DYRK2 - Dual specificity tyrosine-phosphorylation-regulated kinase 2 - human protein (Function)
 
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DYRK2 »  Dual specificity tyrosine-phosphorylation-regulated kinase 2   [ EC 2.7.12.1 ]
 
Gene name:  DYRK2
Entry whose protein(s) existence is based on evidence at protein level
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1 44 2
GENE REF ISO

Function

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Overview 
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
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
Manganese ion bindingdefinition[GO:0030145]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDAUniProtKB
Protein serine/threonine/tyrosine kinase activitydefinition[GO:0004712]  
  • IEAEC 2 GO
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • IDAUniProtKB
Ubiquitin bindingdefinition[GO:0043130]  
1
  • IDAUniProtKB
GO biological process 
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • IEPUniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:0042771]  
1
  • IDAUniProtKB
Negative regulation of NFAT protein import into nucleusdefinition[GO:0051534]  
1
  • IMPUniProtKB
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • IDAGOC
  • IEAUniProtKB KW
Positive regulation of glycogen biosynthetic processdefinition[GO:0045725]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Smoothened signaling pathwaydefinition[GO:0007224]  
1
  • IMPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.12.1: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It requires the following cofactors
Magnesium.  
1
  • CuratedUniProtKB
Manganese.  
1
  • CuratedUniProtKB
It is regulated in the following manner
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
  • CuratedUniProtKB
 
More information is available from:
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: DYRK2
GenomeRNAi: 8445
PRO: PR:Q92630
Chemistry
GuidetoPHARMACOLOGY: 2011