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 04-NOV-2026, entry version 249. 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}, PRAD1 GN {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; DOI=10.1182/blood.v83.12.3689.3689; 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; DOI=10.1182/blood.v88.2.674.bloodjournal882674; 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 UBIQUITINATION, AND PHOSPHORYLATION AT THR-286. RX PubMed=17205132; DOI=10.1371/journal.pone.0000128; RA Okabe H., Lee S.H., Phuchareon J., Albertson D.G., McCormick F., Tetsu O.; RT "A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer RT cell proliferation."; RL PLoS ONE 1:e128-e128(2006). RN [24] 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 [25] 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 [26] 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 [27] 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 [28] RP SUBCELLULAR LOCATION, INTERACTION WITH FBXO32, AND UBIQUITINATION AT RP LYS-58. RX PubMed=40307251; DOI=10.1038/s41467-025-59407-9; RA Li F., Yu H., Zhang Y., Ma Y., Chen X., Zhang J., Sun L., Guo R., Wu Y., RA Zheng P., Wang X., Bie P., He F., Zhang L., Xie C., Xiong H.; RT "F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive RT cancer progression."; RL Nat. Commun. 16:4060-4060(2025). RN [29] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH WILD TYPE AND MUTANTS ALA-172; RP 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). RN [30] {ECO:0007744|PDB:5VZU} RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH FBXO31, SUBCELLULAR LOCATION, RP UBIQUITINATION, AND PHOSPHORYLATION AT THR-286. RX PubMed=29279382; DOI=10.1073/pnas.1708677115; RA Li Y., Jin K., Bunker E., Zhang X., Luo X., Liu X., Hao B.; RT "Structural basis of the phosphorylation-independent recognition of cyclin RT D1 by the SCFFBXO31 ubiquitin ligase."; RL Proc. Natl. Acad. Sci. U.S.A. 115:319-324(2018). 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:1827756, PubMed:1833066, PubMed:19412162, CC PubMed:33854235, PubMed:8114739, PubMed:8302605). 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:1827756, CC PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). CC Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, CC PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). CC Cyclin D-CDK4 complexes are major integrators of various mitogenenic CC and antimitogenic signals (PubMed:1827756, PubMed:1833066, CC PubMed:19412162, PubMed:8302605). 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:19237565, CC PubMed:8114739). The cyclin subunit imparts substrate specificity to CC the complex (PubMed:19237565, PubMed:20399237, 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 UHRF2; the interaction ubiquitinates CC CCND1 and appears to occur independently of phosphorylation CC (PubMed:21952639). Interacts with USP2 (PubMed:19917254). Interacts CC (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the CC interaction competes with the binding of CCND1 to CDK4 during cell CC cycle progression and inhibits CDK4 activity (PubMed:16569215, CC PubMed:18417529, PubMed:19124461). Interacts with CDK4; the interaction CC is prevented with the binding of CCND1 to INSM1 during cell cycle CC progression (PubMed:19124461). Interacts with FBXO32; this interaction CC mediates CCND1 stabilization via 'Lys-27'-linked polyubiquitination CC (PubMed:40307251). {ECO:0000250|UniProtKB:P25322, CC ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529, CC ECO:0000269|PubMed:19124461, ECO:0000269|PubMed:19237565, CC ECO:0000269|PubMed:19917254, ECO:0000269|PubMed:20399237, CC ECO:0000269|PubMed:21952639, ECO:0000269|PubMed:40307251, 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=9; IntAct=EBI-375001, EBI-375096; CC P24385; P11802: CDK4; NbExp=46; IntAct=EBI-375001, EBI-295644; CC P24385; Q00534: CDK6; NbExp=8; IntAct=EBI-375001, EBI-295663; CC P24385; P38936: CDKN1A; NbExp=26; IntAct=EBI-375001, EBI-375077; CC P24385; P46527: CDKN1B; NbExp=13; IntAct=EBI-375001, EBI-519280; CC P24385; Q5XUX0: FBXO31; NbExp=4; IntAct=EBI-375001, EBI-6162477; CC P24385; Q969H0: FBXW7; NbExp=5; IntAct=EBI-375001, EBI-359574; CC P24385; O15379: HDAC3; NbExp=3; IntAct=EBI-375001, EBI-607682; CC P24385; Q16656: NRF1; NbExp=2; IntAct=EBI-375001, EBI-2547810; CC P24385; Q13485: SMAD4; NbExp=4; IntAct=EBI-375001, EBI-347263; CC P24385; P51532: SMARCA4; NbExp=5; IntAct=EBI-375001, EBI-302489; 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:29279382, ECO:0000269|PubMed:40307251, CC ECO:0000269|PubMed:9106657}. Cytoplasm {ECO:0000269|PubMed:29279382, CC ECO:0000269|PubMed:9106657}. Nucleus membrane CC {ECO:0000269|PubMed:9106657}. Note=Cyclin D-CDK4 complexes accumulate CC at the nuclear membrane and are then translocated to the nucleus CC 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:17205132, PubMed:33854232, PubMed:33854235, CC PubMed:33854239). It also plays an essential role for recognition by CC the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex CC following DNA damage (PubMed:19412162). {ECO:0000269|PubMed:10766840, CC ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:19412162, CC ECO:0000269|PubMed:33854232, ECO:0000269|PubMed:33854235, CC 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 the SCF(FBXO4) and Cul7-RING(FBXW8) ubiquitin- CC protein ligase complexes (PubMed:17205132). Following DNA damage it is CC ubiquitinated by the SCF(FBXO31) protein ligase complex CC (PubMed:19412162, PubMed:29279382). SCF(FBXO31) ubiquitination is CC dependent on Thr-286 phosphorylation (PubMed:10766840, PubMed:19412162, CC PubMed:29279382). Ubiquitinated also by UHRF2 apparently in a CC phosphorylation-independent manner (PubMed:21952639). Ubiquitination CC leads to its degradation and G1 arrest. Deubiquitinated by USP2; CC leading to its stabilization (PubMed:19917254). Ubiquitinated by FBXO32 CC at Lys-58 via 'Lys27'-linked polyubiquitination; leading to its CC stabilization (PubMed:40307251). {ECO:0000269|PubMed:10766840, CC ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:19412162, CC ECO:0000269|PubMed:19917254, ECO:0000269|PubMed:21952639, CC ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:33854232, CC ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239, CC ECO:0000269|PubMed:40307251}. 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="https://atlasgeneticsoncology.org/gene/36/BCL1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_053056.3. 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 PDB; 9CSK; X-ray; 2.25 A; A/C=16-271. DR PDB; 9IVD; EM; 3.55 A; E=1-295. DR SMR; P24385; -. DR BioGRID; 107067; 284. 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; 90. DR STRING; 9606.ENSP00000227507; -. DR NDEx; IQUERY-CP-CCND1; 97 NDEx IQuery Curated Pathways. DR BindingDB; P24385; -. DR ChEMBL; CHEMBL3610; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB01169; Arsenic trioxide. DR DrugBank; DB12004; Briciclib. DR DrugBank; DB11752; Bryostatin 1. DR DrugBank; DB11718; Encorafenib. DR DrugBank; DB12340; Navitoclax. 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 CPTAC; CPTAC-2804; -. DR CPTAC; CPTAC-2805; -. DR CPTAC; CPTAC-5761; -. DR CPTAC; CPTAC-5762; -. DR CPTAC; CPTAC-5763; -. DR CPTAC; CPTAC-5764; -. DR CPTAC; CPTAC-5765; -. DR CPTAC; non-CPTAC-5363; -. DR CPTAC; non-CPTAC-5536; -. DR CPTAC; non-CPTAC-5538; -. DR PaxDb; 9606-ENSP00000227507; -. DR PeptideAtlas; P24385; -. DR ProteomicsDB; 54198; -. DR Pumba; P24385; -. DR jPOST; P24385; -. DR MassIVE; P24385; -. DR DNASU; 595; -. DR Ensembl; ENST00000227507.3; ENSP00000227507.2; ENSG00000110092.5. 