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

    Gene ID: 51514, updated on 2-Nov-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, Nov 2024]
    Expression
    Broad expression in testis (RPKM 9.8), bone marrow (RPKM 8.4) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DTL in Genome Data Viewer
    Location:
    1q32.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (212035748..212105013)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (211281835..211351118)
    RS_2024_09 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 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. Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation. Cheung WM, et al. J Biol Chem, 2001 May 18. PMID 11278750
    2. 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
    3. 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
    4. The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase. Olivero M, et al. Oncotarget, 2014 Aug 15. PMID 25115388, Free PMC Article
    5. Ubiquitin E3 ligase CRL4(CDT2/DCAF2) as a potential chemotherapeutic target for ovarian surface epithelial cancer. Pan WW, et al. J Biol Chem, 2013 Oct 11. PMID 23995842, Free PMC Article

    See all (125) 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 Variation Viewer (GRCh37.p13)

    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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    NEW Try the new Transcript table

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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