Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009910
UniProt IDP24385
Primary gene name(s)CCND1
Synonym gene name(s)BCL1, PRAD1
Protein nameG1/S-specific cyclin-D1
Protein functionRegulatory component of the cyclin D1-CDK4, DC complex that phosphorylates and inhibits members of the retinoblastoma, RB protein family including RB1 and regulates the cell-cycle during G(1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1 phase. Hypophosphorylates RB1 in early G(1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:9106657}.
Subcellular locationNucleus {ECO:0000269|PubMed:9106657}. Cytoplasm {ECO:0000269|PubMed:9106657}. Membrane {ECO:0000269|PubMed:9106657}. Note=Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P24385
Gene Ontology
(Biological Process)
Complete annatation
canonical Wnt signaling pathway [GO:0060070];
cell division [GO:0051301];
cellular response to DNA damage stimulus [GO:0006974];
endoplasmic reticulum unfolded protein response [GO:0030968];
fat cell differentiation [GO:0045444];
G1/S transition of mitotic cell cycle [GO:0000082];
lactation [GO:0007595];
Leydig cell differentiation [GO:0033327];
liver regeneration [GO:0097421];
mammary gland alveolus development [GO:0060749];
mammary gland epithelial cell proliferation [GO:0033598];
mitotic G1 DNA damage checkpoint [GO:0031571];
negative regulation of cell cycle arrest [GO:0071157];
negative regulation of epithelial cell differentiation [GO:0030857];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of Wnt signaling pathway [GO:0030178];
positive regulation of cell cycle [GO:0045787];
positive regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045737];
positive regulation of G2/M transition of mitotic cell cycle [GO:0010971];
positive regulation of mammary gland epithelial cell proliferation [GO:0033601];
positive regulation of protein phosphorylation [GO:0001934];
re-entry into mitotic cell cycle [GO:0000320];
response to calcium ion [GO:0051592];
response to corticosterone [GO:0051412];
response to drug [GO:0042493];
response to estradiol [GO:0032355];
response to estrogen [GO:0043627];
response to ethanol [GO:0045471];
response to iron ion [GO:0010039];
response to leptin [GO:0044321];
response to magnesium ion [GO:0032026];
response to organonitrogen compound [GO:0010243];
response to UV-A [GO:0070141];
response to vitamin E [GO:0033197];
response to X-ray [GO:0010165];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
cyclin-dependent protein serine/threonine kinase regulator activity [GO:0016538];
enzyme binding [GO:0019899];
histone deacetylase binding [GO:0042826];
proline-rich region binding [GO:0070064];
protein kinase activity [GO:0004672];
protein kinase binding [GO:0019901];
transcription corepressor activity [GO:0003714];
transcription factor binding [GO:0008134]
Gene Ontology
(Cellular Component)
Complete annatation
bicellular tight junction [GO:0005923];
cyclin-dependent protein kinase holoenzyme complex [GO:0000307];
cytosol [GO:0005829];
intracellular [GO:0005622];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcriptional repressor complex [GO:0017053]
Protein-protein interaction107067
Phylogenetic treeP24385
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.2305036638510260.808417057841640.870186188082668
AZA vs. DISU-0.3898331204815220.6029435160078130.955158276076142
AZA vs. IL7-0.257194109798880.6604757224190310.999311006273513
AZA vs. SAHA-0.6069622310534620.4130744537787850.767967971911865
DISU vs. CD3-0.6317977164761980.5863525142125040.699982402727432
DISU vs. IL70.1231794980645850.8650061388795610.974145458987187
DISU vs. SAHA-0.2166458851227020.7955526820622320.945944578932617
DMSO vs. AZA0.1296470515650030.8310980488831761
DMSO vs. CD3-0.1125202589707960.9037673938716630.934023172715689
DMSO vs. DISU0.5173802189100060.4844039374779220.902712522924543
DMSO vs. IL7-0.3791115821455450.5063574537034770.886801549623031
DMSO vs. SAHA-0.743508725478220.3089913242165040.660707227613834
HIV vs. Mock in Activation-0.1640711085376150.9107084368293040.999983755607037
HIV vs. Mock in Latency0.02416552436739230.9551577569000980.999834320637052
IL7 vs. CD3-0.4807649527490890.5968987412905340.714165322072727
SAHA vs. CD3-0.8633135441891030.4463854157891110.559001846097881
SAHA vs. IL7-0.3540459469071080.6200120826682590.810094663616307
(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) unknown
(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
NOTEST 0.0437072 1
(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
unknown unknown unknown unknown unknown
(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
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01169 Arsenic trioxide approved, investigational yes antagonist

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2W96 X-ray 2.3Å A=1-271.
2W99 X-ray 2.8Å A=1-271.
2W9F X-ray 2.8Å A=1-271.
2W9Z X-ray 2.4Å A=16-271.

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

HIV Partner Interaction Type PubMed
Tat inhibits 20839920
Tat upregulates 16436505
23301033
Tat downregulates 12539042
24469921
Nef upregulates 12241561
23604117

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04921 Oxytocin signaling pathway - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05216 Thyroid cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)
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