Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 2

Gene

DYRK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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. 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

Protein has several cofactor binding sites:

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei251ATPCurated1
Active sitei348Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi228 – 236ATPCurated9
Nucleotide bindingi301 – 304ATPCurated4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
Biological processApoptosis, Ubl conjugation pathway
LigandATP-binding, Magnesium, Manganese, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
ReactomeiR-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkiQ92630
SIGNORiQ92630

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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000127334.10
HGNCiHGNC:3093 DYRK2
MIMi603496 gene
neXtProtiNX_Q92630

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106T → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. 1 Publication1
Mutagenesisi189 – 191KKR → NNN: Impaired nuclear translocation. 1 Publication3
Mutagenesisi251K → R: Abolishes protein serine/threonine kinase activity. 1 Publication1
Mutagenesisi442S → A: Impaired ATM-mediated phosphorylation, reduced affinity with MDM2 and altered MDM2-triggered ubiquitination. 1 Publication1

Organism-specific databases

DisGeNETi8445
OpenTargetsiENSG00000127334
PharmGKBiPA27550

Chemistry databases

ChEMBLiCHEMBL4376
GuidetoPHARMACOLOGYi2011

Polymorphism and mutation databases

BioMutaiDYRK2
DMDMi148887370

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859361 – 601Dual specificity tyrosine-phosphorylation-regulated kinase 2Add BLAST601

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphoserineCombined sources1
Modified residuei106Phosphothreonine; by ATM1 Publication1
Modified residuei381Phosphothreonine; by MAP3K101 Publication1
Modified residuei382Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei442Phosphoserine; by ATM1 Publication1
Modified residuei449Phosphoserine; by MAP3K101 Publication1

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

EPDiQ92630
MaxQBiQ92630
PaxDbiQ92630
PeptideAtlasiQ92630
PRIDEiQ92630
ProteomicsDBi75387
75388 [Q92630-2]

PTM databases

iPTMnetiQ92630
PhosphoSitePlusiQ92630

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

BgeeiENSG00000127334 Expressed in 235 organ(s), highest expression level in neocortex
CleanExiHS_DYRK2
ExpressionAtlasiQ92630 baseline and differential
GenevisibleiQ92630 HS

Organism-specific databases

HPAiHPA027230
HPA056902

Interactioni

Subunit structurei

Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and DCAF1. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2.6 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi114023, 63 interactors
CORUMiQ92630
IntActiQ92630, 13 interactors
STRINGi9606.ENSP00000342105

Chemistry databases

BindingDBiQ92630

Structurei

Secondary structure

1601
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92630
SMRiQ92630
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92630

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini222 – 535Protein kinasePROSITE-ProRule annotationAdd BLAST314

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi189 – 191Nuclear localization signal1 Publication3

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000220863
HOVERGENiHBG051426
InParanoidiQ92630
KOiK18669
OMAiKLTTFEH
OrthoDBiEOG091G0Q46
PhylomeDBiQ92630
TreeFamiTF314624

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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
        10         20         30         40         50
MLTRKPSAAA PAAYPTGRGG DSAVRQLQAS PGLGAGATRS GVGTGPPSPI
60 70 80 90 100
ALPPLRASNA AAAAHTIGGS KHTMNDHLHV GSHAHGQIQV QQLFEDNSNK
110 120 130 140 150
RTVLTTQPNG LTTVGKTGLP VVPERQLDSI HRRQGSSTSL KSMEGMGKVK
160 170 180 190 200
ATPMTPEQAM KQYMQKLTAF EHHEIFSYPE IYFLGLNAKK RQGMTGGPNN
210 220 230 240 250
GGYDDDQGSY VQVPHDHVAY RYEVLKVIGK GSFGQVVKAY DHKVHQHVAL
260 270 280 290 300
KMVRNEKRFH RQAAEEIRIL EHLRKQDKDN TMNVIHMLEN FTFRNHICMT
310 320 330 340 350
FELLSMNLYE LIKKNKFQGF SLPLVRKFAH SILQCLDALH KNRIIHCDLK
360 370 380 390 400
PENILLKQQG RSGIKVIDFG SSCYEHQRVY TYIQSRFYRA PEVILGARYG
410 420 430 440 450
MPIDMWSLGC ILAELLTGYP LLPGEDEGDQ LACMIELLGM PSQKLLDASK
460 470 480 490 500
RAKNFVSSKG YPRYCTVTTL SDGSVVLNGG RSRRGKLRGP PESREWGNAL
510 520 530 540 550
KGCDDPLFLD FLKQCLEWDP AVRMTPGQAL RHPWLRRRLP KPPTGEKTSV
560 570 580 590 600
KRITESTGAI TSISKLPPPS SSASKLRTNL AQMTDANGNI QQRTVLPKLV

