ID CCND1_RAT Reviewed; 295 AA.
AC P39948;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 27-MAR-2024, entry version 169.
DE RecName: Full=G1/S-specific cyclin-D1;
GN Name=Ccnd1;
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].
RC TISSUE=Kidney;
RX PubMed=8336937;
RA Tamura K., Kanaoka Y., Jinno S., Nagata A., Ogiso Y., Shimizu K.,
RA Hayakawa T., Nojima H., Okayama H.;
RT "Cyclin G: a new mammalian cyclin with homology to fission yeast Cig1.";
RL Oncogene 8:2113-2118(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7980531; DOI=10.1006/bbrc.1994.2515;
RA Bianchi S., Fabiani S., Muratori M., Arnold A., Sakaguchi K., Miki T.,
RA Brandi M.L.;
RT "Calcium modulates the cyclin D1 expression in a rat parathyroid cell
RT line.";
RL Biochem. Biophys. Res. Commun. 204:691-700(1994).
CC -!- FUNCTION: Regulatory component of the cyclin D1-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. Also a substrate for SMAD3,
CC phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing
CC its transcriptional activity. Component of the ternary complex, cyclin
CC D1/CDK4/CDKN1B, required for nuclear translocation and activity of the
CC cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity
CC with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent
CC manner. {ECO:0000250|UniProtKB:P24385}.
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. Component of the ternary complex
CC CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of
CC CDK4-mediated kinase activity (By similarity). Interacts directly with
CC CDKN1B. Can form similar complexes with either CDKN1A or CDKN2A.
CC Interacts with FBXO4 (By similarity). Interacts with UHRF2; the
CC interaction ubiquitinates CCND1 and appears to occur independently of
CC phosphorylation. Interacts with USP2. Interacts (via cyclin N-terminal
CC domain) with INSM1 (via N-terminal region); the interaction competes
CC with the binding of CCND1 to CDK4 during cell cycle progression and
CC inhibits CDK4 activity. Interacts with CDK4; the interaction is
CC prevented with the binding of CCND1 to INSM1 during cell cycle
CC progression (By similarity). {ECO:0000250|UniProtKB:P24385,
CC ECO:0000250|UniProtKB:P25322}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P24385}. Cytoplasm
CC {ECO:0000250|UniProtKB:P24385}. Nucleus membrane
CC {ECO:0000250|UniProtKB:P24385}. 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:P24385}.
CC -!- PTM: Phosphorylation at Thr-286 by MAP kinases is required for
CC ubiquitination and degradation by the DCX(AMBRA1) complex. It also
CC plays an essential role for recognition by the FBXO31 component of SCF
CC (SKP1-cullin-F-box) protein ligase complex following DNA damage.
CC {ECO:0000250|UniProtKB:P24385}.
CC -!- PTM: Ubiquitinated at Lys-269 by the DCX(AMBRA1) complex during the
CC transition from G1 to S cell phase, leading to its degradation:
CC ubiquitination is dependent on Thr-286 phosphorylation. The DCX(AMBRA1)
CC complex represents the major regulator of CCND1 stability during the
CC G1/S transition (By similarity). Also ubiquitinated by a SCF (SKP1-
CC CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4
CC and CRYAB (By similarity). Following DNA damage it is ubiquitinated by
CC some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31.
CC SCF-type ubiquitination is dependent on Thr-286 phosphorylation.
CC Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent
CC manner. Ubiquitination leads to its degradation and G1 arrest.
CC Deubiquitinated by USP2; leading to its stabilization (By similarity).
CC {ECO:0000250|UniProtKB:P24385, ECO:0000250|UniProtKB:P25322}.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
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DR EMBL; D14014; BAA03115.1; -; mRNA.
DR EMBL; X75207; CAA53020.1; -; mRNA.
DR PIR; JC2342; JC2342.
DR RefSeq; NP_741989.3; NM_171992.4.
DR AlphaFoldDB; P39948; -.
DR SMR; P39948; -.
DR ComplexPortal; CPX-2075; Cyclin D1-CDK4 complex.
DR IntAct; P39948; 1.
DR STRING; 10116.ENSRNOP00000028411; -.
DR iPTMnet; P39948; -.
DR PhosphoSitePlus; P39948; -.
DR PaxDb; 10116-ENSRNOP00000028411; -.
DR Ensembl; ENSRNOT00000108193.1; ENSRNOP00000083271.1; ENSRNOG00000020918.6.
DR Ensembl; ENSRNOT00055035513; ENSRNOP00055028802; ENSRNOG00055020798.
DR Ensembl; ENSRNOT00060055245; ENSRNOP00060045690; ENSRNOG00060031868.
DR Ensembl; ENSRNOT00065050489; ENSRNOP00065041493; ENSRNOG00065029228.
DR GeneID; 58919; -.
DR KEGG; rno:58919; -.
DR UCSC; RGD:68384; rat.
DR AGR; RGD:68384; -.
DR CTD; 595; -.
DR RGD; 68384; Ccnd1.
DR eggNOG; KOG0656; Eukaryota.
DR GeneTree; ENSGT00940000157816; -.
DR HOGENOM; CLU_052190_0_0_1; -.
DR InParanoid; P39948; -.
DR OrthoDB; 1077601at2759; -.
DR PhylomeDB; P39948; -.
DR TreeFam; TF101004; -.
DR Reactome; R-RNO-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-RNO-3214858; RMTs methylate histone arginines.
DR Reactome; R-RNO-69231; Cyclin D associated events in G1.
DR Reactome; R-RNO-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-RNO-8849470; PTK6 Regulates Cell Cycle.
DR Reactome; R-RNO-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-RNO-8951936; RUNX3 regulates p14-ARF.
DR Reactome; R-RNO-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR PRO; PR:P39948; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020918; Expressed in lung and 19 other cell types or tissues.
DR ExpressionAtlas; P39948; baseline and differential.
DR Genevisible; P39948; RN.
DR GO; GO:0005923; C:bicellular tight junction; ISO:RGD.
DR GO; GO:0097128; C:cyclin D1-CDK4 complex; ISO:RGD.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; ISO:RGD.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0070064; F:proline-rich region binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; ISO:RGD.
DR GO; GO:0033327; P:Leydig cell differentiation; IMP:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0097421; P:liver regeneration; ISO:RGD.
DR GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; ISO:RGD.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; 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; ISS:UniProtKB.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0000320; P:re-entry into mitotic cell cycle; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; 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:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0044321; P:response to leptin; ISO:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IDA:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0070141; P:response to UV-A; ISS:UniProtKB.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0010165; P:response to X-ray; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
DR CDD; cd20573; CYCLIN_CCND1_rpt1; 1.
DR CDD; cd20576; CYCLIN_CCND1_rpt2; 1.
DR Gene3D; 1.10.472.10; Cyclin-like; 2.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR013763; Cyclin-like_dom.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR006671; Cyclin_N.
DR InterPro; IPR048258; Cyclins_cyclin-box.
DR PANTHER; PTHR10177; CYCLINS; 1.
DR PANTHER; PTHR10177:SF67; G1_S-SPECIFIC CYCLIN-D1; 1.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR SMART; SM00385; CYCLIN; 2.
DR SMART; SM01332; Cyclin_C; 1.
DR SUPFAM; SSF47954; Cyclin-like; 2.
DR PROSITE; PS00292; CYCLINS; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Cyclin; Cytoplasm; Isopeptide bond; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..295
FT /note="G1/S-specific cyclin-D1"
FT /id="PRO_0000080433"
FT DOMAIN 28..152
FT /note="Cyclin N-terminal"
FT REGION 269..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 286
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24385"
FT CROSSLNK 269
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P25322"
FT CONFLICT 25..27
FT /note="DRV -> RPG (in Ref. 1; BAA03115)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 33483 MW; C777436B5C79635E CRC64;
MEHQLLCCEV ETIRRAYPDT NLLNDRVLRA MLKTEETCAP SVSYFKCVQR EIVPSMRKIV
ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPLKKSRLQ LLGATCMFVA SKMKETIPLT
AEKLCIYTDN SIRPEELLQM ELLLVNKLKW NLAAMTPHDF IEHFLSKMPE ADENKQIIRK
HAQTFVALCA TDVKFISNPP SMVAAGSVVA AMQGLNLGSP NNFLSCYRTT HFLSRVIKCD
PDCLRACQEQ IEALLESSLR QAQQNIDPKA TEEEGEVEEE AGLACTPTDV RDVDI
//
