Protein:MAPK3 |
Protein Summary |
 Gene summary |
| Gene name: MAPK3 | ASpdb.0 ID: 5595 | Gene | Gene symbol | MAPK3 | Gene ID | 5595 |
| Gene name | mitogen-activated protein kinase 3 |
| Synonyms | ERK-1|ERK1|ERT2|HS44KDAP|HUMKER1A|P44ERK1|P44MAPK|PRKM3|p44-ERK1|p44-MAPK |
| Cytomap | 16p11.2 |
| Type of gene | protein-coding |
| Description | mitogen-activated protein kinase 3MAPK 1extracellular signal-regulated kinase 1extracellular signal-related kinase 1insulin-stimulated MAP2 kinasemicrotubule-associated protein 2 kinase |
| Modification date | 20240323 |
| UniProtAcc | P27361 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | MAPK3 | GO:0004674 | protein serine/threonine kinase activity | 18391015|35216969 |
| Gene | MAPK3 | GO:0004707 | MAP kinase activity | 8388392 |
| Gene | MAPK3 | GO:0005635 | nuclear envelope | 20455999 |
| Gene | MAPK3 | GO:0006468 | protein phosphorylation | 7687743 |
| Gene | MAPK3 | GO:0016310 | phosphorylation | 15950189 |
| Gene | MAPK3 | GO:0034198 | cellular response to amino acid starvation | 11096076 |
| Gene | MAPK3 | GO:0038083 | peptidyl-tyrosine autophosphorylation | 8388392 |
| Gene | MAPK3 | GO:0042770 | signal transduction in response to DNA damage | 17560175 |
| Gene | MAPK3 | GO:0051403 | stress-activated MAPK cascade | 11096076 |
| Gene | MAPK3 | GO:0070849 | response to epidermal growth factor | 18794356|21968647 |
| Gene | MAPK3 | GO:1904262 | negative regulation of TORC1 signaling | 35216969 |
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 |
| P27361-1 | P27361-1_2zoq_A.pdb | 2ZOQ | X-ray | 2.39 | A | 24 | 375 |
| 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 |
| P27361 | MAPK3 | P27361-1 | P27361-2 | 379 | 335 | 259 | 302 | Deletion | none | none | 258 | 258 |
| P27361 | MAPK3 | P27361-1 | P27361-3 | 379 | 357 | 340 | 379 | Substitution | PVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP | VGQSPAAVGLGAGEQGGT | 340 | 357 |
| Multiple sequence alignment of our canonical and alternatively spliced MAPK3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of MAPK3 |
| UniProt-id | ENSG | ENST | ENSP |
| P27361-1 | ENSG00000102882.12 | ENST00000263025.9 | ENSP00000263025.4 |
| P27361-2 | ENSG00000102882.12 | ENST00000322266.9 | ENSP00000327293.5 |
| P27361-2 | ENSG00000102882.12 | ENST00000395202.5 | ENSP00000378628.1 |
| P27361-3 | ENSG00000102882.12 | ENST00000395199.7 | ENSP00000378625.3 |
| UniProt-id | NM ID | NP ID |
| P27361-1 | NM_002746.2 | NP_002737.2 |
| P27361-2 | NM_001109891.1 | NP_001103361.1 |
| P27361-3 | NM_001040056.2 | NP_001035145.1 |
| Amino acid sequences of our canonical and alternatively spliced MAPK3 |
| accession_id | Protein sequence |
| P27361-1 | MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQ ILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLN CIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL |
| P27361-2 | MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQ ILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILALDLLDRMLTFN |
| P27361-3 | MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQ ILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLN |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| MAPK3 (go to UniProt):P27361 |
| 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 |
| P27361 | Domain | 42 | 330 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=259;End=302 |
Gene Isoform Structures and Expression Levels for MAPK3 |
| Gene structures of our canonical and alternative spliced genes of MAPK3 * 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 P27361-1 |
| 3D view using mol* of P27361-2 |
| 3D view using mol* of P27361-3 |
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 P27361-1 |
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| pLDDT distribution across the protein length of P27361-2 |
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| pLDDT distribution across the protein length of P27361-3 |
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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 P27361-1 |
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| Ramachandran plot of P27361-2 |
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| Ramachandran plot of P27361-3 |
