CCNB1

gene
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Summary

CCNB1 (cyclin B1, HGNC:1579) is a protein-coding gene on chromosome 5q13.2, encoding G2/mitotic-specific cyclin-B1 (P14635). Essential for the control of the cell cycle at the G2/M (mitosis) transition. It is a selective cancer dependency (DepMap: 74.0% of cell lines).

The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). The encoded protein is necessary for proper control of the G2/M transition phase of the cell cycle.

Source: NCBI Gene 891 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 66 total
  • Druggable target: yes — 34 molecules with ChEMBL bioactivity
  • Cancer dependency (DepMap): dependent in 74.0% of screened cell lines
  • MANE Select transcript: NM_031966

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1579
Approved symbolCCNB1
Namecyclin B1
Location5q13.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000134057
Ensembl biotypeprotein_coding
OMIM123836
Entrez891

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 24 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000256442, ENST00000503507, ENST00000505500, ENST00000506572, ENST00000507798, ENST00000508407, ENST00000513102, ENST00000870642, ENST00000924407, ENST00000924408, ENST00000924409, ENST00000924410, ENST00000924411, ENST00000924412, ENST00000924413, ENST00000924414, ENST00000924415, ENST00000924416, ENST00000924417, ENST00000924418, ENST00000924419, ENST00000924420, ENST00000924421, ENST00000924422, ENST00000924423, ENST00000960692

RefSeq mRNA: 3 — MANE Select: NM_031966 NM_001354844, NM_001354845, NM_031966

CCDS: CCDS3997

Canonical transcript exons

ENST00000256442 — 9 exons

ExonStartEnd
ENSE000009720256917425169174409
ENSE000009720266917487769175113
ENSE000009720276917539769175537
ENSE000009720286917723969177349
ENSE000018216716916715069167283
ENSE000019389636917752469178245
ENSE000035573106916817369168343
ENSE000036143926916790869168078
ENSE000036397766917127069171452

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.8396 / max 1085.8300, expressed in 1759 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
5683380.82251758
568342.0171863

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065599.83gold quality
oocyteCL:000002399.76gold quality
ventricular zoneUBERON:000305399.26gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099197.47gold quality
ganglionic eminenceUBERON:000402397.03gold quality
endometrium epitheliumUBERON:000481196.77gold quality
embryoUBERON:000092296.70gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047395.59gold quality
mucosa of transverse colonUBERON:000499193.88gold quality
stromal cell of endometriumCL:000225593.82gold quality
lower esophagus mucosaUBERON:003583492.69gold quality
left testisUBERON:000453392.05gold quality
esophagus mucosaUBERON:000246991.81gold quality
right testisUBERON:000453491.73gold quality
testisUBERON:000047391.36gold quality
esophagus squamous epitheliumUBERON:000692091.12gold quality
rectumUBERON:000105290.96gold quality
spermCL:000001990.89gold quality
trabecular bone tissueUBERON:000248390.66gold quality
bone marrowUBERON:000237190.27gold quality
vermiform appendixUBERON:000115490.25gold quality
bone elementUBERON:000147489.50gold quality
adrenal tissueUBERON:001830389.48gold quality
epithelium of esophagusUBERON:000197688.50gold quality
male germ cellCL:000001588.44gold quality
gingival epitheliumUBERON:000194988.40gold quality
oral cavityUBERON:000016788.01gold quality
bone marrow cellCL:000209287.16gold quality
gingivaUBERON:000182886.16gold quality
squamous epitheliumUBERON:000691485.94gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 15.

ExperimentMarker?Max mean expression
E-MTAB-10485yes1406.86
E-GEOD-99795yes1300.76
E-MTAB-7249yes1206.46
E-MTAB-11121yes1166.78
E-MTAB-7052yes1032.55
E-MTAB-8894yes1004.14
E-CURD-79yes941.20
E-MTAB-6505yes684.64
E-MTAB-10290yes540.96
E-HCAD-10yes507.72
E-HCAD-13yes453.95
E-CURD-114yes319.14
E-GEOD-100618yes257.59
E-GEOD-125970yes228.00
E-MTAB-6911no1920.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AGO1, AR, BRCA1, CEBPA, CREB1, DROSHA, E2F1, E2F3, E2F4, ERG, ESR2, FOXM1, FOXO1, GPER1, HLX, IRF1, IRF4, KLF4, KLF5, MAX, MXI1, MYB, MYBL2, MYC, MYOD1, NCOR2, NFKB1, NFKB, NKX2-1, OLIG2, PPARA, PTTG1, RBCK1, RELA, RPRD1B, SP1, SSRP1, STOX1, TBP, TFAP2A

miRNA regulators (miRDB)

57 targeting CCNB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-6798-5P100.0065.77699
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-428299.9975.366408
HSA-MIR-548N99.9871.944170
HSA-MIR-1213699.9872.815713
HSA-MIR-60799.9773.625593
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-55999.9572.283609
HSA-MIR-548AB99.9571.313488
HSA-MIR-548A-5P99.9471.273482
HSA-MIR-548AD-5P99.9471.233502
HSA-MIR-548AE-5P99.9471.233502
HSA-MIR-548AK99.9471.243488
HSA-MIR-548AM-5P99.9471.243488
HSA-MIR-548AP-5P99.9471.143489
HSA-MIR-548AQ-5P99.9471.343426
HSA-MIR-548AR-5P99.9471.283515
HSA-MIR-548AS-5P99.9471.223482
HSA-MIR-548AU-5P99.9471.243488
HSA-MIR-548AY-5P99.9471.233502
HSA-MIR-548B-5P99.9471.233502
HSA-MIR-548BB-5P99.9471.273509
HSA-MIR-548C-5P99.9471.243488
HSA-MIR-548D-5P99.9471.233502
HSA-MIR-548H-5P99.9471.243488
HSA-MIR-548I99.9471.253481
HSA-MIR-548J-5P99.9471.143489

