Q92630 (DYRK2_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	601 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). Ref.1 Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.19 Ref.22 Ref.23
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium. Ref.1 Manganese. Ref.1
Enzyme regulation	Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop. Inhibited by acridine analogs, purvalanol, and barely by harmine. Inhibited by leucettine and leucettine derivatives. Ref.12 Ref.18 Ref.20 Ref.25
Subunit structure	Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and VPRBP. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2. Ref.10 Ref.13 Ref.19 Ref.21
Subcellular location	Cytoplasm. Nucleus. Note: Translocates into the nucleus following DNA damage. Ref.14 Ref.15 Ref.17 Ref.21
Tissue specificity	Testis, after the onset of spermatogenesis. Ref.1
Induction	Accumulates in nucleus upon DNA damage. Induced in both esophageal and lung adenocarcinomas. Ref.7 Ref.12 Ref.18 Ref.20 Ref.21 Ref.25
Post-translational modification	Autophosphorylates cotranslationally on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop, but once mature, does not have any protein tyrosine kinase activity. Phosphorylated at Thr-106 and Ser-442 by ATM in response to genotoxic stress. Ref.1 Ref.15 Ref.16 Ref.21 Ref.25 Under normal conditions, polyubiquitinated in the nucleus by MDM2, leading to its proteasomal degradation. Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation. Polyubiquitinated by SIAH2, leading to its proteasomal degradation. Polyubiquitinated by SIAH2 occurs under normal conditions, and is enhanced in response to hypoxia.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence CAA73885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Apoptosis Ubl conjugation pathway
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 Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from direct assay Ref.14. Source: UniProtKB negative regulation of NFAT protein import into nucleus Inferred from mutant phenotype Ref.13. Source: UniProtKB positive regulation of glycogen biosynthetic process Inferred from direct assay Ref.6. Source: UniProtKB smoothened signaling pathway Inferred from mutant phenotype Ref.16. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.14Ref.16. Source: UniProtKB nucleus Inferred from direct assay Ref.14. Source: UniProtKB ribonucleoprotein complex Inferred from electronic annotation. Source: Compara ubiquitin ligase complex Inferred from direct assay Ref.19. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.6. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB manganese ion binding Inferred from direct assay Ref.1. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.6. Source: UniProtKB protein serine/threonine/tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB ubiquitin binding Inferred from direct assay Ref.21. 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

Motif

189 – 191

3

Nuclear localization signal Probable

Sites

Active site

348

1

Proton acceptor By similarity

Binding site

251

1

ATP By similarity

Amino acid modifications

Modified residue

106

1

Phosphothreonine; by ATM Ref.21

Modified residue

381

1

Phosphothreonine; by MAP3K10 Ref.16

Modified residue

382

1

Phosphotyrosine; by autocatalysis Ref.25

Modified residue

442

1

Phosphoserine; by ATM Ref.21

Modified residue

449

1

Phosphoserine; by MAP3K10 Ref.16

Natural variations

Alternative sequence

1 – 73

73

Missing in isoform 2.

VSP_026115

Natural variant

98

1

S → G. Ref.26
Corresponds to variant rs35139851 [ dbSNP | Ensembl ].

VAR_040458

Natural variant

198

1

P → L in a glioblastoma multiforme sample; somatic mutation. Ref.26

VAR_040459

Natural variant

245

1

H → N. Ref.26
Corresponds to variant rs34166200 [ dbSNP | Ensembl ].

VAR_040460

Natural variant

295

1

N → S. Ref.26
Corresponds to variant rs56293072 [ dbSNP | Ensembl ].

VAR_040461

Natural variant

451

1

R → Q. Ref.26
Corresponds to variant rs35688869 [ dbSNP | Ensembl ].

VAR_040462

Natural variant

455

1

F → Y. Ref.26
Corresponds to variant rs55774594 [ dbSNP | Ensembl ].

VAR_040463

Experimental info

Mutagenesis

106

1

T → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. Ref.21

Mutagenesis

189 – 191

3

KKR → NNN: Impaired nuclear translocation. Ref.21

Mutagenesis

442

1

S → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. Ref.21

Sequence conflict

37

1

A → P in CAA73885. Ref.1

Secondary structure

1

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601

Helix Strand Turn

Details...