S
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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H5L5F5H5L5_HUMAN
Dual-specificity tyrosine-phosphory...
DYRK2
167Annotation score:
F5GXG1F5GXG1_HUMAN
Dual-specificity tyrosine-phosphory...
DYRK2
156Annotation score:
A0A0A0MR56A0A0A0MR56_HUMAN
Dual-specificity tyrosine-phosphory...
DYRK2
93Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37A → P in CAA73885 (PubMed:9748265).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04045898S → G1 PublicationCorresponds to variant dbSNP:rs35139851Ensembl.1
Natural variantiVAR_040459198P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_040460245H → N1 PublicationCorresponds to variant dbSNP:rs34166200Ensembl.1
Natural variantiVAR_040461295N → S1 PublicationCorresponds to variant dbSNP:rs56293072Ensembl.1
Natural variantiVAR_040462451R → Q1 PublicationCorresponds to variant dbSNP:rs35688869Ensembl.1
Natural variantiVAR_040463455F → Y1 PublicationCorresponds to variant dbSNP:rs55774594Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0261151 – 73Missing in isoform 2. 1 PublicationAdd BLAST73

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
XP_016875521.1, XM_017020032.1 [Q92630-2]
UniGeneiHs.173135

Genome annotation databases

EnsembliENST00000344096; ENSP00000342105; ENSG00000127334 [Q92630-1]
ENST00000393555; ENSP00000377186; ENSG00000127334 [Q92630-2]
GeneIDi8445
KEGGihsa:8445
UCSCiuc001str.5 human [Q92630-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
XP_016875521.1, XM_017020032.1 [Q92630-2]
UniGeneiHs.173135

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3K2LX-ray2.36A146-552[»]
3KVWX-ray2.28A146-552[»]
4AZFX-ray2.55A146-540[»]
5LXCX-ray2.15A/B146-552[»]
5LXDX-ray2.58A/B146-552[»]
5ZTNX-ray2.50A/B146-552[»]
ProteinModelPortaliQ92630
SMRiQ92630
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114023, 63 interactors
CORUMiQ92630
IntActiQ92630, 13 interactors
STRINGi9606.ENSP00000342105

Chemistry databases

BindingDBiQ92630
ChEMBLiCHEMBL4376
GuidetoPHARMACOLOGYi2011

PTM databases

iPTMnetiQ92630
PhosphoSitePlusiQ92630

Polymorphism and mutation databases

BioMutaiDYRK2
DMDMi148887370

Proteomic databases

EPDiQ92630
MaxQBiQ92630
PaxDbiQ92630
PeptideAtlasiQ92630
PRIDEiQ92630
ProteomicsDBi75387
75388 [Q92630-2]

Protocols and materials databases

DNASUi8445
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344096; ENSP00000342105; ENSG00000127334 [Q92630-1]
ENST00000393555; ENSP00000377186; ENSG00000127334 [Q92630-2]
GeneIDi8445
KEGGihsa:8445
UCSCiuc001str.5 human [Q92630-1]

Organism-specific databases

CTDi8445
DisGeNETi8445
EuPathDBiHostDB:ENSG00000127334.10
GeneCardsiDYRK2
HGNCiHGNC:3093 DYRK2
HPAiHPA027230
HPA056902
MIMi603496 gene
neXtProtiNX_Q92630
OpenTargetsiENSG00000127334
PharmGKBiPA27550
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000220863
HOVERGENiHBG051426
InParanoidiQ92630
KOiK18669
OMAiKLTTFEH
OrthoDBiEOG091G0Q46
PhylomeDBiQ92630
TreeFamiTF314624

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
ReactomeiR-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkiQ92630
SIGNORiQ92630

Miscellaneous databases

ChiTaRSiDYRK2 human
EvolutionaryTraceiQ92630
GeneWikiiDYRK2
GenomeRNAii8445
PROiPR:Q92630
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127334 Expressed in 235 organ(s), highest expression level in neocortex
CleanExiHS_DYRK2
ExpressionAtlasiQ92630 baseline and differential
GenevisibleiQ92630 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDYRK2_HUMAN
AccessioniPrimary (citable) accession number: Q92630
Secondary accession number(s): B2R9V9, Q9BRB5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: June 12, 2007
Last modified: October 10, 2018
This is version 191 of the entry and version 3 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again