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Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 1A

Gene

Dyrk1a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates such as CRY2, FOXO1, SRSF6 and SIRT1. Modulates alternative splicing by phosphorylating the splice factor SRSF6. Exhibits a sugstrate preference for proline at position P+1 and arginine at position P-3.By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Enzyme regulationi

Inhibited by RANBP9 (By similarity). Inhibited by harmine, leucettamine B and leucettine L41.By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei188 – 1881ATPCurated
Active sitei287 – 2871Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi165 – 1739ATPPROSITE-ProRule annotation
Nucleotide bindingi238 – 2414ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1. 5301.
ReactomeiR-RNO-1538133. G0 and Early G1.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 1A (EC:2.7.12.2)
Alternative name(s):
Dual specificity YAK1-related kinase
Protein kinase minibrain homolog
Short name:
MNBH
RP86
Gene namesi
Name:Dyrk1a
Synonyms:Dyrk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi2528. Dyrk1a.

Subcellular locationi

GO - Cellular componenti

  • intracellular ribonucleoprotein complex Source: Ensembl
  • nuclear speck Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi188 – 1881K → R: Abolishes autophosphorylation. Retains marginal kinase activity towards histones. 2 Publications
Mutagenesisi219 – 2191Y → F: Reduced autophosphorylation on tyrosine, but retains some kinase activity towards histones. 1 Publication
Mutagenesisi319 – 3191Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-321. 1 Publication
Mutagenesisi321 – 3211Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-319. 1 Publication

Chemistry

ChEMBLiCHEMBL5508.
GuidetoPHARMACOLOGYi2009.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 763763Dual specificity tyrosine-phosphorylation-regulated kinase 1APRO_0000085933Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141PhosphoserineBy similarity
Modified residuei111 – 1111Phosphotyrosine; by autocatalysisBy similarity
Modified residuei140 – 1401Phosphotyrosine; by autocatalysisBy similarity
Modified residuei145 – 1451PhosphotyrosineBy similarity
Modified residuei159 – 1591Phosphotyrosine; by autocatalysisBy similarity
Modified residuei177 – 1771Phosphotyrosine; by autocatalysisBy similarity
Modified residuei219 – 2191Phosphotyrosine; by autocatalysis1 Publication
Modified residuei310 – 3101Phosphoserine; by autocatalysisBy similarity
Modified residuei319 – 3191Phosphotyrosine; by autocatalysis1 Publication
Modified residuei321 – 3211Phosphotyrosine; by autocatalysis1 Publication
Modified residuei402 – 4021Phosphothreonine; by autocatalysisBy similarity
Modified residuei449 – 4491Phosphotyrosine; by autocatalysisBy similarity
Modified residuei529 – 5291PhosphoserineBy similarity
Modified residuei538 – 5381PhosphoserineBy similarity
Modified residuei748 – 7481PhosphoserineBy similarity
Modified residuei758 – 7581PhosphoserineBy similarity

Post-translational modificationi

Can also autophosphorylate on serine and threonine residues (in vitro) (By similarity). Autophosphorylated on numerous tyrosine residues.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63470.

PTM databases

iPTMnetiQ63470.
PhosphoSiteiQ63470.

Expressioni

Tissue specificityi

Detected in brain (at protein level). Ubiquitous.4 Publications

Gene expression databases

GenevisibleiQ63470. RN.

Interactioni

Subunit structurei

Interacts with RANBP9. Interacts with RAD54L2/ARIP4. Interacts with CRY2 (By similarity). Interacts with WDR68 (By similarity). Interacts with SRSF6.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247295. 2 interactions.
IntActiQ63470. 3 interactions.
MINTiMINT-2790195.
STRINGi10116.ENSRNOP00000042446.

Chemistry

BindingDBiQ63470.

Structurei

3D structure databases

ProteinModelPortaliQ63470.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini159 – 479321Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi117 – 13418Bipartite nuclear localization signalSequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi509 – 5157Poly-Ser
Compositional biasi599 – 6024Poly-His
Compositional biasi607 – 61913Poly-HisAdd
BLAST
Compositional biasi656 – 67217Ser/Thr-richAdd
BLAST
Compositional biasi664 – 6718Poly-Ser

Domaini

The polyhistidine repeats act as targeting signals to nuclear speckles.By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000220863.
HOVERGENiHBG051425.
InParanoidiQ63470.
KOiK08825.
OMAiRQGIDRE.
OrthoDBiEOG77127N.
PhylomeDBiQ63470.
TreeFamiTF314624.

