DYRK2
entrez
8445
canonical
uniprot
Q92630
canonical
ensembl
ENSG00000127334
resolver
ensp
ENSP00000342105
resolver
ensp
ENSP00000377186
resolver
genesymbol
DYRK2
resolver
hgnc
HGNC:3093
resolver
uniprot
B2R9V9
resolver
uniprot
Q9BRB5
resolver
uniprot_entry
DYRK2_HUMAN
resolver
uniprot_sec
B2R9V9
resolver
uniprot_sec
Q9BRB5
resolver
activity_regulation
ACTIVITY REGULATION: 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. {ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:19796173, ECO:0000269|PubMed:20836251, ECO:0000269|PubMed:22998443}.
uniprot
proteins
amino_acid_sequence
MLTRKPSAAAPAAYPTGRGGDSAVRQLQASPGLGAGATRSGVGTGPPSPIALPPLRASNAAAAAHTIGGSKHTMNDHLHVGSHAHGQIQVQQLFEDNSNKRTVLTTQPNGLTTVGKTGLPVVPERQLDSIHRRQGSSTSLKSMEGMGKVKATPMTPEQAMKQYMQKLTAFEHHEIFSYPEIYFLGLNAKKRQGMTGGPNNGGYDDDQGSYVQVPHDHVAYRYEVLKVIGKGSFGQVVKAYDHKVHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDKDNTMNVIHMLENFTFRNHICMTFELLSMNLYELIKKNKFQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQGRSGIKVIDFGSSCYEHQRVYTYIQSRFYRAPEVILGARYGMPIDMWSLGCILAELLTGYPLLPGEDEGDQLACMIELLGMPSQKLLDASKRAKNFVSSKGYPRYCTVTTLSDGSVVLNGGRSRRGKLRGPPESREWGNALKGCDDPLFLDFLKQCLEWDPAVRMTPGQALRHPWLRRRLPKPPTGEKTSVKRITESTGAITSISKLPPPSSSASKLRTNLAQMTDANGNIQQRTVLPKLVS
uniprot
proteins
ec_number
2.7.12.1
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth (PubMed:11311121, PubMed:12588975, PubMed:16511445, PubMed:16611631, PubMed:17349958, PubMed:18599021, PubMed:22307329, PubMed:9748265). Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1 (PubMed:11311121, PubMed:12588975, PubMed:16511445, PubMed:16611631, PubMed:17349958, PubMed:18599021, PubMed:22307329, PubMed:38968120). Can phosphorylate histone H1, histone H3 and histone H2B (in vitro) (PubMed:9748265). Can phosphorylate CARHSP1 (in vitro) (PubMed:15910284). Functions in part via its role in ubiquitin-dependent proteasomal protein degradation (PubMed:9748265). Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage (PubMed:17349958, PubMed:18599021). Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity (PubMed:16511445). May play a general role in the priming of GSK3 substrates (PubMed:11311121, PubMed:16611631). Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B (PubMed:11311121). Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B (PubMed:16611631). Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis (PubMed:14593110). Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1 (PubMed:19287380). Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex (PubMed:23362280). Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity (PubMed:22878263). Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation (PubMed:22307329). Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI2 and GLI3 in response to smoothened activation, promoting their dissociation from SUFU inhibitor and translocation to the nucleus (PubMed:38968120). Can also acts as a negative regulator of smoothened by catalyzing phosphorylation of GLI2 and GLI3 and promote their proteasomal degradation (PubMed:18455992). Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2 (By similarity). {ECO:0000250|UniProtKB:Q5U4C9, ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:38968120, ECO:0000269|PubMed:9748265}.
uniprot
proteins
mass_dalton
66652
uniprot
proteins
mutagenesis
MUTAGEN 106; /note="T->A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination."; /evidence="ECO:0000269|PubMed:19965871"; MUTAGEN 189..191; /note="KKR->NNN: Impaired nuclear translocation."; /evidence="ECO:0000269|PubMed:19965871"; MUTAGEN 251; /note="K->R: Abolishes protein serine/threonine kinase activity."; /evidence="ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:38968120"; MUTAGEN 442; /note="S->A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination."; /evidence="ECO:0000269|PubMed:19965871
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:19965871}.; PTM: 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. {ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:22878263}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MNB/DYRK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
11311121
uniprot
proteins
pubmed
12588975
uniprot
proteins
pubmed
12874018
uniprot
proteins
pubmed
14593110
uniprot
proteins
pubmed
14623875
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15910284
uniprot
proteins
pubmed
16511445
uniprot
proteins
pubmed
16611631
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17349958
uniprot
proteins
pubmed
18455992
uniprot
proteins
pubmed
18539531
uniprot
proteins
pubmed
18599021
uniprot
proteins
pubmed
19287380
uniprot
proteins
pubmed
19796173
uniprot
proteins
pubmed
19965871
uniprot
proteins
pubmed
20836251
uniprot
proteins
pubmed
22307329
uniprot
proteins
pubmed
22878263
uniprot
proteins
pubmed
22998443
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23362280
uniprot
proteins
pubmed
23665168
uniprot
proteins
pubmed
38968120
uniprot
proteins
pubmed
9748265
uniprot
proteins
sequence_length
601
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18599021}. Nucleus {ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18539531, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19965871}. Note=Translocates into the nucleus following DNA damage. {ECO:0000269|PubMed:17349958}.
uniprot
proteins