CCND3_MOUSE
ID CCND3_MOUSE Reviewed; 292 AA.
AC P30282; Q62391; Q99KP2;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=G1/S-specific cyclin-D3 {ECO:0000303|PubMed:8661116};
GN Name=Ccnd3 {ECO:0000303|PubMed:8661116, ECO:0000312|MGI:MGI:88315};
GN Synonyms=Cyl-3 {ECO:0000303|PubMed:1827757};
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=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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=8661116; DOI=10.1006/geno.1996.0334;
RA Wang Z., Sicinski P., Weinberg R.A., Zhang Y., Ravid K.;
RT "Characterization of the mouse cyclin D3 gene: exon/intron organization and
RT promoter activity.";
RL Genomics 35:156-163(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 SER-264, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas, and Spleen;
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 D3-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. Component of the ternary
CC complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and
CC activity of the cyclin D-CDK4 complex. Shows transcriptional
CC coactivator activity with ATF5 independently of CDK4.
CC {ECO:0000250|UniProtKB:P30281}.
CC -!- SUBUNIT: Interacts with the CDK4 and CDK6 protein kinases to form a
CC serine/threonine kinase holoenzyme complex. The cyclin subunit imparts
CC substrate specificity to the complex. Interacts with ATF5. Interacts
CC with EIF3K. Component of the ternary complex cyclin D/CDK4/CDKN1B
CC required for nuclear translocation and modulation of CDK4-mediated
CC kinase activity. Can form similar complexes with either CDKN1A or
CC CDKN2A. {ECO:0000250|UniProtKB:P30281}.
CC -!- INTERACTION:
CC P30282; Q64261: Cdk6; NbExp=2; IntAct=EBI-847337, EBI-847380;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P30281}. Cytoplasm
CC {ECO:0000250|UniProtKB:P30281}.
CC -!- PTM: Phosphorylation at Thr-283 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-283 phosphorylation (PubMed:33854232,
CC PubMed:33854235). The DCX(AMBRA1) complex represents the major
CC regulator of CCND3 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:P30281, 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; M86183; AAA37504.1; -; mRNA.
DR EMBL; U43844; AAC53363.1; -; Genomic_DNA.
DR EMBL; BC004076; AAH04076.1; -; mRNA.
DR EMBL; BC005605; AAH05605.1; -; mRNA.
DR CCDS; CCDS28850.1; -.
DR PIR; C40035; C40035.
DR RefSeq; NP_001075104.1; NM_001081635.1.
DR RefSeq; NP_001075105.1; NM_001081636.1.
DR RefSeq; NP_031658.1; NM_007632.2.
DR AlphaFoldDB; P30282; -.
DR SMR; P30282; -.
DR BioGRID; 198550; 12.
DR ComplexPortal; CPX-2077; Cyclin D3-CDK4 complex.
DR ComplexPortal; CPX-2079; Cyclin D3-CDK6 complex.
DR IntAct; P30282; 6.
DR STRING; 10090.ENSMUSP00000040488; -.
DR iPTMnet; P30282; -.
DR PhosphoSitePlus; P30282; -.
DR EPD; P30282; -.
DR jPOST; P30282; -.
DR PaxDb; P30282; -.
DR PeptideAtlas; P30282; -.
DR PRIDE; P30282; -.
DR ProteomicsDB; 281251; -.
DR Antibodypedia; 3521; 844 antibodies from 43 providers.
DR DNASU; 12445; -.
DR Ensembl; ENSMUST00000037333; ENSMUSP00000040488; ENSMUSG00000034165.
DR Ensembl; ENSMUST00000171031; ENSMUSP00000126141; ENSMUSG00000034165.
DR Ensembl; ENSMUST00000182209; ENSMUSP00000138091; ENSMUSG00000034165.
DR Ensembl; ENSMUST00000183044; ENSMUSP00000138220; ENSMUSG00000034165.
DR Ensembl; ENSMUST00000183177; ENSMUSP00000138640; ENSMUSG00000034165.
DR GeneID; 12445; -.
DR KEGG; mmu:12445; -.
DR UCSC; uc008cvk.1; mouse.
DR CTD; 896; -.
DR MGI; MGI:88315; Ccnd3.
DR VEuPathDB; HostDB:ENSMUSG00000034165; -.
DR eggNOG; KOG0656; Eukaryota.
DR GeneTree; ENSGT00940000160743; -.
DR InParanoid; P30282; -.
DR OMA; QLLDWEI; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; P30282; -.
DR TreeFam; TF101004; -.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
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; 12445; 11 hits in 76 CRISPR screens.
DR ChiTaRS; Ccnd3; mouse.
DR PRO; PR:P30282; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P30282; protein.
DR Bgee; ENSMUSG00000034165; Expressed in granulocyte and 267 other tissues.
DR ExpressionAtlas; P30282; baseline and differential.
DR Genevisible; P30282; MM.
DR GO; GO:0097130; C:cyclin D3-CDK4 complex; ISO: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:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; 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; IPI:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IC:ComplexPortal.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; ISO:MGI.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA: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:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IGI:MGI.
DR GO; GO:0043434; P:response to peptide hormone; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
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:SF65; PTHR10177:SF65; 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; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..292
FT /note="G1/S-specific cyclin-D3"
FT /id="PRO_0000080443"
FT DOMAIN 27..152
FT /note="Cyclin N-terminal"
FT REGION 256..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30281"
FT MOD_RES 283
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24385"
FT CONFLICT 239
FT /note="C -> Y (in Ref. 3; AAH04076)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 292 AA; 32411 MW; 5441639A9B1B1475 CRC64;
MELLCCEGTR HAPRAGPDPR LLGDQRVLQS LLRLEERYVP RASYFQCVQK EIKPHMRKML
AYWMLEVCEE QRCEEDVFPL AMNYLDRYLS CVPTRKAQLQ LLGTVCLLLA SKLRETTPLT
IEKLCIYTDQ AVAPWQLREW EVLVLGKLKW DLAAVIAHDF LALILHRLSL PSDRQALVKK
HAQTFLALCA TDYTFAMYPP SMIATGSIGA AVLGLGACSM SADELTELLA GITGTEVDCL
RACQEQIEAA LRESLREAAQ TAPSPVPKAP RGSSSQGPSQ TSTPTDVTAI HL
