InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DYRK2

Summary

InnateDB Protein

IDBP-45843.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DYRK2

Protein Name

dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000342105

InnateDB Gene

IDBG-45841 (DYRK2)

Protein Structure

UniProt Annotation

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). {ECO:0000269PubMed:11311121, ECO:0000269PubMed:12588975, ECO:0000269PubMed:14593110, ECO:0000269PubMed:15910284, ECO:0000269PubMed:16511445, ECO:0000269PubMed:16611631, ECO:0000269PubMed:17349958, ECO:0000269PubMed:18455992, ECO:0000269PubMed:18599021, ECO:0000269PubMed:19287380, ECO:0000269PubMed:22307329, ECO:0000269PubMed:22878263, ECO:0000269PubMed:23362280, ECO:0000269PubMed:9748265}.

Subcellular Localization

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

Disease Associations

Tissue Specificity

Testis, after the onset of spermatogenesis. {ECO:0000269PubMed:9748265}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 57 experimentally validated interaction(s) in this database.

Experimentally validated
Total	57 [view]
Protein-Protein	55 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030145	manganese ion binding
GO:0043130	ubiquitin binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006974	cellular response to DNA damage stimulus
GO:0007224	smoothened signaling pathway
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0045725	positive regulation of glycogen biosynthetic process
GO:0051534	negative regulation of NFAT protein import into nucleus

Cellular Component

GO:0000151	ubiquitin ligase complex
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0030529	ribonucleoprotein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt