Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000870
UniProt IDQ9NZJ0
Primary gene name(s)DTL
Synonym gene name(s)CDT2, CDW1, DCAF2, L2DTL, RAMP
Protein nameDenticleless protein homolog
Protein functionSubstrate-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. {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613}.
Subcellular locationNucleus. 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.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NZJ0
Gene Ontology
(Biological Process)
Complete annatation
cellular response to DNA damage stimulus [GO:0006974];
DNA damage response, detection of DNA damage [GO:0042769];
DNA replication [GO:0006260];
G2 DNA damage checkpoint [GO:0031572];
protein monoubiquitination [GO:0006513];
protein polyubiquitination [GO:0000209];
regulation of cell cycle [GO:0051726];
response to UV [GO:0009411];
translesion synthesis [GO:0019985];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
chromosome [GO:0005694];
Cul4A-RING E3 ubiquitin ligase complex [GO:0031464];
Cul4B-RING E3 ubiquitin ligase complex [GO:0031465];
cytoplasm [GO:0005737];
intracellular membrane-bounded organelle [GO:0043231];
nuclear membrane [GO:0031965];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction119582
Phylogenetic treeQ9NZJ0
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD32.983548836430460.04107070089544160.0846346190724769
AZA vs. DISU0.2029700630959070.6844721216390040.967438608681327
AZA vs. IL71.397102578040540.02399575286056710.494785202280886
AZA vs. SAHA0.2631834599464260.376030703189540.741559005484835
DISU vs. CD3-2.795298821135950.0488745378666660.106081322361717
DISU vs. IL71.186437069413630.0830573191842330.381579705066922
DISU vs. SAHA0.06530238219886170.8866377095202280.97143394854122
DMSO vs. AZA0.1006402374261950.7629954212653951
DMSO vs. CD3-2.897091692213720.04826968621602130.0934802446129787
DMSO vs. DISU-0.1050985360046120.8228483769728930.980337437401145
DMSO vs. IL71.303293995723160.02884394514220690.345777308781109
DMSO vs. SAHA0.157868432693430.5304826669779960.829293439441583
HIV vs. Mock in Activation-0.1301768273849730.9562477924977850.999983755607037
HIV vs. Mock in Latency-0.01945108146871470.9441867751916260.999834320637052
IL7 vs. CD3-1.577681533372020.2616639650426340.394642880236904
SAHA vs. CD3-2.739303814970820.08391341615204860.151319275028284
SAHA vs. IL7-1.131247446462190.05873359039430210.204091779991635
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.652756 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.13 0.998 0.731 0.781 1.132
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
218585_s_at 1.67 Yes upregulated in CD4+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found