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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 substrate 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)DescriptionActionsGraphical viewLength
Binding sitei188ATPCurated1
Active sitei287Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi165 – 173ATPPROSITE-ProRule annotation9
Nucleotide bindingi238 – 241ATPPROSITE-ProRule annotation4

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)DescriptionActionsGraphical viewLength
Mutagenesisi188K → R: Abolishes autophosphorylation. Retains marginal kinase activity towards histones. 2 Publications1
Mutagenesisi219Y → F: Reduced autophosphorylation on tyrosine, but retains some kinase activity towards histones. 1 Publication1
Mutagenesisi319Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-321. 1 Publication1
Mutagenesisi321Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-319. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5508.
GuidetoPHARMACOLOGYi2009.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859331 – 763Dual specificity tyrosine-phosphorylation-regulated kinase 1AAdd BLAST763

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineBy similarity1
Modified residuei111Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei140Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei145PhosphotyrosineBy similarity1
Modified residuei159Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei177Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei219Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei310Phosphoserine; by autocatalysisBy similarity1
Modified residuei319Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei321Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei402Phosphothreonine; by autocatalysisBy similarity1
Modified residuei449Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei529PhosphoserineBy similarity1
Modified residuei538PhosphoserineBy similarity1
Modified residuei748PhosphoserineBy similarity1
Modified residuei758PhosphoserineBy similarity1

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.
PRIDEiQ63470.

PTM databases

iPTMnetiQ63470.
PhosphoSitePlusiQ63470.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSRNOG00000001662.
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 interactors.
IntActiQ63470. 3 interactors.
MINTiMINT-2790195.
STRINGi10116.ENSRNOP00000042446.

Chemistry databases

BindingDBiQ63470.

Structurei

3D structure databases

ProteinModelPortaliQ63470.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini159 – 479Protein kinasePROSITE-ProRule annotationAdd BLAST321

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi117 – 134Bipartite nuclear localization signalSequence analysisAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi509 – 515Poly-Ser7
Compositional biasi599 – 602Poly-His4
Compositional biasi607 – 619Poly-HisAdd BLAST13
Compositional biasi656 – 672Ser/Thr-richAdd BLAST17
Compositional biasi664 – 671Poly-Ser8

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.
OrthoDBiEOG091G03J7.
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00492470 – 78Missing in isoform Short. Curated9

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_006248031.3. [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]
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_006248031.3. [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]
UniGeneiRn.9354.

3D structure databases

ProteinModelPortaliQ63470.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiQ63470.
ChEMBLiCHEMBL5508.
GuidetoPHARMACOLOGYi2009.

PTM databases

iPTMnetiQ63470.
PhosphoSitePlusiQ63470.

Proteomic databases

PaxDbiQ63470.
PRIDEiQ63470.

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.
OrthoDBiEOG091G03J7.
PhylomeDBiQ63470.
TreeFamiTF314624.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ63470.

Gene expression databases

BgeeiENSRNOG00000001662.
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...

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: November 2, 2016
This is version 150 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.