CCND2

Function

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).

Involvement in disease

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

MPPH3

A syndrome characterized by megalencephaly, ventriculomegaly that may lead to hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation at Thr-280 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.

Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-280 phosphorylation (PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex represents the major regulator of CCND2 stability during the G1/S transition (PubMed:33854235, PubMed:33854239). Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation (PubMed:22323446).

Sequence Similarities

Belongs to the cyclin family. Cyclin D subfamily.

Cellular localization

• Nucleus
• Cytoplasm
• Nucleus membrane
• Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members.
• Isoform 2
• Cytoplasm

Alternative names

G1/S-specific cyclin-D2, CCND2

Database links

swissprot:P30279 entrezGene:894 omim:123833

Other research areas

• Epigenetics