Reviewed, UniProtKB/Swiss-Prot Q92630 (DYRK2_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

DYRK2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	601 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Role in the regulation of cellular growth and/or development. Regulates 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. Ref.1 Ref.6 Ref.7 Ref.9
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.1 Manganese. Ref.1
Enzyme regulation	Autophosphorylates on tyrosine residues.
Subcellular location	Cytoplasm. Nucleus. Note: Translocates into the nucleus following DNA damage. Ref.9
Tissue specificity	Testis, after the onset of spermatogenesis. Ref.1
Post-translational modification	Phosphorylated on serine/threonine residues 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
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Manganese Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Ref.9 Inferred from direct assay. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of glycogen biosynthetic process Ref.6 Inferred from direct assay. Source: UniProtKB protein amino acid phosphorylation Ref.1 Ref.6 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Ref.9 Inferred from direct assay. Source: UniProtKB nucleus Ref.9 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.6 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.1 Inferred from direct assay. Source: UniProtKB manganese ion binding Ref.1 Inferred from direct assay. Source: UniProtKB protein serine/threonine kinase activity Ref.6 Inferred from direct assay. Source: UniProtKB protein tyrosine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q92630-1)

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 2 (identifier: Q92630-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 601	601	Dual specificity tyrosine-phosphorylation-regulated kinase 2		PRO_0000085936
Regions
	Domain	222 – 535	314	Protein kinase
	Nucleotide binding	228 – 236	9	ATP By similarity
Sites
	Active site	348	1	Proton acceptor By similarity
	Binding site	251	1	ATP By similarity
Amino acid modifications
	Modified residue	382	1	Phosphotyrosine Ref.8 Ref.10
Natural variations
	Alternative sequence	1 – 73	73	Missing in isoform 2.		VSP_026115
	Natural variant	98	1	S → G		VAR_040458
	Natural variant	198	1	P → L in a glioblastoma multiforme sample; somatic mutation. Ref.11		VAR_040459
	Natural variant	245	1	H → N: dbSNP rs34166200. Ref.11		VAR_040460
	Natural variant	295	1	N → S		VAR_040461
	Natural variant	451	1	R → Q		VAR_040462
	Natural variant	455	1	F → Y		VAR_040463

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 12, 2007. Version 3. Checksum: A7BEE25CDF944436	FASTA	601	66,652
	10 20 30 40 50 60 MLTRKPSAAA PAAYPTGRGG DSAVRQLQAS PGLGAGATRS GVGTGPPSPI ALPPLRASNA 70 80 90 100 110 120 AAAAHTIGGS KHTMNDHLHV GSHAHGQIQV QQLFEDNSNK RTVLTTQPNG LTTVGKTGLP 130 140 150 160 170 180 VVPERQLDSI HRRQGSSTSL KSMEGMGKVK ATPMTPEQAM KQYMQKLTAF EHHEIFSYPE 190 200 210 220 230 240 IYFLGLNAKK RQGMTGGPNN GGYDDDQGSY VQVPHDHVAY RYEVLKVIGK GSFGQVVKAY 250 260 270 280 290 300 DHKVHQHVAL KMVRNEKRFH RQAAEEIRIL EHLRKQDKDN TMNVIHMLEN FTFRNHICMT 310 320 330 340 350 360 FELLSMNLYE LIKKNKFQGF SLPLVRKFAH SILQCLDALH KNRIIHCDLK PENILLKQQG 370 380 390 400 410 420 RSGIKVIDFG SSCYEHQRVY TYIQSRFYRA PEVILGARYG MPIDMWSLGC ILAELLTGYP 430 440 450 460 470 480 LLPGEDEGDQ LACMIELLGM PSQKLLDASK RAKNFVSSKG YPRYCTVTTL SDGSVVLNGG 490 500 510 520 530 540 RSRRGKLRGP PESREWGNAL KGCDDPLFLD FLKQCLEWDP AVRMTPGQAL RHPWLRRRLP 550 560 570 580 590 600 KPPTGEKTSV KRITESTGAI TSISKLPPPS SSASKLRTNL AQMTDANGNI QQRTVLPKLV S
	Isoform 2. Checksum: AF2C6822ED9522D7	FASTA	528	59,715
	10 20 30 40 50 60 MNDHLHVGSH AHGQIQVQQL FEDNSNKRTV LTTQPNGLTT VGKTGLPVVP ERQLDSIHRR 70 80 90 100 110 120 QGSSTSLKSM EGMGKVKATP MTPEQAMKQY MQKLTAFEHH EIFSYPEIYF LGLNAKKRQG 130 140 150 160 170 180 MTGGPNNGGY DDDQGSYVQV PHDHVAYRYE VLKVIGKGSF GQVVKAYDHK VHQHVALKMV 190 200 210 220 230 240 RNEKRFHRQA AEEIRILEHL RKQDKDNTMN VIHMLENFTF RNHICMTFEL LSMNLYELIK 250 260 270 280 290 300 KNKFQGFSLP LVRKFAHSIL QCLDALHKNR IIHCDLKPEN ILLKQQGRSG IKVIDFGSSC 310 320 330 340 350 360 YEHQRVYTYI QSRFYRAPEV ILGARYGMPI DMWSLGCILA ELLTGYPLLP GEDEGDQLAC 370 380 390 400 410 420 MIELLGMPSQ KLLDASKRAK NFVSSKGYPR YCTVTTLSDG SVVLNGGRSR RGKLRGPPES 430 440 450 460 470 480 REWGNALKGC DDPLFLDFLK QCLEWDPAVR MTPGQALRHP WLRRRLPKPP TGEKTSVKRI 490 500 510 520 TESTGAITSI SKLPPPSSSA SKLRTNLAQM TDANGNIQQR TVLPKLVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, COFACTOR, PHOSPHORYLATION, TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1 AND 2). Tissue: Muscle and Skin.
[5]	Becker W., Joost H.-G. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 320-528 (ISOFORMS 1/2). Tissue: Placenta.
[6]	"The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase." Woods Y.L., Cohen P., Becker W., Jakes R., Goedert M., Wang X., Proud C.G. Biochem. J. 355:609-615(2001) [PubMed: 11311121] [Abstract] Cited for: FUNCTION.
[7]	"Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases." Skurat A.V., Dietrich A.D. J. Biol. Chem. 279:2490-2498(2004) [PubMed: 14593110] [Abstract] Cited for: FUNCTION.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-382, MASS SPECTROMETRY. Tissue: Lung.
[9]	"DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage." Taira N., Nihira K., Yamaguchi T., Miki Y., Yoshida K. Mol. Cell 25:725-738(2007) [PubMed: 17349958] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-382, MASS SPECTROMETRY.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLY-98; LEU-198; ASN-245; SER-295; GLN-451 AND TYR-455.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Y13493 mRNA. Translation: CAA73885.1. Different initiation. AK313937 mRNA. Translation: BAG36656.1. CH471054 Genomic DNA. Translation: EAW97176.1. BC005809 mRNA. Translation: AAH05809.1. BC006375 mRNA. Translation: AAH06375.1. Y09216 mRNA. Translation: CAA70418.1.
IPI	IPI00022521. IPI00304942.
RefSeq	NP_003574.1. NP_006473.2.
UniGene	Hs.173135
3D structure databases
HSSP	HSSP built from PDB template 1BI8 based on UniProtKB Q00534.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92630. 1 interaction.
STRING	Q92630.
PTM databases
PhosphoSite	Q92630.
Proteomic databases
PRIDE	Q92630.
Genome annotation databases
Ensembl	ENST00000319833; ENSP00000324733; ENSG00000127334; Homo sapiens. [Genome view] ENST00000344096; ENSP00000342105; ENSG00000127334; Homo sapiens. [Genome view] ENST00000393555; ENSP00000377186; ENSG00000127334; Homo sapiens. [Genome view]
GeneID	8445.
KEGG	hsa:8445.
UCSC	uc001str.2. human. uc001sts.2. human.
Organism-specific databases
CTD	8445.
GeneCards	GC12P066328.
H-InvDB	HIX0010797.
HGNC	HGNC:3093. DYRK2.
HPA	HPA027230.
MIM	603496. gene.
PharmGKB	PA27550.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q92630.
OMA	VIHMLEN.
Enzyme and pathway databases
BRENDA	2.7.12.1. 247.
Gene expression databases
ArrayExpress	Q92630.
Bgee	Q92630.
CleanEx	HS_DYRK2.
Genevestigator	Q92630.
GermOnline	ENSG00000127334. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31596.
SOURCE	Search...

Entry information

Entry name

DYRK2_HUMAN

Accession

Primary (citable) accession number: Q92630
Secondary accession number(s): B2R9V9, Q9BRB5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	June 12, 2007
Last modified:	November 3, 2009
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.