G1/S-specific cyclin-D1

Details

Name
G1/S-specific cyclin-D1
Synonyms
  • B-cell lymphoma 1 protein
  • BCL-1
  • BCL-1 oncogene
  • BCL1
  • PRAD1
  • PRAD1 oncogene
Gene Name
CCND1
UniProtKB Entry
P24385Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0019051|G1/S-specific cyclin-D1
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIV
ATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLT
AEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRK
HAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCD
PDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI
Number of residues
295
Molecular Weight
33728.74
Theoretical pI
4.68
GO Classification
Functions
cyclin-dependent protein serine/threonine kinase regulator activity / enzyme binding / histone deacetylase binding / proline-rich region binding / protein kinase activity / protein kinase binding / transcription corepressor activity
Processes
cell division / endoplasmic reticulum unfolded protein response / fat cell differentiation / G1/S transition of mitotic cell cycle / lactation / mammary gland alveolus development / mammary gland epithelial cell proliferation / negative regulation of epithelial cell differentiation / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of mammary gland epithelial cell proliferation / positive regulation of protein phosphorylation / re-entry into mitotic cell cycle / response to UV-A
Components
bicellular tight junction / cyclin-dependent protein kinase holoenzyme complex / cytosol / nucleoplasm / nucleus
General Function
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:33854235, PubMed:8114739, PubMed:8302605). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Hypophosphorylates RB1 in early G(1) phase (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8114739, PubMed:8302605). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1827756, PubMed:1833066, PubMed:19412162, PubMed:8302605). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529)
Specific Function
Cyclin-dependent protein serine/threonine kinase activator activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0019052|G1/S-specific cyclin-D1 (CCND1)
ATGGAACACCAGCTCCTGTGCTGCGAAGTGGAAACCATCCGCCGCGCGTACCCCGATGCC
AACCTCCTCAACGACCGGGTGCTGCGGGCCATGCTGAAGGCGGAGGAGACCTGCGCGCCC
TCGGTGTCCTACTTCAAATGTGTGCAGAAGGAGGTCCTGCCGTCCATGCGGAAGATCGTC
GCCACCTGGATGCTGGAGGTCTGCGAGGAACAGAAGTGCGAGGAGGAGGTCTTCCCGCTG
GCCATGAACTACCTGGACCGCTTCCTGTCGCTGGAGCCCGTGAAAAAGAGCCGCCTGCAG
CTGCTGGGGGCCACTTGCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCCCCCTGACG
GCCGAGAAGCTGTGCATCTACACCGACAACTCCATCCGGCCCGAGGAGCTGCTGCAAATG
GAGCTGCTCCTGGTGAACAAGCTCAAGTGGAACCTGGCCGCAATGACCCCGCACGATTTC
ATTGAACACTTCCTCTCCAAAATGCCAGAGGCGGAGGAGAACAAACAGATCATCCGCAAA
CACGCGCAGACCTTCGTTGCCCTCTGTGCCACAGATGTGAAGTTCATTTCCAATCCGCCC
TCCATGGTGGCAGCGGGGAGCGTGGTGGCCGCAGTGCAAGGCCTGAACCTGAGGAGCCCC
AACAACTTCCTGTCCTACTACCGCCTCACACGCTTCCTCTCCAGAGTGATCAAGTGTGAC
CCGGACTGCCTCCGGGCCTGCCAGGAGCAGATCGAAGCCCTGCTGGAGTCAAGCCTGCGC
CAGGCCCAGCAGAACATGGACCCCAAGGCCGCCGAGGAGGAGGAAGAGGAGGAGGAGGAG
GTGGACCTGGCTTGCACACCCACCGACGTGCGGGACGTGGACATCTGA
Chromosome Location
11
Locus
11q13.3
External Identifiers
ResourceLink
UniProtKB IDP24385
UniProtKB Entry NameCCND1_HUMAN
GenBank Protein ID35632
GenBank Gene IDX59798
GeneCard IDCCND1
GenAtlas IDCCND1
HGNC IDHGNC:1582
PDB ID(s)2W96, 2W99, 2W9F, 2W9Z, 5VZU, 6P8E, 6P8F, 6P8G, 6P8H
KEGG IDhsa:595
NCBI Gene ID595
General References
  1. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV, Kronenberg HM, Arnold A: A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512-5. [Article]