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

  • Up-regulation of CCNB1 is responsible, at least in part, for radioresistance after fractionated irradiation. (PMID:11260656)
  • expression is related to apoptosis in thymus (PMID:11642719)
  • Cyclin b1 promoter activity and functional cdk1 complex formation in G1 phase of human breast cancer cells (PMID:11779217)
  • cyclin b1 is overexpressed in laryngeal squamous cell carcinoma (PMID:11809526)
  • Overexpression of B-type cyclins alters chromosomal segregation (PMID:11960377)
  • The human cyclin Bl gene is cell cycle regulated with maximal activity during G(2)/M. We examined the role of histone deacetylation in cyclin Bl regulation using the histone deacetylase inhibitor trichostatin A (TSA). (PMID:12054478)
  • Overexpression of cyclin B1 is associated with esophageal disease progression (PMID:12115375)
  • H-ras participates in pathways that regulate cyclin B1 expression and therefore controls the G2/M checkpoint in a p53-independent manner. (PMID:12379461)
  • Nuclear accumulation is necessary for cyclin B1-dependent apoptosis. This is consistent with the idea that localization of cyclin B1 is among the factors determining the cellular decision to undergo apoptosis in response to DNA damage. (PMID:12424202)
  • regulation of subcellular localization by cooperative phosphorylation, including activity of polo-like kinase 1 (PMID:12447691)
  • reduction of nuclear level by induction of GADD45 (PMID:12483522)
  • The limitation of detecting cyclin B1 is due to its unscheduled expression, rending cyclin B1 being detected at different time-spots in the G(1) phase. (PMID:12515609)
  • Cyclin B1 transcription is enhanced by the p300 coactivator and regulated during the cell cycle by a cell cycle genes homology region-dependent repression mechanism. (PMID:12586340)
  • increases significantly during colorectal carcinogenesis and during later metastasis to lymph nodes (PMID:12684677)
  • in mammalian cells, the majority of cyclin B1 must be destroyed before the cell can enter anaphase (PMID:12865421)
  • data suggest the maintenance of Cdk1/cyclin B1 activity in HCMV-infected cells can be explained by 3 mechanisms: accumulation of cyclin B1, inactivation of negative regulatory pathways for Cdk1, accumulation of positive factors that promote Cdk1 activity (PMID:14645578)
  • Expression of Cyclin B1 correlated with differentiation and vascular invasion in NSCLC; Cyclin B1 overexpression associated with higher mean values for Ki-67 proliferative index and proliferating cell nuclear antigen labeling index and poorer prognosis. (PMID:14760118)
  • exposure to nonrepairable DNA damage leads to nuclear accumulation of inactive cyclin B1-Cdk1 complexes (PMID:15181148)
  • role in regulating Fas ligand transcription (PMID:15215233)
  • wild-type p53 mediates transcriptional repression of cyclin B1 through the Sp1 transcription factor (PMID:15710382)
  • results show that human papillomavirus type 16 E1 E4 does not inhibit the kinase activity of the Cdk1/cyclin B1 complex; instead, 16E1 E4 uses a novel mechanism in which it sequesters Cdk1/cyclin B1 onto the cytokeratin network (PMID:15767402)
  • results strongly indicate that in response to genotoxic stress, Cdk5 activator-binding protein C53(C53) serves as an important regulatory component of DNA damage checkpoint through modulating cyclin dependent kinase 1-cyclin B1 function (PMID:15790566)
  • Altered expression is associated with therapy failure and death in patients with multiple types of cancer. (PMID:15931389)
  • in nasopharyngeal carcinoma cells, SarCNU-induced apoptosis is p53-dependent while SarCNU-induced G2/M arrest is mediated by the cyclin B1-cdc-2 complex (PMID:16142332)
  • results indicated that chronic Pim-1 kinase overexpression dysregulates cyclin B1 protein expression, which contributes to the development of polyploidy by delaying cytokinesis (PMID:16221667)
  • Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions. (PMID:16237118)
  • Study demonstrates the independent prognostic value of cyclin B1 in diffuse large B-cell lymphoma. (PMID:16273239)
  • Cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1. (PMID:16322753)
  • Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with tendency towards tumor progression: significant role of cyclin B1 in development and pathogenesis of RCC (PMID:16557593)
  • Up-regulation of cyclin B1 expression occurred in cervical cancer and may play an important role in cervical carcinogenesis. (PMID:16614707)
  • hCdc14A is differentially expressed in human cancer cells and can interact with both p53 and the Cdk1/cyclin B complex; it may play a role in carcinogenesis (PMID:16784539)
  • Cdk1-mediated phosphorylation of S439 stabilizes mature SREBP1 during mitosis, thereby preserving a critical pool of active transcription factors to support lipid synthesis. (PMID:16880739)
  • Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and cyclin A, cyclin B, and CDK1 (PMID:17098733)
  • Cyclin B1 overexpression was associated with occult cervical lymph node metastases in tongue carcinoma (PMID:17167975)
  • ATM regulates G(2)/M checkpoint recovery through inhibitory phosphorylations of Artemis that occur soon after DNA damage, thus setting a molecular switch that, hours later upon completion of DNA repair, allows activation of the Cdk1-cyclin B complex. (PMID:17242184)
  • c-Myb protein plays a previously unappreciated role in the G(2)/M cell cycle transition of normal and malignant human hematopoietic cells (PMID:17242210)
  • During both meiotic and mitotic exit in Xenopus eggs, recombinant human cyclin B1-associated cdk1 underwent transient inhibitory phosphorylation at tyr-15. Recominant cyclin B1-cdk1 activity fell more rapidly than the cyclin B1 content. (PMID:17327911)
  • Results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo-like kinase 1 and 14-3-3sigma. (PMID:17359284)
  • data strongly argue against mutational events of CDK1, cyclinB1 and cyclinA2 to play a role in gangliogliomas or focal cortical dysplasia (PMID:17359356)
  • p38 signaling pathway triggering cyclin B1 proteolysis after arsenite exposure may play an important role in connecting G(2) arrest with apoptosis or genome instability. (PMID:17373649)

Cross-species orthologs

15 orthologs

OrganismSymbolGene ID
danio_rerioccnb1ENSDARG00000051923
mus_musculusCcnb1ENSMUSG00000041431
rattus_norvegicusCcnb1ENSRNOG00000058539
drosophila_melanogasterCycAFBGN0000404
drosophila_melanogasterCycBFBGN0000405
drosophila_melanogasterCycDFBGN0010315
drosophila_melanogasterCycEFBGN0010382
caenorhabditis_elegansWBGENE00000863
caenorhabditis_elegansWBGENE00000864
caenorhabditis_elegansWBGENE00000865
caenorhabditis_elegansWBGENE00000866
caenorhabditis_eleganscyb-2.2WBGENE00000867
caenorhabditis_elegansWBGENE00000870
caenorhabditis_eleganscye-1WBGENE00000871
caenorhabditis_elegansWBGENE00017259

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305), CCNI2 (ENSG00000205089)

Protein

Protein identifiers

G2/mitotic-specific cyclin-B1P14635 (reviewed: P14635)

All UniProt accessions (5): P14635, D6RHI0, E9PC90, H0Y9U8, H0YA62

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the control of the cell cycle at the G2/M (mitosis) transition.

Subunit / interactions. Interacts with the CDC2 protein kinase to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Binds HEI10. Interacts with catalytically active RALBP1 and CDC2 during mitosis to form an endocytotic complex during interphase. Interacts with CCNF; interaction is required for nuclear localization. Interacts with CDK5RAP3. Interacts with RFPL4A and UBE2A. Interacts with INCA1.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Ubiquitinated by the SCF(NIPA) complex during interphase, leading to its destruction. Deubiquitinated by USP22 during G2/M phase. Phosphorylated by PLK1 at Ser-133 on centrosomes during prophase: phosphorylation by PLK1 does not cause nuclear import. Phosphorylation at Ser-147 was also reported to be mediated by PLK1 but Ser-133 seems to be the primary phosphorylation site.

Similarity. Belongs to the cyclin family. Cyclin AB subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
P14635-11yes
P14635-22

RefSeq proteins (3): NP_001341773, NP_001341774, NP_114172* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004367Cyclin_C-domDomain
IPR006671Cyclin_NDomain
IPR013763Cyclin-like_domDomain
IPR036915Cyclin-like_sfHomologous_superfamily
IPR039361CyclinFamily
IPR046965Cyclin_A/B-likeFamily
IPR048026CCNB1_first_cyclin-boxDomain
IPR048258Cyclins_cyclin-boxConserved_site

Pfam: PF00134, PF02984

UniProt features (41 total): helix 20, modified residue 6, region of interest 4, turn 3, mutagenesis site 2, sequence conflict 2, strand 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures.

PDBMethodResolution (Å)
6GU2X-RAY DIFFRACTION2
5LQFX-RAY DIFFRACTION2.06
4Y72X-RAY DIFFRACTION2.3
5HQ0X-RAY DIFFRACTION2.3
9FH9ELECTRON MICROSCOPY2.5
6GU3X-RAY DIFFRACTION2.65
4YC3X-RAY DIFFRACTION2.7
6GU4X-RAY DIFFRACTION2.73
2B9RX-RAY DIFFRACTION2.9
2JGZX-RAY DIFFRACTION2.9
9SKQELECTRON MICROSCOPY3.4
8TAUELECTRON MICROSCOPY3.5
7NJ0ELECTRON MICROSCOPY3.6
8TARELECTRON MICROSCOPY4

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P14635-F177.580.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 321, 73, 126, 128, 133, 147

Mutagenesis-validated functional residues (2):

PositionPhenotype
133strongly impairs phosphorylation by plk1.
147does not affect phosphorylation by plk1.

Function

Pathways and Gene Ontology

Reactome pathways

57 pathways

IDPathway
R-HSA-113507E2F-enabled inhibition of pre-replication complex formation
R-HSA-156711Polo-like kinase mediated events
R-HSA-162658Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-174048APC/C:Cdc20 mediated degradation of Cyclin B
R-HSA-176408Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176412Phosphorylation of the APC/C
R-HSA-176417Phosphorylation of Emi1
R-HSA-2299718Condensation of Prophase Chromosomes
R-HSA-2465910MASTL Facilitates Mitotic Progression
R-HSA-2500257Resolution of Sister Chromatid Cohesion
R-HSA-2514853Condensation of Prometaphase Chromosomes
R-HSA-2565942Regulation of PLK1 Activity at G2/M Transition
R-HSA-2980767Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-2995383Initiation of Nuclear Envelope (NE) Reformation
R-HSA-3301854Nuclear Pore Complex (NPC) Disassembly
R-HSA-4419969Depolymerization of the Nuclear Lamina
R-HSA-6804114TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-68875Mitotic Prophase
R-HSA-69273Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69478G2/M DNA replication checkpoint
R-HSA-75035Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8852276The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8878166Transcriptional regulation by RUNX2
R-HSA-9725371Nuclear events stimulated by ALK signaling in cancer
R-HSA-9825892Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
R-HSA-113510E2F mediated regulation of DNA replication
R-HSA-1266738Developmental Biology
R-HSA-1640170Cell Cycle
R-HSA-1643685Disease
R-HSA-174143APC/C-mediated degradation of cell cycle proteins

MSigDB gene sets: 576 (showing top): GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, HORIUCHI_WTAP_TARGETS_DN, MODULE_451, GOBP_MUSCLE_TISSUE_DEVELOPMENT, REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, REACTOME_PHOSPHORYLATION_OF_THE_APC_C

GO Biological Process (31): G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), oocyte maturation (GO:0001556), in utero embryonic development (GO:0001701), mitotic spindle organization (GO:0007052), mitotic metaphase chromosome alignment (GO:0007080), spermatogenesis (GO:0007283), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), negative regulation of gene expression (GO:0010629), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), positive regulation of mRNA 3’-end processing (GO:0031442), tissue regeneration (GO:0042246), positive regulation of mitotic cell cycle (GO:0045931), response to DDT (GO:0046680), positive regulation of fibroblast proliferation (GO:0048146), digestive tract development (GO:0048565), cell division (GO:0051301), positive regulation of attachment of spindle microtubules to kinetochore (GO:0051987), ventricular cardiac muscle cell development (GO:0055015), positive regulation of cardiac muscle cell proliferation (GO:0060045), regulation of chromosome condensation (GO:0060623), protein-containing complex assembly (GO:0065003), cellular response to iron(III) ion (GO:0071283), cellular response to fatty acid (GO:0071398), cellular response to hypoxia (GO:0071456), regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090266), positive regulation of mitochondrial ATP synthesis coupled electron transport (GO:1905448), response to toxic substance (GO:0009636), mitotic cell cycle phase transition (GO:0044772), positive regulation of cell cycle (GO:0045787)

GO Molecular Function (6): patched binding (GO:0005113), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein kinase binding (GO:0019901), ubiquitin-like protein ligase binding (GO:0044389), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), protein binding (GO:0005515)

GO Cellular Component (12): spindle pole (GO:0000922), outer kinetochore (GO:0000940), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cytosol (GO:0005829), membrane (GO:0016020), cyclin B1-CDK1 complex (GO:0097125), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-13 pathways:

CategoryPathways
G2/M Transition3
Mitotic Prophase3
Nuclear Envelope Breakdown3
Mitotic Prometaphase2
E2F mediated regulation of DNA replication1
APC/C:Cdc20 mediated degradation of mitotic proteins1
APC/C-mediated degradation of cell cycle proteins1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins1
Regulation of APC/C activators between G1/S and early anaphase1
Nuclear Envelope (NE) Reassembly1
TP53 Regulates Transcription of Cell Cycle Genes1
M Phase1
G2/M Checkpoints1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure6
mitotic cell cycle5
mitotic cell cycle phase transition2
developmental process involved in reproduction2
cyclin-dependent protein serine/threonine kinase activity2
cell cycle G1/S phase transition1
cell cycle G2/M phase transition1
cell maturation1
oocyte development1
chordate embryonic development1
spindle organization1
microtubule cytoskeleton organization involved in mitosis1
mitotic sister chromatid segregation1
metaphase chromosome alignment1
mitotic cell cycle process1
male gamete generation1
response to chemical1
response to external stimulus1
response to abiotic stimulus1
gene expression1
regulation of gene expression1
negative regulation of macromolecule biosynthetic process1
G2/M transition of mitotic cell cycle1
regulation of G2/M transition of mitotic cell cycle1
positive regulation of mitotic cell cycle phase transition1
positive regulation of cell cycle G2/M phase transition1
mRNA 3’-end processing1
regulation of mRNA 3’-end processing1
positive regulation of mRNA processing1
regeneration1
developmental growth1
regulation of mitotic cell cycle1
positive regulation of cell cycle1
response to insecticide1
positive regulation of cell population proliferation1
fibroblast proliferation1
regulation of fibroblast proliferation1
tube development1
digestive system development1
cellular process1

Protein interactions and networks

STRING

5990 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CCNB1CDK1P06493999
CCNB1CDK2P24941993
CCNB1PLK1P53350982
CCNB1CDC20Q12834970
CCNB1BUB1BO60566967
CCNB1CDC25CP30307951
CCNB1H2AXP16104950
CCNB1WEE1P30291932
CCNB1TOP2AP11388926
CCNB1CKS2P33552923
CCNB1BCLAF1Q9NYF8912
CCNB1TP53P04637909
CCNB1PTCH1Q13635909
CCNB1CCNL2Q96S94909
CCNB1CKS1BP33551902

IntAct

173 interactions, top by confidence:

ABTypeScore
CCNB1CDK1psi-mi:“MI:0217”(phosphorylation reaction)0.980
CCNB1CDK1psi-mi:“MI:0407”(direct interaction)0.980
CDK1CCNB1psi-mi:“MI:0407”(direct interaction)0.980
CDK1CCNB1psi-mi:“MI:0915”(physical association)0.980
CCNB1CDK1psi-mi:“MI:0915”(physical association)0.980
CCNB1CDK1psi-mi:“MI:0570”(protein cleavage)0.980
CCNB1CDK1psi-mi:“MI:0914”(association)0.980
CDK2CCNE2psi-mi:“MI:0914”(association)0.940
CKS1BCDK1psi-mi:“MI:0914”(association)0.920
ESPL1PTTG1psi-mi:“MI:0914”(association)0.900
CDK2CCNB1psi-mi:“MI:0914”(association)0.890
CDK5CCNB1psi-mi:“MI:0915”(physical association)0.890
CDKN1ACCNE2psi-mi:“MI:0914”(association)0.890
PKMYT1CCNB1psi-mi:“MI:0915”(physical association)0.870
CCNB1PKMYT1psi-mi:“MI:0915”(physical association)0.870
PKMYT1CCNB1psi-mi:“MI:2364”(proximity)0.870
CCNB1PKMYT1psi-mi:“MI:2364”(proximity)0.870
CDK2CCNB2psi-mi:“MI:0914”(association)0.860

BioGRID (588): CCNB1 (Affinity Capture-Western), CCNB1 (Affinity Capture-Western), CCNB1 (Affinity Capture-MS), CCNB1 (Biochemical Activity), CCNB1 (Biochemical Activity), CCNB1 (Biochemical Activity), CCNB1 (Biochemical Activity), CCNB1 (Biochemical Activity), CCNB1 (Biochemical Activity), CCNB1 (Reconstituted Complex), CCNB1 (Biochemical Activity), CCNB1 (Reconstituted Complex), CCNB1 (Reconstituted Complex), CCNB1 (Reconstituted Complex), CCNB1 (Reconstituted Complex)

ESM2 similar proteins: F1N2W9, F1QDI9, F1QMB9, O77689, O93229, O95067, P07818, P13350, P13351, P13952, P14100, P14635, P15206, P24860, P24862, P29332, P30276, P30277, P37882, P37883, P54750, Q01061, Q01064, Q01065, Q01066, Q08301, Q08J23, Q0VGM9, Q1HFZ0, Q1LZG6, Q3TZI6, Q3ZBL9, Q4R7A8, Q60FX9, Q60FY0, Q61481, Q64395, Q6H1L8, Q8RWV3, Q92162

Diamond homologs: A0MEB5, A2YH60, O48790, O77689, O93229, O95067, P04962, P07818, P10815, P13350, P13351, P13952, P14635, P14785, P15206, P18606, P20248, P20439, P24860, P24861, P24862, P24871, P25010, P25011, P25012, P29332, P30183, P30274, P30276, P30277, P30278, P30284, P34800, P34801, P37881, P37882, P37883, P39963, P42524, P43449

SIGNOR signaling

21 interactions.

AEffectBMechanism
PLK1“up-regulates activity”CCNB1phosphorylation
CDKN1Adown-regulatesCCNB1binding
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamidedown-regulatesCCNB1“chemical inhibition”
4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamidedown-regulatesCCNB1“chemical inhibition”
PTCH1up-regulatesCCNB1binding
CCNB1“form complex”CyclinB/CDK1binding
R547down-regulatesCCNB1“chemical inhibition”
seliciclibdown-regulatesCCNB1“chemical inhibition”
HLX“up-regulates quantity by expression”CCNB1“transcriptional regulation”
RPRD1B“up-regulates quantity by expression”CCNB1“transcriptional regulation”
MXI1“down-regulates quantity by repression”CCNB1“transcriptional regulation”
CDC20“down-regulates quantity by destabilization”CCNB1binding
CDC25C“up-regulates activity”CCNB1dephosphorylation
CDC25A“up-regulates activity”CCNB1dephosphorylation
AURKA“up-regulates activity”CCNB1phosphorylation
NFY“up-regulates quantity by expression”CCNB1“transcriptional regulation”
APC-c“down-regulates quantity by destabilization”CCNB1ubiquitination
RFPL4A“down-regulates quantity by destabilization”CCNB1ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
G1/S DNA Damage Checkpoints860.4×3e-11
p53-Dependent G1 DNA Damage Response756.1×1e-09
p53-Dependent G1/S DNA damage checkpoint756.1×1e-09
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest648.1×6e-08
TP53 Regulates Transcription of Cell Cycle Genes742.8×9e-09
G1 Phase939.8×6e-11
Cyclin A/B1/B2 associated events during G2/M transition1138.1×5e-13
Cyclin A:Cdk2-associated events at S phase entry1235.8×1e-13

GO biological processes:

GO termPartnersFoldFDR
positive regulation of DNA replication630.1×9e-06
G2/M transition of mitotic cell cycle924.2×3e-08
regulation of mitotic cell cycle1020.8×2e-08
mitotic G2 DNA damage checkpoint signaling519.1×8e-04
G1/S transition of mitotic cell cycle1119.0×7e-09
cell division228.8×6e-12
DNA repair126.6×5e-05
cilium assembly95.7×3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

66 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance50
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1301 predictions. Top by Δscore:

