Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q92630

- DYRK2_HUMAN

UniProt

Q92630 - DYRK2_HUMAN

Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 2

Gene

DYRK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 3 (12 Jun 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    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).14 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.1 Publication
    Manganese.1 Publication

    Enzyme regulationi

    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.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei251 – 2511ATPCurated
    Active sitei348 – 3481Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi228 – 2369ATPCurated
    Nucleotide bindingi301 – 3044ATPCurated

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. magnesium ion binding Source: UniProtKB
    3. manganese ion binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. protein tyrosine kinase activity Source: UniProtKB
    8. ubiquitin binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to DNA damage stimulus Source: UniProtKB
    2. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    3. negative regulation of NFAT protein import into nucleus Source: UniProtKB
    4. peptidyl-tyrosine phosphorylation Source: GOC
    5. positive regulation of glycogen biosynthetic process Source: UniProtKB
    6. protein phosphorylation Source: UniProtKB
    7. smoothened signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Apoptosis, Ubl conjugation pathway

    Keywords - Ligandi

    ATP-binding, Magnesium, Manganese, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.12.1. 2681.
    SignaLinkiQ92630.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC:2.7.12.1)
    Gene namesi
    Name:DYRK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:3093. DYRK2.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Translocates into the nucleus following DNA damage.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB
    3. ribonucleoprotein complex Source: Ensembl
    4. ubiquitin ligase complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi106 – 1061T → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. 1 Publication
    Mutagenesisi189 – 1913KKR → NNN: Impaired nuclear translocation.
    Mutagenesisi251 – 2511K → R: Abolishes protein serine/threonine kinase activity. 1 Publication
    Mutagenesisi442 – 4421S → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. 1 Publication

    Organism-specific databases

    PharmGKBiPA27550.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 601601Dual specificity tyrosine-phosphorylation-regulated kinase 2PRO_0000085936Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei106 – 1061Phosphothreonine; by ATM1 Publication
    Modified residuei381 – 3811Phosphothreonine; by MAP3K101 Publication
    Modified residuei382 – 3821Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei442 – 4421Phosphoserine; by ATM1 Publication
    Modified residuei449 – 4491Phosphoserine; by MAP3K101 Publication

    Post-translational modificationi

    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.1 Publication
    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.2 Publications

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ92630.
    PRIDEiQ92630.

    PTM databases

    PhosphoSiteiQ92630.

    Expressioni

    Tissue specificityi

    Testis, after the onset of spermatogenesis.1 Publication

    Inductioni

    Accumulates in nucleus upon DNA damage. Induced in both esophageal and lung adenocarcinomas.2 Publications

    Gene expression databases

    ArrayExpressiQ92630.
    BgeeiQ92630.
    CleanExiHS_DYRK2.
    GenevestigatoriQ92630.

    Organism-specific databases

    HPAiHPA027230.
    HPA056902.

    Interactioni

    Subunit structurei

    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 CCNL2.6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DYRK4Q9NR203EBI-749432,EBI-3914009

    Protein-protein interaction databases

    BioGridi114023. 45 interactions.
    IntActiQ92630. 5 interactions.
    MINTiMINT-1469581.
    STRINGi9606.ENSP00000342105.

    Structurei

    Secondary structure

    1
    601
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi149 – 1524
    Helixi156 – 1638
    Helixi164 – 1663
    Helixi169 – 1746
    Helixi175 – 1773
    Beta strandi179 – 1813
    Helixi198 – 2014
    Beta strandi206 – 2083
    Turni219 – 2213
    Beta strandi222 – 24120
    Turni242 – 2454
    Beta strandi246 – 2538
    Helixi257 – 27418
    Beta strandi287 – 2937
    Beta strandi296 – 3016
    Helixi308 – 3147
    Turni315 – 3173
    Helixi322 – 34221
    Helixi351 – 3533
    Beta strandi354 – 3585
    Beta strandi364 – 3663
    Helixi375 – 3773
    Helixi386 – 3883
    Helixi391 – 3955
    Helixi402 – 41716
    Helixi427 – 43812
    Helixi443 – 4475
    Helixi452 – 4554
    Beta strandi467 – 4693
    Beta strandi475 – 4773
    Helixi496 – 4994
    Turni500 – 5023
    Helixi506 – 51510
    Turni520 – 5223
    Helixi526 – 5305
    Turni533 – 5353

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3K2LX-ray2.36A146-552[»]
    3KVWX-ray2.28A146-552[»]
    4AZFX-ray2.55A146-540[»]
    ProteinModelPortaliQ92630.
    SMRiQ92630. Positions 146-543.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ92630.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini222 – 535314Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi189 – 1913Nuclear localization signal1 Publication

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000220863.
    HOVERGENiHBG051426.
    InParanoidiQ92630.
    KOiK08825.
    OMAiHTIGGSK.
    OrthoDBiEOG77127N.
    PhylomeDBiQ92630.
    TreeFamiTF314624.

