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Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 2

Gene

Dyrk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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. 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) (By similarity). Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX.By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarity
  • Mn2+By similarity

Enzyme regulationi

Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei249 – 2491ATPPROSITE-ProRule annotationBy similarity
Active sitei346 – 3461Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi226 – 2349ATPPROSITE-ProRule annotationBy similarity
Nucleotide bindingi299 – 3024ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

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

ReactomeiR-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC:2.7.12.1)
Gene namesi
Name:Dyrk2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1330301. Dyrk2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus By similarity

  • Note: Translocates into the nucleus following DNA damage.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 599599Dual specificity tyrosine-phosphorylation-regulated kinase 2PRO_0000291265Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei104 – 1041Phosphothreonine; by ATMBy similarity
Modified residuei379 – 3791Phosphothreonine; by MAP3K10By similarity
Modified residuei380 – 3801Phosphotyrosine; by autocatalysisBy similarity
Modified residuei440 – 4401Phosphoserine; by ATMBy similarity
Modified residuei447 – 4471Phosphoserine; by MAP3K10By similarity

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-104 and Ser-440 by ATM in response to genotoxic stress.
Under normal conditions, polyubiquitinated in the nucleus by MDM2, leading to its proteasomal degradation. Phosphorylation on Thr-104 and Ser-440 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.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ5U4C9.
PaxDbiQ5U4C9.
PRIDEiQ5U4C9.

PTM databases

iPTMnetiQ5U4C9.
PhosphoSiteiQ5U4C9.

Expressioni

Gene expression databases

BgeeiQ5U4C9.
GenevisibleiQ5U4C9. MM.

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000004281.

Structurei

3D structure databases

ProteinModelPortaliQ5U4C9.
SMRiQ5U4C9. Positions 144-541.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini220 – 533314Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi187 – 1893Nuclear localization signalBy similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000220863.
HOVERGENiHBG051426.
InParanoidiQ5U4C9.
KOiK18669.
OMAiKLTTFEH.
OrthoDBiEOG77127N.
PhylomeDBiQ5U4C9.
TreeFamiTF314624.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]

Sequencei

Sequence statusi: Complete.

Q5U4C9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLTRKPSAAA PAAYPTGRGG DTAVRQLQAS PGIGAGAPRS GVGTGPPSPI
60 70 80 90 100
ALPPLRASNA TTTAHTIGGS KHTMNDHLHL NSHGQIQVQQ LFEDNSNKRT
110 120 130 140 150
VLTTQPNGLT TVGKTGLPGV PERQLESIHR RQGSSTSLKS MEGMGKVKAS
160 170 180 190 200
PMTPEQAMKQ YMQKLTAFEH HEIFSYPEIY FLGPNAKKRQ GMTGGPNNGG
210 220 230 240 250
YDDDQGSYVQ VPHDHVAYRY EVLKVIGKGS FGQVVKAYDH KVHQHVALKM
260 270 280 290 300
VRNEKRFHRQ AAEEIRILEH LRKQDKDNTM NVIHMLENFT FRNHICMTFE
310 320 330 340 350
LLSMNLYELI KKNKFQGFSL PLVRKFAHSI LQCLDALHKN RIIHCDLKPE
360 370 380 390 400
NILLKQQGRS SIKVIDFGSS CYEHQRVYTY IQSRFYRAPE VILGARYGMP
410 420 430 440 450
IDMWSLGCIL AELLTGYPLL PGEDEGDQLA CMIELLGMPS QKLLDASKRA
460 470 480 490 500
KNFVSSKGYP RYCTVTTLSD GSVVLNGGRS RRGKLRGPPE SREWGNALKG
510 520 530 540 550
CDDPLFLDFL KQCLEWDPAV RMTPGQALRH PWLRRRLPKP PTGEKTAVKR
560 570 580 590
VTESTGAITS ISKLPPPSSS ASKLRTNLAQ MTDANGNIQQ RTVLPKLVS
Length:599
Mass (Da):66,556
Last modified:December 7, 2004 - v1
Checksum:i2378D39A5E1E8056
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC085145 mRNA. Translation: AAH85145.1.
CCDSiCCDS24201.1.
RefSeqiNP_001014412.1. NM_001014390.2.
UniGeneiMm.45565.
Mm.458174.

Genome annotation databases

EnsembliENSMUST00000004281; ENSMUSP00000004281; ENSMUSG00000028630.
GeneIDi69181.
KEGGimmu:69181.
UCSCiuc007hea.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC085145 mRNA. Translation: AAH85145.1.
CCDSiCCDS24201.1.
RefSeqiNP_001014412.1. NM_001014390.2.
UniGeneiMm.45565.
Mm.458174.

3D structure databases

ProteinModelPortaliQ5U4C9.
SMRiQ5U4C9. Positions 144-541.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000004281.

PTM databases

iPTMnetiQ5U4C9.
PhosphoSiteiQ5U4C9.

Proteomic databases

MaxQBiQ5U4C9.
PaxDbiQ5U4C9.
PRIDEiQ5U4C9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004281; ENSMUSP00000004281; ENSMUSG00000028630.
GeneIDi69181.
KEGGimmu:69181.
UCSCiuc007hea.1. mouse.

Organism-specific databases

CTDi8445.
MGIiMGI:1330301. Dyrk2.

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000220863.
HOVERGENiHBG051426.
InParanoidiQ5U4C9.
KOiK18669.
OMAiKLTTFEH.
OrthoDBiEOG77127N.
PhylomeDBiQ5U4C9.
TreeFamiTF314624.

Enzyme and pathway databases

ReactomeiR-MMU-6804756. Regulation of TP53 Activity through Phosphorylation.

Miscellaneous databases

PROiQ5U4C9.
SOURCEiSearch...

Gene expression databases

BgeeiQ5U4C9.
GenevisibleiQ5U4C9. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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].
    Strain: C57BL/6JImported.
    Tissue: BrainImported.
  2. "DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1."
    Guo X., Williams J.G., Schug T.T., Li X.
    J. Biol. Chem. 285:13223-13232(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  3. "Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization, and neuronal morphology."
    Slepak T.I., Salay L.D., Lemmon V.P., Bixby J.L.
    Cytoskeleton 69:514-527(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiDYRK2_MOUSE
AccessioniPrimary (citable) accession number: Q5U4C9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 12, 2007
Last sequence update: December 7, 2004
Last modified: June 8, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.