VariantEffectΔscore
5:69167074:G:GTdonor_gain1.0000
5:69167282:GG:Gdonor_gain1.0000
5:69167283:GG:Gdonor_gain1.0000
5:69167904:TCAGA:Tacceptor_loss1.0000
5:69167905:CAG:Cacceptor_loss1.0000
5:69167906:A:AGacceptor_gain1.0000
5:69167906:AGA:Aacceptor_loss1.0000
5:69167907:G:GGacceptor_gain1.0000
5:69167907:GA:Gacceptor_gain1.0000
5:69168075:GAAG:Gdonor_gain1.0000
5:69168075:GAAGG:Gdonor_loss1.0000
5:69168076:AAGG:Adonor_loss1.0000
5:69168078:GGTAA:Gdonor_loss1.0000
5:69168079:G:Tdonor_loss1.0000
5:69168080:T:Gdonor_loss1.0000
5:69168167:CTACA:Cacceptor_loss1.0000
5:69168168:TACA:Tacceptor_loss1.0000
5:69168170:CA:Cacceptor_loss1.0000
5:69168171:A:AGacceptor_gain1.0000
5:69168172:G:GGacceptor_gain1.0000
5:69168172:GGAA:Gacceptor_gain1.0000
5:69168314:G:GTdonor_gain1.0000
5:69168340:TTTG:Tdonor_loss1.0000
5:69168343:GGTAA:Gdonor_loss1.0000
5:69168344:G:GGdonor_gain1.0000
5:69168344:GT:Gdonor_loss1.0000
5:69168345:T:Adonor_loss1.0000
5:69171265:TCAA:Tacceptor_loss1.0000
5:69171266:CAAG:Cacceptor_loss1.0000
5:69171267:A:AGacceptor_gain1.0000

AlphaMissense

2841 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:69174318:T:CL205P1.000
5:69174326:T:AW208R1.000
5:69174326:T:CW208R1.000
5:69174327:G:CW208S1.000
5:69174328:G:CW208C1.000
5:69174328:G:TW208C1.000
5:69174330:T:CL209P1.000
5:69174350:T:CF216L1.000
5:69174352:C:AF216L1.000
5:69174352:C:GF216L1.000
5:69174913:G:CG248R1.000
5:69174914:G:AG248D1.000
5:69174922:G:CA251P1.000
5:69174923:C:AA251D1.000
5:69174935:C:AA255E1.000
5:69174937:A:CS256R1.000
5:69174939:C:AS256R1.000
5:69174939:C:GS256R1.000
5:69174941:A:TK257I1.000
5:69174942:A:CK257N1.000
5:69174942:A:TK257N1.000
5:69175028:A:TE286V1.000
5:69175084:T:CF305L1.000
5:69175086:C:AF305L1.000
5:69175086:C:GF305L1.000
5:69175095:A:CR308S1.000
5:69175095:A:TR308S1.000
5:69171439:T:CL178P0.999
5:69174307:G:AM201I0.999
5:69174307:G:CM201I0.999

dbSNP variants (sampled 300 via entrez): RS1000074608 (5:69177084 C>G), RS1000384479 (5:69166395 A>C,G), RS1000415781 (5:69166739 G>A,C,T), RS1000445690 (5:69169396 T>C), RS1000478296 (5:69169082 A>T), RS1000716331 (5:69174129 A>G,T), RS1000750363 (5:69167878 C>G,T), RS1000780793 (5:69175608 T>C), RS1001265980 (5:69166850 G>A), RS1001305163 (5:69166994 G>A,T), RS1001319017 (5:69177970 T>C), RS1001461992 (5:69172381 C>T), RS1001511565 (5:69176259 A>G), RS1001616563 (5:69169978 T>C), RS1001647904 (5:69172598 T>A,C)

Disease associations

OMIM: gene MIM:123836 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1907602 (PROTEIN COMPLEX), CHEMBL2094127 (PROTEIN COMPLEX GROUP), CHEMBL2412 (SINGLE PROTEIN), CHEMBL4523630 (PROTEIN COMPLEX), CHEMBL4680053 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 145,768 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL189963PALBOCICLIB413,102
CHEMBL3301610ABEMACICLIB47,045
CHEMBL1096380PLINABULIN3686
CHEMBL2103840DINACICLIB32,257
CHEMBL4078746-O-BENZYLGUANINE36,988
CHEMBL428690ALVOCIDIB327,781
CHEMBL50QUERCETIN374,559
CHEMBL1230165SILMITASERTIB2593
CHEMBL1276127INDIRUBIN2181
CHEMBL14762SELICICLIB23,787
CHEMBL1944698ZOTIRACICLIB22,915
CHEMBL2347597ASNUCICLIB2100
CHEMBL3115681NARAZACICLIB2287
CHEMBL3655762CYC-0652388
CHEMBL3905910VORUCICLIB2856
CHEMBL4442620RONICICLIB2367
CHEMBL445813AT-751922,614
CHEMBL4462530ZEMIRCICLIB2429
CHEMBL5095094CULMERCICLIB212
CHEMBL564829MILCICLIB2821
CHEMBL8260BAICALEIN2
CHEMBL151LUTEOLIN2
CHEMBL31574FISETIN2
CHEMBL3545283RIVICICLIB2
CHEMBL1230607PHA-7938871
CHEMBL258805SU-95161
CHEMBL296468BMS-3870321
CHEMBL3545083RGB-2866381
CHEMBL4169078SRA-7371
CHEMBL4439321ATUVECICLIB1

