TIFAQ96CG32EBI-1606425,EBI-740711

Protein-protein interaction databases

BioGridi116909, 22 interactors
IntActiQ5TAX3, 7 interactors
STRINGi9606.ENSP00000257177

Structurei

3D structure databases

ProteinModelPortaliQ5TAX3
SMRiQ5TAX3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini628 – 678PAP-associated 1Add BLAST51
Domaini1184 – 1237PAP-associated 2Add BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni901 – 1634Sufficient for monouridylation activityBy similarityAdd BLAST734
Regioni998 – 1001UTP bindingBy similarity4
Regioni1008 – 1011UTP bindingBy similarity4
Regioni1121 – 1125UTP bindingBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1398 – 1483Gln-richAdd BLAST86
Compositional biasi1424 – 1598Pro-richAdd BLAST175

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.By similarity

Sequence similaritiesi

Belongs to the DNA polymerase type-B-like family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri304 – 334Matrin-typePROSITE-ProRule annotationAdd BLAST31
Zinc fingeri913 – 930CCHC-type 1PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1293 – 1310CCHC-type 2PROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1357 – 1374CCHC-type 3PROSITE-ProRule annotationAdd BLAST18

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2277 Eukaryota
COG5260 LUCA
GeneTreeiENSGT00550000074490
InParanoidiQ5TAX3
KOiK13291
PhylomeDBiQ5TAX3
TreeFamiTF315661

Family and domain databases

InterProiView protein in InterPro
IPR002058 PAP_assoc
IPR002934 Polymerase_NTP_transf_dom
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
PfamiView protein in Pfam
PF01909 NTP_transf_2, 1 hit
PF03828 PAP_assoc, 2 hits
PF00098 zf-CCHC, 2 hits
SMARTiView protein in SMART
SM00343 ZnF_C2HC, 3 hits
SUPFAMiSSF57756 SSF57756, 2 hits
PROSITEiView protein in PROSITE
PS50158 ZF_CCHC, 3 hits
PS00028 ZINC_FINGER_C2H2_1, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5TAX3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEESKTLKSE NHEPKKNVIC EESKAVQVIG NQTLKARNDK SVKEIENSSP
60 70 80 90 100
NRNSSKKNKQ NDICIEKTEV KSCKVNAANL PGPKDLGLVL RDQSHCKAKK
110 120 130 140 150
FPNSPVKAEK ATISQAKSEK ATSLQAKAEK SPKSPNSVKA EKASSYQMKS
160 170 180 190 200
EKVPSSPAEA EKGPSLLLKD MRQKTELQQI GKKIPSSFTS VDKVNIEAVG
210 220 230 240 250
GEKCALQNSP RSQKQQTCTD NTGDSDDSAS GIEDVSDDLS KMKNDESNKE
260 270 280 290 300
NSSEMDYLEN ATVIDESALT PEQRLGLKQA EERLERDHIF RLEKRSPEYT
310 320 330 340 350
NCRYLCKLCL IHIENIQGAH KHIKEKRHKK NILEKQEESE LRSLPPPSPA
360 370 380 390 400
HLAALSVAVI ELAKEHGITD DDLRVRQEIV EEMSKVITTF LPECSLRLYG
410 420 430 440 450
SSLTRFALKS SDVNIDIKFP PKMNHPDLLI KVLGILKKNV LYVDVESDFH
460 470 480 490 500
AKVPVVVCRD RKSGLLCRVS AGNDMACLTT DLLTALGKIE PVFIPLVLAF
510 520 530 540 550
RYWAKLCYID SQTDGGIPSY CFALMVMFFL QQRKPPLLPC LLGSWIEGFD
560 570 580 590 600
PKRMDDFQLK GIVEEKFVKW ECNSSSATEK NSIAEENKAK ADQPKDDTKK
610 620 630 640 650
TETDNQSNAM KEKHGKSPLA LETPNRVSLG QLWLELLKFY TLDFALEEYV
660 670 680 690 700
ICVRIQDILT RENKNWPKRR IAIEDPFSVK RNVARSLNSQ LVYEYVVERF
710 720 730 740 750
RAAYRYFACP QTKGGNKSTV DFKKREKGKI SNKKPVKSNN MATNGCILLG
760 770 780 790 800
ETTEKINAER EQPVQCDEMD CTSQRCIIDN NNLLVNELDF ADHGQDSSSL
810 820 830 840 850
STSKSSEIEP KLDKKQDDLA PSETCLKKEL SQCNCIDLSK SPDPDKSTGT
860 870 880 890 900
DCRSNLETES SHQSVCTDTS ATSCNCKATE DASDLNDDDN LPTQELYYVF
910 920 930 940 950
DKFILTSGKP PTIVCSICKK DGHSKNDCPE DFRKIDLKPL PPMTNRFREI
960 970 980 990 1000
LDLVCKRCFD ELSPPCSEQH NREQILIGLE KFIQKEYDEK ARLCLFGSSK
1010 1020 1030 1040 1050
NGFGFRDSDL DICMTLEGHE NAEKLNCKEI IENLAKILKR HPGLRNILPI
1060 1070 1080 1090 1100
TTAKVPIVKF EHRRSGLEGD ISLYNTLAQH NTRMLATYAA IDPRVQYLGY
1110 1120 1130 1140 1150
TMKVFAKRCD IGDASRGSLS SYAYILMVLY FLQQRKPPVI PVLQEIFDGK
1160 1170 1180 1190 1200
QIPQRMVDGW NAFFFDKTEE LKKRLPSLGK NTESLGELWL GLLRFYTEEF
1210 1220 1230 1240 1250
DFKEYVISIR QKKLLTTFEK QWTSKCIAIE DPFDLNHNLG AGVSRKMTNF
1260 1270 1280 1290 1300
IMKAFINGRK LFGTPFYPLI GREAEYFFDS RVLTDGELAP NDRCCRVCGK
1310 1320 1330 1340 1350
IGHYMKDCPK RKSLLFRLKK KDSEEEKEGN EEEKDSRDVL DPRDLHDTRD
1360 1370 1380 1390 1400
FRDPRDLRCF ICGDAGHVRR ECPEVKLARQ RNSSVAAAQL VRNLVNAQQV
1410 1420 1430 1440 1450
AGSAQQQGDQ SIRTRQSSEC SESPSYSPQP QPFPQNSSQS AAITQPSSQP
1460 1470 1480 1490 1500
GSQPKLGPPQ QGAQPPHQVQ MPLYNFPQSP PAQYSPMHNM GLLPMHPLQI
1510 1520 1530 1540 1550
PAPSWPIHGP VIHSAPGSAP SNIGLNDPSI IFAQPAARPV AIPNTSHDGH
1560 1570 1580 1590 1600
WPRTVAPNSL VNSGAVGNSE PGFRGLTPPI PWEHAPRPHF PLVPASWPYG
1610 1620 1630 1640
LHQNFMHQGN ARFQPNKPFY TQDRCATRRC RERCPHPPRG NVSE
Length:1,644
Mass (Da):185,166
Last modified:October 17, 2006 - v3
Checksum:iB7C88D7DCF0F3356
GO
Isoform 2 (identifier: Q5TAX3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     685-719: RSLNSQLVYEYVVERFRAAYRYFACPQTKGGNKST → LQPGRQEWKLCLKKKKKNSVKYTFIYEIQVSLFVI
     720-1644: Missing.

