Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000564
UniProt IDP06493
Primary gene name(s)CDK1
Synonym gene name(s)CDC2, CDC28A, CDKN1, P34CDC2
Protein nameCyclin-dependent kinase 1
Protein functionPlays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex, gTuRC to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis, PubMed:26549230. {ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230}.
Subcellular locationNucleus. Cytoplasm. Mitochondrion. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Note=Cytoplasmic during the interphase. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin-B1. Accumulates in mitochondria in G2-arrested cells upon DNA-damage.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P06493
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
anaphase-promoting complex-dependent catabolic process [GO:0031145];
animal organ regeneration [GO:0031100];
apoptotic process [GO:0006915];
cell aging [GO:0007569];
cell division [GO:0051301];
cell migration [GO:0016477];
cell proliferation [GO:0008283];
cellular response to hydrogen peroxide [GO:0070301];
centrosome cycle [GO:0007098];
chromosome condensation [GO:0030261];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
epithelial cell differentiation [GO:0030855];
G1/S transition of mitotic cell cycle [GO:0000082];
G2/M transition of mitotic cell cycle [GO:0000086];
Golgi disassembly [GO:0090166];
microtubule cytoskeleton organization [GO:0000226];
mitotic G2 DNA damage checkpoint [GO:0007095];
mitotic nuclear division [GO:0007067];
mitotic nuclear envelope disassembly [GO:0007077];
negative regulation of apoptotic process [GO:0043066];
negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle [GO:0051436];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of cardiac muscle cell proliferation [GO:0060045];
positive regulation of DNA replication [GO:0045740];
positive regulation of gene expression [GO:0010628];
positive regulation of mitotic cell cycle [GO:0045931];
positive regulation of protein import into nucleus, translocation [GO:0033160];
positive regulation of protein localization to nucleus [GO:1900182];
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition [GO:0051437];
pronuclear fusion [GO:0007344];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein complex assembly [GO:0006461];
protein localization to kinetochore [GO:0034501];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of embryonic development [GO:0045995];
regulation of Schwann cell differentiation [GO:0014038];
regulation of transcription involved in G1/S transition of mitotic cell cycle [GO:0000083];
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle [GO:0051439];
response to activity [GO:0014823];
response to amine [GO:0014075];
response to axon injury [GO:0048678];
response to cadmium ion [GO:0046686];
response to copper ion [GO:0046688];
response to drug [GO:0042493];
response to ethanol [GO:0045471];
response to organic cyclic compound [GO:0014070];
response to toxic substance [GO:0009636];
ventricular cardiac muscle cell development [GO:0055015]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693];
histone kinase activity [GO:0035173];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
RNA polymerase II carboxy-terminal domain kinase activity [GO:0008353]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
membrane [GO:0016020];
midbody [GO:0030496];
mitochondrion [GO:0005739];
mitotic spindle [GO:0072686];
nuclear chromosome, telomeric region [GO:0000784];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
spindle microtubule [GO:0005876]
Protein-protein interaction107420
Phylogenetic treeP06493
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. CD30.5528943522224210.7023174103462560.787699767696958
AZA vs. DISU0.002409394636666870.9969725964359830.999297613676408
AZA vs. IL70.1039182525925980.8732506158250760.999311006273513
AZA vs. SAHA-0.2010903930325060.7028604871658790.916198459316712
DISU vs. CD3-0.5614760054950680.6954967485876390.786785590109574
DISU vs. IL70.09241653547321470.8833428506871490.978147487995092
DISU vs. SAHA-0.2043248113098690.6819724842620310.904720681056087
DMSO vs. AZA-0.2539502484949710.6658460020626491
DMSO vs. CD3-0.8217938608521240.5736782095451970.673718602026692
DMSO vs. DISU-0.2598679615815880.6425278011818810.9472626202031
DMSO vs. IL70.3660078598436240.5287022230376820.895285946876982
DMSO vs. SAHA0.0451692260970890.914107683932140.979403400357616
HIV vs. Mock in Activation-0.1824418548282880.9391444366404740.999983755607037
HIV vs. Mock in Latency0.2786174884937990.5632810192757030.999834320637052
IL7 vs. CD3-0.4391480429378690.7594459599348290.840030291405012
SAHA vs. CD3-0.7808065255036970.6152533166003380.710705770440525
SAHA vs. IL7-0.3091136753731720.5546523395344950.766415745360984
(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
1.8 0.001157432 1.1 0.810453555 1.2 0.248674969
(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 0.716817 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
0.033 0.002

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
0.994 1.194 1.462 1.469 1.288
(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
203213_at 1.98 Yes upregulated in CD4+ cells
203213_at 4.39 Yes upregulated in CD8+ cells
203214_x_at 2.66 Yes upregulated in CD8+ cells
210559_s_at 4.25 Yes upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04014 Alsterpaullone experimental unknown inhibitor
DB03496 Flavopiridol experimental, investigational unknown unknown
DB02950 Hymenialdisine experimental unknown unknown
DB02052 Indirubin-3&,39;-Monoxime experimental unknown binder
DB02116 Olomoucine experimental unknown binder
DB03428 SU9516 experimental unknown binder
DB05037 AT7519 investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1LC9 Model - A=1-297.
4Y72 X-ray 2.3Å A=1-297.
4YC3 X-ray 2.7Å A=1-297.
4YC6 X-ray 2.6Å A/C/E/G=1-297.
5HQ0 X-ray 2.3Å A=1-297.

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

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04110 Cell cycle - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04540 Gap junction - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
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