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

379 measured of 508 human assays (523 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
4-{[3-(4-aminophenyl)-1H-pyrazol-5-yl]amino}benzene-1-sulfonamideIC500.34 nM
(12Z)-12-{[(4-{[2-(2-hydroxyethoxy)ethyl]sulfamoyl}phenyl)amino]methylidene}-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-11-oneIC500.54 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyrimidin-4-yl)-1,3-thiazol-2-amineIC501 nM
N-methyl-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)-N-(2,5,8,11-tetraoxatridecan-13-yl)benzene-1-sulfonamideIC501 nM
4-{2-[(3Z)-4-(2-methylpropyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamideIC501.2 nM
1-(2,6-difluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}ureaIC501.5 nM
4-{2-[(3Z)-4-(2-methylprop-1-en-1-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamideIC501.5 nM
4-({[(3Z)-4-oxo-5,10-diazatricyclo[7.4.0.0^{2,6}]trideca-1,6,8,10,12-pentaen-3-ylidene]methyl}amino)benzene-1-sulfonamideIC501.5 nM
4-[N -2-Oxo-2,3-dihydropyrrolo[3,2-f]quinolin-1-ylidene)-hydrazino]benzenesulfonamideIC501.6 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-N-(2,6-dimethoxybenzyl)-2-oxo-5-indolinecarboxamideIC501.7 nM
4-({[(3Z)-5-(3-methylbutanoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamideIC501.9 nM
2-N-(1-methanesulfonylpiperidin-4-yl)-5-[(2,3,4-trifluoro-6-methoxyphenyl)carbonyl]pyrimidine-2,4-diamineKI2 nM
N-(2,6-Difluorophenyl)-N-[5-[[[5-tert-butyl-2-oxazolyl]-methyl]thio]-2-thiazolyl]ureaIC502 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyridin-2-yl)-1,3-thiazol-2-amineIC502 nM
N-{4-[(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)amino]phenyl}-2-hydroxyethane-1-sulfonamidoIC502 nM
4-[1-(5-Oxazol-5-yl-2-oxo-1,2-dihydro-indol-3-ylidene)-ethylamino]benzenesulfonamideIC502 nM
4-[[5-Amino-1-[(3-fluoro-2-thienyl)carbonyl]-1H-1,2,4-triazol-3-yl]amino]-benzenesulfonamideIC502.1 nM
methyl (3Z)-2-oxo-3-{[(4-sulfamoylphenyl)amino]methylidene}-2,3-dihydro-1H-indole-5-carboxylateIC502.1 nM
3-{[4-(Aminosulfonyl)phenyl]hydrazono}-2-oxo-N-(3-pyridinylmethyl)-2,3-dihydro-1H-indole-5-carboxamideIC502.1 nM
4-[N -(1-Chloro-7-oxo-6,7-dihydro-3H-pyrrolo[3,2-e]indazol-8-ylidene)-hydrazino]benzenesulfonamideIC502.2 nM
4-{2-[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamideIC502.3 nM
4-({[(3Z)-5-(1,3-oxazol-5-yl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}amino)benzene-1-sulfonamideIC502.5 nM
4-[N’-(4-Isopropyl-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]benzenesulfonamideIC502.5 nM
1-(2-fluorophenyl)-3-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}ureaIC502.8 nM
4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamideIC502.8 nM
2,4-Diamino-5-ketopyrimidine 39KI3 nM
4-N-(2,6-difluorobenzene)-3-N-(4-fluorophenyl)-1H-pyrazole-3,4-diamidoIC503 nM
3-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)-1-(2,6-dichlorophenyl)ureaIC503 nM
N-[5-[[[5-tert-Butyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-[[[bis(hydroxymethyl)methyl]amino]methyl]benzeneacetamide Hydrochloride SaltIC503 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyridin-3-yl)-1,3-thiazol-2-amineIC503 nM
3-[({6-[(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)amino]pyridin-3-yl}methyl)amino]-2,2-dimethylpropan-1-olIC503 nM
Isobutyl 3-{[4-(aminosulfonyl)anilino]methylene}-2-oxo-2,3-dihydro-1H-indole-5-carboxylateIC503 nM
4-[[5-Amino-1-(2,3,6-trifluorobenzoyl)-1H-1,2,4-triazol-3-yl]amino]-benzenesulfonamideIC503.2 nM
4-({5-amino-1-[(3,5-dimethylthiophen-2-yl)carbonyl]-1H-1,2,4-triazol-3-yl}amino)benzene-1-sulfonamideIC503.2 nM
3-amino-N-(2,6-difluorophenyl)-5-[(4-sulfamoylphenyl)amino]-1H-1,2,4-triazole-1-carbothioamideIC503.2 nM
8-{[4-({[Amino(imino)methyl]amino}sulfonyl)anilino]-methylene}-7-oxo-7,8-dihydro-6H-[1,3]thiazolo[5,4-e]indoleIC503.3 nM
4-{2-[(3Z)-2-oxo-4-(propan-2-yloxy)-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamideIC503.4 nM
N-{3-[5-(morpholin-4-ylmethyl)-1H-1,3-benzodiazol-2-yl]-1H-pyrazol-4-yl}benzamideIC503.5 nM
N-[2-(1H-imidazol-5-yl)ethyl]-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamideIC503.6 nM
5-Amino-3-[[4-(aminosulfonyl)phenyl]amino]-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carboamideIC503.7 nM
N-[5-[[[5-(Cyclohexylmethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]acetamideIC504 nM
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-phenyl-1,3-thiazol-2-amineIC504 nM
Pyrazolopyrimidone analog, RGB-286331IC504 nM
4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)-N-phenylbenzene-1-sulfonamideIC504.3 nM
4-[[5-Amino-1-(2-thienylcarbonyl)-1H-1,2,4-triazol-3-yl]amino]-benzenesulfonamideIC504.5 nM
(3Z)-2-oxo-3-[2-(4-sulfamoylphenyl)hydrazin-1-ylidene]-2,3-dihydro-1H-indole-5-carboxamideIC504.5 nM
4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)-N-(2,5,8,11-tetraoxatridecan-13-yl)benzene-1-sulfonamideIC504.5 nM
4-[N’-(4-Iodo-2-oxo-1,2-dihydro-indol-3-ylidene)-hydrazino]benzenesulfonamideIC504.6 nM
4-{2-[(3Z)-4-methyl-5-nitro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzene-1-sulfonamideIC504.6 nM
N,N-dimethyl-4-({[(12Z)-11-oxo-3-thia-5,10-diazatricyclo[7.3.0.0^{2,6}]dodeca-1,4,6,8-tetraen-12-ylidene]methyl}amino)benzene-1-sulfonamideIC504.6 nM

ChEMBL bioactivities

1204 potent at pChembl≥5 of 1487 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.30Ki0.5nMCHEMBL2348843
9.22IC500.6nMCHEMBL261720
9.22IC500.6nMCHEMBL384350
9.22IC500.6nMCHEMBL426509
9.15IC500.7nMCHEMBL511394
9.00Ki1nMCHEMBL2348844
9.00IC501nMCHEMBL3897452
9.00IC501nMCHEMBL212552
8.89IC501.3nMSTAUROSPORINE
8.86IC501.38nMSTAUROSPORINE
8.85IC501.42nMSTAUROSPORINE
8.85IC501.4nMXYLOCYDINE
8.82Ki1.5nMCHEMBL2348842
8.80IC501.6nMSTAUROSPORINE
8.79IC501.63nMSTAUROSPORINE
8.74IC501.8nMCHEMBL3716786
8.72IC501.9nMCHEMBL377449
8.71IC501.97nMSTAUROSPORINE
8.70Ki2nMCHEMBL2348847
8.70IC502nMRGB-286638
8.70IC502nMCHEMBL212299
8.70IC502nMCHEMBL261720
8.70IC502nMCHEMBL4748292
8.68IC502.1nMCHEMBL361900
8.67IC502.16nMSTAUROSPORINE
8.64IC502.3nMCHEMBL4589128
8.62IC502.4nMSTAUROSPORINE
8.60IC502.52nMSTAUROSPORINE
8.52IC503nMCHEMBL363607
8.52IC503nMCHEMBL3604469
8.52IC503nMDINACICLIB
8.52IC503nMCHEMBL212491
8.52Ki3nMDINACICLIB
8.52IC503nMCHEMBL1825101
8.49IC503.2nMCHEMBL425720
8.49IC503.2nMCHEMBL187395
8.49IC503.2nMCHEMBL364927
8.49IC503.2nMSTAUROSPORINE
8.49IC503.2nMCHEMBL1684800
8.48IC503.3nMSTAUROSPORINE
8.43IC503.7nMCHEMBL370698
8.40Ki4nMCHEMBL2348845
8.40Ki4nMASNUCICLIB
8.40IC504nMCHEMBL3604462
8.40IC504nMCHEMBL3604468
8.40IC504nMPURVALANOLA
8.40IC504nMCHEMBL430653
8.40IC504nMCHEMBL1825100
8.35IC504.5nMCHEMBL190643
8.32IC504.8nMCHEMBL363130