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 VEuPathDB; HostDB:ENSG00000110092; -. DR GeneCards; CCND1; -. DR HGNC; HGNC:1582; CCND1. DR AGR; HGNC:1582; -. DR HPA; ENSG00000110092; Low tissue specificity. DR MalaCards; CCND1; -. DR MIM; 168461; gene. DR MIM; 254500; phenotype. DR OpenTargets; ENSG00000110092; -. DR Orphanet; 67038; B-cell chronic lymphocytic leukemia. DR Orphanet; 52416; Mantle cell lymphoma. DR Orphanet; 29073; Multiple myeloma. DR Orphanet; 892; Von Hippel-Lindau disease. DR ClinPGx; PA75; -. DR eggNOG; KOG0656; Eukaryota. DR GeneTree; ENSGT00940000157816; -. DR HOGENOM; CLU_052190_0_0_1; -. DR InParanoid; P24385; -. DR OMA; ADTWIPC; -. DR OrthoDB; 306099at2759; -. DR PhylomeDB; 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 Reactome; R-HSA-9825892; Regulation of MITF-M-dependent genes involved in cell cycle and proliferation. DR Reactome; R-HSA-9929491; SPOP-mediated proteasomal degradation of PD-L1(CD274). DR SignaLink; P24385; -. DR SIGNOR; P24385; -. DR ChiTaRS; CCND1; human. DR EvolutionaryTrace; P24385; -. DR Agora; ENSG00000110092; -. DR GeneWiki; Cyclin_D1; -. DR GenomeRNAi; 595; -. DR PRO; PR:P24385; -. DR Bgee; ENSG00000110092; Expressed in endometrium epithelium and 192 other cell types or tissues. DR ExpressionAtlas; P24385; baseline and differential. DR CDD; cd20573; CYCLIN_CCND1_rpt1; 1. DR CDD; cd20576; CYCLIN_CCND1_rpt2; 1. DR FunFam; 1.10.472.10:FF:000120; G1/S-specific cyclin-D1; 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 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. DR DisProt; DP02226; -. DR GO; GO:0097128; C:cyclin D1-CDK4 complex; IPI:ComplexPortal. DR GO; GO:0097131; C:cyclin D1-CDK6 complex; IPI:ComplexPortal. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005815; C:microtubule organizing center; IBA:GO_Central. DR GO; GO:0031965; C:nuclear membrane; EXP:UniProtKB. 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:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; IDA:UniProt. 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:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl. DR GO; GO:0001889; P:liver development; IEA:Ensembl. DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. 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: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: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 Proteomes; UP000005640; Chromosome 11. DR PathwayCommons; P24385; -. DR Pharos; P24385; Tchem. DR DrugCentral; P24385; -. DR Antibodypedia; 3660; 2379 antibodies from 57 providers. DR CPTC; P24385; 7 antibodies. DR RNAct; P24385; protein. DR BioGRID-ORCS; 595; 538 hits in 1169 CRISPR screens. DR AlphaFoldDB; P24385; -. DR EMDB; EMD-60925; -. DR MDRepo; P24385; -. DR FunCoup; P24385; 2102. DR PAN-GO; P24385; 7 GO annotations based on evolutionary models. DR CIViC; 595; 23 evidence items across 6 molecular profiles. 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 Proteomics identification; Proto-oncogene; Reference proteome; Repressor; KW Transcription; 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 COMPBIAS 272..282 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 286 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19412162, FT ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:33854232, FT ECO:0000269|PubMed:33854235, ECO:0000269|PubMed:33854239, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 58 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:40307251" 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:9CSK" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 54..71 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 77..89 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 99..114 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 121..126 FT /evidence="ECO:0007829|PDB:9CSK" FT TURN 127..130 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 134..147 FT /evidence="ECO:0007829|PDB:9CSK" FT TURN 148..150 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 157..167 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 172..191 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 194..197 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 200..218 FT /evidence="ECO:0007829|PDB:9CSK" FT TURN 220..222 FT /evidence="ECO:0007829|PDB:2W9Z" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 229..237 FT /evidence="ECO:0007829|PDB:9CSK" FT HELIX 241..256 FT /evidence="ECO:0007829|PDB:9CSK" FT TURN 257..259 FT /evidence="ECO:0007829|PDB:2W9F" 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 //