Tchem CCND3 G1/S-specific cyclin-D3

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Kinase Modulator / Kinase Activator / G1/s-specific Cyclin-d3

Protein Summary

Description

Regulatory component of the cyclin D3-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 D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through 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 activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Uniprot Accession IDs

• P30281
• B2RD63
• B3KQ22
• E9PAS4
• E9PB36
• Q5T8J0
• Q6FG62
• Q96F49

Gene Name

• CCND3

Ensembl ID

• ENST00000372988
• ENSP00000362079
• ENSG00000112576
• ENST00000372991
• ENSP00000362082
• ENST00000414200
• ENSP00000397545
• ENST00000415497
• ENSP00000401595
• ENST00000511642
• ENSP00000426212
• ENST00000616010
• ENSP00000484424

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
trait	0.97
transcription factor perturbation	0.97
PubMedID	0.96
transcription factor binding site profile	0.93
chemical	0.91

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: 319.87   (req: < 5)

Gene RIFs: 90   (req: <= 3)

Antibodies: 756   (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: 319.87   (req: >= 5)

Gene RIFs: 90   (req: > 3)

Antibodies: 756   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

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

Active Ligand: 1

Tclin

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

Active Drug: 0

Active Ligands (1)

Explore Active Ligands

1 – 1 of 1

CHEMBL488436

CCND3Tchem

IC50: 7.68

Protein Data Bank (1)

1 – 1 of 1

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (53)

Reactome (15)

KEGG (15)

PathwayCommons (8)

WikiPathways (15)

Cell Cycle (R-HSA-1640170)

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Items per page:

5

1 – 5 of 15

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	Cyclin D associated events in G1	45 targets	R-HSA-69231
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	G1 Phase	45 targets	R-HSA-69236

Name	Explore in Pharos	Explore in Source
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Cyclin D associated events in G1	45 targets	R-HSA-69231
Developmental Biology	1055 targets	R-HSA-1266738
G1 Phase	45 targets	R-HSA-69236

Gene Ontology Terms (21)

Functions (3)

Components (5)

Processes (13)

Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
protein kinase binding	Inferred from Physical Interaction (IPI)	BHF-UCL
cyclin-dependent protein serine/threonine kinase regulator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
cyclin-dependent protein serine/threonine kinase activity	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (178)

Explore Interacting Targets

1 – 10 of 178

• See Interactions on String-DB

CDK6

Tclin

Family: Kinase

Novelty: 0.00168972

p_int: 0.999999998

p_ni: 2e-9

Score: 0.999

Data Source: BioPlex,STRINGDB

CDKN1B

Tbio

Family: Enzyme

Novelty: 0.00079036

p_int: 0.999999932

p_ni: 6.8e-8

Score: 0.999

Data Source: BioPlex,STRINGDB

CDK4

Tclin

Family: Kinase

Novelty: 0.00051528

p_int: 0.999999792

p_ni: 2.08e-7

Score: 0.999

Data Source: BioPlex,STRINGDB

CDKN1C

Tbio

Family: Enzyme

Novelty: 0.00156129

p_int: 0.999999713

p_ni: 2.27e-7

p_wrong: 6e-8

Score: 0.991

Data Source: BioPlex,STRINGDB

RBL2

Tbio

Novelty: 0.00183781

p_int: 0.999995754

p_ni: 0.000004245

Score: 0.99

Data Source: BioPlex,STRINGDB

CDKN1A

Tbio

Family: Enzyme

Novelty: 0.00038005

p_int: 0.999956785

p_ni: 8.64e-7

p_wrong: 0.000042351

Score: 0.999

Data Source: BioPlex,STRINGDB

CDKN2C

Tbio

Family: Enzyme

Novelty: 0.01094308

p_int: 0.999916215

p_ni: 0.000072109

p_wrong: 0.000011676

Score: 0.991

Data Source: BioPlex,STRINGDB

KLK5

Tchem

Family: Enzyme

Novelty: 0.00957513

p_int: 0.999851267

p_ni: 0.00013718

p_wrong: 0.000011553

Data Source: BioPlex

CDK2

Tchem

Family: Kinase

Novelty: 0.00033882

p_int: 0.99931555

p_ni: 0.000684449

Score: 0.999

Data Source: BioPlex,STRINGDB

CDK5

Tchem

Family: Kinase

Novelty: 0.00081843

p_int: 0.996607531

p_ni: 0.003392469

Score: 0.696

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  319.87

PubMed score by year

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PubTator Score  322.54

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MELLCCEGTRHAPRAGPDPRLLGDQRVLQSLLRLEERYVPRASYFQCVQREIKPHMRKMLAYWMLEVCEE

1-70

QRCEEEVFPLAMNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDW

70-140

EVLVLGKLKWDLAAVIAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGA

140-210

AVQGLGACSMSGDELTELLAGITGTEVDCLRACQEQIEAALRESLREASQTSSSPAPKAPRGSSSQGPSQ

210-280

TSTPTDVTAIHL

280-292

MELLCCEGTRHAPRAGPDPRLLGDQRVLQSLLRLEERYVPRASYFQCVQREIKPHMRKMLAYWMLEVCEEQRCEEEVFPLAMNYLDRYLSCVPTRKAQLQLLGAVCMLLASKLRETTPLTIEKLCIYTDHAVSPRQLRDWEVLVLGKLKWDLAAVIAHDFLAFILHRLSLPRDRQALVKKHAQTFLALCATDYTFAMYPPSMIATGSIGAAVQGLGACSMSGDELTELLAGITGTEVDCLRACQEQIEAALRESLREASQTSSSPAPKAPRGSSSQGPSQTSTPTDVTAIHL

Find similar targets by:

Uniprot Keyword

3D-structure
Alternative splicing
Cell cycle
Cell division
Complete proteome
Cyclin
Cytoplasm
Membrane
Nucleus
Phosphoprotein