PubChem BioAssay actives

1524 with measured affinity, of 3345 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-[[4-[2-(methylamino)-4-(trifluoromethyl)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide741494: Inhibition of human recombinant His6 tagged CDK1/Cyclin B expressed in Sf21 insect cells after 40 mins by scintillation counting analysiski0.0005uM
N-[2-methyl-4-(2-pyrrolidin-1-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0006uM
2-[3-methyl-4-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]ethanol270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0006uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0006uM
N-[[5-[3-(6-fluoro-1H-benzimidazol-2-yl)-3H-pyrazolo[3,4-b]pyridin-5-yl]-3-pyridinyl]methyl]ethanamine365550: Inhibition of CDK1/cyclinBic500.0007uM
N-[[5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-4-yl]-4-methyl-3-pyridinyl]methyl]ethanamine1317305: Inhibition of CDK1/cyclin B (unknown origin)ic500.0010uM
N-[2-methyl-4-(2-piperidin-1-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0010uM
(3Z)-5-(2-chloroacetyl)-3-(1H-imidazol-5-ylmethylidene)-1H-indol-2-one606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATPic500.0010uM
(3Z)-5-(2-chloroacetyl)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-1H-indol-2-one606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATPic500.0010uM
N-[(3Z)-3-(1H-imidazol-5-ylmethylidene)-2-oxo-1H-indol-5-yl]prop-2-ynamide606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATPic500.0010uM
N-[(3Z)-3-[(5-methyl-1H-imidazol-4-yl)methylidene]-2-oxo-1H-indol-5-yl]prop-2-ynamide606558: Inhibition of human Cdk1/cyclinB using histone H1 as a substrate and [gamma-32P]ATPic500.0010uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone1796919: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm0606138: “Discovery of 4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5-ylmethanone (R547), a potent and selective cyclin-dependent kinase inhibitor with significant in vivo antitumor activity.”ki0.0010uM
4-[[4-[2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide741494: Inhibition of human recombinant His6 tagged CDK1/Cyclin B expressed in Sf21 insect cells after 40 mins by scintillation counting analysiski0.0010uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one629267: Inhibition of CDK1/Cyclin Bic500.0013uM
4-amino-6-bromo-7-[(2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carboxamide632963: Inhibition of CDK1/Cyclin B in human HeLa cell extracts using histone H1 as substrate preincubated for 30 mins before substrate addition measured after 15 mins by autoradiographyic500.0014uM
3-[[4-[2-(methylamino)-4-(trifluoromethyl)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide741494: Inhibition of human recombinant His6 tagged CDK1/Cyclin B expressed in Sf21 insect cells after 40 mins by scintillation counting analysiski0.0015uM
N-[2-methyl-4-(2-morpholin-4-ylethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0019uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea1317305: Inhibition of CDK1/cyclin B (unknown origin)ic500.0020uM
(2R,3R)-3-[5-bromo-2-[4-(ethylsulfonimidoyl)anilino]pyrimidin-4-yl]oxybutan-2-ol1704619: Inhibition of GST-tagged recombinant human CDK1/GST-tagged human cyclin B expressed in Sf-9 cells incubated for 10 mins by scintillation counting methodic500.0020uM
4-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]cyclohexane-1,4-diamine270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0020uM
4-[[4-[4-cyclopropyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide741494: Inhibition of human recombinant His6 tagged CDK1/Cyclin B expressed in Sf21 insect cells after 40 mins by scintillation counting analysiski0.0020uM
4-[[5-amino-1-(3-fluorothiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0021uM
N-[[5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-5-yl]-4-methyl-3-pyridinyl]methyl]ethanamine1549287: Inhibition of CDK1/Cyclin B (unknown origin) using histone H1 as substrate in presence of gamma[32P] ATP by phosphorimaging analysisic500.0023uM
2-hydroxy-3-[(4-sulfamoylphenyl)diazenyl]-1H-indole-5-carboxamide1796078: Kinase Inhibition SPA Assay from Article 10.1021/jm010117d: “Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.”ic500.0028uM
4-[[1-(2,6-difluoro-3-methylbenzoyl)-5-methyl-1,2,4-triazol-3-yl]amino]benzenesulfonamide241014: Inhibition of Cyclin B-cyclin-dependent kinase 1ic500.0030uM
N-(2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine270821: Inhibition of CDK1/cyclinB by Flashplate assayic500.0030uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol1317325: Inhibition of recombinant CDK1/cyclin B (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotinylated histone H1 as substrate after 1 hr by gamma32P-ATP based liquid scintillation counting analysisic500.0030uM
N-(2-aminoethyl)-N-[5-[(1-cycloheptylpyrazolo[3,4-d]pyrimidin-6-yl)amino]-2-pyridinyl]methanesulfonamide617336: Inhibition of CDK1/Cyclin B assessed as phosphorylation of Z-lyte Peptide at 0.017 to 30 nM by FRET assayic500.0030uM
(2R,3R)-3-[[5-bromo-2-[4-(ethylsulfonimidoyl)anilino]pyrimidin-4-yl]amino]butan-2-ol1239767: Inhibition of recombinant CDK1/GST-fused cyclin B (unknown origin) expressed in baculovirus infected insect Sf9 cells by substrate phosphorylation assay in presence of [33P]-gamma adenosine triphosphateic500.0030uM
4-[[5-methyl-1-(2,3,6-trifluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide241014: Inhibition of Cyclin B-cyclin-dependent kinase 1ic500.0032uM
4-[[5-amino-2-(2,6-difluorobenzenecarbothioyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide241014: Inhibition of Cyclin B-cyclin-dependent kinase 1ic500.0032uM
N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylbenzamide578724: Inhibition of CDK1/cyclin Bic500.0032uM
4-[[5-amino-1-(2,3,6-trifluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0032uM
4-[[5-amino-1-(3,5-dimethylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0032uM
3-amino-N-(2,6-difluorophenyl)-5-(4-sulfamoylanilino)-1,2,4-triazole-1-carbothioamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0032uM
5-amino-N-(2,6-difluorophenyl)-3-(4-sulfamoylanilino)-1,2,4-triazole-1-carboxamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0037uM
N-(4-methoxyphenyl)-4-(2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine1239760: Inhibition of human CDK1/cyclin B1 (unknown origin)ic500.0040uM
4-[[5-bromo-4-[(2R,3R)-3-hydroxybutan-2-yl]oxypyrimidin-2-yl]amino]benzenesulfinamide1239767: Inhibition of recombinant CDK1/GST-fused cyclin B (unknown origin) expressed in baculovirus infected insect Sf9 cells by substrate phosphorylation assay in presence of [33P]-gamma adenosine triphosphateic500.0040uM
(2R)-2-[[6-(3-chloroanilino)-9-propan-2-ylpurin-2-yl]amino]-3-methylbutan-1-ol1798788: CDK Inhibition Assay from Article 10.1021/jm801340z: “Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue.”ic500.0040uM
5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-N-pyridin-2-yl-1,3-thiazol-2-amine1795808: Kinase Inhibition assay from Article 10.1016/j.bmcl.2004.02.105: “Synthesis and biological activity of N-aryl-2-aminothiazoles: potent pan inhibitors of cyclin-dependent kinases.”ic500.0040uM
N-[5-[(1-cycloheptylpyrazolo[3,4-d]pyrimidin-6-yl)amino]-2-pyridinyl]-N-(2-hydroxyethyl)methanesulfonamide617336: Inhibition of CDK1/Cyclin B assessed as phosphorylation of Z-lyte Peptide at 0.017 to 30 nM by FRET assayic500.0040uM
3-[[5-fluoro-4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide1940563: Inhibition of CDK1/Cyclin B (unknown origin) assessed as inhibition constantki0.0040uM
3-[[4-[2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide741494: Inhibition of human recombinant His6 tagged CDK1/Cyclin B expressed in Sf21 insect cells after 40 mins by scintillation counting analysiski0.0040uM
4-[[5-amino-1-(thiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0045uM
4-[[5-amino-1-(3-methylthiophene-2-carbonyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide1795974: Kinase Inhibition Assay from Article 10.1021/jm050267e: “1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities.”ic500.0048uM
4-(4-methylpiperazin-1-yl)-N-[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]quinolin-7-amine1771101: Inhibition of human CDK1/cyclinB using Histone H1 as substrate incubated for 2 hrs by [gamma-33P]-ATP assayic500.0049uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3,4-trifluoro-6-methoxyphenyl)methanone1796919: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm0606138: “Discovery of 4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5-ylmethanone (R547), a potent and selective cyclin-dependent kinase inhibitor with significant in vivo antitumor activity.”ki0.0050uM
4-[[5-chloro-4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide1940568: Inhibition of CDK1/Cyclin B (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysiski0.0050uM
3-[[5-fluoro-4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide1940568: Inhibition of CDK1/Cyclin B (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysiski0.0050uM
3-[[5-chloro-4-(1-methylpyrazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide1940568: Inhibition of CDK1/Cyclin B (unknown origin) assessed as inhibition constant incubated for 30 to 60 mins presence of dithiothreitol by Cheng-Prusoff equation analysiski0.0050uM

