CCND1_HUMAN
ID CCND1_HUMAN Reviewed; 295 AA.
AC P24385; Q6LEF0;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=G1/S-specific cyclin-D1 {ECO:0000303|PubMed:1827756};
DE AltName: Full=B-cell lymphoma 1 protein {ECO:0000303|PubMed:1826542};
DE Short=BCL-1 {ECO:0000303|PubMed:1826542};
DE AltName: Full=BCL-1 oncogene {ECO:0000303|PubMed:1826542};
DE AltName: Full=PRAD1 oncogene {ECO:0000303|PubMed:1826542};
GN Name=CCND1 {ECO:0000303|PubMed:8204893, ECO:0000312|HGNC:HGNC:1582};
GN Synonyms=BCL1 {ECO:0000303|PubMed:1826542},
GN PRAD1 {ECO:0000303|PubMed:1826542};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1826542; DOI=10.1038/350512a0;
RA Motokura T., Bloom T., Kim H.G., Jueppner H., Ruderman J.V.,
RA Kronenberg H.M., Arnold A.;
RT "A novel cyclin encoded by a bcl1-linked candidate oncogene.";
RL Nature 350:512-515(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=1833066; DOI=10.1016/0092-8674(91)90042-w;
RA Lew D.J., Dulic V., Reed S.I.;
RT "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln)
RT function in yeast.";
RL Cell 66:1197-1206(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=1827756; DOI=10.1016/0092-8674(91)90100-d;
RA Xiong Y., Connolly T., Futcher B., Beach D.;
RT "Human D-type cyclin.";
RL Cell 65:691-699(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1833629; DOI=10.1128/mcb.11.10.4846-4853.1991;
RA Withers D.A., Harvey R.C., Faust J.B., Melnyk O., Carey K., Meeker T.C.;
RT "Characterization of a candidate bcl-1 gene.";
RL Mol. Cell. Biol. 11:4846-4853(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8204893;
RA Rimokh R., Berger F., Bastard C., Klein B., French M., Archimbaud E.,
RA Rouault J.-P., Santa Lucia B., Duret L., Vuillaume M.;
RT "Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell
RT lymphomas and t(11q13)-associated leukemias.";
RL Blood 83:3689-3696(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Placenta;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66.
RC TISSUE=Placenta;
RX PubMed=7687458; DOI=10.1002/gcc.2870070205;
RA Motokura T., Arnold A.;
RT "The PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence,
RT and sequence of a tumor-specific rearrangement breakpoint.";
RL Genes Chromosomes Cancer 7:89-95(1993).
RN [10]
RP FUNCTION, AND INTERACTION WITH CDK6.
RX PubMed=8114739; DOI=10.1128/mcb.14.3.2077-2086.1994;
RA Meyerson M., Harlow E.;
RT "Identification of G1 kinase activity for cdk6, a novel cyclin D partner.";
RL Mol. Cell. Biol. 14:2077-2086(1994).
RN [11]
RP FUNCTION, AND INTERACTION WITH CDK4 AND CDK6.
RX PubMed=8302605;
RA Bates S., Bonetta L., McAllan D., Parry D., Holder A., Dickson C.,
RA Peters G.;
RT "CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-
RT dependent kinases that associate with cyclin D1.";
RL Oncogene 9:71-79(1994).
RN [12]
RP INVOLVEMENT IN MULTIPLE MYELOMA.
RX PubMed=8695815;
RA Chesi M., Bergsagel P.L., Brents L.A., Smith C.M., Gerhard D.S.,
RA Kuehl W.M.;
RT "Dysregulation of cyclin D1 by translocation into an IgH gamma switch
RT region in two multiple myeloma cell lines.";
RL Blood 88:674-681(1996).
RN [13]
RP INTERACTION WITH CDK4 IN THE CCND1-CDK4-CDKN COMPLEX, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=9106657; DOI=10.1101/gad.11.7.847;
RA LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C.,
RA Chou H.S., Fattaey A., Harlow E.;
RT "New functional activities for the p21 family of CDK inhibitors.";
RL Genes Dev. 11:847-862(1997).
RN [14]
RP UBIQUITINATION, AND MUTAGENESIS OF THR-286 AND THR-288.
RX PubMed=10766840; DOI=10.1074/jbc.275.16.12074;
RA Germain D., Russell A., Thompson A., Hendley J.;
RT "Ubiquitination of free cyclin D1 is independent of phosphorylation on
RT threonine 286.";
RL J. Biol. Chem. 275:12074-12079(2000).
