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FLASH GENE

Symbol

CCND2

contributors: mct/npt - updated : 27-08-2015

HGNC name	cyclin D2
HGNC id	1583

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MPPH3 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3
Location	12p13.32      Physical location : 4.382.901 - 4.414.521
Synonym name	G1/S-specific cyclin D2
Synonym symbol(s)	VIN1, KIAK0002, MGC102758

DNA

TYPE	functioning gene
STRUCTURE	31.62 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	three consensus ZKSCAN3 binding sites were found in the cyclin D2 promoter

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001759 5 - 6531 NP_001750 33.1 289 - 2008 1871400 cycD2SV - - - - - - 2013 23326442 CycD2SV overexpression in several immortalized cell lines led to formation of ubiquitinated protein aggregates accompanied by a significant decrease in cell proliferation cycD2SV protein aggregates were frequently found in various subcellular compartments such as endosomes, autophagosomes, lysosomes and the microtubule organizing centre mediates cell cycle inhibition by sequestering endogenous cell cycle proteins, such as CCND2 and CDK4, and possibly targeting them for ubiquitin mediated protein degradation.

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine large intestine colon   highly Endocrine pancreas       highly Homo sapiens Hearing/Equilibrium ear       highly Nervous brain forebrain cerebral cortex   highly Homo sapiens Fetal Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY	cyclin family
	cyclin D subfamily

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
	intracellular,nucleus,nucleolus

basic FUNCTION	regulator of progression through G1 phase during the cell cycle 2
	involved in gonadal cell proliferation and oncogenesis
	playing a crucial role in adipocyte differentiation by regulating mitotic clonal expansion
	crucial role of CCND2 for the support of cortical intermediate progenitor cells (IPCs) divisions
	in the basal process of neural progenitors is linked to non-equivalent cell fates
	role for CCND2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival
	has a critical role in cell cycle progression and the tumorigenicity of glioblastoma stem cells (GSCs)
	plays an important role in the induction of early-to-mid G1 phase transition and is required for granulosa cell proliferation during ovarian folliculogenesis
	positive role of cyclin D2 in Hepatitis B virus (HBV) replication

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	translocates CDKN1B from the nucleus into the cytoplasm for its KPC-dependent degradation at the G(0)-G(1) transition
	role for CCND2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival
	SMO signaling, acting through CCND2, is critical for the proper development and maturation of the neocortex
	is a new ETV4 target gene involved in the control of cellular proliferation and migration, a finding that highlights a new negative regulatory loop between ETV4 and CCND2
	PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CCND2, MYC, RBL1 and CDC25B

cell & other

REGULATION

induced by

overexpression of ZKSCAN3 (induced CCND2 promoter activity in a MAF/MAFB-independent manner, and to an extent that was influenced by the number of consensus ZKSCAN3 binding sites)

Other

FSH acutely regulated CCND2 expression through both PKA and PI3K signaling pathways during granulosa cell proliferation and also accelerated its ubiquitination-proteasomal degradation, which may prevent overstimulation of granulosa cell proliferation and follicular growth

ASSOCIATED DISORDERS

corresponding disease(s)

MPPH3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in astrocytomas and glioblastomas tumoral     --low   through high methylation levels in invasive prostatic carcinoma, correlating with clinicopathologic features of tumor aggressiveness

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	NAV2 and CCND2 are novel candidate prognostic markers in uterine leiomyosarcoma (LMS) andlow-grade endometrial stromal sarcoma (LG-ESS), respectively
Therapy target

ANIMAL & CELL MODELS