Q5U4C9 (DYRK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 2
EC=2.7.12.1

Gene names

Name:

Dyrk2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	599 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in the control of mitotic transition and the regulation of cellular growth and/or development. Phosphorylates CRMP4/DPYSL3, EIF2B5, GYS1, p53/TP53, TAU/MAPT, STAT3 and KATNA1. Regulates p53/TP53 by phosphorylation on 'Ser-46' to induce apoptosis in response to DNA damage, functioning downstream of ATM. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3, and may play a more general role in the priming of GSK3 substrates. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of its downstream substrate, KATNA1. Phosphorylation of CRMP4/DPYSL3 promotes its subsequent phosphorylation by GSK3 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q92630
Cofactor	Magnesium By similarity. UniProtKB Q92630 Manganese By similarity. UniProtKB Q92630
Enzyme regulation	Autophosphorylates on tyrosine residues By similarity. UniProtKB Q92630
Subunit structure	Interacts with MDM2. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP proteins (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and VPRBP By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Translocates into the nucleus following DNA damage By similarity. UniProtKB Q92630
Post-translational modification	Phosphorylated on serine/threonine residues By similarity. Phosphorylation on Thr-104 and Ser-440 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasome degradation, thus promoting p53/TP53-mediated apoptosis By similarity. UniProtKB Q9Y463 Ubiquitination in nucleus by MDM2 in normal conditions leads to proteasome degradation 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
Biological process	Apoptosis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Magnesium Manganese Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of glycogen biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB manganese ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine/tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 599	599	Dual specificity tyrosine-phosphorylation-regulated kinase 2		PRO_0000291265
Regions
	Domain	220 – 533	314	Protein kinase
	Nucleotide binding	226 – 234	9	ATP By similarity UniProtKB P28523
	Motif	187 – 189	3	Nuclear localization signal By similarity
Sites
	Active site	346	1	Proton acceptor By similarity UniProtKB P28523
	Binding site	249	1	ATP By similarity UniProtKB P28523
Amino acid modifications
	Modified residue	104	1	Phosphothreonine; by ATM By similarity
	Modified residue	380	1	Phosphotyrosine By similarity
	Modified residue	440	1	Phosphoserine; by ATM By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q5U4C9 [UniParc]. Last modified December 7, 2004. Version 1. Checksum: 2378D39A5E1E8056	FASTA	599	66,556
	10 20 30 40 50 60 MLTRKPSAAA PAAYPTGRGG DTAVRQLQAS PGIGAGAPRS GVGTGPPSPI ALPPLRASNA 70 80 90 100 110 120 TTTAHTIGGS KHTMNDHLHL NSHGQIQVQQ LFEDNSNKRT VLTTQPNGLT TVGKTGLPGV 130 140 150 160 170 180 PERQLESIHR RQGSSTSLKS MEGMGKVKAS PMTPEQAMKQ YMQKLTAFEH HEIFSYPEIY 190 200 210 220 230 240 FLGPNAKKRQ GMTGGPNNGG YDDDQGSYVQ VPHDHVAYRY EVLKVIGKGS FGQVVKAYDH 250 260 270 280 290 300 KVHQHVALKM VRNEKRFHRQ AAEEIRILEH LRKQDKDNTM NVIHMLENFT FRNHICMTFE 310 320 330 340 350 360 LLSMNLYELI KKNKFQGFSL PLVRKFAHSI LQCLDALHKN RIIHCDLKPE NILLKQQGRS 370 380 390 400 410 420 SIKVIDFGSS CYEHQRVYTY IQSRFYRAPE VILGARYGMP IDMWSLGCIL AELLTGYPLL 430 440 450 460 470 480 PGEDEGDQLA CMIELLGMPS QKLLDASKRA KNFVSSKGYP RYCTVTTLSD GSVVLNGGRS 490 500 510 520 530 540 RRGKLRGPPE SREWGNALKG CDDPLFLDFL KQCLEWDPAV RMTPGQALRH PWLRRRLPKP 550 560 570 580 590 PTGEKTAVKR VTESTGAITS ISKLPPPSSS ASKLRTNLAQ MTDANGNIQQ RTVLPKLVS

References

[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC085145 mRNA. Translation: AAH85145.1.
IPI	IPI00468101.
RefSeq	NP_001014412.1. NM_001014390.2.
UniGene	Mm.45565. Mm.458174.
3D structure databases
HSSP	HSSP built from PDB template 1BI8 based on UniProtKB Q00534.
ProteinModelPortal	Q5U4C9.
SMR	Q5U4C9. Positions 144-541.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5U4C9.
PTM databases
PhosphoSite	Q5U4C9.
Proteomic databases
PRIDE	Q5U4C9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000004281; ENSMUSP00000004281; ENSMUSG00000028630.
GeneID	69181.
KEGG	mmu:69181.
UCSC	uc007hea.1. mouse.
Organism-specific databases
CTD	8445.
MGI	MGI:1330301. Dyrk2.
Phylogenomic databases
eggNOG	roNOG07594.
GeneTree	ENSGT00570000079111.
HOGENOM	HBG755340.
HOVERGEN	HBG051426.
InParanoid	Q5U4C9.
OMA	QVPHDHV.
OrthoDB	EOG4QRH3Z.
PhylomeDB	Q5U4C9.
Gene expression databases
ArrayExpress	Q5U4C9.
Bgee	Q5U4C9.
Genevestigator	Q5U4C9.
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	328782.
SOURCE	Search...

Entry information

Entry name

DYRK2_MOUSE

Accession

Primary (citable) accession number: Q5U4C9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 12, 2007
Last sequence update:	December 7, 2004
Last modified:	November 16, 2011
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program