ID CCND1_BOVIN Reviewed; 295 AA.
AC Q2KI22;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 27-MAR-2024, entry version 124.
DE RecName: Full=G1/S-specific cyclin-D1;
GN Name=CCND1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
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-270 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; BC112798; AAI12799.1; -; mRNA.
DR RefSeq; NP_001039738.1; NM_001046273.2.
DR AlphaFoldDB; Q2KI22; -.
DR SMR; Q2KI22; -.
DR STRING; 9913.ENSBTAP00000023277; -.
DR PaxDb; 9913-ENSBTAP00000023277; -.
DR GeneID; 524530; -.
DR KEGG; bta:524530; -.
DR CTD; 595; -.
DR eggNOG; KOG0656; Eukaryota.
DR HOGENOM; CLU_052190_0_0_1; -.
DR InParanoid; Q2KI22; -.
DR OrthoDB; 1077601at2759; -.
DR TreeFam; TF101004; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
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:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0070141; P:response to UV-A; ISS:UniProtKB.
DR CDD; cd20573; CYCLIN_CCND1_rpt1; 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; 1.
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_0000244461"
FT DOMAIN 28..152
FT /note="Cyclin N-terminal"
FT REGION 264..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 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P25322"
SQ SEQUENCE 295 AA; 33407 MW; 4D9E5E0121C3314C CRC64;
MAHQLLCCEM ETIRRAYPDA NLLNDRVLRA MLKAEETCAP SVSYFKCVQK EILPSMRKIV
ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPVKKSRLQ LLGATCMFVA SKMKETIPLT
AEKLCIYTDN SIRPDELLHM ELVLVNKLKW NLAAMTPHDF IEHFLSKMPV AEENKQIIRK
HAQTFVALCA TDVKFISNPP SMVAAGSVAA AAQGLHLGSA NGFLSYHRLT RFLSKVIRCD
PDCLRACQEQ IEALLESSLR QAQQQNLDPK AAEEEEEEEE VDLACTPTDV RDVNI
//