RN [15]
RP FUNCTION OF CCND1-CDK4 COMPLEX IN SMAD PHOSPHORYLATION.
RX PubMed=15241418; DOI=10.1038/nature02650;
RA Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.;
RT "Cyclin-dependent kinases regulate the antiproliferative function of
RT Smads.";
RL Nature 430:226-231(2004).
RN [16]
RP FUNCTION, AND INTERACTION WITH INSM1.
RX PubMed=16569215; DOI=10.1042/bj20051669;
RA Liu W.D., Wang H.W., Muguira M., Breslin M.B., Lan M.S.;
RT "INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene
RT through the recruitment of cyclin D1 and histone deacetylases.";
RL Biochem. J. 397:169-177(2006).
RN [17]
RP FUNCTION, AND INTERACTION WITH INSM1.
RX PubMed=18417529; DOI=10.1677/joe-08-0001;
RA Wang H.W., Muguira M., Liu W.D., Zhang T., Chen C., Aucoin R.,
RA Breslin M.B., Lan M.S.;
RT "Identification of an INSM1-binding site in the insulin promoter: negative
RT regulation of the insulin gene transcription.";
RL J. Endocrinol. 198:29-39(2008).
RN [18]
RP INTERACTION WITH INSM1 AND CDK4.
RX PubMed=19124461; DOI=10.1074/jbc.m808843200;
RA Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.;
RT "Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4
RT binding and induces cell cycle arrest.";
RL J. Biol. Chem. 284:5574-5581(2009).
RN [19]
RP INTERACTION WITH USP2, UBIQUITINATION, AND DEUBIQUITINATION BY USP2.
RX PubMed=19917254; DOI=10.1016/j.molcel.2009.10.018;
RA Shan J., Zhao W., Gu W.;
RT "Suppression of cancer cell growth by promoting cyclin D1 degradation.";
RL Mol. Cell 36:469-476(2009).
RN [20]
RP FUNCTION, PHOSPHORYLATION AT THR-286, UBIQUITINATION, AND MUTAGENESIS OF
RP THR-286.
RX PubMed=19412162; DOI=10.1038/nature08011;
RA Santra M.K., Wajapeyee N., Green M.R.;
RT "F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest
RT after DNA damage.";
RL Nature 459:722-725(2009).
RN [21]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CDK4.
RX PubMed=20399237; DOI=10.1016/j.bbamcr.2010.04.001;
RA Kim H., Kang M., Lee S.A., Kwak T.K., Jung O., Lee H.J., Kim S.H.,
RA Lee J.W.;
RT "TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression
RT and RhoA activity.";
RL Biochim. Biophys. Acta 1803:975-982(2010).
RN [22]
RP UBIQUITINATION, AND INTERACTION WITH UHRF2.
RX PubMed=21952639; DOI=10.4161/cc.10.19.17176;
RA Mori T., Ikeda D.D., Fukushima T., Takenoshita S., Kochi H.;
RT "NIRF constitutes a nodal point in the cell cycle network and is a
RT candidate tumor suppressor.";
RL Cell Cycle 10:3284-3299(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-286, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP UBIQUITINATION, PHOSPHORYLATION AT THR-286, AND MUTAGENESIS OF THR-286.
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 [25]
RP FUNCTION, UBIQUITINATION AT LYS-269, PHOSPHORYLATION AT THR-286, AND
RP MUTAGENESIS OF THR-286 AND PRO-287.
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).
RN [26]
RP UBIQUITINATION, PHOSPHORYLATION AT THR-286, AND MUTAGENESIS OF THR-286.
RX PubMed=33854239; DOI=10.1038/s41586-021-03474-7;
RA Chaikovsky A.C., Li C., Jeng E.E., Loebell S., Lee M.C., Murray C.W.,
RA Cheng R., Demeter J., Swaney D.L., Chen S.H., Newton B.W., Johnson J.R.,
RA Drainas A.P., Shue Y.T., Seoane J.A., Srinivasan P., He A., Yoshida A.,
RA Hipkins S.Q., McCrea E., Poltorack C.D., Krogan N.J., Diehl J.A., Kong C.,
RA Jackson P.K., Curtis C., Petrov D.A., Bassik M.C., Winslow M.M., Sage J.;
RT "The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.";
RL Nature 592:794-798(2021).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-271 IN COMPLEX WITH WILD TYPE
RP AND MUTANTS ALA-172; PHE-172 AND ASP-172 CDK4.
RX PubMed=19237565; DOI=10.1073/pnas.0809645106;
RA Day P.J., Cleasby A., Tickle I.J., O'Reilly M., Coyle J.E., Holding F.P.,
RA McMenamin R.L., Yon J., Chopra R., Lengauer C., Jhoti H.;
RT "Crystal structure of human CDK4 in complex with a D-type cyclin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:4166-4170(2009).
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 (PubMed:1833066, PubMed:1827756, PubMed:8114739,
CC PubMed:8302605, PubMed:19412162, PubMed:33854235). Phosphorylation of
CC RB1 allows dissociation of the transcription factor E2F from the RB/E2F
CC complex and the subsequent transcription of E2F target genes which are
CC responsible for the progression through the G(1) phase (PubMed:1833066,
CC PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162).
CC Hypophosphorylates RB1 in early G(1) phase (PubMed:1833066,
CC PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162).
CC Cyclin D-CDK4 complexes are major integrators of various mitogenenic
CC and antimitogenic signals (PubMed:1833066, PubMed:1827756,
CC PubMed:8302605, PubMed:19412162). Also a substrate for SMAD3,
CC phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing
CC its transcriptional activity (PubMed:15241418). Component of the
CC ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear
CC translocation and activity of the cyclin D-CDK4 complex
CC (PubMed:9106657). Exhibits transcriptional corepressor activity with
CC INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent
CC manner (PubMed:16569215, PubMed:18417529).
CC {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:16569215,
CC ECO:0000269|PubMed:1827756, ECO:0000269|PubMed:1833066,
CC ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19412162,
CC ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:8114739,
CC ECO:0000269|PubMed:8302605, ECO:0000269|PubMed:9106657}.
CC -!- SUBUNIT: Interacts with either CDK4 or CDK6 protein kinase to form a
CC serine/threonine kinase holoenzyme complex (PubMed:8114739,
CC PubMed:19237565). The cyclin subunit imparts substrate specificity to
CC the complex (PubMed:20399237, PubMed:19237565, PubMed:8302605,
CC PubMed:9106657). Component of the ternary complex CCND1/CDK4/CDKN1B
CC required for nuclear translocation and modulation of CDK4-mediated
CC kinase activity (PubMed:9106657). Interacts directly with CDKN1B (By
CC similarity). Can form similar complexes with either CDKN1A or CDKN2A
CC (By similarity). Interacts with FBXO4 (By similarity). Interacts with
CC UHRF2; the interaction ubiquitinates CCND1 and appears to occur
CC independently of phosphorylation (PubMed:21952639). Interacts with USP2
CC (PubMed:19917254). Interacts (via cyclin N-terminal domain) with INSM1
CC (via N-terminal region); the interaction competes with the binding of
CC CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity
CC (PubMed:16569215, PubMed:18417529, PubMed:19124461). Interacts with
CC CDK4; the interaction is prevented with the binding of CCND1 to INSM1
CC during cell cycle progression (PubMed:19124461).
CC {ECO:0000250|UniProtKB:P25322, ECO:0000269|PubMed:16569215,
CC ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19124461,
CC ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:19917254,
CC ECO:0000269|PubMed:20399237, ECO:0000269|PubMed:21952639,
CC ECO:0000269|PubMed:8114739, ECO:0000269|PubMed:8302605,
CC ECO:0000269|PubMed:9106657}.
CC -!- INTERACTION:
CC P24385; P10275: AR; NbExp=4; IntAct=EBI-375001, EBI-608057;
CC P24385; P38398: BRCA1; NbExp=3; IntAct=EBI-375001, EBI-349905;
CC P24385; P30260: CDC27; NbExp=3; IntAct=EBI-375001, EBI-994813;
CC P24385; P24941: CDK2; NbExp=4; IntAct=EBI-375001, EBI-375096;
CC P24385; P11802: CDK4; NbExp=42; IntAct=EBI-375001, EBI-295644;
CC P24385; Q00534: CDK6; NbExp=4; IntAct=EBI-375001, EBI-295663;
CC P24385; P38936: CDKN1A; NbExp=20; IntAct=EBI-375001, EBI-375077;
CC P24385; P46527: CDKN1B; NbExp=5; IntAct=EBI-375001, EBI-519280;
CC P24385; Q5XUX0: FBXO31; NbExp=4; IntAct=EBI-375001, EBI-6162477;
CC P24385; O15379: HDAC3; NbExp=3; IntAct=EBI-375001, EBI-607682;
CC P24385; Q16656: NRF1; NbExp=2; IntAct=EBI-375001, EBI-2547810;
CC P24385; Q96PU4: UHRF2; NbExp=4; IntAct=EBI-375001, EBI-625304;
CC P24385; Q96TE0; NbExp=3; IntAct=EBI-375001, EBI-10201595;
CC P24385; P30285: Cdk4; Xeno; NbExp=2; IntAct=EBI-375001, EBI-847225;
CC P24385; P59595: N; Xeno; NbExp=3; IntAct=EBI-375001, EBI-7602718;
CC P24385; Q62796: Ralbp1; Xeno; NbExp=2; IntAct=EBI-375001, EBI-3956409;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20399237,
CC ECO:0000269|PubMed:9106657}. Cytoplasm {ECO:0000269|PubMed:9106657}.
