Human Gene DTL (uc009xdc.3) Description and Page Index
  Description: Homo sapiens denticleless E3 ubiquitin protein ligase homolog (Drosophila) (DTL), mRNA.
Transcript (Including UTRs)
   Position: hg19 chr1:212,208,919-212,278,187 Size: 69,269 Total Exon Count: 15 Strand: +
Coding Region
   Position: hg19 chr1:212,209,233-212,276,282 Size: 67,050 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:212,208,919-212,278,187)mRNA (may differ from genome)Protein (730 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Denticleless protein homolog; AltName: Full=DDB1- and CUL4-associated factor 2; AltName: Full=Lethal(2) denticleless protein homolog; AltName: Full=Retinoic acid-regulated nuclear matrix-associated protein;
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 and CDKN1A/p21(CIP1). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. 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.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: 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.
INTERACTION: Q16531:DDB1; NbExp=3; IntAct=EBI-1176075, EBI-350322;
SUBCELLULAR LOCATION: Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm, cytoskeleton, centrosome. Note=Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis.
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.
DEVELOPMENTAL STAGE: Expressed in all fetal tissues examined, included brain, lung, liver, and kidney.
PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
SIMILARITY: Belongs to the WD repeat cdt2 family.
SIMILARITY: Contains 7 WD repeats.
SEQUENCE CAUTION: Sequence=BAA91552.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA91586.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DTL
CDC HuGE Published Literature: DTL
Positive Disease Associations: Stroke
Related Studies:
  1. Stroke
    , , . [PubMed 0]
  2. Stroke
    , , . [PubMed 0]

-  MalaCards Disease Associations
  MalaCards Gene Search: DTL
Diseases sorted by gene-association score: myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C006780 bisphenol A
  • D001564 Benzo(a)pyrene
  • C028474 1,4-bis(2-(3,5-dichloropyridyloxy))benzene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • C547126 AZM551248
  • D000082 Acetaminophen
  • D016604 Aflatoxin B1
  • D002117 Calcitriol
  • D002251 Carbon Tetrachloride
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.89 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 34.66 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -127.10314-0.405 Picture PostScript Text
3' UTR -454.761905-0.239 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR019775 - WD40_repeat_CS
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00400 - WD domain, G-beta repeat

SCOP Domains:
50952 - Soluble quinoprotein glucose dehydrogenase
50960 - TolB, C-terminal domain
63829 - Calcium-dependent phosphotriesterase
69304 - Tricorn protease N-terminal domain
101898 - NHL repeat
50965 - Galactose oxidase, central domain
75011 - 3-carboxy-cis,cis-mucoante lactonizing enzyme
101908 - Putative isomerase YbhE
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50974 - Nitrous oxide reductase, N-terminal domain
50978 - WD40 repeat-like
50993 - Prolyl oligopeptidase, N-terminal domain
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
82171 - Dipeptidyl peptidase IV/CD26, N-terminal domain

ModBase Predicted Comparative 3D Structure on Q9NZJ0
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  Protein SequenceProtein SequenceProtein Sequence 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0004842 ubiquitin-protein transferase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006260 DNA replication
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0006513 protein monoubiquitination
GO:0006974 cellular response to DNA damage stimulus
GO:0009411 response to UV
GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
GO:0016567 protein ubiquitination
GO:0019985 translesion synthesis
GO:0042769 DNA damage response, detection of DNA damage
GO:0043687 post-translational protein modification
GO:0045732 positive regulation of protein catabolic process
GO:0051726 regulation of cell cycle
GO:0072425 signal transduction involved in G2 DNA damage checkpoint

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0016020 membrane
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
GO:0031965 nuclear membrane
GO:0080008 Cul4-RING E3 ubiquitin ligase complex

-  Descriptions from all associated GenBank mRNAs
  AK292343 - Homo sapiens cDNA FLJ77821 complete cds.
AK000742 - Homo sapiens cDNA FLJ20735 fis, clone HEP08479.
AK303346 - Homo sapiens cDNA FLJ53398 complete cds, highly similar to Homo sapiens denticleless homolog (DTL), mRNA.
BC033540 - Homo sapiens denticleless homolog (Drosophila), mRNA (cDNA clone MGC:42657 IMAGE:4826434), complete cds.
AF345896 - Homo sapiens RA-regulated nuclear matrix-associated protein mRNA, complete cds.
AF195765 - Homo sapiens L2DTL protein (L2DTL) mRNA, complete cds.
AK299649 - Homo sapiens cDNA FLJ60847 complete cds, highly similar to Homo sapiens denticleless homolog (DTL), mRNA.
BC033297 - Homo sapiens denticleless homolog (Drosophila), mRNA (cDNA clone MGC:24863 IMAGE:4342989), complete cds.
AK027651 - Homo sapiens cDNA FLJ14745 fis, clone NT2RP3002785, weakly similar to LETHAL(2)DENTICLELESS PROTEIN.
CU689648 - Synthetic construct Homo sapiens gateway clone IMAGE:100017470 5' read DTL mRNA.
CU689622 - Synthetic construct Homo sapiens gateway clone IMAGE:100020042 5' read DTL mRNA.
JF432257 - Synthetic construct Homo sapiens clone IMAGE:100073427 denticleless homolog (Drosophila) (DTL) gene, encodes complete protein.
KJ898910 - Synthetic construct Homo sapiens clone ccsbBroadEn_08304 DTL gene, encodes complete protein.
KJ898911 - Synthetic construct Homo sapiens clone ccsbBroadEn_08305 DTL gene, encodes complete protein.
DQ641253 - Homo sapiens CDW1 (DTL) mRNA, complete cds.
AK001261 - Homo sapiens cDNA FLJ10399 fis, clone NT2RM4000354, weakly similar to LETHAL(2)DENTICLELESS PROTEIN.
AK001206 - Homo sapiens cDNA FLJ10344 fis, clone NT2RM2000952.
JD130177 - Sequence 111201 from Patent EP1572962.
JD163682 - Sequence 144706 from Patent EP1572962.
JD265350 - Sequence 246374 from Patent EP1572962.
JD168220 - Sequence 149244 from Patent EP1572962.
JD243009 - Sequence 224033 from Patent EP1572962.
JD086934 - Sequence 67958 from Patent EP1572962.
DQ574685 - Homo sapiens piRNA piR-42797, complete sequence.
JD167563 - Sequence 148587 from Patent EP1572962.
JD314745 - Sequence 295769 from Patent EP1572962.
JD422950 - Sequence 403974 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_tall1Pathway - TACI and BCMA stimulation of B cell immune responses.

Reactome (by CSHL, EBI, and GO)

Protein Q9NZJ0 (Reactome details) participates in the following event(s):

R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA
R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA
R-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus
R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex
R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex
R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex
R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-8951664 Neddylation
R-HSA-73893 DNA Damage Bypass
R-HSA-597592 Post-translational protein modification
R-HSA-73894 DNA Repair
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8K8H8, CDT2, CDW1, D3DT98, DCAF2, DTL_HUMAN, L2DTL, NM_016448, NP_057532, Q5VT77, Q96SN0, Q9NW03, Q9NW34, Q9NWM5, Q9NZJ0, RAMP
UCSC ID: uc009xdc.3
RefSeq Accession: NM_016448
Protein: Q9NZJ0 (aka DTL_HUMAN)
CCDS: CCDS1502.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_016448.2
exon count: 15CDS single in 3' UTR: no RNA size: 4428
ORF size: 2193CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4375.00frame shift in genome: no % Coverage: 99.64
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.