  2. Lew DJ, Dulic V, Reed SI: Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell. 1991 Sep 20;66(6):1197-206. [Article]
  3. Xiong Y, Connolly T, Futcher B, Beach D: Human D-type cyclin. Cell. 1991 May 17;65(4):691-9. [Article]
  4. Withers DA, Harvey RC, Faust JB, Melnyk O, Carey K, Meeker TC: Characterization of a candidate bcl-1 gene. Mol Cell Biol. 1991 Oct;11(10):4846-53. [Article]
  5. Rimokh R, Berger F, Bastard C, Klein B, French M, Archimbaud E, Rouault JP, Santa Lucia B, Duret L, Vuillaume M, et al.: Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias. Blood. 1994 Jun 15;83(12):3689-96. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Motokura T, Arnold A: PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes Chromosomes Cancer. 1993 Jun;7(2):89-95. [Article]
  8. Bates S, Bonetta L, MacAllan D, Parry D, Holder A, Dickson C, Peters G: CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene. 1994 Jan;9(1):71-9. [Article]
  9. Chesi M, Bergsagel PL, Brents LA, Smith CM, Gerhard DS, Kuehl WM: Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines. Blood. 1996 Jul 15;88(2):674-81. [Article]
  10. LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E: New functional activities for the p21 family of CDK inhibitors. Genes Dev. 1997 Apr 1;11(7):847-62. [Article]
  11. Germain D, Russell A, Thompson A, Hendley J: Ubiquitination of free cyclin D1 is independent of phosphorylation on threonine 286. J Biol Chem. 2000 Apr 21;275(16):12074-9. [Article]
  12. Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F: Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004 Jul 8;430(6996):226-31. [Article]
  13. Liu WD, Wang HW, Muguira M, Breslin MB, Lan MS: INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases. Biochem J. 2006 Jul 1;397(1):169-77. [Article]
  14. Wang HW, Muguira M, Liu WD, Zhang T, Chen C, Aucoin R, Breslin MB, Lan MS: Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription. J Endocrinol. 2008 Jul;198(1):29-39. doi: 10.1677/JOE-08-0001. Epub 2008 Apr 16. [Article]
  15. Zhang T, Liu WD, Saunee NA, Breslin MB, Lan MS: Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest. J Biol Chem. 2009 Feb 27;284(9):5574-81. doi: 10.1074/jbc.M808843200. Epub 2009 Jan 5. [Article]
  16. Shan J, Zhao W, Gu W: Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol Cell. 2009 Nov 13;36(3):469-76. doi: 10.1016/j.molcel.2009.10.018. [Article]
  17. Santra MK, Wajapeyee N, Green MR: F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature. 2009 Jun 4;459(7247):722-5. doi: 10.1038/nature08011. Epub 2009 May 3. [Article]
  18. Mori T, Ikeda DD, Fukushima T, Takenoshita S, Kochi H: NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Cell Cycle. 2011 Oct 1;10(19):3284-99. doi: 10.4161/cc.10.19.17176. Epub 2011 Oct 1. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  20. Day PJ, Cleasby A, Tickle IJ, O'Reilly M, Coyle JE, Holding FP, McMenamin RL, Yon J, Chopra R, Lengauer C, Jhoti H: Crystal structure of human CDK4 in complex with a D-type cyclin. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4166-70. doi: 10.1073/pnas.0809645106. Epub 2009 Feb 23. [Article]

Associated Data

Bio-Entities
Bio-EntityType
G1/S-specific cyclin-D1 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Arsenic trioxideapproved, investigationalyestargetantagonistDetails
Encorafenibapproved, investigationalyestargetinhibitorDetails
Acetylsalicylic acidapproved, vet_approvedunknowntargetdownregulatorDetails
Bryostatin 1investigationalunknowntargetinhibitorDetails
BriciclibinvestigationalyestargetinhibitorDetails
NavitoclaxinvestigationalyestargetinhibitorDetails