Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004193
UniProt IDP46527
Primary gene name(s)CDKN1B
Synonym gene name(s)KIP1
Protein nameCyclin-dependent kinase inhibitor 1B
Protein functionImportant regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005}.
Subcellular locationNucleus. Cytoplasm. Endosome {ECO:0000250}. Note=Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3, translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with SNX6;
this leads to lysosomal degradation, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P46527
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
autophagic cell death [GO:0048102];
cell cycle arrest [GO:0007050];
cellular response to antibiotic [GO:0071236];
cellular response to lithium ion [GO:0071285];
cellular response to organic cyclic compound [GO:0071407];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
G1/S transition of mitotic cell cycle [GO:0000082];
inner ear development [GO:0048839];
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 cellular component movement [GO:0051271];
negative regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045736];
negative regulation of epithelial cell proliferation involved in prostate gland development [GO:0060770];
negative regulation of kinase activity [GO:0033673];
negative regulation of mitotic cell cycle [GO:0045930];
negative regulation of phosphorylation [GO:0042326];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of vascular smooth muscle cell proliferation [GO:1904706];
Notch signaling pathway [GO:0007219];
positive regulation of cell cycle [GO:0045787];
positive regulation of cell death [GO:0010942];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0045737];
positive regulation of microtubule polymerization [GO:0031116];
positive regulation of protein catabolic process [GO:0045732];
potassium ion transport [GO:0006813];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
response to amino acid [GO:0043200];
response to cadmium ion [GO:0046686];
response to drug [GO:0042493];
response to estradiol [GO:0032355];
response to glucose [GO:0009749];
response to hypoxia [GO:0001666];
response to peptide hormone [GO:0043434];
sensory perception of sound [GO:0007605]
Gene Ontology
(Molecular Function)
Complete annatation
cyclin-dependent protein serine/threonine kinase inhibitor activity [GO:0004861];
protein phosphatase binding [GO:0019903];
transforming growth factor beta receptor, cytoplasmic mediator activity [GO:0005072]
Gene Ontology
(Cellular Component)
Complete annatation
Cul4A-RING E3 ubiquitin ligase complex [GO:0031464];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome [GO:0005768];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction107461
Phylogenetic treeP46527
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. CD3-1.490863781990289.59453892146467e-065.95588511632271e-05
AZA vs. DISU-0.05592241262088150.8246839034510290.984968319516742
AZA vs. IL7-0.5505612162726120.004224146934899140.200853522869826
AZA vs. SAHA-0.2254445892497240.3556913834479380.724709117054083
DISU vs. CD31.422470574260750.0001340198303489970.000731431905387683
DISU vs. IL7-0.5038139551181730.04567521150215440.28318383538101
DISU vs. SAHA-0.1687844758171580.562567429548740.857114616519963
DMSO vs. AZA-0.1092823291070750.5129747413445911
DMSO vs. CD31.369445479559643.00580522009097e-050.000153760460579526
DMSO vs. DISU-0.0554905595582320.8197385892581490.980295078677667
DMSO vs. IL7-0.4340338376141780.01577169000583590.262650076359751
DMSO vs. SAHA-0.1232167666883010.6012097598986280.865078507870175
HIV vs. Mock in Activation-0.01577477554939570.9798526893713750.999983755607037
HIV vs. Mock in Latency0.1304601972662510.4285693104200120.999834320637052
IL7 vs. CD30.9485730265243810.003774005456384620.0132507766699477
SAHA vs. CD31.240611023514650.0006738220077947550.00254498688157067
SAHA vs. IL70.3209209130558570.1877817724038210.417927423182518
(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
OK -0.661256 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
1.028 0.836 0.588 0.737 0.761
(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
209112_at 1.52 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
1H27 X-ray 2.2Å E=25-35.
1JSU X-ray 2.3Å C=23-106.
2AST X-ray 2.3Å D=181-190.

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

HIV Partner Interaction Type PubMed
Tat relocalizes 25760044
Envelope surface glycoprotein gp120 upregulates 16554660
Tat interacts with 15050687

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine 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)
hsa04151 PI3K-Akt 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)
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)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)