UniProtKB - Q63470 (DYR1A_RAT)
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Dyrk1a
Functioni
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:18938227).
Plays an important role in double-strand breaks (DSBs) repair following DNA damage. Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (By similarity).
May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity).
Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Has pro-survival function and negatively regulates the apoptotic process. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (By similarity).
Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (PubMed:18938227).
By similarity4 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 188 | ATPCurated | 1 | |
Active sitei | 287 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 165 – 173 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 238 – 241 | ATPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- identical protein binding Source: RGD
- non-membrane spanning protein tyrosine kinase activity Source: RGD
- protein kinase activity Source: RGD
- protein self-association Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB
- tau protein binding Source: RGD
- transcription coactivator activity Source: GO_Central
GO - Biological processi
- amyloid-beta formation Source: RGD
- circadian rhythm Source: UniProtKB
- negative regulation of DNA damage response, signal transduction by p53 class mediator Source: RGD
- negative regulation of microtubule polymerization Source: RGD
- negative regulation of mRNA splicing, via spliceosome Source: RGD
- peptidyl-serine phosphorylation Source: UniProtKB
- peptidyl-threonine phosphorylation Source: ARUK-UCL
- peptidyl-tyrosine autophosphorylation Source: RGD
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of protein deacetylation Source: RGD
- positive regulation of RNA splicing Source: ARUK-UCL
- positive regulation of transcription, DNA-templated Source: GO_Central
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of alternative mRNA splicing, via spliceosome Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 5301 |
Reactomei | R-RNO-1538133, G0 and Early G1 |
Names & Taxonomyi
Protein namesi | Recommended name: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (EC:2.7.12.11 Publication)Alternative name(s): Dual specificity YAK1-related kinase Protein kinase minibrain homolog Short name: MNBH RP86 |
Gene namesi | Name:Dyrk1a Synonyms:Dyrk |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 2528, Dyrk1a |
Subcellular locationi
Nucleus
- Nucleus speckle 2 Publications
Cytoskeleton
- cytoskeleton Source: RGD
Nucleus
- nuclear speck Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- axon Source: RGD
- cytoplasm Source: UniProtKB
- dendrite Source: RGD
- ribonucleoprotein complex Source: RGD
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 188 | K → R: Abolishes autophosphorylation. Retains marginal kinase activity towards histones. 2 Publications | 1 | |
Mutagenesisi | 219 | Y → F: Reduced autophosphorylation on tyrosine, but retains some kinase activity towards histones. 1 Publication | 1 | |
Mutagenesisi | 319 | Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-321. 1 Publication | 1 | |
Mutagenesisi | 321 | Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-319. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5508 |
DrugCentrali | Q63470 |
GuidetoPHARMACOLOGYi | 2009 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085933 | 1 – 763 | Dual specificity tyrosine-phosphorylation-regulated kinase 1AAdd BLAST | 763 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 14 | PhosphoserineBy similarity | 1 | |
Modified residuei | 111 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 140 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 145 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 159 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 177 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 219 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 310 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 319 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 321 | Phosphotyrosine; by autocatalysis1 Publication | 1 | |
Modified residuei | 402 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 449 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 529 | PhosphoserineBy similarity | 1 | |
Modified residuei | 538 | PhosphoserineBy similarity | 1 | |
Modified residuei | 748 | PhosphoserineBy similarity | 1 | |
Modified residuei | 758 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q63470 |
PRIDEi | Q63470 |
PTM databases
iPTMneti | Q63470 |
PhosphoSitePlusi | Q63470 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSRNOG00000001662, Expressed in skeletal muscle tissue and 21 other tissues |
Genevisiblei | Q63470, RN |
Interactioni
Subunit structurei
GO - Molecular functioni
- identical protein binding Source: RGD
- protein self-association Source: UniProtKB
- tau protein binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 247295, 6 interactors |
ELMi | Q63470 |
IntActi | Q63470, 5 interactors |
MINTi | Q63470 |
STRINGi | 10116.ENSRNOP00000042446 |
Chemistry databases
BindingDBi | Q63470 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 159 – 479 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 321 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 33 – 56 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 115 – 136 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 408 – 442 | DisorderedSequence analysisAdd BLAST | 35 | |
Regioni | 485 – 540 | DisorderedSequence analysisAdd BLAST | 56 | |
Regioni | 596 – 679 | DisorderedSequence analysisAdd BLAST | 84 | |
Regioni | 744 – 763 | DisorderedSequence analysisAdd BLAST | 20 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 117 – 134 | Bipartite nuclear localization signalSequence analysisAdd BLAST | 18 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 34 – 56 | Polar residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 485 – 528 | Polar residuesSequence analysisAdd BLAST | 44 | |
Compositional biasi | 601 – 624 | Basic residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 627 – 679 | Polar residuesSequence analysisAdd BLAST | 53 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0667, Eukaryota |
GeneTreei | ENSGT00940000157408 |
HOGENOMi | CLU_000288_5_6_1 |
InParanoidi | Q63470 |
OMAi | PPIGWTA |
OrthoDBi | 689446at2759 |
PhylomeDBi | Q63470 |
TreeFami | TF314624 |
Family and domain databases
CDDi | cd14226, PKc_DYRK1, 1 hit |
InterProi | View protein in InterPro IPR028318, DYRK1A/B_MNB IPR011009, Kinase-like_dom_sf IPR044131, PKc_DYR1A/1B IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR24058:SF121, PTHR24058:SF121, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AAQMPHSHQY SDRRQPNISD
60 70 80 90 100
QQVSALSYSD QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL
110 120 130 140 150
IKTYKHINEV YYAKKKRRHQ QGQGDDSSHK KERKVYNDGY DDDNYDYIVK
160 170 180 190 200
NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV EQEWVAIKII KNKKAFLNQA
210 220 230 240 250
QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM LSYNLYDLLR
260 270 280 290 300
NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR
310 320 330 340 350
SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI
360 370 380 390 400
LVEMHTGEPL FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD
410 420 430 440 450
GTWSLKKTKD GKREYKPPGT RKLHNILGVE TGGPGGRRAG ESGHTVADYL
460 470 480 490 500
KFKDLILRML DYDPKTRIQP YYALQHSFFK KTADEGTNTS NSVSTSPAME
510 520 530 540 550
QSQSSGTTSS TSSSSGGSSG TSNSGRARSD PTHQHRHSGG HFAAAVQAMD
560 570 580 590 600
CETHSPQVRQ QFPAPLGWSG TEAPTQVTVE THPVQETTFH VAPQQNALHH
610 620 630 640 650
HHGNSSHHHH HHHHHHHHHG QQALGNRTRP RVYNSPTNSS STQDSMEVGH
660 670 680 690 700
SHHSMTSLSS STTSSSTSSS STGNQGNQAY QNRPVAANTL DFGQNGAMDV
710 720 730 740 750
NLTVYSNPRQ ETGIAGHPTY QFSANTGPAH YMTEGHLTMR QGADREESPM
760
TGVCVQQSPV ASS
The sequence of this isoform differs from the canonical sequence as follows:
70-78: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004924 | 70 – 78 | Missing in isoform Short. Curated | 9 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X79769 mRNA Translation: CAA56164.1 |
RefSeqi | NP_036923.1, NM_012791.3 [Q63470-1] XP_006248093.1, XM_006248031.3 [Q63470-1] XP_008766785.1, XM_008768563.2 [Q63470-1] XP_008766786.1, XM_008768564.1 [Q63470-1] XP_008766787.1, XM_008768565.2 [Q63470-2] |
Genome annotation databases
Ensembli | ENSRNOT00000050342; ENSRNOP00000042446; ENSRNOG00000001662 [Q63470-1] |
GeneIDi | 25255 |
KEGGi | rno:25255 |
UCSCi | RGD:2528, rat [Q63470-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X79769 mRNA Translation: CAA56164.1 |
RefSeqi | NP_036923.1, NM_012791.3 [Q63470-1] XP_006248093.1, XM_006248031.3 [Q63470-1] XP_008766785.1, XM_008768563.2 [Q63470-1] XP_008766786.1, XM_008768564.1 [Q63470-1] XP_008766787.1, XM_008768565.2 [Q63470-2] |
3D structure databases
SMRi | Q63470 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 247295, 6 interactors |
ELMi | Q63470 |
IntActi | Q63470, 5 interactors |
MINTi | Q63470 |
STRINGi | 10116.ENSRNOP00000042446 |
Chemistry databases
BindingDBi | Q63470 |
ChEMBLi | CHEMBL5508 |
DrugCentrali | Q63470 |
GuidetoPHARMACOLOGYi | 2009 |
PTM databases
iPTMneti | Q63470 |
PhosphoSitePlusi | Q63470 |
Proteomic databases
PaxDbi | Q63470 |
PRIDEi | Q63470 |
Genome annotation databases
Ensembli | ENSRNOT00000050342; ENSRNOP00000042446; ENSRNOG00000001662 [Q63470-1] |
GeneIDi | 25255 |
KEGGi | rno:25255 |
UCSCi | RGD:2528, rat [Q63470-1] |
Organism-specific databases
CTDi | 1859 |
RGDi | 2528, Dyrk1a |
Phylogenomic databases
eggNOGi | KOG0667, Eukaryota |
GeneTreei | ENSGT00940000157408 |
HOGENOMi | CLU_000288_5_6_1 |
InParanoidi | Q63470 |
OMAi | PPIGWTA |
OrthoDBi | 689446at2759 |
PhylomeDBi | Q63470 |
TreeFami | TF314624 |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 5301 |
Reactomei | R-RNO-1538133, G0 and Early G1 |
Miscellaneous databases
PROi | PR:Q63470 |
Gene expression databases
Bgeei | ENSRNOG00000001662, Expressed in skeletal muscle tissue and 21 other tissues |
Genevisiblei | Q63470, RN |
Family and domain databases
CDDi | cd14226, PKc_DYRK1, 1 hit |
InterProi | View protein in InterPro IPR028318, DYRK1A/B_MNB IPR011009, Kinase-like_dom_sf IPR044131, PKc_DYR1A/1B IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR24058:SF121, PTHR24058:SF121, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DYR1A_RAT | |
Accessioni | Q63470Primary (citable) accession number: Q63470 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | January 1, 1998 | |
Last modified: | February 23, 2022 | |
This is version 179 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families