    Family and domain databases

    InterProiIPR011009. 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]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q92630-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MLTRKPSAAA PAAYPTGRGG DSAVRQLQAS PGLGAGATRS GVGTGPPSPI    50
    ALPPLRASNA AAAAHTIGGS KHTMNDHLHV GSHAHGQIQV QQLFEDNSNK 100
    RTVLTTQPNG LTTVGKTGLP VVPERQLDSI HRRQGSSTSL KSMEGMGKVK 150
    ATPMTPEQAM KQYMQKLTAF EHHEIFSYPE IYFLGLNAKK RQGMTGGPNN 200
    GGYDDDQGSY VQVPHDHVAY RYEVLKVIGK GSFGQVVKAY DHKVHQHVAL 250
    KMVRNEKRFH RQAAEEIRIL EHLRKQDKDN TMNVIHMLEN FTFRNHICMT 300
    FELLSMNLYE LIKKNKFQGF SLPLVRKFAH SILQCLDALH KNRIIHCDLK 350
    PENILLKQQG RSGIKVIDFG SSCYEHQRVY TYIQSRFYRA PEVILGARYG 400
    MPIDMWSLGC ILAELLTGYP LLPGEDEGDQ LACMIELLGM PSQKLLDASK 450
    RAKNFVSSKG YPRYCTVTTL SDGSVVLNGG RSRRGKLRGP PESREWGNAL 500
    KGCDDPLFLD FLKQCLEWDP AVRMTPGQAL RHPWLRRRLP KPPTGEKTSV 550
    KRITESTGAI TSISKLPPPS SSASKLRTNL AQMTDANGNI QQRTVLPKLV 600
    S 601
    Length:601
    Mass (Da):66,652
    Last modified:June 12, 2007 - v3
    Checksum:iA7BEE25CDF944436
    GO
    Isoform 2 (identifier: Q92630-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:528
    Mass (Da):59,715
    Checksum:iAF2C6822ED9522D7
    GO

    Sequence cautioni

    The sequence CAA73885.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti37 – 371A → P in CAA73885. (PubMed:9748265)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti98 – 981S → G.1 Publication
    Corresponds to variant rs35139851 [ dbSNP | Ensembl ].
    VAR_040458
    Natural varianti198 – 1981P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication
    VAR_040459
    Natural varianti245 – 2451H → N.1 Publication
    Corresponds to variant rs34166200 [ dbSNP | Ensembl ].
    VAR_040460
    Natural varianti295 – 2951N → S.1 Publication
    Corresponds to variant rs56293072 [ dbSNP | Ensembl ].
    VAR_040461
    Natural varianti451 – 4511R → Q.1 Publication
    Corresponds to variant rs35688869 [ dbSNP | Ensembl ].
    VAR_040462
    Natural varianti455 – 4551F → Y.1 Publication
    Corresponds to variant rs55774594 [ dbSNP | Ensembl ].
    VAR_040463

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7373Missing in isoform 2. 1 PublicationVSP_026115Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS8978.1. [Q92630-1]
    CCDS8979.1. [Q92630-2]
    RefSeqiNP_003574.1. NM_003583.3. [Q92630-2]
    NP_006473.2. NM_006482.2. [Q92630-1]
    UniGeneiHs.173135.

    Genome annotation databases

    EnsembliENST00000344096; ENSP00000342105; ENSG00000127334. [Q92630-1]
    ENST00000393555; ENSP00000377186; ENSG00000127334. [Q92630-2]
    GeneIDi8445.
    KEGGihsa:8445.
    UCSCiuc001str.4. human. [Q92630-1]

    Polymorphism databases

    DMDMi148887370.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS8978.1. [Q92630-1 ]
    CCDS8979.1. [Q92630-2 ]
    RefSeqi NP_003574.1. NM_003583.3. [Q92630-2 ]
    NP_006473.2. NM_006482.2. [Q92630-1 ]
    UniGenei Hs.173135.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali Q92630.
    SMRi Q92630. Positions 146-543.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114023. 45 interactions.
    IntActi Q92630. 5 interactions.
    MINTi MINT-1469581.
    STRINGi 9606.ENSP00000342105.

    Chemistry

    BindingDBi Q92630.
    ChEMBLi CHEMBL4376.
    GuidetoPHARMACOLOGYi 2011.

    PTM databases

    PhosphoSitei Q92630.

    Polymorphism databases

    DMDMi 148887370.

    Proteomic databases

    PaxDbi Q92630.
    PRIDEi Q92630.

    Protocols and materials databases

    DNASUi 8445.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000344096 ; ENSP00000342105 ; ENSG00000127334 . [Q92630-1 ]
    ENST00000393555 ; ENSP00000377186 ; ENSG00000127334 . [Q92630-2 ]
    GeneIDi 8445.
    KEGGi hsa:8445.
    UCSCi uc001str.4. human. [Q92630-1 ]

    Organism-specific databases

    CTDi 8445.
    GeneCardsi GC12P068042.
    HGNCi HGNC:3093. DYRK2.
    HPAi HPA027230.
    HPA056902.
    MIMi 603496. gene.
    neXtProti NX_Q92630.
    PharmGKBi PA27550.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000220863.
    HOVERGENi HBG051426.
    InParanoidi Q92630.
    KOi K08825.
    OMAi HTIGGSK.
    OrthoDBi EOG77127N.
    PhylomeDBi Q92630.
    TreeFami TF314624.

    Enzyme and pathway databases

    BRENDAi 2.7.12.1. 2681.
    SignaLinki Q92630.

    Miscellaneous databases

    EvolutionaryTracei Q92630.
    GeneWikii DYRK2.
    GenomeRNAii 8445.
    NextBioi 31596.
    PROi Q92630.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92630.
    Bgeei Q92630.
    CleanExi HS_DYRK2.
    Genevestigatori Q92630.

    Family and domain databases

    InterProi IPR011009. 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.
      , 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.

    Entry informationi

    Entry nameiDYRK2_HUMAN
    AccessioniPrimary (citable) accession number: Q92630
    Secondary accession number(s): B2R9V9, Q9BRB5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: June 12, 2007
    Last modified: October 1, 2014
    This is version 151 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3