Family and domain databases

InterProiIPR028318. DYRK1A.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24058:SF28. PTHR24058:SF28. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q63470-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:763
Mass (Da):85,541
Last modified:January 1, 1998 - v2
Checksum:iCB5EC7EC4C1F9A47
GO
Isoform Short (identifier: Q63470-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-78: Missing.

Show »
Length:754
Mass (Da):84,513
Checksum:i0369D12D7BB33668
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei70 – 789Missing in isoform Short. CuratedVSP_004924

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79769 mRNA. Translation: CAA56164.1.
RefSeqiNP_036923.1. NM_012791.2. [Q63470-1]
XP_006248093.1. XM_006248031.2. [Q63470-1]
XP_008766784.1. XM_008768562.1. [Q63470-1]
XP_008766785.1. XM_008768563.1. [Q63470-1]
XP_008766786.1. XM_008768564.1. [Q63470-1]
XP_008766787.1. XM_008768565.1. [Q63470-2]
UniGeneiRn.9354.

Genome annotation databases

EnsembliENSRNOT00000050342; ENSRNOP00000042446; ENSRNOG00000001662. [Q63470-1]
GeneIDi25255.
KEGGirno:25255.
UCSCiRGD:2528. rat. [Q63470-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79769 mRNA. Translation: CAA56164.1.
RefSeqiNP_036923.1. NM_012791.2. [Q63470-1]
XP_006248093.1. XM_006248031.2. [Q63470-1]
XP_008766784.1. XM_008768562.1. [Q63470-1]
XP_008766785.1. XM_008768563.1. [Q63470-1]
XP_008766786.1. XM_008768564.1. [Q63470-1]
XP_008766787.1. XM_008768565.1. [Q63470-2]
UniGeneiRn.9354.

3D structure databases

ProteinModelPortaliQ63470.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247295. 2 interactions.
IntActiQ63470. 3 interactions.
MINTiMINT-2790195.
STRINGi10116.ENSRNOP00000042446.

Chemistry

BindingDBiQ63470.
ChEMBLiCHEMBL5508.
GuidetoPHARMACOLOGYi2009.

PTM databases

iPTMnetiQ63470.
PhosphoSiteiQ63470.

Proteomic databases

PaxDbiQ63470.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000050342; ENSRNOP00000042446; ENSRNOG00000001662. [Q63470-1]
GeneIDi25255.
KEGGirno:25255.
UCSCiRGD:2528. rat. [Q63470-1]

Organism-specific databases

CTDi1859.
RGDi2528. Dyrk1a.

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000220863.
HOVERGENiHBG051425.
InParanoidiQ63470.
KOiK08825.
OMAiRQGIDRE.
OrthoDBiEOG77127N.
PhylomeDBiQ63470.
TreeFamiTF314624.

Enzyme and pathway databases

BRENDAi2.7.12.1. 5301.
ReactomeiR-RNO-1538133. G0 and Early G1.

Miscellaneous databases

PROiQ63470.

Gene expression databases

GenevisibleiQ63470. RN.

Family and domain databases

InterProiIPR028318. DYRK1A.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24058:SF28. PTHR24058:SF28. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII."
    Kentrup H., Becker W., Heukelbach J., Wilmes A., Schuermann A., Huppertz C., Kainulainen H., Joost H.-G.
    J. Biol. Chem. 271:3488-3495(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-219; TYR-319 AND TYR-321, MUTAGENESIS OF LYS-188; TYR-219; TYR-319 AND TYR-321.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. Kentrup H.
    Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  3. "Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases."
    Becker W., Weber Y., Wetzel K., Eirmbter K., Tejedor F.J., Joost H.-G.
    J. Biol. Chem. 273:25893-25902(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  4. "Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) modulates serine/arginine-rich protein 55 (SRp55)-promoted Tau exon 10 inclusion."
    Yin X., Jin N., Gu J., Shi J., Zhou J., Gong C.X., Iqbal K., Grundke-Iqbal I., Liu F.
    J. Biol. Chem. 287:30497-30506(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SRSF6, FUNCTION, MUTAGENESIS OF LYS-188, TISSUE SPECIFICITY.
  5. "Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B."
    Tahtouh T., Elkins J.M., Filippakopoulos P., Soundararajan M., Burgy G., Durieu E., Cochet C., Schmid R.S., Lo D.C., Delhommel F., Oberholzer A.E., Pearl L.H., Carreaux F., Bazureau J.P., Knapp S., Meijer L.
    J. Med. Chem. 55:9312-9330(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiDYR1A_RAT
AccessioniPrimary (citable) accession number: Q63470
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: July 6, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.