Protein:DYRK1A |
Protein Summary |
 Gene summary |
| Gene name: DYRK1A | ASpdb.0 ID: 1859 | Gene | Gene symbol | DYRK1A | Gene ID | 1859 |
| Gene name | dual specificity tyrosine phosphorylation regulated kinase 1A |
| Synonyms | DYRK|DYRK1|HP86|MNB|MNBH|MRD7 |
| Cytomap | 21q22.13 |
| Type of gene | protein-coding |
| Description | dual specificity tyrosine-phosphorylation-regulated kinase 1AMNB/DYRK protein kinasedual specificity YAK1-related kinasedual specificity tyrosine-(Y)-phosphorylation regulated kinase 1Amnb protein kinase homolog hp86protein kinase minibrain homologs |
| Modification date | 20240411 |
| UniProtAcc | Q13627 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | DYRK1A | GO:0004715 | non-membrane spanning protein tyrosine kinase activity | 9748265 |
| Gene | DYRK1A | GO:0005634 | nucleus | 25620562 |
| Gene | DYRK1A | GO:0005634 | nucleus | 15694837|23415227 |
| Gene | DYRK1A | GO:0005737 | cytoplasm | 15694837 |
| Gene | DYRK1A | GO:0005856 | cytoskeleton | 24327345 |
| Gene | DYRK1A | GO:0008353 | RNA polymerase II CTD heptapeptide repeat kinase activity | 25620562|29849146 |
| Gene | DYRK1A | GO:0018108 | peptidyl-tyrosine phosphorylation | 9748265 |
| Gene | DYRK1A | GO:0033120 | positive regulation of RNA splicing | 28377597 |
| Gene | DYRK1A | GO:0038083 | peptidyl-tyrosine autophosphorylation | 24327345 |
| Gene | DYRK1A | GO:0090310 | negative regulation of DNA methylation-dependent heterochromatin formation | 24820035 |
| Gene | DYRK1A | GO:0106310 | protein serine kinase activity | 30773093 |
| Gene | DYRK1A | GO:0140857 | histone H3T45 kinase activity | 24820035 |
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 |
| Q13627-1 | Q13627-1_6a1f_A.pdb | 6A1F | X-ray | 1.5 | A | 134 | 483 |
| 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 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-2 | 763 | 754 | 70 | 78 | Deletion | none | none | 69 | 69 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-3 | 763 | 529 | 516 | 529 | Substitution | GGSSGTSNSGRARS | GASAISCSSWLVRH | 516 | 529 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-3 | 763 | 529 | 530 | 763 | Deletion | none | none | 529 | 529 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-4 | 763 | 525 | 516 | 525 | Substitution | GGSSGTSNSG | GGAALDARCL | 516 | 525 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-4 | 763 | 525 | 526 | 763 | Deletion | none | none | 525 | 525 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-5 | 763 | 584 | 559 | 584 | Substitution | RQQFPAPLGWSGTEAPTQVTVETHPV | SSHVVHLLVSPAILRWSSTGCQVPLE | 559 | 584 |
| Q13627 | DYRK1A | Q13627-1 | Q13627-5 | 763 | 584 | 585 | 763 | Deletion | none | none | 584 | 584 |
| Multiple sequence alignment of our canonical and alternatively spliced DYRK1A |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of DYRK1A |
| UniProt-id | ENSG | ENST | ENSP |
| Q13627-1 | ENSG00000157540.22 | ENST00000398960.7 | ENSP00000381932.2 |
| Q13627-1 | ENSG00000157540.22 | ENST00000644942.1 | ENSP00000494544.1 |
| Q13627-2 | ENSG00000157540.22 | ENST00000643624.1 | ENSP00000493627.1 |
| Q13627-2 | ENSG00000157540.22 | ENST00000646548.1 | ENSP00000495908.1 |
| Q13627-2 | ENSG00000157540.22 | ENST00000647188.2 | ENSP00000494572.1 |
| Q13627-2 | ENSG00000157540.22 | ENST00000647425.1 | ENSP00000496748.1 |
| Q13627-3 | ENSG00000157540.22 | ENST00000398956.2 | ENSP00000381929.2 |
| Q13627-4 | ENSG00000157540.22 | ENST00000645424.1 | ENSP00000494897.1 |
| Q13627-5 | ENSG00000157540.22 | ENST00000338785.8 | ENSP00000342690.3 |
| UniProt-id | NM ID | NP ID |
| Q13627-1 | NM_001396.4 | NP_001387.2 |
| Q13627-2 | NM_001347721.1 | NP_001334650.1 |
| Q13627-2 | NM_001347722.1 | NP_001334651.1 |
| Q13627-2 | NM_130436.2 | NP_569120.1 |
| Q13627-3 | NM_130438.2 | NP_569122.1 |
| Q13627-5 | NM_101395.2 | NP_567824.1 |
| Amino acid sequences of our canonical and alternatively spliced DYRK1A |
| accession_id | Protein sequence |
| Q13627-1 | MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLTNQVMPDIVMLQRRMPQTFRDPAT APLRKLSVDLIKTYKHINEVYYAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRV EQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMC TALLFLATPELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPL FSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYL KFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSSSGGSSGTSNSGRARSDPTHQHRHSGG HFTAAVQAMDCETHSPQVRQQFPAPLGWSGTEAPTQVTVETHPVQETTFHVAPQQNALHHHHGNSSHHHHHHHHHHHHHGQQALGNRTRP RVYNSPTNSSSTQDSMEVGHSHHSMTSLSSSTTSSSTSSSSTGNQGNQAYQNRPVAANTLDFGQNGAMDVNLTVYSNPRQETGIAGHPTY |
| Q13627-2 | MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLTNQRRMPQTFRDPATAPLRKLSVD LIKTYKHINEVYYAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRVEQEWVAIKI IKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMCTALLFLATP ELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPLFSGANEVDQ MNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYLKFKDLILRM LDYDPKTRIQPYYALQHSFFKKTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSSSGGSSGTSNSGRARSDPTHQHRHSGGHFTAAVQAM DCETHSPQVRQQFPAPLGWSGTEAPTQVTVETHPVQETTFHVAPQQNALHHHHGNSSHHHHHHHHHHHHHGQQALGNRTRPRVYNSPTNS SSTQDSMEVGHSHHSMTSLSSSTTSSSTSSSSTGNQGNQAYQNRPVAANTLDFGQNGAMDVNLTVYSNPRQETGIAGHPTYQFSANTGPA |
| Q13627-3 | MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLTNQVMPDIVMLQRRMPQTFRDPAT APLRKLSVDLIKTYKHINEVYYAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRV EQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMC TALLFLATPELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPL FSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYL |
| Q13627-4 | MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLTNQVMPDIVMLQRRMPQTFRDPAT APLRKLSVDLIKTYKHINEVYYAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRV EQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMC TALLFLATPELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPL FSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYL |
| Q13627-5 | MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLTNQVMPDIVMLQRRMPQTFRDPAT APLRKLSVDLIKTYKHINEVYYAKKKRRHQQGQGDDSSHKKERKVYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRV EQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTEMKYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQMC TALLFLATPELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRFYRSPEVLLGMPYDLAIDMWSLGCILVEMHTGEPL FSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFEKLPDGTWNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYL KFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSSSGGSSGTSNSGRARSDPTHQHRHSGG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| DYRK1A (go to UniProt):Q13627 |
| 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 |
| Q13627 | Region | 485 | 540 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=516;End=529 |
| Q13627 | Region | 485 | 540 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=530;End=763 |
| Q13627 | Region | 485 | 540 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=516;End=525 |
| Q13627 | Region | 485 | 540 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=526;End=763 |
| Q13627 | Region | 595 | 625 | Note=Histidine-rich domain (HRD);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=530;End=763 |
| Q13627 | Region | 595 | 625 | Note=Histidine-rich domain (HRD);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=526;End=763 |
| Q13627 | Region | 595 | 625 | Note=Histidine-rich domain (HRD);Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=585;End=763 |
| Q13627 | Region | 596 | 679 | Note=Disordered;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=530;End=763 |
| Q13627 | Region | 596 | 679 | Note=Disordered;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=526;End=763 |
| Q13627 | Region | 596 | 679 | Note=Disordered;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29849146;Dbxref=PMID:29849146 | Type=Deletion;Start=585;End=763 |
| Q13627 | Region | 744 | 763 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=530;End=763 |
| Q13627 | Region | 744 | 763 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=526;End=763 |
| Q13627 | Region | 744 | 763 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=585;End=763 |
| Q13627 | Compositional bias | 485 | 528 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=516;End=529 |
| Q13627 | Compositional bias | 485 | 528 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=516;End=525 |
| Q13627 | Compositional bias | 485 | 528 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=526;End=763 |
| Q13627 | Compositional bias | 601 | 624 | Note=Basic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=530;End=763 |
| Q13627 | Compositional bias | 601 | 624 | Note=Basic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=526;End=763 |
| Q13627 | Compositional bias | 601 | 624 | Note=Basic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=585;End=763 |
| Q13627 | Compositional bias | 627 | 679 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=530;End=763 |
| Q13627 | Compositional bias | 627 | 679 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=526;End=763 |
| Q13627 | Compositional bias | 627 | 679 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=585;End=763 |
Gene Isoform Structures and Expression Levels for DYRK1A |
| Gene structures of our canonical and alternative spliced genes of DYRK1A * 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 Q13627-1 |
| 3D view using mol* of Q13627-2 |
| 3D view using mol* of Q13627-3 |
| 3D view using mol* of Q13627-4 |
| 3D view using mol* of Q13627-5 |
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 Q13627-1 |
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| pLDDT distribution across the protein length of Q13627-2 |
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| pLDDT distribution across the protein length of Q13627-3 |
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| pLDDT distribution across the protein length of Q13627-4 |
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| pLDDT distribution across the protein length of Q13627-5 |
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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 Q13627-1 |
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| Ramachandran plot of Q13627-2 |
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| Ramachandran plot of Q13627-3 |
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| Ramachandran plot of Q13627-4 |
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| Ramachandran plot of Q13627-5 |
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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 |
| Q13627-1 | 1.136 | 180 | 1.188 | 363.923 | 0.439 | 0.812 | 1.056 | 2.296 | 0.734 | 3.128 | 0.708 | 151,163,164,165,166,170,173,186,188,203,207,222,23 8,239,240,241,242,243,244,291,292,294,306,307,308, 753,755,756,757,758,759,760 |
| Q13627-2 | 1.167 | 136 | 1.211 | 310.758 | 0.385 | 0.87 | 1.122 | 2.657 | 0.772 | 3.443 | 0.745 | 155,156,161,164,177,179,194,198,213,229,230,232,23 3,234,235,282,283,285,297,298,299,744,746,747,748, 749,751 |
| Q13627-3 | 1.077 | 443 | 1.125 | 1169.63 | 0.504 | 0.745 | 0.976 | 1.288 | 0.804 | 1.602 | 0.702 | 15,16,17,18,19,20,21,22,23,24,25,26,27,28,30,164,1 65,166,167,168,169,170,173,186,188,190,195,196,199 ,200,203,207,222,238,239,240,241,242,243,244,247,2 50,251,285,286,287,289,291,292,294,306,307,308,309 ,310,318,319,320,321,322,323,324,325,328 |
| Q13627-4 | 1.134 | 181 | 1.156 | 375.242 | 0.427 | 0.867 | 1.145 | 1.771 | 0.933 | 1.897 | 0.963 | 15,16,17,18,19,20,22,165,166,167,168,169,170,173,1 86,188,203,207,222,238,239,240,241,242,243,244,247 ,250,251,287,289,291,292,294,306,307,308 |
| Q13627-5 | 1.059 | 507 | 1.086 | 1237.201 | 0.475 | 0.759 | 1.002 | 0.966 | 0.95 | 1.017 | 1.059 | 15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,16 4,165,166,167,168,169,170,173,186,188,190,195,196, 198,199,200,203,207,222,238,239,240,241,242,243,24 4,246,247,250,286,287,289,291,292,294,306,307,308, 309,310,317,318,319,320,321,322,323,324,325,326,32 7,328,332,335,336,337,338,353,359,366,390 |
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 Q13627-1_Q13627-1_6a1f_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 Q13627-1_6a1f_A_Q13627-2.pdb |
| 3D view using mol* of Q13627-1_6a1f_A_Q13627-3.pdb |
| 3D view using mol* of Q13627-1_6a1f_A_Q13627-4.pdb |
| 3D view using mol* of Q13627-1_6a1f_A_Q13627-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q13627-1_Q13627-2.pdb |
| 3D view using mol* of Q13627-1_Q13627-3.pdb |
| 3D view using mol* of Q13627-1_Q13627-4.pdb |
| 3D view using mol* of Q13627-1_Q13627-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q13627-1_vs_Q13627-2.png |
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| ./stats/secondary_structure/figure/Q13627-1_vs_Q13627-3.png |
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| ./stats/secondary_structure/figure/Q13627-1_vs_Q13627-4.png |
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| ./stats/secondary_structure/figure/Q13627-1_vs_Q13627-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q13627-1_vs_Q13627-2.png |
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| ./stats/relative_asa/Q13627-1_vs_Q13627-3.png |
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| ./stats/relative_asa/Q13627-1_vs_Q13627-4.png |
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| ./stats/relative_asa/Q13627-1_vs_Q13627-5.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 DYRK1A |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| Q13627 | DYRK1A | DB12010 | Fostamatinib | approved, investigational | inhibitor |
| Q13627 | DYRK1A | DB07608 | N-(5-{[(2S)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1H-indazol-3-yl)benzamide | experimental |
Related Diseases to DYRK1A |
