Details for: CCNB1

Gene ID: 891

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CCNB1

Ensembl ID: ENSG00000134057

Description: cyclin B1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • transit amplifying cell of colon CL0009011
    CSI 14.2
    rCSI 16.68%
    PRS 96.07
  • plasmablast CL0000980
    CSI 9.72
    rCSI 7.65%
    PRS 96.48
  • radial glial cell CL0000681
    CSI 8.19
    rCSI 11.37%
    PRS 94.87
  • neural crest cell CL0011012
    CSI 8.07
    rCSI 6.38%
    PRS 92.42
  • suprabasal keratinocyte CL4033013
    CSI 7.86
    rCSI 12.83%
    PRS 73.39
  • large pre-B-II cell CL0000957
    CSI 7.34
    rCSI 20.97%
    PRS 95
  • erythrocyte CL0000232
    CSI 7.22
    rCSI 16.38%
    PRS 94.21
  • pro-B cell CL0000826
    CSI 7.12
    rCSI 5.9%
    PRS 96.62
  • chondrocyte CL0000138
    CSI 7.03
    rCSI 11.19%
    PRS 93.06
  • goblet cell CL0000160
    CSI 6.7
    rCSI 6.33%
    PRS 94.22
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 6.64
    rCSI 7.66%
    PRS 90.8
  • promonocyte CL0000559
    CSI 5.58
    rCSI 9.57%
    PRS 96.77
  • transit amplifying cell of small intestine CL0009012
    CSI 5.29
    rCSI 23.25%
    PRS 97.11
  • respiratory hillock cell CL4030023
    CSI 5.21
    rCSI 9.29%
    PRS 97.35
  • placental villous trophoblast CL2000060
    CSI 5.19
    rCSI 8.01%
    PRS 94.57
  • basal cell of epidermis CL0002187
    CSI 4.89
    rCSI 8.67%
    PRS 73.15
  • basal cell CL0000646
    CSI 4.39
    rCSI 5.87%
    PRS 93.86
  • mesodermal cell CL0000222
    CSI 3.98
    rCSI 4.78%
    PRS 95.83
  • stem cell CL0000034
    CSI 3.96
    rCSI 3.81%
    PRS 93.81
  • extravillous trophoblast CL0008036
    CSI 3.71
    rCSI 4.59%
    PRS 94.64
  • ciliated epithelial cell CL0000067
    CSI 3.64
    rCSI 3.2%
    PRS 90.11
  • transit amplifying cell CL0009010
    CSI 3.48
    rCSI 5.32%
    PRS 97.18
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.07
    rCSI 2.95%
    PRS 94.8
  • epithelial cell of lung CL0000082
    CSI 2.93
    rCSI 2.43%
    PRS 96.73
  • erythroid lineage cell CL0000764
    CSI 2.89
    rCSI 18.57%
    PRS 96.27
  • fraction A pre-pro B cell CL0002045
    CSI 2.84
    rCSI 3.25%
    PRS 97.48
  • glioblast CL0000030
    CSI 2.76
    rCSI 4.4%
    PRS 90.98
  • promyelocyte CL0000836
    CSI 2.74
    rCSI 3.95%
    PRS 96.57
  • intestinal epithelial cell CL0002563
    CSI 2.74
    rCSI 2.86%
    PRS 94.29
  • ciliated cell CL0000064
    CSI 2.71
    rCSI 4.4%
    PRS 91.01
  • germinal center B cell CL0000844
    CSI 2.7
    rCSI 8.05%
    PRS 97.45
  • erythroid progenitor cell CL0000038
    CSI 2.68
    rCSI 15.38%
    PRS 96.84
  • common myeloid progenitor CL0000049
    CSI 2.62
    rCSI 2.12%
    PRS 96.72
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.59
    rCSI 2.64%
    PRS 98.15
  • enteric smooth muscle cell CL0002504
    CSI 2.58
    rCSI 3.68%
    PRS 96
  • erythroblast CL0000765
    CSI 2.56
    rCSI 6.8%
    PRS 95.64
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.42
    rCSI 3.11%
    PRS 93.45
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.41
    rCSI 2.09%
    PRS 96.87
  • regulatory T cell CL0000815
    CSI 2.41
    rCSI 2.8%
    PRS 89.55
  • primitive red blood cell CL0002355
    CSI 2.38
    rCSI 12.82%
    PRS 96.27
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.35
    rCSI 2.13%
    PRS 95.28
  • common dendritic progenitor CL0001029
    CSI 2.31
    rCSI 2.89%
    PRS 97.96
  • mesenchymal cell CL0008019
    CSI 2.12
    rCSI 5.37%
    PRS 93.59
  • colon epithelial cell CL0011108
    CSI 2.06
    rCSI 2.16%
    PRS 94.36
  • neural progenitor cell CL0011020
    CSI 1.59
    rCSI 7%
    PRS 87.79
  • mammary gland epithelial cell CL0002327
    CSI 1.19
    rCSI 4.17%
    PRS 97.62
  • pluripotent stem cell CL0002248
    CSI 1.05
    rCSI 31.44%
    PRS 98.07
  • deuterosomal cell CL4033044
    CSI 1.03
    rCSI 3.48%
    PRS 91.14
  • melanocyte of skin CL1000458
    CSI 0.92
    rCSI 1.25%
    PRS 73.19
  • pre-conventional dendritic cell CL0002010
    CSI 0.34
    rCSI 4.45%
    PRS 99.04

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CCNB1](/details-gene/891), or Cyclin B1, is a protein-coding gene located on chromosome 5q13.2. It encodes a crucial regulatory protein that is a member of the cyclin family, specifically G2/mitotic-specific cyclin-B1. As a key component of the cell cycle machinery, [CCNB1](/details-gene/891) forms a complex with Cyclin-Dependent Kinase 1 (CDK1) to create the M-phase promoting factor (MPF). This complex is essential for driving the G2/M transition and orchestrating the events of mitosis. Its expression is tightly regulated and peaks during the G2 and M phases of the cell cycle. Reflecting its fundamental role in cell division, [CCNB1](/details-gene/891) shows highly significant expression in a wide array of actively proliferating cell types, including epithelial progenitors such as [transit amplifying cell of colon](/details-cell/CL0009011), activated immune cells like [plasmablast](/details-cell/CL0000980), and developmental precursors such as [radial glial cell](/details-cell/CL0000681). Alterations in its expression are associated with various human cancers (OMIM: [123836](https://omim.org/entry/123836)). ## Cellular Roles and Expression Landscape The expression profile of [CCNB1](/details-gene/891) underscores its identity as a canonical marker of cellular proliferation. **Overall**, the gene exhibits its highest significance in tissues and cell populations characterized by rapid cell division. - **Epithelial Progenitors:** It is a defining marker for [transit amplifying cell of colon](/details-cell/CL0009011) and [transit amplifying cell of small intestine](/details-cell/CL0009012), as well as [suprabasal keratinocyte](/details-cell/CL4033013) and [goblet cell](/details-cell/CL0000160), all of which are involved in the continuous renewal of epithelial tissues. - **Immune System Development and Activation:** High significance is observed in developing B-lymphocytes, including [pro-B cell](/details-cell/CL0000826) and [large pre-B-II cell](/details-cell/CL0000957), and in terminally differentiating, highly proliferative [plasmablast](/details-cell/CL0000980). Its expression in [promonocyte](/details-cell/CL0000559) is also consistent with its role in hematopoiesis. - **Embryonic and Neural Development:** [CCNB1](/details-gene/891) is prominently expressed in key developmental cell types such as [radial glial cell](/details-cell/CL0000681), [neural crest cell](/details-cell/CL0011012), and [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), highlighting its essential function during organogenesis and nervous system formation. Its activity in [placental villous trophoblast](/details-cell/CL2000060) further supports its critical role in embryonic development. - **Other Proliferative Tissues:** The gene is also significant in [chondrocyte](/details-cell/CL0000138) and hematopoietic precursors leading to [erythrocyte](/details-cell/CL0000232), reflecting its broad importance in tissue growth and maintenance. This widespread expression pattern across diverse, unrelated cell lineages that share the common feature of active division cements the role of [CCNB1](/details-gene/891) as a universal engine of the mitotic cell cycle. ## Pathways and Molecular Function The functional annotations for [CCNB1](/details-gene/891) confirm its central role in cell cycle regulation. Its primary molecular function is [cyclin-dependent protein serine/threonine kinase activator activity](/details-go/GO:0061575), achieved through its binding to protein kinases ([GO:0019901](https://www.ebi.ac.uk/QuickGO/term/GO:0019901)). This activity is embodied in the formation of the [cyclin B1-CDK1 complex](/details-go/GO:0097125), which is the master regulator of mitotic entry. **Biological Processes:** [CCNB1](/details-gene/891) is integral to the overarching process of [Cell division](/details-go/GO:0051301) and is specifically implicated in the regulation of the [G2/m transition of mitotic cell cycle](/details-go/GO:0000086), a process it positively regulates ([GO:0010971](https://www.ebi.ac.uk/QuickGO/term/GO:0010971)). Its functions extend to the physical execution of mitosis, including [Mitotic spindle organization](/details-go/GO:0007052) and [Mitotic