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Aliases for DTL Gene

Aliases for DTL Gene

  • Denticleless E3 Ubiquitin Protein Ligase Homolog 2 3 5
  • Retinoic Acid-Regulated Nuclear Matrix-Associated Protein 3 4
  • Lethal(2) Denticleless Protein Homolog 3 4
  • DDB1- And CUL4-Associated Factor 2 3 4
  • DCAF2 3 4
  • L2DTL 3 4
  • CDT2 3 4
  • RAMP 3 4
  • Denticleless E3 Ubiquitin Protein Ligase Homolog (Drosophila) 2
  • RA Regulated Nuclear Matrix Associated Protein 2
  • RA-Regulated Nuclear Matrix-Associated Protein 3
  • DDB1 And CUL4 Associated Factor 2 2
  • Denticleless Homolog (Drosophila) 2
  • Denticleless Protein Homolog 3
  • CDW1 4

External Ids for DTL Gene

Previous GeneCards Identifiers for DTL Gene

  • GC01P208598
  • GC01P210275
  • GC01P212208
  • GC01P182885

Summaries for DTL Gene

GeneCards Summary for DTL Gene

DTL (Denticleless E3 Ubiquitin Protein Ligase Homolog) is a Protein Coding gene. Diseases associated with DTL include Myasthenic Syndrome, Congenital, 8, With Pre- And Postsynaptic Defects. Among its related pathways are Telomere C-strand (Lagging Strand) Synthesis and DNA Double-Strand Break Repair. GO annotations related to this gene include ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot for DTL Gene

  • Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBXO18/FBH1 and KMT5A (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the K+4 motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the Lys-164 monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613).

Gene Wiki entry for DTL Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DTL Gene

Genomics for DTL Gene

Regulatory Elements for DTL Gene

Enhancers for DTL Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G212087 1.5 FANTOM5 Ensembl ENCODE 10.9 +53.0 53017 1.3 FOXA2 PKNOX1 ARNT FEZF1 ZNF2 YY1 TCF12 ZNF766 GATA2 TSHZ1 INTS7 DTL LOC102723727 PPP2R5A GC01P212093 MIR3122
GH01G212315 1.3 Ensembl ENCODE dbSUPER 11.2 +280.6 280559 0.7 NFRKB RAD21 YY1 SMARCA5 ZNF654 ZNF362 USF2 REST HDAC8 TBX21 DTL INTS7 ENSG00000212187 RPL23AP18 ENSG00000234915
GH01G212430 1.4 ENCODE dbSUPER 10 +396.6 396620 4.2 ARNT CREB3L1 SIN3A YBX1 FEZF1 ZNF2 ZNF766 ZNF143 ZNF207 KLF13 LOC101929541 TMEM206 PPP2R5A FLVCR1 INTS7 DTL ENSG00000212187 BATF3 LOC105372906
GH01G212309 1.2 Ensembl ENCODE dbSUPER 11 +275.1 275084 1.4 SOX13 TFAP4 CEBPG RBBP5 ZNF155 ZFHX2 ZNF157 EGR2 EZH2 GATAD2A PPP2R5A TMEM206 DTL INTS7 RPL23AP18 ENSG00000234915
GH01G211674 1.2 ENCODE 10.3 -360.0 -359951 2.3 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 ZNF143 SP3 NFYC MEF2D DTL INTS7 SNX25P1 SLC30A1 LOC91548 NEK2 FDPSP8
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around DTL on UCSC Golden Path with GeneCards custom track

Promoters for DTL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000019650 147 3401 CREB3L1 DMAP1 YY1 SLC30A9 ZNF143 SP3 NFYC TBX21 MEF2D GLIS1

Genomic Location for DTL Gene

Chromosome:
1
Start:
212,035,553 bp from pter
End:
212,107,400 bp from pter
Size:
71,848 bases
Orientation:
Plus strand

Genomic View for DTL Gene

Genes around DTL on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for DTL Gene

Proteins for DTL Gene

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

    Protein Symbol:
    Q9NZJ0-DTL_HUMAN
    Recommended name:
    Denticleless protein homolog
    Protein Accession:
    Q9NZJ0
    Secondary Accessions:
    • A8K8H8
    • D3DT98
    • Q5VT77
    • Q96SN0
    • Q9NW03
    • Q9NW34
    • Q9NWM5

    Protein attributes for DTL Gene

    Size:
    730 amino acids
    Molecular mass:
    79468 Da
    Quaternary structure:
    • Component of the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)), at least composed of CUL4 (CUL4A or CUL4B), DDB1, DTL/CDT2 and RBX1. Interacts with CDKN1A and CDT1. Interacts with FBXO11; SCF(FBXWO11) controls DTL stability but DCX(DTL) does not control FBXO11 stability.
    SequenceCaution:
    • Sequence=BAA91552.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91586.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for DTL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DTL Gene

Post-translational modifications for DTL Gene

  • Phosphorylated at Thr-464 by CDK1/Cyclin-B and CDK2/Cyclin-A but not by CDK2/Cyclin-E, MAPK1 or PLK1. Phosphorylation at Thr-464 inhibits the interaction with FBXO11 and decreases upon cell cycle exit induced by TGF-beta or serum starvation.
  • Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C). Autoubiquitinated through Lys-48-polyubiquitin chains in a PCNA-independent reaction, allowing proteasomal turnover. Polyubiquitinated by SCF(FBXO11) when not phosphorylated, leading to its degradation. A tight regulation of the polyubiquitination by SCF(FBXO11) is involved in the control of different processes such as TGF-beta signaling, cell cycle progression and exit.
  • Ubiquitination at Lys128, isoforms=2137, Lys260, Lys386, Lys397, and Lys437
  • Modification sites at PhosphoSitePlus

Other Protein References for DTL Gene

No data available for DME Specific Peptides for DTL Gene

Domains & Families for DTL Gene

Suggested Antigen Peptide Sequences for DTL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9NZJ0

UniProtKB/Swiss-Prot:

DTL_HUMAN :
  • Belongs to the WD repeat cdt2 family.
Family:
  • Belongs to the WD repeat cdt2 family.
genes like me logo Genes that share domains with DTL: view

Function for DTL Gene

Molecular function for DTL Gene

UniProtKB/Swiss-Prot Function:
Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBXO18/FBH1 and KMT5A (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the K+4 motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the Lys-164 monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613).
UniProtKB/Swiss-Prot Induction:
Induced by TGF-beta, the up-regulation is immediate and transient.

Gene Ontology (GO) - Molecular Function for DTL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IDA 18794347
GO:0005515 protein binding IPI 17041588
genes like me logo Genes that share ontologies with DTL: view
genes like me logo Genes that share phenotypes with DTL: view

Animal Models for DTL Gene

MGI Knock Outs for DTL:
  • Dtl tm1b(EUCOMM)Wtsi
  • Dtl tm1Hch

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for DTL

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DTL Gene

Localization for DTL Gene

Subcellular locations from UniProtKB/Swiss-Prot for DTL Gene

Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Chromosome. Note=Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis.

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 DTL gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
mitochondrion 1

Gene Ontology (GO) - Cellular Components for DTL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 17106265
GO:0005654 nucleoplasm TAS --
GO:0005694 chromosome IEA --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with DTL: view

Pathways & Interactions for DTL Gene

genes like me logo Genes that share pathways with DTL: view

Pathways by source for DTL Gene

UniProtKB/Swiss-Prot Q9NZJ0-DTL_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for DTL Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for DTL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS 17085480
GO:0006260 DNA replication IEA --
GO:0006511 ubiquitin-dependent protein catabolic process TAS 17085480
GO:0006513 protein monoubiquitination IDA 20129063
GO:0006974 cellular response to DNA damage stimulus IDA,IEA 20129063
genes like me logo Genes that share ontologies with DTL: view

Drugs & Compounds for DTL Gene

No Compound Related Data Available

Transcripts for DTL Gene

Unigene Clusters for DTL Gene

Denticleless E3 ubiquitin protein ligase homolog (Drosophila):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for DTL

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

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16a · 16b
SP1: - -
SP2: - - - -
SP3:
SP4:

Relevant External Links for DTL Gene

GeneLoc Exon Structure for
DTL
ECgene alternative splicing isoforms for
DTL

Expression for DTL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for DTL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DTL Gene

This gene is overexpressed in Testis (x8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for DTL Gene



NURSA nuclear receptor signaling pathways regulating expression of DTL Gene:

DTL

SOURCE GeneReport for Unigene cluster for DTL Gene:

Hs.656473

mRNA Expression by UniProt/SwissProt for DTL Gene:

Q9NZJ0-DTL_HUMAN
Tissue specificity: Expressed in placenta and testis, very low expression seen in skeletal muscle. Detected in all hematopoietic tissues examined, with highest expression in thymus and bone marrow. A low level detected in the spleen and lymph node, and barely detectable level in the peripheral leukocytes. RA treatment down-regulated the expression in NT2 cell.
genes like me logo Genes that share expression patterns with DTL: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for DTL Gene

Orthologs for DTL Gene

This gene was present in the common ancestor of animals.

Orthologs for DTL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DTL 34 35
  • 99.59 (n)
dog
(Canis familiaris)
Mammalia DTL 34 35
  • 92.47 (n)
cow
(Bos Taurus)
Mammalia DTL 34 35
  • 90.09 (n)
mouse
(Mus musculus)
Mammalia Dtl 34 16 35
  • 87.97 (n)
rat
(Rattus norvegicus)
Mammalia Dtl 34
  • 86.74 (n)
oppossum
(Monodelphis domestica)
Mammalia DTL 35
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DTL 35
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves DTL 34 35
  • 65.55 (n)
lizard
(Anolis carolinensis)
Reptilia DTL 35
  • 57 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dtl 34
  • 61.63 (n)
MGC75574 34
zebrafish
(Danio rerio)
Actinopterygii dtl 34 35
  • 56.74 (n)
fruit fly
(Drosophila melanogaster)
Insecta l(2)dtl 35
  • 27 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea cdt-2 35
  • 21 (a)
OneToOne
Species where no ortholog for DTL 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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 DTL Gene

ENSEMBL:
Gene Tree for DTL (if available)
TreeFam:
Gene Tree for DTL (if available)

Paralogs for DTL Gene

(1) SIMAP similar genes for DTL Gene using alignment to 2 proteins:

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

No data available for Paralogs for DTL Gene

Variants for DTL Gene

Sequence variations from dbSNP and Humsavar for DTL Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs1000023006 -- 212,041,177(+) AGTGA(A/G)GTGTG intron-variant
rs1000033015 -- 212,062,239(+) TTAAG(G/T)GCTCA intron-variant
rs1000077903 -- 212,059,855(+) CATAC(-/A)AAAAA intron-variant
rs1000084737 -- 212,052,736(+) TATAT(A/G)TATAT intron-variant, upstream-variant-2KB
rs1000100761 -- 212,103,427(+) ATAAT(C/G)TTTTC utr-variant-3-prime

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

Variant ID Type Subtype PubMed ID
nsv4432 CNV insertion 18451855
nsv506979 OTHER sequence alteration 20534489
nsv945281 CNV duplication 23825009

Variation tolerance for DTL Gene

Residual Variation Intolerance Score: 3.84% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.45; 43.06% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for DTL Gene

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

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

Disorders for DTL Gene

MalaCards: The human disease database

(1) MalaCards diseases for DTL Gene - From: DISEASES

Disorder Aliases PubMed IDs
myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects
  • congenital myasthenic syndrome 8
- elite association - COSMIC cancer census association via MalaCards
Search DTL in MalaCards View complete list of genes associated with diseases

Relevant External Links for DTL

Genetic Association Database (GAD)
DTL
Human Genome Epidemiology (HuGE) Navigator
DTL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
DTL
genes like me logo Genes that share disorders with DTL: view

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

Publications for DTL Gene

  1. Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation. (PMID: 11278750) Cheung W.M. … Ip N.Y. (J. Biol. Chem. 2001) 2 3 4 22 64
  2. L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. (PMID: 16861906) Higa L.A. … Zhang H. (Cell Cycle 2006) 3 4 22 64
  3. Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase. (PMID: 23478441) Rossi M. … Pagano M. (Mol. Cell 2013) 3 4 64
  4. The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated proteolysis in human cells. (PMID: 23677613) Bacquin A. … Kannouche P.L. (Nucleic Acids Res. 2013) 3 4 64
  5. CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. (PMID: 23478445) Abbas T. … Dutta A. (Mol. Cell 2013) 3 4 64

Products for DTL Gene

Sources for DTL Gene

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