Note: No experimental confirmation available.
Show »
Length:719
Mass (Da):81,141
Checksum:i51037667A4C3D3A1
GO

Sequence cautioni

The sequence CAI23477 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1313S → SS in AAI31735 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028402796D → Y. Corresponds to variant dbSNP:rs12127732Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038135685 – 719RSLNS…GNKST → LQPGRQEWKLCLKKKKKNSV KYTFIYEIQVSLFVI in isoform 2. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_038136720 – 1644Missing in isoform 2. 1 PublicationAdd BLAST925

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK303532 mRNA Translation: BAH13981.1
AL138849 Genomic DNA Translation: CAI23476.1
AL138849 Genomic DNA Translation: CAI23477.1 Sequence problems.
AL138849 Genomic DNA Translation: CAI23478.1
CH471059 Genomic DNA Translation: EAX06778.1
CH471059 Genomic DNA Translation: EAX06780.1
BC131734 mRNA Translation: AAI31735.1
D83776 mRNA Translation: BAA12105.1
CCDSiCCDS30716.1 [Q5TAX3-1]
RefSeqiNP_001009881.1, NM_001009881.2
NP_056084.1, NM_015269.2 [Q5TAX3-1]
UniGeneiHs.655407

Genome annotation databases

EnsembliENST00000371544; ENSP00000360599; ENSG00000134744 [Q5TAX3-1]
GeneIDi23318
KEGGihsa:23318
UCSCiuc001ctx.3 human [Q5TAX3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTUT4_HUMAN
AccessioniPrimary (citable) accession number: Q5TAX3
Secondary accession number(s): A2RRP0
, B7Z8J5, D3DQ35, Q12764, Q5TAX2, Q5TAX4, Q86XZ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: October 17, 2006
Last modified: July 18, 2018
This is version 128 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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