P25322 (CCND1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 135. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||295 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 G1/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 G1 phase. Hypophosphorylates RB1 in early G1 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 By similarity.
Interacts with USP2. Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears independently of phosphorylation. Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity. Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression By similarity. Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Interacts directly with CDKN1B. Can form similar complexes with either CDKN1A or CDKN2A. Interacts with FBXO4. Ref.4 Ref.5 Ref.6
Nucleus. Cytoplasm By similarity. Membrane By similarity. Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members. Ref.6
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 By similarity.
Ubiquitinated, primarily as 'Lys-48'-linked polyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation. Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner By similarity. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization. Ref.5 Ref.6
Contains 1 cyclin N-terminal domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 295||295||G1/S-specific cyclin-D1||PRO_0000080431|
|Domain||28 – 152||125||Cyclin N-terminal|
|Compositional bias||273 – 280||8||Glu-rich|
Amino acid modifications
|Modified residue||286||1||Phosphothreonine Ref.5|
|Cross-link||269||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.6|
|Mutagenesis||269||1||K → R: Promotes location to the nucleus. Reduces proteasomal degradation, but does not prevent ubiquitination. Ref.6|
|Mutagenesis||286||1||T → A: Constitutively nuclear. Strongly reduced interaction with FBXO4. Strongly reduced ubiquitination. Ref.5 Ref.6|
|||"Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle."|
Matsushime H., Roussel M.F., Ashmun R.A., Sherr C.J.
Cell 65:701-713(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Genomic organization of the mouse cyclin D1 gene (Cyl-1)."|
Smith R., Peters G., Dickson C.
Genomics 25:85-92(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
|||"Redistribution of the CDK inhibitor p27 between different cyclin.CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation."|
Poon R.Y., Toyoshima H., Hunter T.
Mol. Biol. Cell 6:1197-1213(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1B IN THE CCND1-CDK4-CDKN1B COMPLEX.
|||"Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex."|
Lin D.I., Barbash O., Kumar K.G., Weber J.D., Harper J.W., Klein-Szanto A.J., Rustgi A., Fuchs S.Y., Diehl J.A.
Mol. Cell 24:355-366(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXO4, INTERACTION WITH A UBIQUITIN LIGASE COMPLEX CONTAINING CRYAB, SKP1, CUL1 AND FBXO4, MUTAGENESIS OF THR-286, PHOSPHORYLATION AT THR-286.
|||"Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation."|
Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.
Oncogene 28:4317-4325(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-269, INTERACTION WITH CDKN1B AND CDK4, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-269 AND THR-286.
|+||Additional computationally mapped references.|
|M64403 mRNA. Translation: AAA37502.1.|
S78355 mRNA. Translation: AAB34495.1.
BC044841 mRNA. Translation: AAH44841.1.
|RefSeq||NP_031657.1. NM_007631.2. |
3D structure databases
|SMR||P25322. Positions 22-267. |
Protein-protein interaction databases
|BioGrid||198548. 16 interactions.|
|IntAct||P25322. 16 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000093962; ENSMUSP00000091495; ENSMUSG00000070348. |
|UCSC||uc009kqt.1. mouse. |
|MGI||MGI:88313. Ccnd1. |
Enzyme and pathway databases
|Reactome||REACT_188257. Signal Transduction. |
REACT_188804. Cell Cycle.
Gene expression databases
Family and domain databases
|Gene3D||1.10.472.10. 2 hits. |
|InterPro||IPR013763. Cyclin-like. |
|PANTHER||PTHR10177:SF67. PTHR10177:SF67. 1 hit. |
|Pfam||PF02984. Cyclin_C. 1 hit. |
PF00134. Cyclin_N. 1 hit.
|PIRSF||PIRSF001771. Cyclin_A_B_D_E. 1 hit. |
|SMART||SM00385. CYCLIN. 2 hits. |
|SUPFAM||SSF47954. SSF47954. 2 hits. |
|PROSITE||PS00292. CYCLINS. 1 hit. |
|Accession||Primary (citable) accession number: P25322|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|