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Aliases for DTL Gene

Aliases for DTL Gene

  • Denticleless E3 Ubiquitin Protein Ligase Homolog 2 3
  • Denticleless E3 Ubiquitin Protein Ligase Homolog (Drosophila) 2 5
  • Retinoic Acid-Regulated Nuclear Matrix-Associated Protein 3 4
  • RA Regulated Nuclear Matrix Associated Protein 2 3
  • Lethal(2) Denticleless Protein Homolog 3 4
  • DDB1- And CUL4-Associated Factor 2 3 4
  • DDB1 And CUL4 Associated Factor 2 2 3
  • DCAF2 3 4
  • L2DTL 3 4
  • CDT2 3 4
  • RAMP 3 4
  • RA-Regulated Nuclear Matrix-Associated Protein 3
  • Denticleless Homolog (Drosophila) 2
  • 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. Among its related pathways are Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template 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 , 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 Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

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

ENSRs around DTL on UCSC Golden Path with GeneCards custom track

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, 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

Proteomics data for DTL Gene at MOPED

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 Lys 128, Lys 137, Lys 260, Lys 386, Lys 397, and Lys 437
  • Modification sites at PhosphoSitePlus

Other Protein References for DTL Gene

Antibody Products

No data available for DME Specific Peptides for DTL Gene

Domains & Families for DTL Gene

Protein Domains 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.
  • Contains 7 WD repeats.
Family:
  • Belongs to the WD repeat cdt2 family.
Similarity:
  • Contains 7 WD repeats.
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.
genes like me logo Genes that share phenotypes with DTL: view

Animal Models for DTL Gene

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

Animal Model Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , 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
Jensen Localization Image for DTL Gene COMPARTMENTS Subcellular localization image for DTL gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for DTL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005813 centrosome IDA 17106265
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex IDA 17085480
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex IDA 18794347
GO:0031965 nuclear membrane 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:0006974 cellular response to DNA damage stimulus IDA 20129063
GO:0031572 G2 DNA damage checkpoint IMP 17085480
GO:0051726 regulation of cell cycle IMP 17085480
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:

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 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, MOPED, and MaxQB for DTL Gene



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

In Situ Assay Products

No data available for Protein differential expression in normal tissues and Protein tissue co-expression partners 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
cow
(Bos Taurus)
Mammalia DTL 35
  • 90.09 (n)
  • 90.55 (a)
DTL 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia DTL 35
  • 92.47 (n)
  • 93.29 (a)
DTL 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Dtl 35
  • 87.97 (n)
  • 89.57 (a)
Dtl 16
Dtl 36
  • 90 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia DTL 35
  • 99.59 (n)
  • 99.86 (a)
DTL 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Dtl 35
  • 86.74 (n)
  • 88.07 (a)
oppossum
(Monodelphis domestica)
Mammalia DTL 36
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DTL 36
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves DTL 35
  • 65.55 (n)
  • 64.44 (a)
DTL 36
  • 61 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DTL 36
  • 57 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dtl 35
  • 61.63 (n)
  • 59.2 (a)
MGC75574 35
zebrafish
(Danio rerio)
Actinopterygii dtl 35
  • 56.74 (n)
  • 55.23 (a)
dtl 36
  • 53 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta l(2)dtl 36
  • 27 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea cdt-2 36
  • 21 (a)
OneToOne
Species with no ortholog for DTL:
  • 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
rs3135474 - 212,100,297(+) CAGGG(A/C/T)AAAGT reference, missense
rs6540718 - 212,101,071(+) AAAGA(A/C)ATTGC reference, missense
rs35137676 - 212,100,264(+) AACGA(A/G)TAGCC reference, missense
rs15647 -- 212,100,943(+) GTAGG(A/C)AAAGA reference, synonymous-codon
rs1017979 -- 212,073,614(+) AGTTG(C/T)GAAAA intron-variant

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

Variant ID Type Subtype PubMed ID
nsv4432 CNV Insertion 18451855
nsv506979 CNV Insertion 20534489

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

HapMap Linkage Disequilibrium report
DTL

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

Disorders for DTL Gene

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

No disorders were found for DTL Gene.

No data available for MalaCards , 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 23 67
  2. Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer. (PMID: 19672268) Li J. … Leung W.K. (Br. J. Cancer 2009) 3 23
  3. 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 23
  4. MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication. (PMID: 26771714) Evans D.L. … Lou Z. (Cell Cycle 2016) 3
  5. CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis. (PMID: 25411249) Rizzardi L.F. … Cook J.G. (J. Biol. Chem. 2015) 3

Products for DTL Gene

Sources for DTL Gene

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