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DTL denticleless E3 ubiquitin protein ligase homolog [ Homo sapiens (human) ]

Gene ID: 51514, updated on 3-Apr-2024

Summary

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Official Symbol
DTLprovided by HGNC
Official Full Name
denticleless E3 ubiquitin protein ligase homologprovided by HGNC
Primary source
HGNC:HGNC:30288
See related
Ensembl:ENSG00000143476 MIM:610617; AllianceGenome:HGNC:30288
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CDT2; RAMP; DCAF2; L2DTL
Summary
Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in testis (RPKM 9.8), bone marrow (RPKM 8.4) and 15 other tissues See more
Orthologs
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Genomic context

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Location:
1q32.3
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (212035748..212105013)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (211281835..211351118)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (212209090..212278355)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene peptidyl-prolyl cis-trans isomerase NIMA-interacting 4-like Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2491 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2492 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2493 Neighboring gene NANOG hESC enhancer GRCh37_chr1:212120901-212121513 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212141376-212141876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212141877-212142377 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2494 Neighboring gene integrator complex subunit 7 Neighboring gene small nucleolar RNA SNORA26 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2495 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:212208838-212209374 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:212209375-212209909 Neighboring gene MPRA-validated peak685 silencer Neighboring gene ribosomal protein L21 pseudogene 28 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3330 Neighboring gene microRNA 3122 Neighboring gene RN7SK pseudogene 98 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212299717-212300218 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2498 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:212347425-212347676 Neighboring gene Sharpr-MPRA regulatory region 12199 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2500 Neighboring gene long intergenic non-protein coding RNA 2608 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:212426200-212426446 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:212429519-212430020 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3428 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_3455 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2502 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1793 Neighboring gene protein phosphatase 2 regulatory subunit B'alpha Neighboring gene ribosomal protein L23a pseudogene 18

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment. Li Z, et al. Front Immunol, 2022. PMID 35392073, Free PMC Article
  2. DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis. Luo Y, et al. Oxid Med Cell Longev, 2022. PMID 35103094, Free PMC Article
  3. Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis. Liu S, et al. Cell Death Dis, 2021 Oct 11. PMID 34635635, Free PMC Article
  4. Identification of a functional polymorphism within the 3'-untranslated region of denticleless E3 ubiquitin protein ligase homolog associated with survival in acral melanoma. Yang L, et al. Eur J Cancer, 2019 Sep. PMID 31325875
  5. Overexpression of denticleless E3 ubiquitin protein ligase homolog (DTL) is related to poor outcome in gastric carcinoma. Kobayashi H, et al. Oncotarget, 2015 Nov 3. PMID 26472028, Free PMC Article

See all (112) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression.
    Title: Circ-DTL sponges miR-758-3p to accelerate cervical cancer malignant progression by regulating DCUN1D1 expression.
  2. Epithelial CRL4[DCAF2] Is Critical for Maintaining Intestinal Homeostasis Against DSS-Induced Colitis by Regulating the Proliferation and Repair of Intestinal Epithelial Cells.
    Title: Epithelial CRL4(DCAF2) Is Critical for Maintaining Intestinal Homeostasis Against DSS-Induced Colitis by Regulating the Proliferation and Repair of Intestinal Epithelial Cells.
  3. Regular or DCAF2: How CRL4[DCAF2] Affects IBD-Related Mucosal Injury.
    Title: Regular or DCAF2: How CRL4(DCAF2) Affects IBD-Related Mucosal Injury.
  4. DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma.
    Title: DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma.
  5. miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells.
    Title: miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells.
  6. Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.
    Title: Role of DTL in Hepatocellular Carcinoma and Its Impact on the Tumor Microenvironment.
  7. DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis.
    Title: DTL Is a Prognostic Biomarker and Promotes Bladder Cancer Progression through Regulating the AKT/mTOR axis.
  8. Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.
    Title: Overexpression of DTL enhances cell motility and promotes tumor metastasis in cervical adenocarcinoma by inducing RAC1-JNK-FOXO1 axis.
  9. CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.
    Title: CRL4A(DTL) degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.
  10. The rs11275300:G allele in the 3'UTR of DTL may lead to a poor prognosis and allele-specific increase in the expression of DTL by post-transcriptional regulation in acral melanoma.
    Title: Identification of a functional polymorphism within the 3'-untranslated region of denticleless E3 ubiquitin protein ligase homolog associated with survival in acral melanoma.
Submit: New GeneRIF Correction See all GeneRIFs (52)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
contributes_to ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in DNA damage response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in DNA replication IEA
Inferred from Electronic Annotation
more info
  
involved_in mitotic G2 DNA damage checkpoint signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitotic G2 DNA damage checkpoint signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of G2/M transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein monoubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein polyubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein polyubiquitination TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in response to UV IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in rhythmic process IEA
Inferred from Electronic Annotation
more info
  
involved_in translesion synthesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
part_of Cul4-RING E3 ubiquitin ligase complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 
part_of Cul4A-RING E3 ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Cul4B-RING E3 ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in chromosome IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in nuclear membrane IEA
Inferred from Electronic Annotation
more info
  
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
denticleless protein homolog
Names
DDB1- and CUL4-associated factor 2
RA-regulated nuclear matrix-associated protein
lethal(2) denticleless protein homolog
retinoic acid-regulated nuclear matrix-associated protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001286229.2 → NP_001273158.2  denticleless protein homolog isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and lacks an exon in the coding region compared to variant 1. These differences result in the use of a alternate AUG, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus compared isoform 1.
    Source sequence(s)
    AC092814, AL592297, AL606468
    Related
    ENST00000475419.5
    Conserved Domains (2) summary
    sd00039
    Location:50 → 85
    7WD40; WD40 repeat [structural motif]
    cl29593
    Location:4 → 118
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

  2. NM_001286230.2 → NP_001273159.2  denticleless protein homolog isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks an in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AC092814, AL592297, AL606468
    Consensus CDS
    CCDS65778.1
    UniProtKB/TrEMBL
    B4E0E6, F5GZ90
    Related
    ENSP00000443870.1, ENST00000542077.5
    Conserved Domains (2) summary
    cd00200
    Location:23 → 347
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:59 → 95
    7WD40; WD40 repeat [structural motif]

  3. NM_016448.4 → NP_057532.4  denticleless protein homolog isoform 1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC092814, AL592297, AL606468
    Consensus CDS
    CCDS1502.1
    UniProtKB/Swiss-Prot
    A8K8H8, D3DT98, Q5VT77, Q96SN0, Q9NW03, Q9NW34, Q9NWM5, Q9NZJ0
    UniProtKB/TrEMBL
    B4E0E6
    Related
    ENSP00000355958.4, ENST00000366991.5
    Conserved Domains (2) summary
    cd00200
    Location:55 → 389
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:55 → 96
    7WD40; WD40 repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    212035748..212105013
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011509614.2 → XP_011507916.1  denticleless protein homolog isoform X1

    UniProtKB/TrEMBL
    B4E0E6
    Conserved Domains (3) summary
    COG2319
    Location:2 → 352
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:3 → 327
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:39 → 75
    7WD40; WD40 repeat [structural motif]

  2. XM_047422489.1 → XP_047278445.1  denticleless protein homolog isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    211281835..211351118
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336974.1 → XP_054192949.1  denticleless protein homolog isoform X1

  2. XM_054336975.1 → XP_054192950.1  denticleless protein homolog isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NZJ0.3 GenPept UniProtKB/Swiss-Prot:Q9NZJ0

Gene LinkOut

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