metaphase chromosome alignment](/details-go/GO:0007080). This is consistent with its localization to key mitotic structures such as the [centrosome](/details-go/GO:0005813), [spindle pole](/details-go/GO:0000922), and [outer kinetochore](/details-go/GO:0000940). The importance of this protein is highlighted in research demonstrating that active cyclin B1-Cdk1 first localizes to centrosomes during prophase ([Link](https://pubmed.ncbi.nlm.nih.gov/12524548/)). **Reactome Pathways:** The Reactome database provides a detailed map of its involvement. [CCNB1](/details-gene/891) is a key player in the [Cell cycle, mitotic](/details-reactome/R-HSA-69278) pathway, particularly in [M phase](/details-reactome/R-HSA-68886) and the preceding [G2/m transition](/details-reactome/R-HSA-69275). Its activity is tightly controlled by checkpoint mechanisms, including the [G2/m checkpoints](/details-reactome/R-HSA-69481) and its inactivation by CHK1/CHK2 ([R-HSA-75035](https://reactome.org/content/detail/R-HSA-75035)). The cyclical nature of its function is governed by its eventual degradation, a process mediated by the Anaphase-Promoting Complex/Cyclosome (APC/C) as detailed in pathways like [Apc/c:cdc20 mediated degradation of cyclin b](/details-reactome/R-HSA-174048). Furthermore, its transcriptional regulation is linked to major signaling pathways, including those governed by TP53 ([R-HSA-6791312](https://reactome.org/content/detail/R-HSA-6791312)) and E2F ([R-HSA-113510](https://reactome.org/content/detail/R-HSA-113510)). ## Research Directions The established role of [CCNB1](/details-gene/891) as a core driver of cell proliferation makes it a subject of intense interest, particularly in oncology and developmental biology. **Testable Hypotheses:** 1. Given that many cancers rely on deregulated cell cycle progression, the targeted inhibition of the [CCNB1](/details-gene/891)-CDK1 complex may represent a viable strategy to induce cell cycle arrest and apoptosis selectively in tumor cells, which are more dependent on this pathway than quiescent, non-cancerous cells. 2. The high significance of [CCNB1](/details-gene/891) in neural progenitors like [radial glial cell](/details-cell/CL0000681) suggests that its precise temporal and spatial regulation is critical for proper neurogenesis. Perturbations in [CCNB1](/details-gene/891) expression or function during fetal development could lead to severe neurodevelopmental disorders, such as microcephaly or lissencephaly, by disrupting the balance between progenitor proliferation and neuronal differentiation. **Proposed Experimental Approach:** To test the second hypothesis regarding the role of [CCNB1](/details-gene/891) in neurogenesis, a conditional knockout mouse model could be employed. Specifically, crossing a mouse with a floxed *Ccnb1* allele to a mouse expressing Cre recombinase under the control of a neural progenitor-specific promoter (e.g., Nestin or Emx1) would allow for targeted deletion of the gene in the developing central nervous system. The resulting embryos could be analyzed at various developmental stages using immunohistochemistry for markers of proliferation (Ki67), apoptosis (cleaved caspase-3), and neuronal differentiation (Tuj1, NeuN). This approach would definitively establish the in vivo requirement for [CCNB1](/details-gene/891) in maintaining the neural progenitor pool and regulating cortical development. **Therapeutic Potential:** [CCNB1](/details-gene/891) is a well-established and attractive target for anti-cancer therapies. As an intracellular regulatory protein, it is not directly targetable with antibodies. Therefore, the primary therapeutic strategy is **inhibition**, typically aimed at its catalytic partner, CDK1. Numerous small-molecule CDK inhibitors have been developed, although achieving specificity and managing toxicity remain significant challenges due to the essential role of CDKs in normal proliferating tissues (e.g., bone marrow, gut epithelium). Future strategies may focus on developing drugs that disrupt the specific CCNB1-CDK1 interaction, potentially offering a more targeted approach than broad CDK inhibition. Such inhibitors would hold promise for treating a wide range of aggressive, highly proliferative cancers.

