Protein:CDKN2A |
Protein Summary |
 Gene summary |
| Gene name: CDKN2A | ASpdb.0 ID: 1029 | Gene | Gene symbol | CDKN2A | Gene ID | 1029 |
| Gene name | cyclin dependent kinase inhibitor 2A |
| Synonyms | ARF|CAI2|CDK4I|CDKN2|CMM2|INK4|INK4A|MLM|MTS-1|MTS1|P14|P14ARF|P16|P16-INK4A|P16INK4|P16INK4A|P19|P19ARF|TP16 |
| Cytomap | 9p21.3 |
| Type of gene | protein-coding |
| Description | cyclin-dependent kinase inhibitor 2ACDK4 inhibitor p16-INK4CDKN2A/ARF Intron 2 lncRNAalternative reading framecell cycle negative regulator betacyclin-dependent kinase 4 inhibitor Acyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) |
| Modification date | 20240407 |
| UniProtAcc | P42771 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CDKN2A | GO:0004861 | cyclin-dependent protein serine/threonine kinase inhibitor activity | 7739547|8259215 |
| Gene | CDKN2A | GO:0005634 | nucleus | 16243918 |
| Gene | CDKN2A | GO:0005737 | cytoplasm | 16243918 |
| Gene | CDKN2A | GO:0008285 | negative regulation of cell population proliferation | 15149599 |
| Gene | CDKN2A | GO:0030308 | negative regulation of cell growth | 10208428 |
| Gene | CDKN2A | GO:0032088 | negative regulation of NF-kappaB transcription factor activity | 10353611 |
| Gene | CDKN2A | GO:0035985 | senescence-associated heterochromatin focus | 16901784 |
| Gene | CDKN2A | GO:0042326 | negative regulation of phosphorylation | 8259215|10208428 |
| Gene | CDKN2A | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 7739547 |
| Gene | CDKN2A | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 8259215 |
| Gene | CDKN2A | GO:0051059 | NF-kappaB binding | 10353611 |
| Gene | CDKN2A | GO:0051726 | regulation of cell cycle | 15149599 |
| Gene | CDKN2A | GO:2000045 | regulation of G1/S transition of mitotic cell cycle | 10208428 |
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 |
| P42771-1 | P42771-1_1bi7_B.pdb | 1BI7 | X-ray | 3.4 | B | 10 | 134 |
| 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 |
| P42771 | CDKN2A | P42771-1 | P42771-2 | 156 | 105 | 1 | 51 | Deletion | none | none | 0 | 0 |
| P42771 | CDKN2A | P42771-1 | P42771-3 | 156 | 116 | 52 | 116 | Substitution | MMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGARLDVRDAWGRLPVD | GRGSAAGAGDGGRLWRTKFAGELESGSASILRKKGRLPGEFSEGVCNHRPPPGDALGAWEAKEEE | 52 | 116 |
| P42771 | CDKN2A | P42771-1 | P42771-3 | 156 | 116 | 117 | 156 | Deletion | none | none | 116 | 116 |
| P42771 | CDKN2A | P42771-1 | P42771-4 | 156 | 167 | 153 | 156 | Substitution | DIPD | EMIGNHLWVCRSRHA | 153 | 167 |
| Multiple sequence alignment of our canonical and alternatively spliced CDKN2A |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CDKN2A |
| UniProt-id | ENSG | ENST | ENSP |
| P42771-1 | ENSG00000147889.18 | ENST00000304494.10 | ENSP00000307101.5 |
| P42771-2 | ENSG00000147889.18 | ENST00000494262.5 | ENSP00000464952.1 |
| P42771-2 | ENSG00000147889.18 | ENST00000498628.6 | ENSP00000467857.1 |
| P42771-2 | ENSG00000147889.18 | ENST00000578845.2 | ENSP00000467390.1 |
| P42771-3 | ENSG00000147889.18 | ENST00000380151.3 | ENSP00000369496.3 |
| P42771-4 | ENSG00000147889.18 | ENST00000498124.1 | ENSP00000418915.1 |
| UniProt-id | NM ID | NP ID |
| P42771-1 | NM_000077.4 | NP_000068.1 |
| P42771-3 | NM_058197.4 | NP_478104.2 |
| P42771-4 | NM_001195132.1 | NP_001182061.1 |
| Amino acid sequences of our canonical and alternatively spliced CDKN2A |
| accession_id | Protein sequence |
| P42771-1 | MEPAAGSSMEPSADWLATAAARGRVEEVRALLEAGALPNAPNSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGF |
| P42771-2 | MMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAGGTRGSN |
| P42771-3 | MEPAAGSSMEPSADWLATAAARGRVEEVRALLEAGALPNAPNSYGRRPIQVGRGSAAGAGDGGRLWRTKFAGELESGSASILRKKGRLPG |
| P42771-4 | MEPAAGSSMEPSADWLATAAARGRVEEVRALLEAGALPNAPNSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGF |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CDKN2A (go to UniProt):P42771 |
| 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 |
| P42771 | Repeat | 11 | 40 | Note=ANK 1 | Type=Deletion;Start=1;End=51 |
| P42771 | Repeat | 44 | 72 | Note=ANK 2 | Type=Deletion;Start=1;End=51 |
| P42771 | Repeat | 44 | 72 | Note=ANK 2 | Type=Substitution;Start=52;End=116 |
| P42771 | Repeat | 77 | 106 | Note=ANK 3 | Type=Substitution;Start=52;End=116 |
| P42771 | Repeat | 110 | 139 | Note=ANK 4 | Type=Substitution;Start=52;End=116 |
| P42771 | Repeat | 110 | 139 | Note=ANK 4 | Type=Deletion;Start=117;End=156 |
Gene Isoform Structures and Expression Levels for CDKN2A |
| Gene structures of our canonical and alternative spliced genes of CDKN2A * 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 P42771-1 |
| 3D view using mol* of P42771-2 |
| 3D view using mol* of P42771-3 |
| 3D view using mol* of P42771-4 |
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 P42771-1 |
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| pLDDT distribution across the protein length of P42771-2 |
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| pLDDT distribution across the protein length of P42771-3 |
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| pLDDT distribution across the protein length of P42771-4 |
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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 P42771-1 |
