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Q92630 (DYRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 2

EC=2.7.12.1
Gene names
Name:DYRK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length601 AA.
Sequence statusComplete.
Protein existenceEvidence 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 TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. 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 Ref.24

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.26

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.26

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.26

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.26

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 processApoptosis
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Magnesium
Manganese
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to DNA damage stimulus

Inferred from expression pattern Ref.21. Source: UniProtKB

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

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.1. Source: GOC

positive regulation of glycogen biosynthetic process

Inferred from direct assay Ref.6. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.6. Source: UniProtKB

smoothened signaling pathway

Inferred from mutant phenotype Ref.16. Source: UniProtKB

   Cellular_componentcytoplasm

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: Ensembl

ubiquitin ligase complex

Inferred from direct assay Ref.19. Source: UniProtKB

   Molecular_functionATP 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: UniProtKB-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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DYRK4Q9NR203EBI-749432,EBI-3914009

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 601601Dual specificity tyrosine-phosphorylation-regulated kinase 2
PRO_0000085936

Regions

Domain222 – 535314Protein kinase
Nucleotide binding228 – 2369ATP Probable
Nucleotide binding301 – 3044ATP Probable
Motif189 – 1913Nuclear localization signal Probable

Sites

Active site3481Proton acceptor By similarity
Binding site2511ATP Probable

Amino acid modifications

Modified residue1061Phosphothreonine; by ATM Ref.21
Modified residue3811Phosphothreonine; by MAP3K10 Ref.16
Modified residue3821Phosphotyrosine; by autocatalysis Ref.26
Modified residue4421Phosphoserine; by ATM Ref.21
Modified residue4491Phosphoserine; by MAP3K10 Ref.16

Natural variations

Alternative sequence1 – 7373Missing in isoform 2.
VSP_026115
Natural variant981S → G. Ref.28
Corresponds to variant rs35139851 [ dbSNP | Ensembl ].
VAR_040458
Natural variant1981P → L in a glioblastoma multiforme sample; somatic mutation. Ref.28
VAR_040459
Natural variant2451H → N. Ref.28
Corresponds to variant rs34166200 [ dbSNP | Ensembl ].
VAR_040460
Natural variant2951N → S. Ref.28
Corresponds to variant rs56293072 [ dbSNP | Ensembl ].
VAR_040461
Natural variant4511R → Q. Ref.28
Corresponds to variant rs35688869 [ dbSNP | Ensembl ].
VAR_040462
Natural variant4551F → Y. Ref.28
Corresponds to variant rs55774594 [ dbSNP | Ensembl ].
VAR_040463

Experimental info

Mutagenesis1061T → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. Ref.21
Mutagenesis189 – 1913KKR → NNN: Impaired nuclear translocation. Ref.21
Mutagenesis2511K → R: Abolishes protein serine/threonine kinase activity. Ref.24
Mutagenesis4421S → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. Ref.21
Sequence conflict371A → P in CAA73885. Ref.1

Secondary structure

................................................................. 601
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 12, 2007. Version 3.
Checksum: A7BEE25CDF944436

FASTA60166,652
        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 

« Hide

Isoform 2 [UniParc].

Checksum: AF2C6822ED9522D7
Show »

FASTA52859,715

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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]"Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation."
Jung H.Y., Wang X., Jun S., Park J.I.
J. Biol. Chem. 288:7252-7262(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-251.
[25]"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.
[26]"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, CATALYTIC ACTIVITY.
[27]"Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition."
Soundararajan M., Roos A.K., Savitsky P., Filippakopoulos P., Kettenbach A.N., Olsen J.V., Gerber S.A., Eswaran J., Knapp S., Elkins J.M.
Structure 21:986-996(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 146-552.
[28]"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. expand/collapse author list , 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.
RefSeqNP_003574.1. NM_003583.3.
NP_006473.2. NM_006482.2.
UniGeneHs.173135.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3K2LX-ray2.36A146-552[»]
3KVWX-ray2.28A146-552[»]
4AZFX-ray2.55A146-540[»]
ProteinModelPortalQ92630.
SMRQ92630. Positions 146-543.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114023. 44 interactions.
IntActQ92630. 5 interactions.
MINTMINT-1469581.
STRING9606.ENSP00000342105.

Chemistry

BindingDBQ92630.
ChEMBLCHEMBL4376.
GuidetoPHARMACOLOGY2011.

PTM databases

PhosphoSiteQ92630.

Polymorphism databases

DMDM148887370.

Proteomic databases

PaxDbQ92630.
PRIDEQ92630.

Protocols and materials databases

DNASU8445.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344096; ENSP00000342105; ENSG00000127334. [Q92630-1]
ENST00000393555; ENSP00000377186; ENSG00000127334. [Q92630-2]
GeneID8445.
KEGGhsa:8445.
UCSCuc001str.4. human. [Q92630-1]

Organism-specific databases

CTD8445.
GeneCardsGC12P068042.
HGNCHGNC:3093. DYRK2.
HPAHPA027230.
HPA056902.
MIM603496. gene.
neXtProtNX_Q92630.
PharmGKBPA27550.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000220863.
HOVERGENHBG051426.
InParanoidQ92630.
KOK08825.
OMAHTIGGSK.
OrthoDBEOG77127N.
PhylomeDBQ92630.
TreeFamTF314624.

Enzyme and pathway databases

BRENDA2.7.12.1. 2681.
SignaLinkQ92630.

Gene expression databases

ArrayExpressQ92630.
BgeeQ92630.
CleanExHS_DYRK2.
GenevestigatorQ92630.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ92630.
GeneWikiDYRK2.
GenomeRNAi8445.
NextBio31596.
PROQ92630.
SOURCESearch...

Entry information

Entry nameDYRK2_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM