CCND2_MOUSE
ID CCND2_MOUSE Reviewed; 289 AA.
AC P30280;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=G1/S-specific cyclin-D2;
GN Name=Ccnd2 {ECO:0000312|MGI:MGI:88314};
GN Synonyms=Cyl-2 {ECO:0000303|PubMed:1372445};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1372445; DOI=10.1073/pnas.89.6.2444;
RA Kiyokawa H., Bousquets X., Powell C.T., Ngo L., Rifkind R.A., Marks P.A.;
RT "Cloning of a D-type cyclin from murine erythroleukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2444-2447(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1827757; DOI=10.1016/0092-8674(91)90101-4;
RA Matsushime H., Roussel M.F., Ashmun R.A., Sherr C.J.;
RT "Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of
RT the cell cycle.";
RL Cell 65:701-713(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-280, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP UBIQUITINATION.
RX PubMed=33854232; DOI=10.1038/s41586-021-03422-5;
RA Maiani E., Milletti G., Nazio F., Holdgaard S.G., Bartkova J., Rizza S.,
RA Cianfanelli V., Lorente M., Simoneschi D., Di Marco M., D'Acunzo P.,
RA Di Leo L., Rasmussen R., Montagna C., Raciti M., De Stefanis C.,
RA Gabicagogeascoa E., Rona G., Salvador N., Pupo E., Merchut-Maya J.M.,
RA Daniel C.J., Carinci M., Cesarini V., O'sullivan A., Jeong Y.T., Bordi M.,
RA Russo F., Campello S., Gallo A., Filomeni G., Lanzetti L., Sears R.C.,
RA Hamerlik P., Bartolazzi A., Hynds R.E., Pearce D.R., Swanton C., Pagano M.,
RA Velasco G., Papaleo E., De Zio D., Maya-Mendoza A., Locatelli F.,
RA Bartek J., Cecconi F.;
RT "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.";
RL Nature 592:799-803(2021).
RN [6]
RP UBIQUITINATION.
RX PubMed=33854235; DOI=10.1038/s41586-021-03445-y;
RA Simoneschi D., Rona G., Zhou N., Jeong Y.T., Jiang S., Milletti G.,
RA Arbini A.A., O'Sullivan A., Wang A.A., Nithikasem S., Keegan S., Siu Y.,
RA Cianfanelli V., Maiani E., Nazio F., Cecconi F., Boccalatte F., Fenyoe D.,
RA Jones D.R., Busino L., Pagano M.;
RT "CRL4AMBRA1 is a master regulator of D-type cyclins.";
RL Nature 592:789-793(2021).
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-280 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-280 phosphorylation (PubMed:33854232,
CC PubMed:33854235). The DCX(AMBRA1) complex represents the major
CC regulator of CCND2 stability during the G1/S transition
CC (PubMed:33854232, PubMed:33854235). Polyubiquitinated by the SCF(FBXL2)
CC complex, leading to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P30279, ECO:0000269|PubMed:33854232,
CC ECO:0000269|PubMed:33854235}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
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DR EMBL; M83749; AAA37519.1; -; mRNA.
DR EMBL; M86182; AAA37503.1; -; mRNA.
DR EMBL; BC049086; AAH49086.1; -; mRNA.
DR CCDS; CCDS20564.1; -.
DR PIR; A41984; A41984.
DR RefSeq; NP_033959.1; NM_009829.3.
DR RefSeq; XP_006505522.1; XM_006505459.2.
DR RefSeq; XP_006505523.1; XM_006505460.1.
DR AlphaFoldDB; P30280; -.
DR SMR; P30280; -.
DR BioGRID; 198549; 5.
DR ComplexPortal; CPX-2074; Cyclin D2-CDK4 complex.
DR CORUM; P30280; -.
DR DIP; DIP-24177N; -.
DR IntAct; P30280; 4.
DR STRING; 10090.ENSMUSP00000000188; -.
DR iPTMnet; P30280; -.
DR PhosphoSitePlus; P30280; -.
DR EPD; P30280; -.
DR PaxDb; P30280; -.
DR PeptideAtlas; P30280; -.
DR PRIDE; P30280; -.
DR ProteomicsDB; 265616; -.
DR DNASU; 12444; -.
DR Ensembl; ENSMUST00000000188; ENSMUSP00000000188; ENSMUSG00000000184.
DR GeneID; 12444; -.
DR KEGG; mmu:12444; -.
DR UCSC; uc009dvr.1; mouse.
DR CTD; 894; -.
DR MGI; MGI:88314; Ccnd2.
DR VEuPathDB; HostDB:ENSMUSG00000000184; -.
DR eggNOG; KOG0656; Eukaryota.
DR GeneTree; ENSGT00940000155180; -.
DR InParanoid; P30280; -.
DR OMA; CLEMDTN; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; P30280; -.
DR TreeFam; TF101004; -.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-MMU-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR BioGRID-ORCS; 12444; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ccnd2; mouse.
DR PRO; PR:P30280; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P30280; protein.
DR Bgee; ENSMUSG00000000184; Expressed in rostral migratory stream and 309 other tissues.
DR ExpressionAtlas; P30280; baseline and differential.
DR Genevisible; P30280; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0097129; C:cyclin D2-CDK4 complex; IDA:MGI.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071481; P:cellular response to X-ray; IMP:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0007616; P:long-term memory; IMP:MGI.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; ISO:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
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..289
FT /note="G1/S-specific cyclin-D2"
FT /id="PRO_0000080438"
FT DOMAIN 26..151
FT /note="Cyclin N-terminal"
FT REGION 264..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30279"
FT MOD_RES 280
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 289 AA; 32897 MW; 58F322771DD1DA3D CRC64;
MELLCCEVDP VRRAVPDRNL LEDRVLQNLL TIEERYLPQC SYFKCVQKDI QPYMRRMVAT
WMLEVCEEQK CEEEVFPLAM NYLDRFLAGV PTPKTHLQLL GAVCMFLASK LKETIPLTAE
KLCIYTDNSV KPQELLEWEL VVLGKLKWNL AAVTPHDFIE HILRKLPQQK EKLSLIRKHA
QTFIALCATD FKFAMYPPSM IATGSVGAAI CGLQQDDEVN TLTCDALTEL LAKITHTDVD
CLKACQEQIE ALLLNSLQQF RQEQHNAGSK SVEDPDQATT PTDVRDVDL