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| Ramachandran plot of P42771-2 |
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| Ramachandran plot of P42771-3 |
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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 |
| P42771-1 | 0.467 | 19 | 0.353 | 37.044 | 0.762 | 0.52 | 0.669 | 0 | 1.131 | 0 | 0.423 | 98,102,103,104,105,106,133,134,137
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| P42771-2 | 0.961 | 65 | 0.997 | 170.128 | 0.564 | 0.726 | 0.937 | 1.961 | 0.601 | 3.261 | 3.711 | 5,8,9,12,13,17,18,19,20,21,22,23,29,30,31,33,34,37 ,39,42,46 |
| P42771-3 | 1 | 39 | 1.002 | 53.165 | 0.443 | 0.943 | 1.254 | 4.326 | 0.462 | 9.36 | 0.158 | 16,17,20,28,32,38,48,49,51,52,66,70,73,74
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| P42771-4 | 0.602 | 30 | 0.552 | 100.842 | 0.804 | 0.565 | 0.725 | 0.248 | 0.925 | 0.268 | 0.916 | 46,50,51,52,53,54,55,79,83,84,87,88,90,108,110,112 ,117 |
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 P42771-1_P42771-1_1bi7_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 P42771-1_1bi7_B_P42771-2.pdb |
| 3D view using mol* of P42771-1_1bi7_B_P42771-3.pdb |
| 3D view using mol* of P42771-1_1bi7_B_P42771-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P42771-1_P42771-2.pdb |
| 3D view using mol* of P42771-1_P42771-3.pdb |
| 3D view using mol* of P42771-1_P42771-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P42771-1_vs_P42771-2.png |
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| ./stats/secondary_structure/figure/P42771-1_vs_P42771-3.png |
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| ./stats/secondary_structure/figure/P42771-1_vs_P42771-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P42771-1_vs_P42771-2.png |
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| ./stats/relative_asa/P42771-1_vs_P42771-3.png |
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| ./stats/relative_asa/P42771-1_vs_P42771-4.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 CDKN2A |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to CDKN2A |
| Previous studies relating to the alternative splicing of CDKN2A and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CDKN2A | 10445844 | Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus. | The INK4a/ARF locus on human chromosome 9p resides at the nexus of two critical cell cycle regulatory pathways, the p53 pathway and the retinoblastoma (pRb) gene pathway. Through the use of shared coding regions and alternative reading frames two distinct proteins are produced: INK4a is a cyclin-dependent kinase inhibitor whereas ARF binds the MDM2 proto-oncogene and stabilizes p53. We have examined the expression patterns of the INK4a/ARF locus at the RNA level in normal human and murine tissues to determine if these genes are coordinately regulated. We found that both INK4a and ARF were expressed in most tissues at low levels detectable only by RT-PCR. The pancreas was an exception in that it expressed no detectable ARF mRNA but expressed high levels of INK4a mRNA. Furthermore, human pancreas expressed an additional previously unrecognized splice variant of INK4a, termed p12, through the use of an alternative splice donor site within intron 1. The p12 transcript produced a 12 kD protein composed of INK4a exon 1alpha and a novel intron-derived C-terminus. This novel protein did not interact with cdk4 but was capable of suppressing growth in a pRb-independent manner. The implications of the capacity of the INK4a/ARF locus to encode a third transcript, and for pancreatic cancer, in which the INK4a/ARF locus is nearly always altered, are considered. | D010190 | Pancreatic Neoplasms |
| CDKN2A | 10445844 | Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus. | The INK4a/ARF locus on human chromosome 9p resides at the nexus of two critical cell cycle regulatory pathways, the p53 pathway and the retinoblastoma (pRb) gene pathway. Through the use of shared coding regions and alternative reading frames two distinct proteins are produced: INK4a is a cyclin-dependent kinase inhibitor whereas ARF binds the MDM2 proto-oncogene and stabilizes p53. We have examined the expression patterns of the INK4a/ARF locus at the RNA level in normal human and murine tissues to determine if these genes are coordinately regulated. We found that both INK4a and ARF were expressed in most tissues at low levels detectable only by RT-PCR. The pancreas was an exception in that it expressed no detectable ARF mRNA but expressed high levels of INK4a mRNA. Furthermore, human pancreas expressed an additional previously unrecognized splice variant of INK4a, termed p12, through the use of an alternative splice donor site within intron 1. The p12 transcript produced a 12 kD protein composed of INK4a exon 1alpha and a novel intron-derived C-terminus. This novel protein did not interact with cdk4 but was capable of suppressing growth in a pRb-independent manner. The implications of the capacity of the INK4a/ARF locus to encode a third transcript, and for pancreatic cancer, in which the INK4a/ARF locus is nearly always altered, are considered. | D002583 | Uterine Cervical Neoplasms |
Clinically important variants in CDKN2A |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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