Reviewed,
UniProtKB/Swiss-Prot P24385 (CCND1_HUMAN)
Last modified
June 16, 2009.
Version 108.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
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Names and origin
| Protein names | Recommended name: G1/S-specific cyclin-D1 Alternative name(s): PRAD1 oncogene BCL-1 oncogene | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 295 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Essential for the control of the cell cycle at the G1/S (start) transition. |
| Subunit structure | Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Ref.10 |
| Post-translational modification | Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. Ubiquitination leads to its degradation and G1 arrest. |
| Involvement in disease | A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle. A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas [MIM:168461]. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer. A chromosomal aberration involving CCND1 may be a cause of multiple myeloma [MIM:254500]. Translocation t(11;14)(q13;q32) with the IgH locus. |
| Sequence similarities | Belongs to the cyclin family. Cyclin D subfamily. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| BRCA1 | P38398 | 2 | EBI-375001,EBI-349905 | |
| CDK4 | P11802 | 6 | EBI-375001,EBI-295644 | |
| CDK6 | Q00534 | 1 | EBI-375001,EBI-295663 | |
| CDKN1A | P38936 | 2 | EBI-375001,EBI-375077 | |
| CDKN1B | P46527 | 2 | EBI-375001,EBI-519280 | |
| MCM10 | Q7L590 | 1 | EBI-375001,EBI-374912 | |
| ORC4L | O43929 | 1 | EBI-375001,EBI-374889 | |
| PPP1CB | P62140 | 1 | EBI-375001,EBI-352350 | |
| PPP1CC | P36873-1 | 1 | EBI-375001,EBI-356289 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 295 | 295 | G1/S-specific cyclin-D1 | PRO_0000080430 | |||||
Amino acid modifications | |||||||||
| Modified residue | 226 | 1 | Phosphotyrosine Ref.12 | ||||||
| Modified residue | 286 | 1 | Phosphothreonine | ||||||
Experimental info | |||||||||
| Mutagenesis | 286 | 1 | T → A: Abolishes ubiquitination and subsequent degradation following DNA damage. | ||||||
| Sequence conflict | 130 | 1 | N → G in AAA52136. Ref.3 | ||||||
| Sequence conflict | 168 – 169 | 2 | MP → IA in M74092. Ref.2 | ||||||
| Sequence conflict | 188 | 1 | L → S in AAA52136. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A novel cyclin encoded by a bcl1-linked candidate oncogene." Motokura T., Bloom T., Kim H.G., Jueppner H., Ruderman J.V., Kronenberg H.M., Arnold A. Nature 350:512-515(1991) [PubMed: 1826542] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast." Lew D.J., Dulic V., Reed S.I. Cell 66:1197-1206(1991) [PubMed: 1833066] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [3] | "Human D-type cyclin." Xiong Y., Connolly T., Futcher B., Beach D. Cell 65:691-699(1991) [PubMed: 1827756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [4] | "Characterization of a candidate bcl-1 gene." Withers D.A., Harvey R.C., Faust J.B., Melnyk O., Carey K., Meeker T.C. Mol. Cell. Biol. 11:4846-4853(1991) [PubMed: 1833629] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [5] | "Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias." Rimokh R., Berger F., Bastard C., Klein B., French M., Archimbaud E., Rouault J.-P., Santa Lucia B., Duret L., Vuillaume M. Blood 83:3689-3696(1994) [PubMed: 8204893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [6] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [7] | NIEHS SNPs program Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Placenta. |
| [9] | "The PRAD1/cyclin D1 proto-oncogene: genomic organization, 5' DNA sequence, and sequence of a tumor-specific rearrangement breakpoint." Motokura T., Arnold A. Genes Chromosomes Cancer 7:89-95(1993) [PubMed: 7687458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66. Tissue: Placenta. |
| [10] | "CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1." Bates S., Bonetta L., McAllan D., Parry D., Holder A., Dickson C., Peters G. Oncogene 9:71-79(1994) [PubMed: 8302605] [Abstract] Cited for: INTERACTION WITH CDK4 AND CDK6. |
| [11] | "Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines." Chesi M., Bergsagel P.L., Brents L.A., Smith C.M., Gerhard D.S., Kuehl W.M. Blood 88:674-681(1996) [PubMed: 8695815] [Abstract] Cited for: INVOLVEMENT IN MULTIPLE MYELOMA. |
| [12] | "Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-226, MASS SPECTROMETRY. |
| [13] | "F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage." Santra M.K., Wajapeyee N., Green M.R. Nature 0:0-0(2009) [PubMed: 19412162] [Abstract] Cited for: PHOSPHORYLATION AT THR-286, UBIQUITINATION, MUTAGENESIS OF THR-286. |
| + | Additional computationally mapped references. |
Web resources
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| NIEHS-SNPs |
| SHMPD The Singapore human mutation and polymorphism database |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| X59798 mRNA. Translation: CAA42470.1. M74092 mRNA. No translation available. M64349 mRNA. Translation: AAA52136.1. M73554 mRNA. Translation: AAA58392.1. Z23022 mRNA. Translation: CAA80558.1. BT019845 mRNA. Translation: AAV38648.1. AF511593 Genomic DNA. Translation: AAM34300.2. BC000076 mRNA. Translation: AAH00076.1. BC001501 mRNA. Translation: AAH01501.1. BC014078 mRNA. Translation: AAH14078.1. BC023620 mRNA. Translation: AAH23620.1. BC025302 mRNA. Translation: AAH25302.1. L09054 Genomic DNA. Translation: AAA36481.1. | |||||||||||||||||||||||||||||||
| IPI | IPI00028098. | ||||||||||||||||||||||||||||||
| PIR | A38977. | ||||||||||||||||||||||||||||||
| RefSeq | NP_444284.1. | ||||||||||||||||||||||||||||||
| UniGene | Hs.523852 | ||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||
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| ModBase | Search... | ||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||
| DIP | DIP:123N. | ||||||||||||||||||||||||||||||
| IntAct | P24385. 10 interactions. | ||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||
| PhosphoSite | P24385. | ||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||
| PRIDE | P24385. | ||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||
| Ensembl | ENSG00000110092. Homo sapiens. [Contig view] | ||||||||||||||||||||||||||||||
| GeneID | 595. | ||||||||||||||||||||||||||||||
| KEGG | hsa:595. | ||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||
| GeneCards | GC11P069165. | ||||||||||||||||||||||||||||||
| H-InvDB | HIX0009889. | ||||||||||||||||||||||||||||||
| HGNC | HGNC:1582. CCND1. | ||||||||||||||||||||||||||||||
| HPA | CAB000024. | ||||||||||||||||||||||||||||||
| MIM | 168461. gene. 254500. phenotype. | ||||||||||||||||||||||||||||||
| Orphanet | 67038. Leukemia, B-cell lymphocytic, chronic. | ||||||||||||||||||||||||||||||
| PharmGKB | PA75. | ||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||
| HOGENOM | P24385. | ||||||||||||||||||||||||||||||
| HOVERGEN | P24385. | ||||||||||||||||||||||||||||||
| OMA | P24385. LCCEVET. | ||||||||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||||||||
| Pathway_Interaction_DB | wnt_canonical_pathway. Canonical Wnt signaling pathway. ar_pathway. Coregulation of Androgen receptor activity. foxm1pathway. FOXM1 transcription factor network. trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. ps1pathway. Presenilin action in Notch and Wnt signaling. telomerasepathway. Regulation of Telomerase. p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta. pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma. | ||||||||||||||||||||||||||||||
| Reactome | REACT_152. Cell Cycle, Mitotic. | ||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||
| ArrayExpress | P24385. | ||||||||||||||||||||||||||||||
| Bgee | P24385. | ||||||||||||||||||||||||||||||
| CleanEx | HS_CCND1. | ||||||||||||||||||||||||||||||
| GermOnline | ENSG00000110092. Homo sapiens. | ||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||
| InterPro | IPR015451. CycD. IPR006670. Cyclin. IPR014400. Cyclin_A_B_D_E. IPR004367. Cyclin_C. IPR006671. Cyclin_N. IPR013763. Cyclin_related. [Graphical view] | ||||||||||||||||||||||||||||||
| Gene3D | G3DSA:1.10.472.10. Cyclin_related. 1 hit. | ||||||||||||||||||||||||||||||
| PANTHER | PTHR10177:SF12. CycD. 1 hit. | ||||||||||||||||||||||||||||||
| Pfam | PF02984. Cyclin_C. 1 hit. PF00134. Cyclin_N. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| PIRSF | PIRSF001771. Cyclin_A_B_D_E. 1 hit. | ||||||||||||||||||||||||||||||
| SMART | SM00385. CYCLIN. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| PROSITE | PS00292. CYCLINS. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||||||||
| DrugBank | DB01169. Arsenic trioxide. | ||||||||||||||||||||||||||||||
| NextBio | 2419. | ||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||
Entry information
| Entry name | CCND1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P24385 Secondary accession number(s): Q6LEF0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


