TUT4 Gene (Protein Coding)

Terminal Uridylyl Transferase 4

GC01M052410
GIFtS:
29
ZCCHC11 is an RNA uridyltransferase (EC 2.7.7.52) that uses UTP to add uridines to the 3-prime end of substrate RNA molecules (Jones et al., 2009 [PubMed 19701194]).[supplied by OMIM, Jan 2011] See more...

Aliases for TUT4 Gene

Aliases for TUT4 Gene

  • Terminal Uridylyl Transferase 4 2 3 5
  • Zinc Finger CCHC Domain-Containing Protein 11 3 4
  • Zinc Finger CCHC-Type Containing 11 2 3
  • Terminal Uridylyltransferase 4 3 4
  • TUTase 4 3 4
  • ZCCHC11 3 4
  • Zinc Finger, CCHC Domain Containing 11 3
  • PAP Associated Domain Containing 3 3
  • EC 2.7.7.52 4
  • KIAA0191 4
  • TUTase4 2
  • TENT3A 3
  • PAPD3 3

External Ids for TUT4 Gene

Previous HGNC Symbols for TUT4 Gene

  • ZCCHC11

Summaries for TUT4 Gene

Entrez Gene Summary for TUT4 Gene

  • ZCCHC11 is an RNA uridyltransferase (EC 2.7.7.52) that uses UTP to add uridines to the 3-prime end of substrate RNA molecules (Jones et al., 2009 [PubMed 19701194]).[supplied by OMIM, Jan 2011]

GeneCards Summary for TUT4 Gene

TUT4 (Terminal Uridylyl Transferase 4) is a Protein Coding gene. Diseases associated with TUT4 include Perlman Syndrome and Spastic Ataxia 4. An important paralog of this gene is TUT7.

UniProtKB/Swiss-Prot Summary for TUT4 Gene

  • Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesis using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Adds oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (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). 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 (PubMed:30122351).

Additional gene information for TUT4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TUT4 Gene

Genomics for TUT4 Gene

GeneHancer (GH) Regulatory Elements for TUT4 Gene

Promoters and enhancers for TUT4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TUT4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TUT4

Genomic Locations for TUT4 Gene

Genomic Locations for TUT4 Gene
chr1:52,408,282-52,553,487
(GRCh38/hg38)
Size:
145,206 bases
Orientation:
Minus strand
chr1:52,873,954-53,019,159
(GRCh37/hg19)
Size:
145,206 bases
Orientation:
Minus strand

Genomic View for TUT4 Gene

Genes around TUT4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TUT4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TUT4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for TUT4 Gene

Proteins for TUT4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for TUT4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5TAX3-TUT4_HUMAN
    Recommended name:
    Terminal uridylyltransferase 4
    Protein Accession:
    Q5TAX3
    Secondary Accessions:
    • A2RRP0
    • B7Z8J5
    • D3DQ35
    • Q12764
    • Q5TAX2
    • Q5TAX4
    • Q86XZ3

    Protein attributes for TUT4 Gene

    Size:
    1644 amino acids
    Molecular mass:
    185166 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:19703396, PubMed:22118463, PubMed:31036859). Interacts with T2BP (PubMed:16643855). Interacts with MOV10; the interaction is RNA-dependent (PubMed:30122351).

    Three dimensional structures from OCA and Proteopedia for TUT4 Gene

    Alternative splice isoforms for TUT4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TUT4 Gene

Post-translational modifications for TUT4 Gene

  • Ubiquitination at Lys680, Lys1000, Lys1036, and Lys1260
  • Modification sites at PhosphoSitePlus

Other Protein References for TUT4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TUT4 Gene

Domains & Families for TUT4 Gene

Gene Families for TUT4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for TUT4 Gene

Blocks:
  • DNA polymerase, beta-like region
  • PAP/25A-associated domain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TUT4 Gene

GenScript: Design optimal peptide antigens:
  • Zinc finger CCHC domain-containing protein 11 (TUT4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q5TAX3

UniProtKB/Swiss-Prot:

TUT4_HUMAN :
  • 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.
  • Belongs to the DNA polymerase type-B-like family.
Domain:
  • 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.
Family:
  • Belongs to the DNA polymerase type-B-like family.
genes like me logo Genes that share domains with TUT4: view

Function for TUT4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
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Molecular function for TUT4 Gene

UniProtKB/Swiss-Prot Function:
Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesis using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Adds oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (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). 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 (PubMed:30122351).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=RNA(n) + UTP = diphosphate + RNA(n)-3'-uridine ribonucleotide; Xref=Rhea:RHEA:14785, Rhea:RHEA-COMP:11128, Rhea:RHEA-COMP:14648, ChEBI:CHEBI:33019, ChEBI:CHEBI:46398, ChEBI:CHEBI:83400, ChEBI:CHEBI:140627; EC=2.7.7.52; Evidence=. ;.

Enzyme Numbers (IUBMB) for TUT4 Gene

Phenotypes From GWAS Catalog for TUT4 Gene

Gene Ontology (GO) - Molecular Function for TUT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003723 RNA binding HDA 22658674
GO:0005515 protein binding IPI 19703396
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with TUT4: view
genes like me logo Genes that share phenotypes with TUT4: view

Animal Models for TUT4 Gene

MGI Knock Outs for TUT4:
  • Tut4 Tut4<tm1a(KOMP)Wtsi>
  • Tut4 Tut4<tm3.1Doca>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TUT4

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TUT4 Gene

Localization for TUT4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TUT4 Gene

Nucleus. Cytoplasm. Cytoplasm, Cytoplasmic ribonucleoprotein granule. Note=Mainly cytoplasmic (PubMed:19703396, PubMed:25480299). Translocates into the cytoplasm following treatment of the cell with LPS (PubMed:16643855). Co-enriched in cytoplasmic foci with MOV10 (PubMed:30122351). {ECO:0000269 PubMed:30122351}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TUT4 gene
Compartment Confidence
nucleus 5
cytosol 4
extracellular 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoli (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TUT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space HDA 22664934
GO:0005634 nucleus IEA --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IDA,IEA 19703396
GO:0005829 cytosol IDA,TAS --
genes like me logo Genes that share ontologies with TUT4: view

Pathways & Interactions for TUT4 Gene

PathCards logo

SuperPathways for TUT4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for TUT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening TAS --
GO:0001556 oocyte maturation ISS --
GO:0001816 cytokine production IEA --
GO:0010526 negative regulation of transposition, RNA-mediated IDA 30122351
GO:0010586 miRNA metabolic process ISS --
genes like me logo Genes that share ontologies with TUT4: view

No data available for Pathways by source and SIGNOR curated interactions for TUT4 Gene

Drugs & Compounds for TUT4 Gene

Products:

  1. Drug

(1) Drugs for TUT4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Uridine triphosphate Experimental, Investigational Pharma 0

(1) Additional Compounds for TUT4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
 14000-31-8
genes like me logo Genes that share compounds with TUT4: view

Transcripts for TUT4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for TUT4 Gene

3 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
21 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TUT4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TUT4 Gene

No ASD Table

Relevant External Links for TUT4 Gene

GeneLoc Exon Structure for
TUT4

Expression for TUT4 Gene

Products:

  1. Primer

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TUT4

Evidence on tissue expression from TISSUES for TUT4 Gene

  • Bone marrow(4.2)
  • Nervous system(2.9)
No Expression Related Data Available

Primer Products

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TUT4 Gene

Orthologs for TUT4 Gene

This gene was present in the common ancestor of animals.

Orthologs for TUT4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia ZCCHC11 31 30
  • 99.66 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia ZCCHC11 31 30
  • 92.76 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia LOC528986 30
  • 92.69 (n)
ZCCHC11 31
  • 90 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Zcchc11 31 30
  • 89.11 (n)
 OneToOne
Tut4 17
rat
(Rattus norvegicus)
 Mammalia Zcchc11 30
  • 88.51 (n)
oppossum
(Monodelphis domestica)
 Mammalia ZCCHC11 31
  • 71 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia ZCCHC11 31
  • 66 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves ZCCHC11 31 30
  • 73.79 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia ZCCHC11 31
  • 62 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia zcchc11 30
  • 65.48 (n)
Str.15797 30
zebrafish
(Danio rerio)
 Actinopterygii LOC795358 30
  • 64.94 (n)
zcchc11 31
  • 47 (a)
 OneToOne
Dr.17857 30
fruit fly
(Drosophila melanogaster)
 Insecta mkg-p 31
  • 15 (a)
 ManyToMany
worm
(Caenorhabditis elegans)
 Secernentea pup-2 31
  • 26 (a)
 ManyToMany
cid-1 31
  • 20 (a)
 ManyToMany
Y34F4.3 31
  • 20 (a)
 ManyToMany
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.5065 31
  • 41 (a)
 OneToMany
Cin.4240 30
sea squirt
(Ciona intestinalis)
 Ascidiacea Cin.4240 30
Species where no ortholog for TUT4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TUT4 Gene

ENSEMBL:
Gene Tree for TUT4 (if available)
TreeFam:
Gene Tree for TUT4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TUT4: view image

Paralogs for TUT4 Gene

Paralogs for TUT4 Gene

genes like me logo Genes that share paralogs with TUT4: view

Variants for TUT4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TUT4 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
719704 Benign: not provided 52,461,743(-) T/C SYNONYMOUS_VARIANT
719705 Benign: not provided 52,525,715(-) G/A MISSENSE_VARIANT
769514 Benign: not provided 52,475,173(-) C/A MISSENSE_VARIANT
780240 Benign: not provided 52,525,897(-) T/C SYNONYMOUS_VARIANT
791794 Benign: not provided 52,461,623(-) T/A INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for TUT4 Gene

Structural Variations from Database of Genomic Variants (DGV) for TUT4 Gene

Variant ID Type Subtype PubMed ID
esv3586051 CNV loss 21293372
esv988243 CNV insertion 20482838
nsv1137759 CNV deletion 24896259

Variation tolerance for TUT4 Gene

Residual Variation Intolerance Score: 2.47% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.40; 54.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TUT4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TUT4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TUT4 Gene

Disorders for TUT4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for TUT4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
perlman syndrome
  • nephroblastoma
spastic ataxia 4
cardiomyopathy, familial hypertrophic, 13
  • cmh13
- elite association - COSMIC cancer census association via MalaCards
Search TUT4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TUT4

ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TUT4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TUT4 Gene

Publications for TUT4 Gene

  1. Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1. (PMID: 8724849) Nagase T … Nomura N (DNA research : an international journal for rapid publication of reports on genes and genomes 1996) 2 3 4 54
  2. Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s. (PMID: 30122351) Warkocki Z … Dziembowski A (Cell 2018) 3 4 54
  3. TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms. (PMID: 25979828) Kim B … Kim VN (The EMBO journal 2015) 3 4 54
  4. Uridylation by TUT4 and TUT7 marks mRNA for degradation. (PMID: 25480299) Lim J … Kim VN (Cell 2014) 3 4 54
  5. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. (PMID: 19703396) Heo I … Kim VN (Cell 2009) 3 4 54

ExternalLinks

View latest publications for TUT4 gene in Mastermind

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