CTD chemical–gene interactions

422 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Resveratrolaffects expression, affects binding, decreases activity, decreases expression, affects cotreatment (+2 more)12
sodium arsenitedecreases degradation, increases stability, affects reaction, decreases reaction, decreases expression (+2 more)11
Doxorubicinaffects response to substance, affects expression, increases reaction, decreases reaction, affects cotreatment (+3 more)11
Paclitaxelincreases reaction, decreases reaction, increases response to substance, affects reaction, increases activity (+5 more)11
bisphenol Adecreases expression, affects cotreatment, decreases reaction, increases expression, affects expression10
Quercetinaffects cotreatment, increases expression, affects binding, decreases reaction, decreases expression10
Arsenic Trioxidedecreases reaction, affects cotreatment, increases expression, decreases expression9
Cisplatinaffects binding, decreases reaction, increases expression, affects cotreatment, decreases expression (+1 more)7
Estradiolaffects expression, affects cotreatment, increases expression, decreases expression, decreases reaction6
ochratoxin Aaffects reaction, affects binding, decreases reaction, decreases expression, affects cotreatment (+1 more)5
diallyl trisulfidedecreases activity, decreases expression, increases expression, affects localization, affects binding (+1 more)5
alvocidibaffects cotreatment, decreases expression, decreases reaction, increases expression, decreases activity5
Benzo(a)pyrenedecreases expression, increases degradation, increases expression5
Cadmiumincreases abundance, increases expression, decreases expression, affects reaction5
Camptothecinaffects cotreatment, decreases expression, increases expression, affects reaction5
Fluorouracildecreases expression, increases reaction, affects reaction, decreases reaction5
Troglitazonedecreases expression, decreases reaction, affects response to substance, decreases activity, increases response to substance4
trichostatin Adecreases expression3
perfluorooctanoic acidaffects expression, decreases expression, increases expression3
ON 01910decreases expression, increases expression3
2,2’,4,4’-tetrabromodiphenyl etheraffects expression, affects cotreatment, increases expression3
(+)-JQ1 compoundaffects cotreatment, decreases expression3
Bortezomibincreases expression, increases ubiquitination, increases response to substance3
Acroleinincreases oxidation, decreases expression, increases abundance, affects localization, affects response to substance (+1 more)3
Air Pollutantsincreases abundance, increases oxidation, decreases expression, affects cotreatment3
Curcumindecreases expression3
Oxygenaffects cotreatment, decreases expression, increases reaction, affects expression, affects reaction (+1 more)3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases expression3
Cyclosporinedecreases expression3
Cadmium Chlorideaffects cotreatment, decreases reaction, increases expression, decreases expression, increases abundance (+1 more)3

ChEMBL screening assays

631 unique, capped per target: 620 binding, 8 admet, 2 functional, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1000364BindingInhibition of Cdc2/cyclin B assessed as inhibition of histone H1 phosphorylation in human HT29 cellsSynthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases. — Eur J Med Chem
CHEMBL4004950ADMETInhibition of recombinant human CDK1/Cyclin B expressed in baculovirus infected Sf9 cells at using PKTPKKAKKL-NH2 as substrate relative to untreated controlCyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. — J Med Chem
CHEMBL700201FunctionalIn vitro antiproliferative activity against myeloid leukemia K562 cell linePyrazolo[4,3-d]pyrimidines as new generation of cyclin-dependent kinase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B9ERAbcam A-549 CCNB1 KOCancer cell lineMale
CVCL_SH30HAP1 CCNB1 (-) 1Cancer cell lineMale
CVCL_SH31HAP1 CCNB1 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.