P30281 (CCND3_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 137.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: G1/S-specific cyclin-D3 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 292 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Regulatory component of the cyclin D3-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 D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Ref.12 |
| 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. Interacts with ATF5. Interacts with EIF3K. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Can form similar complexes with either CDKN1A or CDKN2A. Ref.11 Ref.12 Ref.13 Ref.14 |
| Subcellular location | Nucleus. Cytoplasm. Membrane. Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members By similarity. Ref.12 |
| Post-translational modification | Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation. |
| Sequence similarities | Belongs to the cyclin family. Cyclin D subfamily. Contains 1 cyclin N-terminal domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CDK14 | O94921 | 5 | EBI-375013,EBI-1043945 | |
| CDK4 | P11802 | 6 | EBI-375013,EBI-295644 | |
| CDK6 | Q00534 | 2 | EBI-375013,EBI-295663 | |
| CDKN1A | P38936 | 3 | EBI-375013,EBI-375077 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P30281-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P30281-2) The sequence of this isoform differs from the canonical sequence as follows: 1-81: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: P30281-3) The sequence of this isoform differs from the canonical sequence as follows: 67-138: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: P30281-4) The sequence of this isoform differs from the canonical sequence as follows: 1-196: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 292 | 292 | G1/S-specific cyclin-D3 | PRO_0000080442 | |||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||
| Domain | 27 – 152 | 126 | Cyclin N-terminal | ||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 279 | 1 | Phosphoserine Ref.16 | ||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 196 | 196 | Missing in isoform 4. | VSP_046266 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 81 | 81 | Missing in isoform 2. | VSP_042649 | |||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 67 – 138 | 72 | Missing in isoform 3. | VSP_046267 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 134 | 1 | P → S. Corresponds to variant rs3218089 [ dbSNP | Ensembl ]. | VAR_020412 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 253 | 1 | E → D. Corresponds to variant rs33966734 [ dbSNP | Ensembl ]. | VAR_033726 | |||||||||||||||||||||||||||||||||||||||
| Natural variant | 259 | 1 | S → A. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Corresponds to variant rs1051130 [ dbSNP | Ensembl ]. | VAR_014205 | |||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||
| Helix | 24 – 34 | 11 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 35 – 38 | 4 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 45 – 47 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 49 – 51 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 54 – 70 | 17 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 77 – 91 | 15 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 96 – 98 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 99 – 114 | 16 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 123 – 127 | 5 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 128 – 130 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 134 – 147 | 14 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 148 – 150 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 157 – 160 | 4 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 161 – 166 | 6 | |||||||||||||||||||||||||||||||||||||||||
| Turn | 172 – 174 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 175 – 191 | 17 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 193 – 195 | 3 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 200 – 213 | 14 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 222 – 233 | 12 | |||||||||||||||||||||||||||||||||||||||||
| Helix | 237 – 252 | 16 | |||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins." Xiong Y., Menninger J., Beach D., Ward D.C. Genomics 13:575-584(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-259. |
| [2] | "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene." Motokura T., Keyomarsi K., Kronenberg H.M., Arnold A. J. Biol. Chem. 267:20412-20415(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-259. |
| [4] | "Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ALA-259. Tissue: Cervix carcinoma. |
| [5] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4), VARIANT ALA-259. Tissue: Synovium, Thymus and Umbilical cord blood. |
| [6] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-259. |
| [7] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-259. |
| [9] | "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] (ISOFORM 1). Tissue: Lung. |
| [10] | "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes." Inaba T., Matsushime H., Valentine M., Roussel M.F., Sherr C.J., Look A.T. Genomics 13:565-574(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 52-237. Tissue: Placenta. |
| [11] | "New functional activities for the p21 family of CDK inhibitors." LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., Chou H.S., Fattaey A., Harlow E. Genes Dev. 11:847-862(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDK4 AND CDKN1A. |
| [12] | "Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity." Liu W., Sun M., Jiang J., Shen X., Sun Q., Liu W., Shen H., Gu J. Biochem. Biophys. Res. Commun. 321:954-960(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATF5, FUNCTION, SUBCELLULAR LOCATION. |
| [13] | "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3." Shen X., Yang Y., Liu W., Sun M., Jiang J., Zong H., Gu J. FEBS Lett. 573:139-146(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF3K. |
| [14] | "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'." Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., de Launoit Y., Roger P.P., Coulonval K. Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDK4; CDKN2A AND CDKN1B. |
| [15] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [16] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [17] | "F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest." Chen B.B., Glasser J.R., Coon T.A., Mallampalli R.K. Oncogene 31:2566-2579(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY SCF(FBXL2). |
| [18] | "The structure of CDK4/cyclin D3 has implications for models of CDK activation." Takaki T., Echalier A., Brown N.R., Hunt T., Endicott J.A., Noble M.E. Proc. Natl. Acad. Sci. U.S.A. 106:4171-4176(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH CDK4. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | M90814 mRNA. Translation: AAA51927.1. M92287 mRNA. Translation: AAA52137.1. AF517525 Genomic DNA. Translation: AAM51826.1. BX400719 mRNA. No translation available. AK057206 mRNA. Translation: BAG51884.1. AK097856 mRNA. No translation available. AK315421 mRNA. Translation: BAG37810.1. CR542246 mRNA. Translation: CAG47042.1. AL160163 Genomic DNA. Translation: CAI23491.1. AL513008 Genomic DNA. No translation available. CH471081 Genomic DNA. Translation: EAX04071.1. BC011616 mRNA. Translation: AAH11616.1. M88087 M88086 Genomic DNA. Translation: AAA51929.1. | ||||||||||||
| IPI | IPI00025817. IPI00914637. IPI00940490. | ||||||||||||
| PIR | B42822. | ||||||||||||
| RefSeq | NP_001129489.1. NM_001136017.2. NP_001129597.1. NM_001136125.1. NP_001129598.1. NM_001136126.1. NP_001751.1. NM_001760.3. | ||||||||||||
| UniGene | Hs.534307. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | P30281. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-31734N. | ||||||||||||
| IntAct | P30281. 24 interactions. | ||||||||||||
| MINT | MINT-1201666. | ||||||||||||
| STRING | 9606.ENSP00000362082. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P30281. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 20981685. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | P30281. | ||||||||||||
| PRIDE | P30281. | ||||||||||||
Protocols and materials databases | |||||||||||||
| DNASU | 896. | ||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000372988; ENSP00000362079; ENSG00000112576. ENST00000372991; ENSP00000362082; ENSG00000112576. ENST00000414200; ENSP00000397545; ENSG00000112576. ENST00000415497; ENSP00000401595; ENSG00000112576. ENST00000511642; ENSP00000426212; ENSG00000112576. | ||||||||||||
| GeneID | 896. | ||||||||||||
| KEGG | hsa:896. | ||||||||||||
| UCSC | uc003orn.3. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 896. | ||||||||||||
| GeneCards | GC06M041949. | ||||||||||||
| HGNC | HGNC:1585. CCND3. | ||||||||||||
| HPA | CAB000116. | ||||||||||||
| MIM | 123834. gene. | ||||||||||||
| neXtProt | NX_P30281. | ||||||||||||
| PharmGKB | PA26152. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | COG5024. | ||||||||||||
| HOGENOM | HOG000008182. | ||||||||||||
| HOVERGEN | HBG050837. | ||||||||||||
| InParanoid | P30281. | ||||||||||||
| KO | K10152. | ||||||||||||
| OMA | ISGETEC. | ||||||||||||
| OrthoDB | EOG4JWVF1. | ||||||||||||
| PhylomeDB | P30281. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Pathway_Interaction_DB | ar_pathway. Coregulation of Androgen receptor activity. il2_stat5pathway. IL2 signaling events mediated by STAT5. | ||||||||||||
| Reactome | REACT_115566. Cell Cycle. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P30281. | ||||||||||||
| Bgee | P30281. | ||||||||||||
| CleanEx | HS_CCND3. | ||||||||||||
| Genevestigator | P30281. | ||||||||||||
| GermOnline | ENSG00000112576. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 1.10.472.10. 1 hit. | ||||||||||||
| InterPro | IPR013763. Cyclin-like. IPR014400. Cyclin_A/B/D/E. IPR004367. Cyclin_C-dom. IPR006671. Cyclin_N. [Graphical view] | ||||||||||||
| 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] | ||||||||||||
| SUPFAM | SSF47954. Cyclin_like. 1 hit. | ||||||||||||
| PROSITE | PS00292. CYCLINS. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| BindingDB | P30281. | ||||||||||||
| ChEMBL | CHEMBL2422. | ||||||||||||
| ChiTaRS | CCND3. human. | ||||||||||||
| EvolutionaryTrace | P30281. | ||||||||||||
| GenomeRNAi | 896. | ||||||||||||
| NextBio | 3702. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | CCND3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P30281 Secondary accession number(s): B2RD63 Q96F49 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| 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
