UniProtKB - O43781 (DYRK3_HUMAN)
Dual specificity tyrosine-phosphorylation-regulated kinase 3
DYRK3
Functioni
Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724).
Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:9748265, PubMed:29634919).
Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724).
Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724).
Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724).
Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227).
When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227).
Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429).
Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429).
Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603).
6 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 238 | ATPPROSITE-ProRule annotation2 Publications | 1 | |
Active sitei | 335 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 215 – 223 | ATPPROSITE-ProRule annotation1 Publication | 9 | |
Nucleotide bindingi | 288 – 291 | ATPPROSITE-ProRule annotation1 Publication | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- protein kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB-KW
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- cell division Source: UniProtKB-KW
- erythrocyte differentiation Source: UniProtKB
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
- nuclear speck organization Source: UniProtKB
- organelle disassembly Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- peptidyl-threonine phosphorylation Source: GO_Central
- positive regulation of cell cycle G2/M phase transition Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of cellular response to stress Source: UniProtKB
- regulation of TORC1 signaling Source: UniProtKB
- stress granule disassembly Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Biological process | Cell cycle, Cell division, Mitosis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 2681 |
PathwayCommonsi | O43781 |
SignaLinki | O43781 |
SIGNORi | O43781 |
Names & Taxonomyi
Protein namesi | Recommended name: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC:2.7.12.14 Publications)Alternative name(s): Regulatory erythroid kinase1 Publication Short name: REDK1 Publication |
Gene namesi | Name:DYRK3Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3094, DYRK3 |
MIMi | 603497, gene |
neXtProti | NX_O43781 |
VEuPathDBi | HostDB:ENSG00000143479 |
Subcellular locationi
Cytoskeleton
- centrosome 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Nucleus
- Nucleus 3 Publications
- Nucleus speckle 1 Publication
Other locations
- Cytoplasmic granule 3 Publications
Note: Associates with membraneless organelles in the cytoplasm and nucleus (PubMed:29973724). Shuttles between cytoplasm and stress granules (PubMed:20167603). Localized predominantly on distinct speckles distributed throughout the cytoplasm of the cell (PubMed:20167603). At low concentration, showns a homogeneous distribution throughout the cytoplasm and does not condense in speckles. During oxidative and osmotic stress, localizes to stress granules (PubMed:20167603).2 Publications
Cytoskeleton
- cytoskeleton Source: GO_Central
- pericentriolar material Source: UniProtKB
Cytosol
- cytosol Source: HPA
Nucleus
- nuclear speck Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- cytoplasmic stress granule Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 238 | K → M: Kinase dead; Induces formation of stress granules-like in absence of stress. Impaired dissolution of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material. 3 Publications | 1 | |
Mutagenesisi | 350 | S → A: Decreased stability of the protein. 1 Publication | 1 | |
Mutagenesisi | 350 | S → E or D: Phosphomimetic mutant; increased stability of the protein. 1 Publication | 1 | |
Mutagenesisi | 470 – 474 | RRGKK → AAGAA: Abolishes localization to the nucleus, leading to impaired dissolution of nuclear speckles during mitosis. 1 Publication | 5 |
Organism-specific databases
DisGeNETi | 8444 |
OpenTargetsi | ENSG00000143479 |
PharmGKBi | PA27551 |
Miscellaneous databases
Pharosi | O43781, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4575 |
GuidetoPHARMACOLOGYi | 2012 |
Genetic variation databases
BioMutai | DYRK3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085938 | 1 – 588 | Dual specificity tyrosine-phosphorylation-regulated kinase 3Add BLAST | 588 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 350 | Phosphoserine1 Publication | 1 | |
Modified residuei | 369 | PhosphotyrosineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | O43781 |
MassIVEi | O43781 |
MaxQBi | O43781 |
PaxDbi | O43781 |
PeptideAtlasi | O43781 |
PRIDEi | O43781 |
ProteomicsDBi | 49168 [O43781-1] 49169 [O43781-2] |
PTM databases
iPTMneti | O43781 |
PhosphoSitePlusi | O43781 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000143479, Expressed in testis and 183 other tissues |
ExpressionAtlasi | O43781, baseline and differential |
Genevisiblei | O43781, HS |
Organism-specific databases
HPAi | ENSG00000143479, Tissue enhanced (testis) |
Interactioni
Subunit structurei
Interacts with SIRT1.
By similarityBinary interactionsi
Isoform 2 [O43781-2]
With | #Exp. | IntAct |
---|---|---|
GORASP2 [Q9H8Y8] | 5 | EBI-13332019,EBI-739467 |
Protein-protein interaction databases
BioGRIDi | 114022, 10 interactors |
IntActi | O43781, 28 interactors |
MINTi | O43781 |
STRINGi | 9606.ENSP00000356076 |
Chemistry databases
BindingDBi | O43781 |
Miscellaneous databases
RNActi | O43781, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O43781 |
SMRi | O43781 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 209 – 522 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 314 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 188 | Disordered1 PublicationAdd BLAST | 188 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 468 – 481 | Nuclear localization signal1 PublicationAdd BLAST | 14 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0667, Eukaryota |
GeneTreei | ENSGT00940000159878 |
HOGENOMi | CLU_000288_5_13_1 |
InParanoidi | O43781 |
OMAi | CDDPTFI |
OrthoDBi | 870358at2759 |
PhylomeDBi | O43781 |
TreeFami | TF314624 |
Family and domain databases
Gene3Di | 3.30.10.30, 1 hit |
InterProi | View protein in InterPro IPR042521, DYRK IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGGTARGPGR KDAGPPGAGL PPQQRRLGDG VYDTFMMIDE TKCPPCSNVL
60 70 80 90 100
CNPSEPPPPR RLNMTTEQFT GDHTQHFLDG GEMKVEQLFQ EFGNRKSNTI
110 120 130 140 150
QSDGISDSEK CSPTVSQGKS SDCLNTVKSN SSSKAPKVVP LTPEQALKQY
160 170 180 190 200
KHHLTAYEKL EIINYPEIYF VGPNAKKRHG VIGGPNNGGY DDADGAYIHV
210 220 230 240 250
PRDHLAYRYE VLKIIGKGSF GQVARVYDHK LRQYVALKMV RNEKRFHRQA
260 270 280 290 300
AEEIRILEHL KKQDKTGSMN VIHMLESFTF RNHVCMAFEL LSIDLYELIK
310 320 330 340 350
KNKFQGFSVQ LVRKFAQSIL QSLDALHKNK IIHCDLKPEN ILLKHHGRSS
360 370 380 390 400
TKVIDFGSSC FEYQKLYTYI QSRFYRAPEI ILGSRYSTPI DIWSFGCILA
410 420 430 440 450
ELLTGQPLFP GEDEGDQLAC MMELLGMPPP KLLEQSKRAK YFINSKGIPR
460 470 480 490 500
YCSVTTQADG RVVLVGGRSR RGKKRGPPGS KDWGTALKGC DDYLFIEFLK
510 520 530 540 550
RCLHWDPSAR LTPAQALRHP WISKSVPRPL TTIDKVSGKR VVNPASAFQG
560 570 580
LGSKLPPVVG IANKLKANLM SETNGSIPLC SVLPKLIS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5SY34 | Q5SY34_HUMAN | Dual-specificity tyrosine-phosphory... | DYRK3 | 243 | Annotation score: | ||
A0A3B3ISB2 | A0A3B3ISB2_HUMAN | Dual-specificity tyrosine-phosphory... | DYRK3 | 71 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 313 | R → H in AAH15501 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 396 | G → R in CAA73266 (PubMed:9748265).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040464 | 239 | M → L1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026178 | 1 – 20 | Missing in isoform 2. 3 PublicationsAdd BLAST | 20 | |
Alternative sequenceiVSP_026179 | 21 – 26 | PPQQRR → MKWKEK in isoform 2. 3 Publications | 6 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12735 mRNA Translation: CAA73266.2 AF186773 mRNA Translation: AAG17028.1 AF186774 mRNA Translation: AAG17029.1 AF327561 mRNA Translation: AAK16443.1 AY590695 mRNA Translation: AAT06103.1 AL591846 Genomic DNA No translation available. CH471100 Genomic DNA Translation: EAW93533.1 CH471100 Genomic DNA Translation: EAW93534.1 BC015501 mRNA Translation: AAH15501.1 |
CCDSi | CCDS30999.1 [O43781-1] CCDS31000.1 [O43781-2] |
RefSeqi | NP_001004023.1, NM_001004023.1 [O43781-2] NP_003573.2, NM_003582.2 [O43781-1] XP_005273372.1, XM_005273315.4 [O43781-2] |
Genome annotation databases
Ensembli | ENST00000367106.1; ENSP00000356073.1; ENSG00000143479.18 [O43781-2] ENST00000367108.7; ENSP00000356075.3; ENSG00000143479.18 [O43781-2] ENST00000367109.8; ENSP00000356076.2; ENSG00000143479.18 |
GeneIDi | 8444 |
KEGGi | hsa:8444 |
MANE-Selecti | ENST00000367109.8; ENSP00000356076.2; NM_003582.4; NP_003573.2 |
UCSCi | uc001hei.4, human [O43781-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12735 mRNA Translation: CAA73266.2 AF186773 mRNA Translation: AAG17028.1 AF186774 mRNA Translation: AAG17029.1 AF327561 mRNA Translation: AAK16443.1 AY590695 mRNA Translation: AAT06103.1 AL591846 Genomic DNA No translation available. CH471100 Genomic DNA Translation: EAW93533.1 CH471100 Genomic DNA Translation: EAW93534.1 BC015501 mRNA Translation: AAH15501.1 |
CCDSi | CCDS30999.1 [O43781-1] CCDS31000.1 [O43781-2] |
RefSeqi | NP_001004023.1, NM_001004023.1 [O43781-2] NP_003573.2, NM_003582.2 [O43781-1] XP_005273372.1, XM_005273315.4 [O43781-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5Y86 | X-ray | 1.90 | A | 1-588 | [»] | |
AlphaFoldDBi | O43781 | |||||
SMRi | O43781 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114022, 10 interactors |
IntActi | O43781, 28 interactors |
MINTi | O43781 |
STRINGi | 9606.ENSP00000356076 |
Chemistry databases
BindingDBi | O43781 |
ChEMBLi | CHEMBL4575 |
GuidetoPHARMACOLOGYi | 2012 |
PTM databases
iPTMneti | O43781 |
PhosphoSitePlusi | O43781 |
Genetic variation databases
BioMutai | DYRK3 |
Proteomic databases
jPOSTi | O43781 |
MassIVEi | O43781 |
MaxQBi | O43781 |
PaxDbi | O43781 |
PeptideAtlasi | O43781 |
PRIDEi | O43781 |
ProteomicsDBi | 49168 [O43781-1] 49169 [O43781-2] |
Protocols and materials databases
Antibodypediai | 34587, 237 antibodies from 28 providers |
DNASUi | 8444 |
Genome annotation databases
Ensembli | ENST00000367106.1; ENSP00000356073.1; ENSG00000143479.18 [O43781-2] ENST00000367108.7; ENSP00000356075.3; ENSG00000143479.18 [O43781-2] ENST00000367109.8; ENSP00000356076.2; ENSG00000143479.18 |
GeneIDi | 8444 |
KEGGi | hsa:8444 |
MANE-Selecti | ENST00000367109.8; ENSP00000356076.2; NM_003582.4; NP_003573.2 |
UCSCi | uc001hei.4, human [O43781-1] |
Organism-specific databases
CTDi | 8444 |
DisGeNETi | 8444 |
GeneCardsi | DYRK3 |
HGNCi | HGNC:3094, DYRK3 |
HPAi | ENSG00000143479, Tissue enhanced (testis) |
MIMi | 603497, gene |
neXtProti | NX_O43781 |
OpenTargetsi | ENSG00000143479 |
PharmGKBi | PA27551 |
VEuPathDBi | HostDB:ENSG00000143479 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0667, Eukaryota |
GeneTreei | ENSGT00940000159878 |
HOGENOMi | CLU_000288_5_13_1 |
InParanoidi | O43781 |
OMAi | CDDPTFI |
OrthoDBi | 870358at2759 |
PhylomeDBi | O43781 |
TreeFami | TF314624 |
Enzyme and pathway databases
BRENDAi | 2.7.12.1, 2681 |
PathwayCommonsi | O43781 |
SignaLinki | O43781 |
SIGNORi | O43781 |
Miscellaneous databases
BioGRID-ORCSi | 8444, 11 hits in 1114 CRISPR screens |
ChiTaRSi | DYRK3, human |
GeneWikii | DYRK3 |
GenomeRNAii | 8444 |
Pharosi | O43781, Tchem |
PROi | PR:O43781 |
RNActi | O43781, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000143479, Expressed in testis and 183 other tissues |
ExpressionAtlasi | O43781, baseline and differential |
Genevisiblei | O43781, HS |
Family and domain databases
Gene3Di | 3.30.10.30, 1 hit |
InterProi | View protein in InterPro IPR042521, DYRK IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DYRK3_HUMAN | |
Accessioni | O43781Primary (citable) accession number: O43781 Secondary accession number(s): D3DT79 Q9HBY7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | June 26, 2007 | |
Last modified: | May 25, 2022 | |
This is version 190 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families