CCND3_RAT
ID CCND3_RAT Reviewed; 293 AA.
AC P48961; Q63628;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=G1/S-specific cyclin-D3 {ECO:0000303|PubMed:7926809};
GN Name=Ccnd3 {ECO:0000312|RGD:2293};
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=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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8973324; DOI=10.1016/s0378-1119(96)00499-4;
RA Yang M., Hosokawa Y., Kaneko S., Tanaka M., Nakashima K.;
RT "Structure and characterization of rat cyclin D3 promoter.";
RL Gene 181:153-159(1996).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY
RP 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 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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P30281}. Cytoplasm
CC {ECO:0000250|UniProtKB:P30281}.
CC -!- PTM: Phosphorylation at Thr-284 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-284 phosphorylation. The DCX(AMBRA1) complex
CC represents the major regulator of CCND3 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:P30281, ECO:0000250|UniProtKB:P30282}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
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DR EMBL; D16309; BAA03816.1; -; mRNA.
DR EMBL; U49935; AAB40713.1; -; Genomic_DNA.
DR PIR; JC4012; JC4012.
DR RefSeq; NP_036898.1; NM_012766.1.
DR AlphaFoldDB; P48961; -.
DR SMR; P48961; -.
DR BioGRID; 247241; 1.
DR ComplexPortal; CPX-2078; Cyclin D3-CDK4 complex.
DR STRING; 10116.ENSRNOP00000064704; -.
DR iPTMnet; P48961; -.
DR PhosphoSitePlus; P48961; -.
DR PaxDb; P48961; -.
DR GeneID; 25193; -.
DR KEGG; rno:25193; -.
DR CTD; 896; -.
DR RGD; 2293; Ccnd3.
DR eggNOG; KOG0656; Eukaryota.
DR InParanoid; P48961; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; P48961; -.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
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:P48961; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097130; C:cyclin D3-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:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISO: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:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEP:RGD.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; IMP:RGD.
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; ISO: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: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:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IMP:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0042098; P:T cell proliferation; ISO: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: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..293
FT /note="G1/S-specific cyclin-D3"
FT /id="PRO_0000080444"
FT DOMAIN 27..152
FT /note="Cyclin N-terminal"
FT REGION 257..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30281"
FT MOD_RES 284
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24385"
FT CONFLICT 11
FT /note="L -> H (in Ref. 2; AAB40713)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 293 AA; 32434 MW; 35A84447C30A82B4 CRC64;
MELLCCEGTR LAPRAGPDPR LLGDQRVLQS LLRLEERYVP RGSYFQCVQK EIKPHMRKML
AYWMLEVCEE QRCEEDVFPL AMNYLDRYLS CVPTRKAQLQ LLGTVCLLLA SKLRETTPLT
IEKLCIYTDQ AMAPWQLREW EVLVLGKLKW DLAAVIAHDF LALILHRLSL PSDRQALVKK
HAQTFLALCA TDYTFAMYPP SMIATGSIGA AVLGLGACSM SADELTELLA GITGTEVDCL
RACQEQQIEA ALRESLREAA QTAPSPVPKA PGGSSSQGPS QTSTPTDVTA IHL