Genular Protein ID: 4253425813

Symbol: CCNB1_HUMAN

Name: G2/mitotic-specific cyclin-B1

UniProtKB Accession Codes:

P14635 A8K066 Q5TZP9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CORUM 1 CPTAC 4 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 DrugCentral 1 ELM 1 EMBL 7 EMDB 3 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 27 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 12 PDBsum 12 PIR 1 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 25 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2570636

Title: Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.

PubMed ID: 2570636

DOI: 10.1016/0092-8674(89)90936-7

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7843284

Title: Structure and growth-dependent regulation of the human cyclin B1 promoter.

PubMed ID: 7843284

DOI: 10.1006/excr.1995.1050

PubMed ID: 10716937

Title: Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction.

PubMed ID: 10716937

DOI: 10.1093/emboj/19.6.1378

PubMed ID: 12447691

Title: Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1.

PubMed ID: 12447691

DOI: 10.1038/sj.onc.1206011

PubMed ID: 12775724

Title: RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis.

PubMed ID: 12775724

DOI: 10.1074/jbc.m302191200

PubMed ID: 12612082

Title: A novel RING finger protein, human enhancer of invasion 10, alters mitotic progression through regulation of cyclin B levels.

PubMed ID: 12612082

DOI: 10.1128/mcb.23.6.2109-2122.2003

PubMed ID: 12524548

Title: Active cyclin B1-Cdk1 first appears on centrosomes in prophase.

PubMed ID: 12524548

DOI: 10.1038/ncb918

PubMed ID: 16009132

Title: NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry.

PubMed ID: 16009132

DOI: 10.1016/j.cell.2005.04.034

PubMed ID: 15181148

Title: p21-mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress.

PubMed ID: 15181148

DOI: 10.1091/mbc.e03-12-0871

PubMed ID: 15790566

Title: Cdk5 activator-binding protein C53 regulates apoptosis induced by genotoxic stress via modulating the G2/M DNA damage checkpoint.

PubMed ID: 15790566

DOI: 10.1074/jbc.m413431200

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21540187

Title: Inhibitor of cyclin-dependent kinase (CDK) interacting with cyclin A1 (INCA1) regulates proliferation and is repressed by oncogenic signaling.

PubMed ID: 21540187

DOI: 10.1074/jbc.m110.203471

PubMed ID: 27030811

Title: Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.

PubMed ID: 27030811

DOI: 10.1038/celldisc.2015.28

PubMed ID: 17495531

Title: Cyclin B and cyclin A confer different substrate recognition properties on CDK2.

PubMed ID: 17495531

DOI: 10.4161/cc.6.11.4278

PubMed ID: 17495533

Title: The crystal structure of human cyclin B.

PubMed ID: 17495533

DOI: 10.4161/cc.6.11.4297

Sequence Information:

  • Length: 433
  • Mass: 48337
  • Checksum: E2C4767AE8A11EC0
  • Sequence:
    • MALRVTRNSK INAENKAKIN MAGAKRVPTA PAATSKPGLR PRTALGDIGN KVSEQLQAKM 
PMKKEAKPSA TGKVIDKKLP KPLEKVPMLV PVPVSEPVPE PEPEPEPEPV KEEKLSPEPI 
LVDTASPSPM ETSGCAPAEE DLCQAFSDVI LAVNDVDAED GADPNLCSEY VKDIYAYLRQ 
LEEEQAVRPK YLLGREVTGN MRAILIDWLV QVQMKFRLLQ ETMYMTVSII DRFMQNNCVP 
KKMLQLVGVT AMFIASKYEE MYPPEIGDFA FVTDNTYTKH QIRQMEMKIL RALNFGLGRP 
LPLHFLRRAS KIGEVDVEQH TLAKYLMELT MLDYDMVHFP PSQIAAGAFC LALKILDNGE 
WTPTLQHYLS YTEESLLPVM QHLAKNVVMV NQGLTKHMTV KNKYATSKHA KISTLPQLNS 
ALVQDLAKAV AKV