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Q61214 (DYR1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 1A

EC=2.7.12.1
Alternative name(s):
Dual specificity YAK1-related kinase
MP86
Protein kinase minibrain homolog
Short name=MNBH
Gene names
Name:Dyrk1a
Synonyms:Dyrk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length763 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates such as CRY2, FOXO1, SRSF6 and SIRT1. Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Inhibited by RANBP9 By similarity.

Subunit structure

Interacts with RANBP9 By similarity. Interacts with RAD54L2/ARIP4. Interacts with WDR68 By similarity. Interacts with CRY2. Ref.2 Ref.3 Ref.5

Subcellular location

Nucleus speckle Ref.2.

Tissue specificity

Detected in brain (at protein level). Expressed in a variety of embryonic and adult tissues. Expressed abundantly in neurons of the brain, spinal cord, and retina in developing embryos. Ref.1 Ref.6

Domain

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

Post-translational modification

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

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentNucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian rhythm

Inferred from mutant phenotype Ref.5. Source: UniProtKB

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from direct assay PubMed 20736167. Source: BHF-UCL

peptidyl-serine phosphorylation

Inferred from direct assay Ref.5. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 20736167. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein deacetylation

Inferred from direct assay PubMed 20736167. Source: BHF-UCL

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentnuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.2. Source: UniProtKB

ribonucleoprotein complex

Inferred from direct assay PubMed 21709260. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 21965663Ref.2. Source: IntAct

non-membrane spanning protein tyrosine kinase activity

Inferred from sequence orthology PubMed 9748265. Source: MGI

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

protein self-association

Inferred from physical interaction Ref.2. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.5. Source: UniProtKB

protein serine/threonine/tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

tau protein binding

Inferred from physical interaction PubMed 20736167. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-80344,EBI-80344
RCAN1P53805-25EBI-80344,EBI-1541912From a different organism.
Rcan1Q9JHG62EBI-80344,EBI-644061
Sirt1Q923E44EBI-80344,EBI-1802585

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 763763Dual specificity tyrosine-phosphorylation-regulated kinase 1A
PRO_0000085932

Regions

Domain159 – 479321Protein kinase
Nucleotide binding165 – 1739ATP By similarity
Nucleotide binding238 – 2414ATP By similarity
Motif117 – 13418Bipartite nuclear localization signal Potential
Compositional bias509 – 5157Poly-Ser
Compositional bias599 – 6024Poly-His
Compositional bias607 – 61913Poly-His
Compositional bias656 – 67217Ser/Thr-rich
Compositional bias664 – 6718Poly-Ser

Sites

Active site2871Proton acceptor By similarity
Binding site1881ATP By similarity

Amino acid modifications

Modified residue1111Phosphotyrosine; by autocatalysis By similarity
Modified residue1401Phosphotyrosine; by autocatalysis By similarity
Modified residue1451Phosphotyrosine Ref.4
Modified residue1591Phosphotyrosine; by autocatalysis By similarity
Modified residue1771Phosphotyrosine; by autocatalysis By similarity
Modified residue2191Phosphotyrosine; by autocatalysis By similarity
Modified residue3101Phosphoserine; by autocatalysis By similarity
Modified residue3191Phosphotyrosine; by autocatalysis By similarity
Modified residue3211Phosphotyrosine; by autocatalysis
Modified residue4021Phosphothreonine; by autocatalysis By similarity
Modified residue4491Phosphotyrosine; by autocatalysis By similarity
Modified residue7481Phosphoserine By similarity
Modified residue7581Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q61214 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: E117DDD6C5E8C74F

FASTA76385,494
        10         20         30         40         50         60 
MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AAQMPHSHQY SDRRQPSISD QQVSALPYSD 

        70         80         90        100        110        120 
QIQQPLTNQV MPDIVMLQRR MPQTFRDPAT APLRKLSVDL IKTYKHINEV YYAKKKRRHQ 

       130        140        150        160        170        180 
QGQGDDSSHK KERKVYNDGY DDDNYDYIVK NGEKWMDRYE IDSLIGKGSF GQVVKAYDRV 

       190        200        210        220        230        240 
EQEWVAIKII KNKKAFLNQA QIEVRLLELM NKHDTEMKYY IVHLKRHFMF RNHLCLVFEM 

