Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008200
UniProt IDP38936
Primary gene name(s)CDKN1A
Synonym gene name(s)CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1
Protein nameCyclin-dependent kinase inhibitor 1
Protein functionMay be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding, PubMed:11595739. {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}.
Subcellular locationCytoplasm. Nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P38936
Gene Ontology
(Biological Process)
Complete annatation
animal organ regeneration [GO:0031100];
cell cycle arrest [GO:0007050];
cellular response to amino acid starvation [GO:0034198];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to extracellular stimulus [GO:0031668];
cellular response to gamma radiation [GO:0071480];
cellular response to heat [GO:0034605];
cellular response to ionizing radiation [GO:0071479];
cellular response to UV-B [GO:0071493];
cellular senescence [GO:0090398];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978];
G1/S transition of mitotic cell cycle [GO:0000082];
G2/M transition of mitotic cell cycle [GO:0000086];
intestinal epithelial cell maturation [GO:0060574];
intrinsic apoptotic signaling pathway [GO:0097193];
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771];
mitotic cell cycle arrest [GO:0071850];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell growth [GO:0030308];
negative regulation of cell proliferation [GO:0008285];
negative regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045736];
negative regulation of G1/S transition of mitotic cell cycle [GO:2000134];
negative regulation of gene expression [GO:0010629];
negative regulation of phosphorylation [GO:0042326];
positive regulation of B cell proliferation [GO:0030890];
positive regulation of fibroblast proliferation [GO:0048146];
positive regulation of programmed cell death [GO:0043068];
positive regulation of protein kinase activity [GO:0045860];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
protein stabilization [GO:0050821];
Ras protein signal transduction [GO:0007265];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
regulation of DNA biosynthetic process [GO:2000278];
regulation of protein import into nucleus, translocation [GO:0033158];
response to arsenic-containing substance [GO:0046685];
response to corticosterone [GO:0051412];
response to drug [GO:0042493];
response to hyperoxia [GO:0055093];
response to organonitrogen compound [GO:0010243];
response to toxic substance [GO:0009636];
response to X-ray [GO:0010165];
stress-induced premature senescence [GO:0090400]
Gene Ontology
(Molecular Function)
Complete annatation
cyclin-dependent protein kinase activating kinase activity [GO:0019912];
cyclin-dependent protein serine/threonine kinase inhibitor activity [GO:0004861];
metal ion binding [GO:0046872];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cyclin-dependent protein kinase holoenzyme complex [GO:0000307];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PCNA-p21 complex [GO:0070557];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction107460
Phylogenetic treeP38936
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. CD31.658131734938465.26700824876603e-063.47567199323124e-05
AZA vs. DISU0.1963107132540650.4605220393485860.924263941482596
AZA vs. IL70.3080263416912690.4399699839811840.999311006273513
AZA vs. SAHA-0.3939329956704320.2456454073291230.617439069477895
DISU vs. CD3-1.475716349717517.34341307525588e-050.000433247000768717
DISU vs. IL70.1014249703093450.7648824236521950.945053892021707
DISU vs. SAHA-0.5856731690256180.04772885535311480.272264034453744
DMSO vs. AZA-0.6127522344275850.0295116826622431
DMSO vs. CD3-2.279807179025451.33422162207353e-112.41297103679924e-10
DMSO vs. DISU-0.8102066034166450.001074290243590180.0666236788926092
DMSO vs. IL70.9277220144631740.009076189571256330.198008043106641
DMSO vs. SAHA0.214282757760330.4399429085845270.773402493325255
HIV vs. Mock in Activation0.4583605361444090.4621240106437160.999983755607037
HIV vs. Mock in Latency0.156709144347780.6388020577192320.999834320637052
IL7 vs. CD3-1.346707322710530.001193517331981590.0049477136262262
SAHA vs. CD3-2.074078722154153.37326837573926e-084.01541504126308e-07
SAHA vs. IL7-0.7015884678457190.08926260911867980.268160849174775
(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
0.4173 0.02239

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 1.086 8.94E-12 2.78E-09
Infected vs. Bystander 1.144 3.05E-12 5.65E-10
(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
OK 1.47189 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
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
202284_s_at 2.13 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1AXC X-ray 2.6Å B/D/F=139-160.
2ZVV X-ray 2.0Å X/Y=139-160.
2ZVW X-ray 2.5Å I/J/K/L/M/N/O/P=139-160.
4RJF X-ray 2.0Å B/D/F=139-160.
5E0U X-ray 1.9Å D/E/F=139-160.

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

HIV Partner Interaction Type PubMed
Vpr interacts with 15302882
Tat activates 15179054
Vpr upregulates 15302882
Tat upregulates 24469921
integrase complexes with 17273559
Vif upregulates 23333304
Envelope surface glycoprotein gp120 upregulates 16554660
Vpr activates 12573582
Nef upregulates 25847297

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - 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)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04921 Oxytocin signaling pathway - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation 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)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)