Tchem CCND1 G1/S-specific cyclin-D1

Protein Summary

Description

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner. The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P24385
• Q6LEF0

Gene Name

• CCND1

Ensembl ID

• ENST00000227507
• ENSP00000227507
• ENSG00000110092

Symbol

• BCL1
• PRAD1
• BCL1
• PRAD1
• U21B31
• D11S287E

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
chemical	1
hub protein	1
transcription factor perturbation	1
biological term	0.99

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Kinase Modulator / Kinase Activator / G1/s-specific Cyclin-d1

DTO Classes

Protein / Enzyme Modulator / Kinase Modulator / Kinase Activator / G1/s-specific Cyclin-d1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7678.22   (req: < 5)

Gene RIFs: 1176   (req: <= 3)

Antibodies: 1839   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7678.22   (req: >= 5)

Gene RIFs: 1176   (req: > 3)

Antibodies: 1839   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 50

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GENEVA

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ARCHS4

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Approved Drugs (1)

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1 – 1 of 1

palbociclib

CCND1Tchem

INHIBITOR pIC50 : 7.96

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (847)

Explore Interacting Targets

1 – 10 of 847

• See Interactions on String-DB

CDKN1B

Tbio

Family:  Enzyme

Novelty:  0.00069449

p_int:  0.99999993

p_ni:  7e-8

Score:  0.996

Data Source:  BioPlex,Reactome,STRINGDB

CDKN1C

Tbio

Family:  Enzyme

Novelty:  0.00220485

p_int:  0.999999617

p_ni:  3.82e-7

p_wrong:  1e-9

Score:  0.992

Data Source:  BioPlex,STRINGDB

CDKN1A

Tchem

Family:  Enzyme

Novelty:  0.00033009

p_int:  0.999998862

p_ni:  0.000001135

p_wrong:  2e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

CDKN2C

Tbio

Family:  Enzyme

Novelty:  0.00806886

p_int:  0.999966718

p_ni:  0.000033279

p_wrong:  3e-9

Score:  0.985

Data Source:  BioPlex,STRINGDB

TCHH

Tbio

Novelty:  0.00303837

p_int:  0.999778397

p_ni:  0.00004013

p_wrong:  0.000181473

Score:  0.233

Data Source:  BioPlex,STRINGDB

CDK5

Tchem

Family:  Kinase

Novelty:  0.00071394

p_int:  0.998468706

p_ni:  0.001531294

Score:  0.748

Data Source:  BioPlex,STRINGDB

CDK2

Tchem

Family:  Kinase

Novelty:  0.00032118

p_int:  0.993217704

p_ni:  0.006782296

Score:  0.999

Data Source:  BioPlex,STRINGDB

TSR3

Tdark

Novelty:  0.09337944

p_int:  0.938940283

p_ni:  0.061059717

Data Source:  BioPlex

CDK1

Tchem

Family:  Kinase

Novelty:  0.00040776

p_int:  0.83998219

p_ni:  0.16001781

Score:  0.985

Data Source:  BioPlex,STRINGDB

CDK4

Tclin

Family:  Kinase

Novelty:  0.00036742

p_int:  0.750000029

p_ni:  0.249999971

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

Nearest Tclin Targets (7)

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Upstream (5)

Downstream (2)

1 – 5 of 5

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  21

1: PI3K-Akt signaling pathway

2: Gastric cancer

3: Focal adhesion

4: Kaposi sarcoma-associated herpesvirus infection

more:  17 more common pathways

CDK6

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  22

1: PI3K-Akt signaling pathway

2: Non-small cell lung cancer

3: Chronic myeloid leukemia

4: Kaposi sarcoma-associated herpesvirus infection

more:  18 more common pathways

CDK4

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  26

1: PI3K-Akt signaling pathway

2: Endocrine resistance

3: Non-small cell lung cancer

4: Chronic myeloid leukemia

more:  22 more common pathways

ESR1

Tclin

Family:  Nuclear Receptor

KEGG Distance:  1

Common Pathways:  6

1: Endocrine resistance

2: Breast cancer

3: Thyroid hormone signaling pathway

4: Proteoglycans in cancer

more:  2 more common pathways

THRB

Tclin

Family:  Nuclear Receptor

KEGG Distance:  1

Common Pathways:  1

1: Thyroid hormone signaling pathway

Pathways (216)

Reactome (39)

KEGG (46)

PathwayCommons (24)

WikiPathways (107)

Cell Cycle (R-HSA-1640170)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle, Mitotic	495 targets	R-HSA-69278
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509
Reactome	Chromatin organization	238 targets	R-HSA-4839726
Reactome	Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656

Name	Explore in Pharos	Explore in Source
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (59)

Functions (9)

Components (9)

Processes (41)

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1 – 9 of 9

GO Term	Evidence	Assigned by
cyclin-dependent protein serine/threonine kinase activity	Inferred from Experiment (EXP)	Reactome
proline-rich region binding	Inferred from Direct Assay (IDA)	UniProtKB
transcription corepressor activity	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
histone deacetylase binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
cyclin-dependent protein serine/threonine kinase regulator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
protein-containing complex binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (24)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	4	4	2	1.1	91.2
breast carcinoma	EFO_0000305	2	2	0	1.3	85.3
BMI-adjusted hip circumference	EFO_0008039	1	2	2		64.8
IgG isotype profile measurement	EFO_0008366	3	1	0	1.6	54.4
AL amyloidosis	Orphanet_85443	5	1	0	1.4	54.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
type II diabetes mellitus	EFO_0001360	2	1.1	91.2
breast carcinoma	EFO_0000305	0	1.3	85.3
BMI-adjusted hip circumference	EFO_0008039	2		64.8
IgG isotype profile measurement	EFO_0008366	0	1.6	54.4
AL amyloidosis	Orphanet_85443	0	1.4	54.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Cell cycle
Cell division
Chromosomal rearrangement
Complete proteome
Cyclin
Cytoplasm
DNA damage
Isopeptide bond
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
AL amyloidosis
birth weight
BMI-adjusted hip circumference
BMI-adjusted waist-hip ratio
body fat distribution
body height
body mass index
breast carcinoma
calcium measurement
comparative body size at age 10, self-reported

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	cyclin D1		574320
Mouse	cyclin D1	MGI:88313	12443
Rat	cyclin D1	RGD:68384	58919
Dog	cyclin D1	VGNC:54266	449028
Cow	cyclin D1	VGNC:26962	524530

Species	Name	OMA	EggNOG	Inparanoid
Macaque	cyclin D1
Mouse	cyclin D1
Rat	cyclin D1
Dog	cyclin D1
Cow	cyclin D1

Publication Statistics

PubMed Score 7678.22

PubMed score by year

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PubTator Score 6284.81

PubTator score by year

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Related Publications

Text Mined References (1361)

GeneRif Annotations (1176)

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PMID	Year	Title