CCND2_RAT
ID CCND2_RAT Reviewed; 288 AA.
AC Q04827;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=G1/S-specific cyclin-D2;
DE AltName: Full=Vin-1 proto-oncogene;
GN Name=Ccnd2; Synonyms=Vin-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8502486;
RA Hanna Z., Jankowski M., Tremblay P., Jiang X.M., Milatovich A., Francke U.,
RA Jolicoeur P.;
RT "The Vin-1 gene, identified by provirus insertional mutagenesis, is the
RT cyclin D2.";
RL Oncogene 8:1661-1666(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7926809; DOI=10.1016/0378-1119(94)90075-2;
RA Hosokawa Y., Onga T., Nakashima K.;
RT "Induction of D2 and D3 cyclin-encoding genes during promotion of the G1/S
RT transition by prolactin in rat Nb2 cells.";
RL Gene 147:249-252(1994).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Regulatory component of the cyclin D2-CDK4 (DC) complex that
CC phosphorylates and inhibits members of the retinoblastoma (RB) protein
CC family including RB1 and regulates the cell-cycle during G(1)/S
CC transition. Phosphorylation of RB1 allows dissociation of the
CC transcription factor E2F from the RB/E2F complex and the subsequent
CC transcription of E2F target genes which are responsible for the
CC progression through the G(1) phase. Hypophosphorylates RB1 in early
CC G(1) phase. Cyclin D-CDK4 complexes are major integrators of various
CC mitogenenic and antimitogenic signals. {ECO:0000250|UniProtKB:P30279}.
CC -!- SUBUNIT: Interacts with either CDK4 or CDK6 protein kinase to form a
CC serine/threonine kinase holoenzyme complex. The cyclin subunit imparts
CC substrate specificity to the complex. {ECO:0000250|UniProtKB:P30279}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P30279}. Cytoplasm
CC {ECO:0000250|UniProtKB:P30279}. Nucleus membrane
CC {ECO:0000250|UniProtKB:P30279}. Note=Cyclin D-CDK4 complexes accumulate
CC at the nuclear membrane and are then translocated into the nucleus
CC through interaction with KIP/CIP family members.
CC {ECO:0000250|UniProtKB:P30279}.
CC -!- PTM: Phosphorylation at Thr-279 by MAP kinases is required for
CC ubiquitination and degradation by the DCX(AMBRA1) complex.
CC {ECO:0000250|UniProtKB:P24385}.
CC -!- PTM: Ubiquitinated by the DCX(AMBRA1) complex during the transition
CC from G1 to S cell phase, leading to its degradation: ubiquitination is
CC dependent on Thr-279 phosphorylation. The DCX(AMBRA1) complex
CC represents the major regulator of CCND2 stability during the G1/S
CC transition (By similarity). Polyubiquitinated by the SCF(FBXL2)
CC complex, leading to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P30279, ECO:0000250|UniProtKB:P30280}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L09752; AAA41010.1; -; mRNA.
DR EMBL; D16308; BAA03815.1; -; mRNA.
DR PIR; I58372; I58372.
DR PIR; JC4011; JC4011.
DR RefSeq; NP_071603.1; NM_022267.1.
DR AlphaFoldDB; Q04827; -.
DR SMR; Q04827; -.
DR BioGRID; 248951; 3.
DR ComplexPortal; CPX-2076; Cyclin D2-CDK4 complex.
DR STRING; 10116.ENSRNOP00000027084; -.
DR PaxDb; Q04827; -.
DR GeneID; 64033; -.
DR KEGG; rno:64033; -.
DR UCSC; RGD:621083; rat.
DR CTD; 894; -.
DR RGD; 621083; Ccnd2.
DR eggNOG; KOG0656; Eukaryota.
DR InParanoid; Q04827; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; Q04827; -.
DR Reactome; R-RNO-69231; Cyclin D associated events in G1.
DR Reactome; R-RNO-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-RNO-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR PRO; PR:Q04827; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0097129; C:cyclin D2-CDK4 complex; ISO:RGD.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071378; P:cellular response to growth hormone stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEP:RGD.
DR GO; GO:0071481; P:cellular response to X-ray; ISO:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0007616; P:long-term memory; ISO:RGD.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IDA:RGD.
DR GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0045664; P:regulation of neuron differentiation; IEP:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEP:RGD.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR CDD; cd00043; CYCLIN; 1.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR015451; Cyclin_D.
DR InterPro; IPR006671; Cyclin_N.
DR PANTHER; PTHR10177; PTHR10177; 1.
DR PANTHER; PTHR10177:SF66; PTHR10177:SF66; 1.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR SMART; SM00385; CYCLIN; 1.
DR SMART; SM01332; Cyclin_C; 1.
DR SUPFAM; SSF47954; SSF47954; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cyclin; Cytoplasm; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..288
FT /note="G1/S-specific cyclin-D2"
FT /id="PRO_0000080439"
FT DOMAIN 26..151
FT /note="Cyclin N-terminal"
FT REGION 264..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30279"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30280"
FT CONFLICT 68
FT /note="E -> G (in Ref. 2; BAA03815)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="C -> V (in Ref. 2; BAA03815)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="T -> A (in Ref. 2; BAA03815)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 288 AA; 32826 MW; 4B522BF4E9835FC1 CRC64;
MELLCCEVDP VRRAVPDRNL LEDRVLQNLL TIEERYLPQC SYFKCVQKDI QPYMRRMVAT
WMLEVCEEQK CEEEVFPLAM NYLDRFLAGV PTPKTHLQLL GAVCMFLASK LKETIPLTAE
KLCIYTDNSV KPQELLEWEL VVLGKLKWNL AAVTPHDFIE HILRKLPQQK EKLSLIRKHA
QTFIALCATD FKFAMYPPSM IATGSVGAAI CGLQQDEEVN ALTCDALTEL LTKITHTDVD
CLKACQEQIE AVLLNSLQQF RQEQHNGSKS VEDPDQATTP TDVRDVDL