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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 |
| P27361-1 | 1.087 | 118 | 1.052 | 391.706 | 0.48 | 0.828 | 1.063 | 0.557 | 1.181 | 0.471 | 0.809 | 48,49,50,51,52,53,56,69,71,84,88,101,122,123,124,1 25,126,127,128,131,166,168,170,171,173,183,184,187 ,206,207 |
| P27361-2 | 1.047 | 241 | 0.988 | 673.652 | 0.522 | 0.768 | 0.986 | 0.556 | 1.266 | 0.439 | 0.756 | 48,49,50,51,52,53,54,56,58,67,69,71,80,84,87,88,10 1,122,123,124,125,126,127,128,130,131,133,134,165, 166,168,169,170,171,173,183,184,186,187,189,197,20 0,201,202,203,204,205,206,207,209,210,211,215,216, 222,237,241,242,243 |
| P27361-3 | 1.035 | 158 | 1.029 | 566.979 | 0.526 | 0.75 | 0.974 | 0.389 | 1.108 | 0.351 | 0.857 | 48,49,50,51,52,53,54,56,69,71,84,88,92,101,122,123 ,124,125,126,127,128,130,131,166,168,169,170,171,1 73,183,184,186,187,200,202,203,204,205,206,207,209 ,210 |
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 P27361-1_P27361-1_2zoq_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P27361-1_2zoq_A_P27361-2.pdb |
| 3D view using mol* of P27361-1_2zoq_A_P27361-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P27361-1_P27361-2.pdb |
| 3D view using mol* of P27361-1_P27361-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P27361-1_vs_P27361-2.png |
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| ./stats/secondary_structure/figure/P27361-1_vs_P27361-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P27361-1_vs_P27361-2.png |
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| ./stats/relative_asa/P27361-1_vs_P27361-3.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 MAPK3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P27361 | MAPK3 | DB08862 | Cholecystokinin | approved, investigational | |
| P27361 | MAPK3 | DB01169 | Arsenic trioxide | approved, investigational | inducer |
| P27361 | MAPK3 | DB06195 | Seliciclib | investigational | |
| P27361 | MAPK3 | DB04604 | 5-iodotubercidin | experimental | |
| P27361 | MAPK3 | DB13930 | Ulixertinib | investigational | inhibitor |
| P27361 | MAPK3 | DB02733 | Purvalanol | experimental | inhibitor |
| P27361 | MAPK3 | DB00605 | Sulindac | approved, investigational | inhibitor |
Related Diseases to MAPK3 |
| Previous studies relating to the alternative splicing of MAPK3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| MAPK3 | 20351270 | Alternative splicing of human papillomavirus type-16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation. | Certain types of human papillomaviruses (HPVs) are etiologically linked to cervical cancer. Their transforming capacity is encoded by a polycistronic premRNA, where alternative splicing leads to the translation of functional distinct proteins such as E6, E6*, and E7. Here we show that splicing of HPV16 E6/E7 ORF cassette is regulated by the epidermal growth factor (EGF) pathway. The presence of EGF was coupled to preferential E6 expression, whereas depletion of EGF, or treatment with EGF receptor (EGFR) neutralizing antibodies or the EGFR inhibitor tyrphostin AG1478, resulted in E6 exon exclusion in favor of E6*. As a consequence, increased p53 levels and enhanced translation of E7 with a subsequent reduction of the retinoblastoma protein pRb could be discerned. E6 exon exclusion upon EGF depletion was independent from promoter usage, mRNA stability, or selective mRNA transport. Time-course experiments and incubation with cycloheximide demonstrated that E6 alternative splicing is a direct and reversible effect of EGF signal transduction, not depending on de novo protein synthesis. Within this process, Erk1/2-kinase activation was the critical event for E6 exon inclusion, mediated by the upstream MAP kinase MEK1/2. Moreover, siRNA knockdown experiments revealed an involvement of splicing factors hnRNPA1 and hnRNPA2 in E6 exon exclusion, whereas the splicing factors Brm and Sam68 were found to promote E6 exon inclusion. Because there is a natural gradient of EGF and EGF receptor expression in the stratified epithelium, it is reasonable to assume that EGF modulates E6/E7 splicing during the viral life cycle and transformation. | D002583 | Uterine Cervical Neoplasms |
Clinically important variants in MAPK3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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