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Reviewed, UniProtKB/Swiss-Prot Q92630 (DYRK2_HUMAN)

Last modified November 3, 2009. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length601 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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.

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 By similarity

Sites

Active site3481Proton acceptor By similarity
Binding site2511ATP By similarity

Amino acid modifications

Modified residue3821Phosphotyrosine Ref.8 Ref.10

Natural variations

Alternative sequence1 – 7373Missing in isoform 2.
VSP_026115
Natural variant981S → G
VAR_040458
Natural variant1981P → L in a glioblastoma multiforme sample; somatic mutation. Ref.11
VAR_040459
Natural variant2451H → N: dbSNP rs34166200. Ref.11
VAR_040460
Natural variant2951N → S
VAR_040461
Natural variant4511R → Q
VAR_040462
Natural variant4551F → Y
VAR_040463

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.

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: 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. 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: 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. 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: 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. expand/collapse author list , 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. 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: 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

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.
IPIIPI00022521.
IPI00304942.
RefSeqNP_003574.1.
NP_006473.2.
UniGeneHs.173135

3D structure databases

HSSPHSSP built from PDB template 1BI8 based on UniProtKB Q00534.
ModBaseSearch...

Protein-protein interaction databases

IntActQ92630. 1 interaction.
STRINGQ92630.

PTM databases

PhosphoSiteQ92630.

Proteomic databases

PRIDEQ92630.

Genome annotation databases

EnsemblENST00000319833; ENSP00000324733; ENSG00000127334; Homo sapiens. [Genome view]
ENST00000344096; ENSP00000342105; ENSG00000127334; Homo sapiens. [Genome view]
ENST00000393555; ENSP00000377186; ENSG00000127334; Homo sapiens. [Genome view]
GeneID8445.
KEGGhsa:8445.
UCSCuc001str.2. human.
uc001sts.2. human.

Organism-specific databases

CTD8445.
GeneCardsGC12P066328.
H-InvDBHIX0010797.
HGNCHGNC:3093. DYRK2.
HPAHPA027230.
MIM603496. gene.
PharmGKBPA27550.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ92630.
OMAVIHMLEN.

Enzyme and pathway databases

BRENDA2.7.12.1. 247.

Gene expression databases

ArrayExpressQ92630.
BgeeQ92630.
CleanExHS_DYRK2.
GenevestigatorQ92630.
GermOnlineENSG00000127334. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio31596.
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: November 3, 2009
This is version 98 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents