Q63470 (DYR1A_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Dyrk1a
Synonyms:	Dyrk

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	763 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Inhibited by RANBP9 By similarity.
Subunit structure	Interacts with RANBP9. Interacts with RAD54L2/ARIP4 By similarity. Interacts with WDR68 By similarity.
Subcellular location	Nucleus speckle Ref.3.
Tissue specificity	Ubiquitous. Ref.1 Ref.3
Post-translational modification	Autophosphorylated on tyrosine residues. Ref.1
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 component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	nervous system development Traceable author statement. Source: RGD peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.1. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.1. Source: UniProtKB regulation of endocytosis Traceable author statement. Source: RGD
Cellular component	nuclear speck Inferred from direct assay Ref.3. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein self-association Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q63470-1)

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.

Isoform Short (identifier: Q63470-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 763	763	Dual specificity tyrosine-phosphorylation-regulated kinase 1A		PRO_0000085933
Regions
	Domain	159 – 479	321	Protein kinase
	Nucleotide binding	165 – 173	9	ATP By similarity
	Motif	117 – 134	18	Bipartite nuclear localization signal Potential
	Compositional bias	509 – 515	7	Poly-Ser
	Compositional bias	599 – 602	4	Poly-His
	Compositional bias	607 – 619	13	Poly-His
	Compositional bias	656 – 672	17	Ser/Thr-rich
	Compositional bias	664 – 671	8	Poly-Ser
Sites
	Active site	287	1	Proton acceptor By similarity
	Binding site	188	1	ATP By similarity
Amino acid modifications
	Modified residue	145	1	Phosphotyrosine By similarity
	Modified residue	219	1	Phosphotyrosine; by autocatalysis Ref.1
	Modified residue	319	1	Phosphotyrosine; by autocatalysis Ref.1
	Modified residue	321	1	Phosphotyrosine; by autocatalysis Ref.1
	Modified residue	324	1	Phosphoserine By similarity
	Modified residue	748	1	Phosphoserine By similarity
	Modified residue	758	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	70 – 78	9	Missing in isoform Short.		VSP_004924
Experimental info
	Mutagenesis	188	1	K → R: Reduced kinase activity but retains some kinase activity towards histones. Ref.1
	Mutagenesis	219	1	Y → F: Reduced autophosphorylation on tyrosine, but retains some kinase activity towards histones. Ref.1
	Mutagenesis	319	1	Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-321. Ref.1
	Mutagenesis	321	1	Y → F: Suppressed autophosphorylation on tyrosine and reduced tyrosine, threonine and serine kinase activity towards histones; when associated with F-319. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified January 1, 1998. Version 2. Checksum: CB5EC7EC4C1F9A47	FASTA	763	85,541
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AAQMPHSHQY SDRRQPNISD QQVSALSYSD 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 YMTEGHLTMR QGADREESPM TGVCVQQSPV ASS
	Isoform Short [UniParc]. Checksum: 0369D12D7BB33668	FASTA	754	84,513
	10 20 30 40 50 60 MHTGGETSAC KPSSVRLAPS FSFHAAGLQM AAQMPHSHQY SDRRQPNISD QQVSALSYSD 70 80 90 100 110 120 QIQQPLTNQR RMPQTFRDPA TAPLRKLSVD LIKTYKHINE VYYAKKKRRH QQGQGDDSSH 130 140 150 160 170 180 KKERKVYNDG YDDDNYDYIV KNGEKWMDRY EIDSLIGKGS FGQVVKAYDR VEQEWVAIKI 190 200 210 220 230 240 IKNKKAFLNQ AQIEVRLLEL MNKHDTEMKY YIVHLKRHFM FRNHLCLVFE MLSYNLYDLL 250 260 270 280 290 300 RNTNFRGVSL NLTRKFAQQM CTALLFLATP ELSIIHCDLK PENILLCNPK RSAIKIVDFG 310 320 330 340 350 360 SSCQLGQRIY QYIQSRFYRS PEVLLGMPYD LAIDMWSLGC ILVEMHTGEP LFSGANEVDQ 370 380 390 400 410 420 MNKIVEVLGI PPAHILDQAP KARKFFEKLP DGTWSLKKTK DGKREYKPPG TRKLHNILGV 430 440 450 460 470 480 ETGGPGGRRA GESGHTVADY LKFKDLILRM LDYDPKTRIQ PYYALQHSFF KKTADEGTNT 490 500 510 520 530 540 SNSVSTSPAM EQSQSSGTTS STSSSSGGSS GTSNSGRARS DPTHQHRHSG GHFAAAVQAM 550 560 570 580 590 600 DCETHSPQVR QQFPAPLGWS GTEAPTQVTV ETHPVQETTF HVAPQQNALH HHHGNSSHHH 610 620 630 640 650 660 HHHHHHHHHH GQQALGNRTR PRVYNSPTNS SSTQDSMEVG HSHHSMTSLS SSTTSSSTSS 670 680 690 700 710 720 SSTGNQGNQA YQNRPVAANT LDFGQNGAMD VNLTVYSNPR QETGIAGHPT YQFSANTGPA 730 740 750 HYMTEGHLTM RQGADREESP MTGVCVQQSP VASS

References

[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: 8631952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION 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: 9748265] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X79769 mRNA. Translation: CAA56164.1.
IPI	IPI00209116. IPI00231347.
RefSeq	NP_036923.1. NM_012791.1.
UniGene	Rn.9354.
3D structure databases
ProteinModelPortal	Q63470.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2790195.
STRING	Q63470.
PTM databases
PhosphoSite	Q63470.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000050342; ENSRNOP00000042446; ENSRNOG00000001662.
GeneID	25255.
KEGG	rno:25255.
UCSC	NM_012791. rat.
Organism-specific databases
CTD	1859.
RGD	2528. Dyrk1a.
Phylogenomic databases
eggNOG	roNOG07169.
GeneTree	ENSGT00550000074148.
HOVERGEN	HBG051425.
InParanoid	Q63470.
OrthoDB	EOG4MW85K.
Enzyme and pathway databases
BRENDA	2.7.12.1. 5301.
Gene expression databases
ArrayExpress	Q63470.
Genevestigator	Q63470.
GermOnline	ENSRNOG00000001662. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08825.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	605887.

Entry information

Entry name

DYR1A_RAT

Accession

Primary (citable) accession number: Q63470

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	November 16, 2011
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program