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   25-NOV-2008, entry version 100.
DE   RecName: Full=G1/S-specific cyclin-D1;
DE   AltName: Full=PRAD1 oncogene;
DE   AltName: Full=BCL-1 oncogene;
GN   Name=CCND1; Synonyms=BCL1, PRAD1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RX   MEDLINE=91194766; 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].
RX   MEDLINE=92005671; 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].
RX   MEDLINE=91235304; 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   MEDLINE=92017758; PubMed=1833629;
RA   Withers D.A., Harvey R.C., Faust J.B., Melnyk O., Carey K.,
RA   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   MEDLINE=94264323; 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-
RT   cell 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
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W.,
RA   Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA   Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT   "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT   of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
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
RT   project: 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   MEDLINE=93326527; PubMed=7687458;
RA   Motokura T., Arnold A.;
RT   "The PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA
RT   sequence, and sequence of a tumor-specific rearrangement breakpoint.";
RL   Genes Chromosomes Cancer 7:89-95(1993).
RN   [10]
RP   INTERACTION WITH CDK4 AND CDK6.
RX   MEDLINE=94134440; 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   [11]
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   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226, AND MASS
RP   SPECTROMETRY.
RX   PubMed=17053785; DOI=10.1038/sj.emboj.7601384;
RA   Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A.,
RA   Lottspeich F., Chen Z.;
RT   "Tyrosine phosphorylated Par3 regulates epithelial tight junction
RT   assembly promoted by EGFR signaling.";
RL   EMBO J. 25:5058-5070(2006).
CC   -!- FUNCTION: Essential for the control of the cell cycle at the G1/S
CC       (start) transition.
CC   -!- SUBUNIT: Interacts with the CDK4 and CDK6 protein kinases to form
CC       a serine/threonine kinase holoenzyme complex. The cyclin subunit
CC       imparts substrate specificity to the complex.
CC   -!- INTERACTION:
CC       P38398:BRCA1; NbExp=2; IntAct=EBI-375001, EBI-349905;
CC       P11802:CDK4; NbExp=6; IntAct=EBI-375001, EBI-295644;
CC       Q00534:CDK6; NbExp=1; IntAct=EBI-375001, EBI-295663;
CC       P38936:CDKN1A; NbExp=2; IntAct=EBI-375001, EBI-375077;
CC       P46527:CDKN1B; NbExp=2; IntAct=EBI-375001, EBI-519280;
CC       Q7L590:MCM10; NbExp=1; IntAct=EBI-375001, EBI-374912;
CC       O43929:ORC4L; NbExp=1; IntAct=EBI-375001, EBI-374889;
CC       P62140:PPP1CB; NbExp=1; IntAct=EBI-375001, EBI-352350;
CC       P36873-1:PPP1CC; NbExp=1; IntAct=EBI-375001, EBI-356289;
CC   -!- DISEASE: A chromosomal aberration involving CCND1 may be a cause
CC       of B-lymphocytic malignancy, particularly mantle-cell lymphoma
CC       (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene
CC       regions. Activation of CCND1 may be oncogenic by directly altering
CC       progression through the cell cycle.
CC   -!- DISEASE: A chromosomal aberration involving CCND1 may be a cause
CC       of parathyroid adenomas [MIM:168461]. Translocation
CC       t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer.
CC   -!- DISEASE: A chromosomal aberration involving CCND1 may be a cause
CC       of multiple myeloma [MIM:254500]. Translocation t(11;14)(q13;q32)
CC       with the IgH locus.
CC   -!- SIMILARITY: Belongs to the cyclin family. Cyclin D subfamily.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/BCL1.html";
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=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   PIR; A38977; A38977.
DR   RefSeq; NP_444284.1; -.
DR   UniGene; Hs.523852; -.
DR   UniGene; Hs.702537; -.
DR   DIP; DIP:123N; -.
DR   IntAct; P24385; -.
DR   PhosphoSite; P24385; -.
DR   Ensembl; ENSG00000110092; Homo sapiens.
DR   GeneID; 595; -.
DR   KEGG; hsa:595; -.
DR   H-InvDB; HIX0009889; -.
DR   HGNC; HGNC:1582; CCND1.
DR   HPA; CAB000024; -.
DR   MIM; 168461; gene.
DR   MIM; 254500; phenotype.
DR   Orphanet; 67038; B-cell chronic lymphocytic leukaemia.
DR   PharmGKB; PA75; -.
DR   HOGENOM; P24385; -.
DR   HOVERGEN; P24385; -.
DR   Reactome; REACT_152; Cell Cycle, Mitotic.
DR   DrugBank; DB01169; Arsenic trioxide.
DR   LinkHub; P24385; -.
DR   NextBio; 2419; -.
DR   ArrayExpress; P24385; -.
DR   CleanEx; HS_CCND1; -.
DR   GermOnline; ENSG00000110092; Homo sapiens.
DR   GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme ...; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; EXP:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; EXP:Reactome.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; NAS:UniProtKB.
DR   GO; GO:0045737; P:positive regulation of cyclin-dependent pro...; IDA:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein amino acid p...; IDA:UniProtKB.
DR   InterPro; IPR015451; CycD.
DR   InterPro; IPR006670; Cyclin.
DR   InterPro; IPR014400; Cyclin_A_B_D_E.
DR   InterPro; IPR004367; Cyclin_C.
DR   InterPro; IPR006671; Cyclin_N.
DR   InterPro; IPR013763; Cyclin_related.
DR   Gene3D; G3DSA:1.10.472.10; Cyclin_related; 1.
DR   PANTHER; PTHR10177:SF12; CycD; 1.
DR   Pfam; PF02984; Cyclin_C; 1.
DR   Pfam; PF00134; Cyclin_N; 1.
DR   PIRSF; PIRSF001771; Cyclin_A_B_D_E; 1.
DR   SMART; SM00385; CYCLIN; 1.
DR   PROSITE; PS00292; CYCLINS; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Cell division; Chromosomal rearrangement; Cyclin;
KW   Phosphoprotein; Proto-oncogene.
FT   CHAIN         1    295       G1/S-specific cyclin-D1.
FT                                /FTId=PRO_0000080430.
FT   MOD_RES     226    226       Phosphotyrosine.
FT   CONFLICT    130    130       N -> G (in Ref. 3; AAA52136).
FT   CONFLICT    168    169       MP -> IA (in Ref. 2; M74092).
FT   CONFLICT    188    188       L -> S (in Ref. 3; AAA52136).
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
//