Beta strand

149 – 152

4

Helix

156 – 163

8

Helix

164 – 166

3

Helix

169 – 174

6

Helix

175 – 177

3

Beta strand

179 – 181

3

Helix

198 – 201

4

Beta strand

206 – 208

3

Turn

219 – 221

3

Beta strand

222 – 241

20

Turn

242 – 245

4

Beta strand

246 – 253

8

Helix

257 – 274

18

Beta strand

287 – 293

7

Beta strand

296 – 301

6

Helix

308 – 314

7

Turn

315 – 317

3

Helix

322 – 342

21

Helix

351 – 353

3

Beta strand

354 – 358

5

Beta strand

364 – 366

3

Helix

375 – 377

3

Helix

386 – 388

3

Helix

391 – 395

5

Helix

402 – 417

16

Helix

427 – 438

12

Helix

443 – 447

5

Helix

452 – 455

4

Beta strand

467 – 469

3

Beta strand

475 – 477

3

Helix

496 – 499

4

Turn

500 – 502

3

Helix

506 – 515

10

Turn

520 – 522

3

Helix

526 – 530

5

Turn

533 – 535

3

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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas." Miller C.T., Aggarwal S., Lin T.K., Dagenais S.L., Contreras J.I., Orringer M.B., Glover T.W., Beer D.G., Lin L. Cancer Res. 63:4136-4143(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION IN CANCER.
[8]	"The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation." Wang X., Li W., Parra J.L., Beugnet A., Proud C.G. Mol. Cell. Biol. 23:1546-1557(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Characterization of cyclin L2, a novel cyclin with an arginine/serine-rich domain: phosphorylation by DYRK1A and colocalization with splicing factors." de Graaf K., Hekerman P., Spelten O., Herrmann A., Packman L.C., Bussow K., Muller-Newen G., Becker W. J. Biol. Chem. 279:4612-4624(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CCNL2.
[11]	"Identification of calcium-regulated heat-stable protein of 24 kDa (CRHSP24) as a physiological substrate for PKB and RSK using KESTREL." Auld G.C., Campbell D.G., Morrice N., Cohen P. Biochem. J. 389:775-783(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo." Cole A.R., Causeret F., Yadirgi G., Hastie C.J., McLauchlan H., McManus E.J., Hernandez F., Eickholt B.J., Nikolic M., Sutherland C. J. Biol. Chem. 281:16591-16598(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS CRMP4/DPYSL3 KINASE, ENZYME REGULATION BY PURVALANOL.
[13]	"A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT." Gwack Y., Sharma S., Nardone J., Tanasa B., Iuga A., Srikanth S., Okamura H., Bolton D., Feske S., Hogan P.G., Rao A. Nature 441:646-650(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NFATC1.
[14]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]	"Role for DYRK family kinases on regulation of apoptosis." Yoshida K. Biochem. Pharmacol. 76:1389-1394(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS AS P53/TP53 KINASE, SUBCELLULAR LOCATION, PHOSPHORYLATION BY ATM, GENE FAMILY.
[16]	"Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling." Varjosalo M., Bjorklund M., Cheng F., Syvanen H., Kivioja T., Kilpinen S., Sun Z., Kallioniemi O., Stunnenberg H.G., He W.W., Ojala P., Taipale J. Cell 133:537-548(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-381 AND SER-449.
[17]	"Nuclear trafficking of pro-apoptotic kinases in response to DNA damage." Yoshida K. Trends Mol. Med. 14:305-313(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[18]	"Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation." Goeckler N., Jofre G., Papadopoulos C., Soppa U., Tejedor F.J., Becker W. FEBS J. 276:6324-6337(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION BY HARMINE.
[19]	"Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase." Maddika S., Chen J. Nat. Cell Biol. 11:409-419(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN E3 LIGASE REGULATION, FUNCTION AS KATNA1 KINASE, INTERACTION WITH EDVP COMPLEX.
[20]	"Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors." Cuny G.D., Robin M., Ulyanova N.P., Patnaik D., Pique V., Casano G., Liu J.-F., Lin X., Xian J., Glicksman M.A., Stein R.L., Higgins J.M.G. Bioorg. Med. Chem. Lett. 20:3491-3494(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION BY ACRIDINE ANALOGS.
[21]	"ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage." Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K. J. Biol. Chem. 285:4909-4919(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-106 AND SER-442 BY ATM, UBIQUITINATION BY MDM2, INTERACTION WITH MDM2, MUTAGENESIS OF THR-106; SER-442 AND 189-LYS--ARG-191, NUCLEAR LOCALIZATION SIGNAL, INDUCTION BY DNA DAMAGE.
[22]	"DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells." Taira N., Mimoto R., Kurata M., Yamaguchi T., Kitagawa M., Miki Y., Yoshida K. J. Clin. Invest. 122:859-872(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways." Perez M., Garcia-Limones C., Zapico I., Marina A., Schmitz M.L., Munoz E., Calzado M.A. J. Mol. Cell Biol. 4:316-330(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, UBIQUITINATION BY SIAH2.
[24]	"Crystal structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) in complex with an indirubin ligand." Structural genomics consortium (SGC) Submitted (JAN-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 146-552 IN COMPLEX WITH INDIRUBIN.
[25]	"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: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 146-540 IN COMPLEX WITH LEUCETTAMINE DERIVATIVE, PHOSPHORYLATION AT TYR-382, AUTOPHOSPHORYLATION, ENZYME REGULATION.
[26]	"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] [Europe PMC] [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

EMBL
GenBank
DDBJ

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. NM_003583.3.
NP_006473.2. NM_006482.2.

UniGene

Hs.173135.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3K2L	X-ray	2.36	A	146-552	[»]
3KVW	X-ray	2.28	A	146-552	[»]
4AZF	X-ray	2.55	A	146-540	[»]

ProteinModelPortal

Q92630.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q92630. 2 interactions.

MINT

MINT-1469581.

STRING

9606.ENSP00000342105.

PTM databases

PhosphoSite

Q92630.

Polymorphism databases

DMDM

148887370.

Proteomic databases

PaxDb

Q92630.

PRIDE

Q92630.

Protocols and materials databases

DNASU

8445.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344096; ENSP00000342105; ENSG00000127334.
ENST00000393555; ENSP00000377186; ENSG00000127334.

GeneID

8445.

KEGG

hsa:8445.

UCSC

uc001str.4. human.

Organism-specific databases

CTD

8445.

GeneCards

GC12P068042.

HGNC

HGNC:3093. DYRK2.

HPA

HPA027230.

MIM

603496. gene.

neXtProt

NX_Q92630.

PharmGKB

PA27550.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000220863.

HOVERGEN

HBG051426.

InParanoid

Q92630.

KO

K08825.

OMA

HTIGGSK.

OrthoDB

EOG4QRH3Z.

PhylomeDB

Q92630.

Enzyme and pathway databases

BRENDA

2.7.12.1. 2681.

Gene expression databases

ArrayExpress

Q92630.

Bgee

Q92630.

CleanEx

HS_DYRK2.

Genevestigator

Q92630.

GermOnline

ENSG00000127334. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

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

BindingDB

Q92630.

ChEMBL

CHEMBL4376.

EvolutionaryTrace

Q92630.

GenomeRNAi

8445.

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:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.