CC Nucleus membrane {ECO:0000269|PubMed:9106657}. Note=Cyclin D-CDK4
CC complexes accumulate at the nuclear membrane and are then translocated
CC to the nucleus through interaction with KIP/CIP family members.
CC {ECO:0000269|PubMed:9106657}.
CC -!- PTM: Phosphorylation at Thr-286 by MAP kinases is required for
CC ubiquitination and degradation by the DCX(AMBRA1) complex
CC (PubMed:10766840, PubMed:33854232, PubMed:33854235, PubMed:33854239).
CC It also plays an essential role for recognition by the FBXO31 component
CC of SCF (SKP1-cullin-F-box) protein ligase complex following DNA damage
CC (PubMed:19412162). {ECO:0000269|PubMed:10766840,
CC ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:33854232,
CC ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239}.
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
CC (PubMed:33854232, PubMed:33854235, PubMed:33854239). The DCX(AMBRA1)
CC complex represents the major regulator of CCND1 stability during the
CC G1/S transition (PubMed:33854232, PubMed:33854235, PubMed:33854239).
CC Also ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein
CC ligase complex containing FBXO4 and CRYAB (By similarity). Following
CC DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein
CC ligase complex containing FBXO31 (PubMed:19412162). SCF-type
CC ubiquitination is dependent on Thr-286 phosphorylation
CC (PubMed:10766840, PubMed:19412162). Ubiquitinated also by UHRF2
CC apparently in a phosphorylation-independent manner (PubMed:21952639).
CC Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated
CC by USP2; leading to its stabilization (PubMed:19917254).
CC {ECO:0000250|UniProtKB:P25322, ECO:0000269|PubMed:10766840,
CC ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:19917254,
CC ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:33854232,
CC ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239}.
CC -!- DISEASE: Note=A chromosomal aberration involving CCND1 may be a cause
CC of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL).
CC Translocation t(11;14)(q13;q32) with immunoglobulin gene regions.
CC Activation of CCND1 may be oncogenic by directly altering progression
CC through the cell cycle. {ECO:0000269|PubMed:1826542,
CC ECO:0000269|PubMed:8204893, ECO:0000269|PubMed:8695815}.
CC -!- DISEASE: Note=A chromosomal aberration involving CCND1 may be a cause
CC of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the
CC parathyroid hormone (PTH) enhancer. {ECO:0000269|PubMed:1826542}.
CC -!- DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of
CC plasma cells usually arising in the bone marrow and characterized by
CC diffuse involvement of the skeletal system, hyperglobulinemia, Bence-
CC Jones proteinuria and anemia. Complications of multiple myeloma are
CC bone pain, hypercalcemia, renal failure and spinal cord compression.
CC The aberrant antibodies that are produced lead to impaired humoral
CC immunity and patients have a high prevalence of infection. Amyloidosis
CC may develop in some patients. Multiple myeloma is part of a spectrum of
CC diseases ranging from monoclonal gammopathy of unknown significance
CC (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:8695815}. Note=The
CC gene represented in this entry is involved in disease pathogenesis. A
CC chromosomal aberration involving CCND1 is found in multiple myeloma.
CC Translocation t(11;14)(q13;q32) with the IgH locus.
CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL1ID36.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ccnd1/";
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DR EMBL; X59798; CAA42470.1; -; mRNA.
DR EMBL; M74092; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M64349; AAA52136.1; -; mRNA.
DR EMBL; M73554; AAA58392.1; -; mRNA.
DR EMBL; Z23022; CAA80558.1; -; mRNA.
DR EMBL; BT019845; AAV38648.1; -; mRNA.
DR EMBL; AF511593; AAM34300.2; -; Genomic_DNA.
DR EMBL; BC000076; AAH00076.1; -; mRNA.
DR EMBL; BC001501; AAH01501.1; -; mRNA.
DR EMBL; BC014078; AAH14078.1; -; mRNA.
DR EMBL; BC023620; AAH23620.1; -; mRNA.
DR EMBL; BC025302; AAH25302.1; -; mRNA.
DR EMBL; L09054; AAA36481.1; -; Genomic_DNA.
DR CCDS; CCDS8191.1; -.
DR PIR; A38977; A38977.
DR RefSeq; NP_444284.1; NM_053056.2.
DR PDB; 2W96; X-ray; 2.30 A; A=1-271.
DR PDB; 2W99; X-ray; 2.80 A; A=1-271.
DR PDB; 2W9F; X-ray; 2.85 A; A=1-271.
DR PDB; 2W9Z; X-ray; 2.45 A; A=16-271.
DR PDB; 5VZU; X-ray; 2.70 A; E/F=279-295.
DR PDB; 6P8E; X-ray; 2.30 A; A=19-267.
DR PDB; 6P8F; X-ray; 2.89 A; A=19-267.
DR PDB; 6P8G; X-ray; 2.80 A; A=19-267.
DR PDB; 6P8H; X-ray; 3.19 A; A=19-267.
DR PDBsum; 2W96; -.
DR PDBsum; 2W99; -.
DR PDBsum; 2W9F; -.
DR PDBsum; 2W9Z; -.
DR PDBsum; 5VZU; -.
DR PDBsum; 6P8E; -.
DR PDBsum; 6P8F; -.
DR PDBsum; 6P8G; -.
DR PDBsum; 6P8H; -.
DR AlphaFoldDB; P24385; -.
DR SMR; P24385; -.
DR BioGRID; 107067; 257.
DR ComplexPortal; CPX-2010; Cyclin D1-CDK4 complex.
DR ComplexPortal; CPX-2014; Cyclin D1-CDK6 complex.
DR CORUM; P24385; -.
DR DIP; DIP-123N; -.
DR IntAct; P24385; 70.
DR MINT; P24385; -.
DR STRING; 9606.ENSP00000227507; -.
DR BindingDB; P24385; -.
DR ChEMBL; CHEMBL3610; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB11752; Bryostatin 1.
DR DrugBank; DB11718; Encorafenib.
DR DrugCentral; P24385; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; P24385; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P24385; -.
DR PhosphoSitePlus; P24385; -.
DR BioMuta; CCND1; -.
DR DMDM; 116152; -.
DR EPD; P24385; -.
DR jPOST; P24385; -.
DR MassIVE; P24385; -.
DR PaxDb; P24385; -.
DR PeptideAtlas; P24385; -.
DR PRIDE; P24385; -.
DR ProteomicsDB; 54198; -.
DR Antibodypedia; 3660; 2089 antibodies from 53 providers.
DR CPTC; P24385; 7 antibodies.
DR DNASU; 595; -.
DR Ensembl; ENST00000227507.3; ENSP00000227507.2; ENSG00000110092.4.
DR GeneID; 595; -.
DR KEGG; hsa:595; -.
DR MANE-Select; ENST00000227507.3; ENSP00000227507.2; NM_053056.3; NP_444284.1.
DR CTD; 595; -.
DR DisGeNET; 595; -.
DR GeneCards; CCND1; -.
DR HGNC; HGNC:1582; CCND1.
DR HPA; ENSG00000110092; Low tissue specificity.
DR MalaCards; CCND1; -.
DR MIM; 168461; gene.
DR MIM; 254500; phenotype.
DR neXtProt; NX_P24385; -.
DR OpenTargets; ENSG00000110092; -.
DR Orphanet; 67038; B-cell chronic lymphocytic leukemia.
DR Orphanet; 52416; Mantle cell lymphoma.
DR Orphanet; 29073; Multiple myeloma.
DR PharmGKB; PA75; -.
DR VEuPathDB; HostDB:ENSG00000110092; -.
DR eggNOG; KOG0656; Eukaryota.
DR GeneTree; ENSGT00940000157816; -.
DR HOGENOM; CLU_052190_0_0_1; -.
DR InParanoid; P24385; -.
DR OMA; SCYRTTH; -.
DR OrthoDB; 1234739at2759; -.
DR PhylomeDB; P24385; -.
DR TreeFam; TF101004; -.
DR PathwayCommons; P24385; -.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-HSA-8849470; PTK6 Regulates Cell Cycle.
DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-HSA-8951430; RUNX3 regulates WNT signaling.
DR Reactome; R-HSA-8951936; RUNX3 regulates p14-ARF.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3).
DR Reactome; R-HSA-9754119; Drug-mediated inhibition of CDK4/CDK6 activity.
DR SignaLink; P24385; -.
DR SIGNOR; P24385; -.
DR BioGRID-ORCS; 595; 528 hits in 1083 CRISPR screens.
DR ChiTaRS; CCND1; human.
DR EvolutionaryTrace; P24385; -.
DR GeneWiki; Cyclin_D1; -.
DR GenomeRNAi; 595; -.
DR Pharos; P24385; Tchem.
DR PRO; PR:P24385; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P24385; protein.
DR Bgee; ENSG00000110092; Expressed in endometrium epithelium and 190 other tissues.
DR ExpressionAtlas; P24385; baseline and differential.
DR Genevisible; P24385; HS.
DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl.
DR GO; GO:0097128; C:cyclin D1-CDK4 complex; IPI:ComplexPortal.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0070064; F:proline-rich region binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0000320; P:re-entry into mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0044321; P:response to leptin; IDA:UniProtKB.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0070141; P:response to UV-A; IDA:BHF-UCL.
DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
DR CDD; cd00043; CYCLIN; 1.
DR DisProt; DP02226; -.
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:SF67; PTHR10177:SF67; 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 3D-structure; Cell cycle; Cell division; Chromosomal rearrangement; Cyclin;
KW Cytoplasm; DNA damage; Isopeptide bond; Membrane; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..295
FT /note="G1/S-specific cyclin-D1"
FT /id="PRO_0000080430"
FT DOMAIN 28..152
FT /note="Cyclin N-terminal"
FT REGION 262..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 286
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19412162,
FT ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235,
FT ECO:0000269|PubMed:33854239, ECO:0007744|PubMed:24275569"
FT CROSSLNK 269
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:33854235"
FT MUTAGEN 286..288
FT /note="TPT->ATA: Reduced ubiquitination and subsequent
FT degradation by the proteasome."
FT /evidence="ECO:0000269|PubMed:10766840"
FT MUTAGEN 286
FT /note="T->A: Reduced interaction with the DCX(AMBRA1)
FT complex, and subsequent ubiquitination and degradation by
FT the proteasome. Abolished ubiquitination and subsequent
FT degradation following DNA damage."
FT /evidence="ECO:0000269|PubMed:19412162,
FT ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235,
FT ECO:0000269|PubMed:33854239"
FT MUTAGEN 287
FT /note="P->A,L,S: Reduced interaction with the DCX(AMBRA1)
FT complex, and subsequent ubiquitination and degradation by
FT the proteasome."
FT /evidence="ECO:0000269|PubMed:33854235"
FT CONFLICT 130
FT /note="N -> G (in Ref. 3; AAA52136)"
FT /evidence="ECO:0000305"
FT CONFLICT 168..169
FT /note="MP -> IA (in Ref. 2; M74092)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="L -> S (in Ref. 3; AAA52136)"
FT /evidence="ECO:0000305"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:6P8G"
FT HELIX 26..37
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 54..70
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 77..89
FT /evidence="ECO:0007829|PDB:2W96"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 99..114
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 121..127
FT /evidence="ECO:0007829|PDB:2W96"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:2W96"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 172..190
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 200..218
FT /evidence="ECO:0007829|PDB:2W96"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:2W9Z"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 229..237
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 241..255
FT /evidence="ECO:0007829|PDB:2W96"
FT TURN 256..260
FT /evidence="ECO:0007829|PDB:2W96"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:2W96"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:5VZU"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:5VZU"
SQ SEQUENCE 295 AA; 33729 MW; 3CC00C9905F58D3A CRC64;
MEHQLLCCEV ETIRRAYPDA NLLNDRVLRA MLKAEETCAP SVSYFKCVQK EVLPSMRKIV
ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPVKKSRLQ LLGATCMFVA SKMKETIPLT
AEKLCIYTDN SIRPEELLQM ELLLVNKLKW NLAAMTPHDF IEHFLSKMPE AEENKQIIRK
HAQTFVALCA TDVKFISNPP SMVAAGSVVA AVQGLNLRSP NNFLSYYRLT RFLSRVIKCD
PDCLRACQEQ IEALLESSLR QAQQNMDPKA AEEEEEEEEE VDLACTPTDV RDVDI
