Protein:CDK4 |
Protein Summary |
 Gene summary |
| Gene name: CDK4 | ASpdb.0 ID: 1019 | Gene | Gene symbol | CDK4 | Gene ID | 1019 |
| Gene name | cyclin dependent kinase 4 |
| Synonyms | CMM3|PSK-J3 |
| Cytomap | 12q14.1 |
| Type of gene | protein-coding |
| Description | cyclin-dependent kinase 4cell division protein kinase 4 |
| Modification date | 20240416 |
| UniProtAcc | P11802 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CDK4 | GO:0000082 | G1/S transition of mitotic cell cycle | 19237565 |
| Gene | CDK4 | GO:0000307 | cyclin-dependent protein kinase holoenzyme complex | 17420273|18827403 |
| Gene | CDK4 | GO:0000785 | chromatin | 18827403 |
| Gene | CDK4 | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity | 8114739|19237565 |
| Gene | CDK4 | GO:0005634 | nucleus | 16109376|18827403|20399237 |
| Gene | CDK4 | GO:0005654 | nucleoplasm | - |
| Gene | CDK4 | GO:0005730 | nucleolus | 18827403 |
| Gene | CDK4 | GO:0005829 | cytosol | 18827403 |
| Gene | CDK4 | GO:0006468 | protein phosphorylation | 8114739 |
| Gene | CDK4 | GO:0010971 | positive regulation of G2/M transition of mitotic cell cycle | 19124461 |
| Gene | CDK4 | GO:0031965 | nuclear membrane | 18827403 |
| Gene | CDK4 | GO:0051726 | regulation of cell cycle | 19124461 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P11802-1 | P11802-1_2w9z_B.pdb | 2W9Z | X-ray | 2.45 | B | 2 | 295 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P11802 | CDK4 | P11802-1 | P11802-2 | 303 | 183 | 1 | 120 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced CDK4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CDK4 |
| UniProt-id | ENSG | ENST | ENSP |
| P11802-1 | ENSG00000135446.17 | ENST00000257904.11 | ENSP00000257904.5 |
| UniProt-id | NM ID | NP ID |
| P11802-1 | NM_000075.3 | NP_000066.1 |
| Amino acid sequences of our canonical and alternatively spliced CDK4 |
| accession_id | Protein sequence |
| P11802-1 | MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVT LVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWY RAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQ |
| P11802-2 | MRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRR KPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CDK4 (go to UniProt):P11802 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P11802 | Domain | 6 | 295 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=1;End=120 |
| P11802 | Region | 50 | 56 | Note=Required for binding D-type cyclins | Type=Deletion;Start=1;End=120 |
Gene Isoform Structures and Expression Levels for CDK4 |
| Gene structures of our canonical and alternative spliced genes of CDK4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P11802-1 |
| 3D view using mol* of P11802-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P11802-1 |
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| pLDDT distribution across the protein length of P11802-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P11802-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P11802-1 | 1.062 | 93 | 0.982 | 265.825 | 0.486 | 0.83 | 1.135 | 0.49 | 1.295 | 0.378 | 1.237 | 17,137,138,139,140,141,142,158,159,160,161,162,165 ,166,169,176,177,180,181,182,185,191,195,196,199 |
| P11802-2 | 1.087 | 77 | 0.966 | 120.736 | 0.342 | 0.963 | 1.401 | 1.062 | 1.339 | 0.793 | 1.007 | 18,19,20,21,41,52,53,54,56,57,60,61,62,65,68,71,75 ,76,79 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P11802-1_P11802-1_2w9z_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11802-1_2w9z_B_P11802-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P11802-1_P11802-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P11802-1_vs_P11802-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P11802-1_vs_P11802-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CDK4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P11802 | CDK4 | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| P11802 | CDK4 | DB15442 | Trilaciclib | approved, investigational | inhibitor |
| P11802 | CDK4 | DB03496 | Alvocidib | experimental, investigational | |
| P11802 | CDK4 | DB12001 | Abemaciclib | approved, investigational | inhibitor |
| P11802 | CDK4 | DB02733 | Purvalanol | experimental | |
| P11802 | CDK4 | DB09073 | Palbociclib | approved, investigational | inhibitor |
| P11802 | CDK4 | DB11730 | Ribociclib | approved, investigational | antagonist, inhibitor |
Related Diseases to CDK4 |
| Previous studies relating to the alternative splicing of CDK4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CDK4 | 17873913 | Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization. | We have previously reported the identification of a novel 17 kDa truncated isoform of the cyclin D2 activated in 13% of the leukemias induced by the Graffi murine leukemia retrovirus. Retroviral integration in the Gris1 locus causes an alternative splicing of the mouse cyclin D2 gene and expression of a truncated protein of 159 amino acids that is detected at high levels in the Gris1 tumors and also in normal mouse tissues mainly the brain and ovaries. A truncated form of the cyclin D2 was also found in human. We show here that both mouse- and human-truncated cyclin D2 are able to transform primary mouse embryo fibroblasts (MEF) when co-expressed with an activated Ras protein. The truncated cyclin D2 localizes only to the cytoplasm of transfected cells. It has retained the ability to interact with cyclin-dependent kinases (CDKs), although it is a poor catalyst of pRb phosphorylation. Interestingly, the presence of a similar, alternatively spliced cyclin D2 mRNA was also detected in some human brain tumors. | D002471 | Cell Transformation, Neoplastic |
Clinically important variants in CDK4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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