| Previous studies relating to the alternative splicing of DYRK1A and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| DYRK1A | 10329007 | Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. | The human homologue (MNBH/DYRK1) of the Drosophila minibrain gene maps to human chromosome 21 within the Down syndrome (DS) critical region and is within the region minimally deleted in chromosome 21-linked microcephaly. As a first step in gaining insight into the role that MNBH may have in human neurogenesis, and as a lead-up to the development of mouse models for MNBH overexpression, we have characterized the gene at the molecular level. We describe here the MNBH full-length transcript, alternative splicing, expression profile, and genomic organization. The full-length cDNA of MNBH is 5. 2 kb and is composed of 17 exons spanning 150 kb, between markers D21S335 and D21S337. Transcripts MNBHa and MNBHb arise from the use of different first exons in the 5'-UTR and are differentially expressed. MNBHa is expressed ubiquitiously in a broad spectrum of tissues and is apparently under the control of a CpG island. MNBHb is expressed only in heart and skeletal muscle and is apparently under the control of a TATA-like box. Four alternative splicing events affecting the C-terminus of the protein yield at least four isoforms of MNBH (MNBH-iso1, MNBH-iso2, MNBH-iso3, and MNBH-iso4). A PEST sequence, potentially involved in the rapid degradation of the protein, is present in all the isoforms. A histidine repeat and a serine/threonine domain are present only in the largest form of the protein (MNBH-iso1). MNBH was overexpressed 1.5-fold in DS brains and Dyrk1 about 2.1-fold in the brains of the Ts65Dn mice. The information provided here should be valuable for MNBH mutation studies and aid in the development of DS animal models. | D004314 | Down Syndrome |
| DYRK1A | 21156028 | The role of DYRK1A in neurodegenerative diseases. | Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and is overexpressed in Down syndrome (DS), may play a significant role in developmental brain defects and in early onset neurodegeneration, neuronal loss and dementia in DS. The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain, with structural and functional alterations including mental retardation and dementia. DYRK1A overexpression in DS brains may contribute to early onset neurofibrillary degeneration directly through hyperphosphorylation of tau and indirectly through phosphorylation of alternative splicing factor, leading to an imbalance between 3R-tau and 4R-tau. The several-fold increases in the number of DYRK1A-positive and 3R-tau-positive neurofibrillary tangles in DS support this hypothesis. Moreover, the enhanced phosphorylation of amyloid precursor protein by overexpressed DYRK1A facilitates amyloidogenic amyloid precursor protein cleavage elevating Aβ40 and 42 levels, and leading to brain β-amyloidosis. Therefore, inhibiting DYRK1A activity in DS may serve to counteract the phenotypic effects of its overexpression and is a potential method of treatment of developmental defects and the prevention of age-associated neurodegeneration, including Alzheimer-type pathology. | D004314 | Down Syndrome |
| DYRK1A | 21156028 | The role of DYRK1A in neurodegenerative diseases. | Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and is overexpressed in Down syndrome (DS), may play a significant role in developmental brain defects and in early onset neurodegeneration, neuronal loss and dementia in DS. The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain, with structural and functional alterations including mental retardation and dementia. DYRK1A overexpression in DS brains may contribute to early onset neurofibrillary degeneration directly through hyperphosphorylation of tau and indirectly through phosphorylation of alternative splicing factor, leading to an imbalance between 3R-tau and 4R-tau. The several-fold increases in the number of DYRK1A-positive and 3R-tau-positive neurofibrillary tangles in DS support this hypothesis. Moreover, the enhanced phosphorylation of amyloid precursor protein by overexpressed DYRK1A facilitates amyloidogenic amyloid precursor protein cleavage elevating Aβ40 and 42 levels, and leading to brain β-amyloidosis. Therefore, inhibiting DYRK1A activity in DS may serve to counteract the phenotypic effects of its overexpression and is a potential method of treatment of developmental defects and the prevention of age-associated neurodegeneration, including Alzheimer-type pathology. | D019636 | Neurodegenerative Diseases |
| DYRK1A | 21156028 | The role of DYRK1A in neurodegenerative diseases. | Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene, which is located on chromosome 21q22.2 and is overexpressed in Down syndrome (DS), may play a significant role in developmental brain defects and in early onset neurodegeneration, neuronal loss and dementia in DS. The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain, with structural and functional alterations including mental retardation and dementia. DYRK1A overexpression in DS brains may contribute to early onset neurofibrillary degeneration directly through hyperphosphorylation of tau and indirectly through phosphorylation of alternative splicing factor, leading to an imbalance between 3R-tau and 4R-tau. The several-fold increases in the number of DYRK1A-positive and 3R-tau-positive neurofibrillary tangles in DS support this hypothesis. Moreover, the enhanced phosphorylation of amyloid precursor protein by overexpressed DYRK1A facilitates amyloidogenic amyloid precursor protein cleavage elevating Aβ40 and 42 levels, and leading to brain β-amyloidosis. Therefore, inhibiting DYRK1A activity in DS may serve to counteract the phenotypic effects of its overexpression and is a potential method of treatment of developmental defects and the prevention of age-associated neurodegeneration, including Alzheimer-type pathology. | D024801 | Tauopathies |
| DYRK1A | 21157379 | Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome. | Triplication of chromosome 21 in Down syndrome (DS) results in overexpression of the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A gene (DYRK1A). DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs). We have previously shown significantly more DYRK1A-positive NFTs in DS brains than in sporadic Alzheimer disease (AD) brains. This study demonstrates a gene dosage-proportional increase in the level of DYRK1A in DS in the cytoplasm and the cell nucleus, and enhanced cytoplasmic and nuclear immunoreactivity of DYRK1A in DS. The results suggest that overexpressed DYRK1A may alter both phosphorylation of tau and alternative splicing factor (ASF). Two-dimensional electrophoresis revealed modification of ASF phosphorylation in DS/AD and AD in comparison to controls. Altered phosphorylation of ASF by overexpressed nuclear DYRK1A may contribute to the alternative splicing of the tau gene and an increase by 2.68 × of the 3R/4R ratio in DS/AD, and a several-fold increase in the number of 3R tau-positive NFTs in DS/AD subjects compared with that in sporadic AD subjects. These data support the hypothesis that phosphorylation of ASF by overexpressed DYRK1A may contribute to alternative splicing of exon 10, increased expression of 3R tau, and early onset of neurofibrillary degeneration in DS. | D004314 | Down Syndrome |
| DYRK1A | 21157379 | Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome. | Triplication of chromosome 21 in Down syndrome (DS) results in overexpression of the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A gene (DYRK1A). DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs). We have previously shown significantly more DYRK1A-positive NFTs in DS brains than in sporadic Alzheimer disease (AD) brains. This study demonstrates a gene dosage-proportional increase in the level of DYRK1A in DS in the cytoplasm and the cell nucleus, and enhanced cytoplasmic and nuclear immunoreactivity of DYRK1A in DS. The results suggest that overexpressed DYRK1A may alter both phosphorylation of tau and alternative splicing factor (ASF). Two-dimensional electrophoresis revealed modification of ASF phosphorylation in DS/AD and AD in comparison to controls. Altered phosphorylation of ASF by overexpressed nuclear DYRK1A may contribute to the alternative splicing of the tau gene and an increase by 2.68 × of the 3R/4R ratio in DS/AD, and a several-fold increase in the number of 3R tau-positive NFTs in DS/AD subjects compared with that in sporadic AD subjects. These data support the hypothesis that phosphorylation of ASF by overexpressed DYRK1A may contribute to alternative splicing of exon 10, increased expression of 3R tau, and early onset of neurofibrillary degeneration in DS. | D009410 | Nerve Degeneration |
| DYRK1A | 22767602 | Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion. | Tau exon 10, which encodes the second microtubule-binding repeat, is regulated by alternative splicing. Its alternative splicing generates Tau isoforms with three- or four-microtubule-binding repeats, named 3R-tau and 4R-tau. Adult human brain expresses equal levels of 3R-tau and 4R-tau. Imbalance of 3R-tau and 4R-tau causes Tau aggregation and neurofibrillary degeneration. In the present study, we found that splicing factor SRp55 (serine/arginine-rich protein 55) promoted Tau exon 10 inclusion. Knockdown of SRp55 significantly promoted Tau exon 10 exclusion. The promotion of Tau exon 10 inclusion by SRp55 required the arginine/serine-rich region, which was responsible for the subnucleic speckle localization. Dyrk1A (dual specificity tyrosine-phosphorylated and regulated kinase 1A) interacted with SRp55 and mainly phosphorylated its proline-rich domain. Phosphorylation of SRp55 by Dyrk1A suppressed its ability to promote Tau exon 10 inclusion. Up-regulation of Dyrk1A as in Down syndrome could lead to neurofibrillary degeneration by shifting the alternative splicing of Tau exon 10 to an increase in the ratio of 3R-tau/4R-tau. | D004314 | Down Syndrome |
Clinically important variants in DYRK1A |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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