       250        260        270        280        290        300 
LSYNLYDLLR NTNFRGVSLN LTRKFAQQMC TALLFLATPE LSIIHCDLKP ENILLCNPKR 

       310        320        330        340        350        360 
SAIKIVDFGS SCQLGQRIYQ YIQSRFYRSP EVLLGMPYDL AIDMWSLGCI LVEMHTGEPL 

       370        380        390        400        410        420 
FSGANEVDQM NKIVEVLGIP PAHILDQAPK ARKFFEKLPD GTWSLKKTKD GKREYKPPGT 

       430        440        450        460        470        480 
RKLHNILGVE TGGPGGRRAG ESGHTVADYL KFKDLILRML DYDPKTRIQP YYALQHSFFK 

       490        500        510        520        530        540 
KTADEGTNTS NSVSTSPAME QSQSSGTTSS TSSSSGGSSG TSNSGRARSD PTHQHRHSGG 

       550        560        570        580        590        600 
HFAAAVQAMD CETHSPQVRQ QFPAPLGWSG TEAPTQVTVE THPVQETTFH VAPQQNALHH 

       610        620        630        640        650        660 
HHGNSSHHHH HHHHHHHHHG QQALGNRTRP RVYNSPTNSS STQDSMEVGH SHHSMTSLSS 

       670        680        690        700        710        720 
STTSSSTSSS STGNQGNQAY QNRPVAANTL DFGQNGAMDV NLTVYSNPRQ ETGIAGHPTY 

       730        740        750        760 
QFSANTGPAH YMTEGHLAMR QGADREESPM TGVCVQQSPV ASS 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome 'critical region'."
Song W.J., Sternberg L.R., Kasten-Sportes C., van Keuren M.L., Chung S.H., Slack A.C., Miller D.E., Glover T.W., Chiang P.W., Lou L., Kurnit D.W.
Genomics 38:331-339(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: Swiss Webster / NIH.
Tissue: Embryo.
[2]"The murine Dyrk protein maps to chromosome 16, localizes to the nucleus, and can form multimers."
Song W.J., Chung S.H., Kurnit D.M.
Biochem. Biophys. Res. Commun. 231:640-644(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUBUNIT.
[3]"Dyrk1A potentiates steroid hormone-induced transcription via the chromatin remodeling factor Arip4."
Sitz J.H., Tigges M., Baumgaertel K., Khaspekov L.G., Lutz B.
Mol. Cell. Biol. 24:5821-5834(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD54L2.
[4]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-145, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[5]"DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping."
Kurabayashi N., Hirota T., Sakai M., Sanada K., Fukada Y.
Mol. Cell. Biol. 30:1757-1768(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CRY2.
[6]"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: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58497 mRNA. Translation: AAC52994.1.
CCDSCCDS28350.1.
RefSeqNP_001106860.1. NM_001113389.1.
NP_031916.1. NM_007890.2.
UniGeneMm.310973.

3D structure databases

ProteinModelPortalQ61214.
SMRQ61214. Positions 148-481.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199347. 2 interactions.
IntActQ61214. 4 interactions.
MINTMINT-1205474.

Chemistry

BindingDBQ61214.
ChEMBLCHEMBL4750.

PTM databases

PhosphoSiteQ61214.

Proteomic databases

MaxQBQ61214.
PaxDbQ61214.
PRIDEQ61214.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023614; ENSMUSP00000023614; ENSMUSG00000022897.
ENSMUST00000119878; ENSMUSP00000113660; ENSMUSG00000022897.
GeneID13548.
KEGGmmu:13548.
UCSCuc008abg.2. mouse.

Organism-specific databases

CTD1859.
MGIMGI:1330299. Dyrk1a.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117228.
HOGENOMHOG000220863.
HOVERGENHBG051425.
InParanoidQ61214.
KOK08825.
OMALTNQRRM.
OrthoDBEOG77127N.
PhylomeDBQ61214.
TreeFamTF314624.

Enzyme and pathway databases

BRENDA2.7.12.1. 3474.

Gene expression databases

ArrayExpressQ61214.
BgeeQ61214.
GenevestigatorQ61214.

Family and domain databases

InterProIPR028318. DYRK1A.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24058:SF28. PTHR24058:SF28. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio284158.
PROQ61214.
SOURCESearch...

Entry information

Entry nameDYR1A_MOUSE
AccessionPrimary (citable) accession number: Q61214
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot