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
Organism
Humans
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 / transcription factor binding
Processes
canonical Wnt signaling pathway / cell division / cellular response to DNA damage stimulus / chromatin organization / endoplasmic reticulum unfolded protein response / fat cell differentiation / G1/S transition of mitotic cell cycle / lactation / Leydig cell differentiation / liver development / mammary gland alveolus development / mammary gland epithelial cell proliferation / mitotic cell cycle / mitotic G1 DNA damage checkpoint / negative regulation of cell cycle arrest / negative regulation of epithelial cell differentiation / negative regulation of transcription from RNA polymerase II promoter / negative regulation of Wnt signaling pathway / Notch signaling pathway / organ regeneration / 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 calcium ion / response to corticosterone / response to drug / response to estradiol / response to ethanol / response to iron ion / response to magnesium ion / response to organonitrogen compound / response to UV-A / response to vitamin E / response to X-ray / transcription, DNA-templated
Components
bicellular tight junction / cyclin-dependent protein kinase holoenzyme complex / cytosol / intracellular / membrane / nucleoplasm / nucleus / transcriptional repressor complex
General Function
Transcription factor binding
Specific 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. 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. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.
Pfam Domain Function
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
External Identifiers
ResourceLink
UniProtKB IDP24385
UniProtKB Entry NameCCND1_HUMAN
GenBank Protein ID35632
GenBank Gene IDX59798
GenAtlas IDCCND1
HGNC IDHGNC:1582
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. [PubMed:1826542]
  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. [PubMed:1833066]
  3. Xiong Y, Connolly T, Futcher B, Beach D: Human D-type cyclin. Cell. 1991 May 17;65(4):691-9. [PubMed:1827756]
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  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. [PubMed:8204893]
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  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. [PubMed:7687458]
  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. [PubMed:8302605]
  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. [PubMed:8695815]
  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. [PubMed:9106657]
  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. [PubMed:10766840]
  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. [PubMed:15241418]
  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. [PubMed:16569215]
  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. [PubMed:18417529]
  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. [PubMed:19124461]
  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. [PubMed:19917254]
  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. [PubMed:19412162]
  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. [PubMed:21952639]
  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. [PubMed:24275569]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01169Arsenic trioxideapproved, investigationalyesantagonistDetails
DB11718Encorafenibapproved, investigationalyesinhibitorDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknowndownregulatorDetails