Back to discover

Protein / target

G1/S-specific cyclin-D2

Encoded byCCND2P30279Homo sapiensSwiss-Prot
UniProt: P30279Ensembl: ENSG00000118971HGNC: HGNC:1583NCBI Gene: 894
Small-molecule tractable
Druggability
High-Quality Ligand
1
Research papers

Protein at a glance

Biological role

Protein serine/threonine kinase activator

Strongest disease association

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus

Via encoding gene CCND2 · Genetic literature evidence · score 0.85

Research activity

Emerging research

1 papers · latest 2005

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Regulatory component of the cyclin D2-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.

View complete UniProt function annotation

Regulatory component of the cyclin D2-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 (PubMed:18827403, PubMed:8114739). 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 (PubMed:18827403, PubMed:8114739). Hypophosphorylates RB1 in early G(1) phase (PubMed:18827403, PubMed:8114739). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:18827403, PubMed:8114739)

Subcellular location

NucleusCytoplasmNucleus membrane
Domains and Gene Ontology detail (20)

Domains & features

Cyclin N-terminal

Gene Ontology

  • Cchromatin
  • Ccyclin D2-CDK4 complex
  • Ccyclin-dependent protein kinase holoenzyme complex
  • Ccytoplasm
  • Ccytosol
  • Cmicrotubule organizing center
  • Cnuclear membrane
  • Cnucleolus
  • Cnucleoplasm
  • Cnucleus
  • Fcyclin-dependent protein serine/threonine kinase activator activity
  • Fcyclin-dependent protein serine/threonine kinase regulator activity

289 aa · 33 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationGOCell proliferation & survivalGOKinase signallingGO
View supporting evidence

Cell-cycle regulation

  • ·G1/S transition of mitotic cell cycle
  • ·positive regulation of G1/S transition of mitotic cell cycle

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Kinase signalling

  • ·cyclin-dependent protein kinase holoenzyme complex
  • ·cyclin-dependent protein serine/threonine kinase activator activity
  • ·cyclin-dependent protein serine/threonine kinase regulator activity
  • ·protein kinase binding

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CCND2

Gene-level evidence surfaced through the gene CCND2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn
0.84Well supported

Genetic evidence dominant · Open Targets 0.51

Diabetes Mellitus
0.84Well supported

Genetic evidence dominant · Open Targets 0.51

Diabetes Mellitus, Type 2
0.80Well supported

Genetic evidence dominant · Open Targets 0.49

Colorectal Neoplasms
0.75Well supported

Genetic evidence dominant · Open Targets 0.46

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus
0.72Moderately supported

Genetic literature evidence dominant · Open Targets 0.73

View evidence synthesis (5)
Genetic Diseases, InbornWell supported
0.84
agreement 0.72–0.96
Genetic100%

Open Targets aggregate 0.51 · 1 independent evidence family

Diabetes MellitusWell supported
0.84
agreement 0.72–0.96
Genetic87%Animal model11%Literature2%

Open Targets aggregate 0.51 · 3 independent evidence families

Diabetes Mellitus, Type 2Well supported
0.80
agreement 0.66–0.94
Genetic95%Literature5%

Open Targets aggregate 0.49 · 2 independent evidence families

Colorectal NeoplasmsWell supported
0.75
agreement 0.61–0.89
Genetic95%Literature5%

Open Targets aggregate 0.46 · 2 independent evidence families

Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalusModerately supported
0.72
agreement 0.59–0.84
Genetic literature85%Animal model14%Literature1%Geneticdup

Open Targets aggregate 0.73 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus0.73
Neurodegenerative Diseases0.57
Genetic Diseases, Inborn0.51
Diabetes Mellitus0.51
Diabetes Mellitus, Type 20.49
Colorectal Neoplasms0.46
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 10.45
Colorectal adenocarcinoma0.41

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand and druggable family) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · High-Quality LigandSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database Ubiquitination

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2005

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.795 cites

Glennie S · Blood · 2005

Recent

Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.

Glennie S · Blood · 2005

Europe PMC papers linked directly to this protein.

Related family literature

3

Papers about “Cyclins” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers.

Navarro-Yepes J · Cancer research · 2023

via Cyclins

Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models.

Kim H · Nature communications · 2020

via Cyclins

Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.

Glennie S · Blood · 2005

via Cyclins

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.