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Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 3

Gene

DYRK3

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

Functioni

Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Negative regulator of EPO-dependent erythropoiesis, may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). May act by regulating CREB/CRE signaling (By similarity). Stabilizes and prevents stress granule disassembly thereby regulating mTORC1 signaling during cellular stress. During stressful conditions, DYRK3 partitions to the stress granule from the cytosol, as well as mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol, and promotes the phosphorylation of the mTORC1 inhibitor, AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (PubMed:20167603).By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Activity regulationi

Inhibited by harmine, leucettamine B and leucettine L41.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei238ATPPROSITE-ProRule annotation1 Publication1
Active sitei335Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi215 – 223ATPPROSITE-ProRule annotation9
Nucleotide bindingi288 – 291ATPPROSITE-ProRule annotation4

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 tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiO43781
SIGNORiO43781

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC:2.7.12.11 Publication)
Alternative name(s):
Regulatory erythroid kinase1 Publication
Short name:
REDK1 Publication
Gene namesi
Name:DYRK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143479.15
HGNCiHGNC:3094 DYRK3
MIMi603497 gene
neXtProtiNX_O43781

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi238K → M: Kinase dead; Induces formation of stress granules-like in absence of stress. 1 Publication1

Organism-specific databases

DisGeNETi8444
OpenTargetsiENSG00000143479
PharmGKBiPA27551

Chemistry databases

ChEMBLiCHEMBL4575
GuidetoPHARMACOLOGYi2012

Polymorphism and mutation databases

BioMutaiDYRK3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859381 – 588Dual specificity tyrosine-phosphorylation-regulated kinase 3Add BLAST588

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei369PhosphotyrosineBy similarity1

Post-translational modificationi

Autophosphorylated on tyrosine residues (PubMed:9748265).1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO43781
PaxDbiO43781
PeptideAtlasiO43781
PRIDEiO43781
ProteomicsDBi49168
49169 [O43781-2]

PTM databases

iPTMnetiO43781
PhosphoSitePlusiO43781

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow. Isoform 2 is the predominant form in testis. Isoform 1 is the predominant form in fetal liver and bone marrow. Isoform 1 and isoform 2 are present at low levels in heart, pancreas, lymph node, and thymus.1 Publication

Inductioni

By EPO/erythropoietin.1 Publication

Gene expression databases

BgeeiENSG00000143479 Expressed in 163 organ(s), highest expression level in testis
CleanExiHS_DYRK3
ExpressionAtlasiO43781 baseline and differential
GenevisibleiO43781 HS

Organism-specific databases

HPAiHPA075041

Interactioni

Subunit structurei

Interacts with SIRT1.By similarity

Protein-protein interaction databases

BioGridi114022, 6 interactors
IntActiO43781, 5 interactors
STRINGi9606.ENSP00000356076

Chemistry databases

BindingDBiO43781

Structurei

Secondary structure

1588
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43781
SMRiO43781
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 522Protein kinasePROSITE-ProRule annotationAdd BLAST314

Domaini

The N-terminal domain is required for stress granule localization (PubMed:23415227).

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000220863
HOVERGENiHBG051426
InParanoidiO43781
KOiK18669
OMAiLKQYKHH
OrthoDBiEOG091G0Q46
PhylomeDBiO43781
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 1 potential isoform that is computationally mapped.iShow all

Isoform 1 (identifier: O43781-1) [UniParc]FASTAAdd to basket
Also known as: Long

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
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
Length:588
Mass (Da):65,714
Last modified:June 26, 2007 - v3
Checksum:i9950F51C39AFED82
GO
Isoform 2 (identifier: O43781-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-26: PPQQRR → MKWKEK

Show »
Length:568
Mass (Da):63,977
Checksum:i9B710ECC413873F7
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SY34Q5SY34_HUMAN
Dual-specificity tyrosine-phosphory...
DYRK3
243Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti313R → H in AAH15501 (PubMed:15489334).Curated1
Sequence conflicti396G → R in CAA73266 (PubMed:9748265).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040464239M → L1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0261781 – 20Missing in isoform 2. 3 PublicationsAdd BLAST20
Alternative sequenceiVSP_02617921 – 26PPQQRR → MKWKEK in isoform 2. 3 Publications6

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
CCDSiCCDS30999.1 [O43781-1]
CCDS31000.1 [O43781-2]
RefSeqiNP_001004023.1, NM_001004023.1 [O43781-2]
NP_003573.2, NM_003582.2 [O43781-1]
XP_005273372.1, XM_005273315.4 [O43781-2]
UniGeneiHs.164267

Genome annotation databases

EnsembliENST00000367106; ENSP00000356073; ENSG00000143479 [O43781-2]
ENST00000367108; ENSP00000356075; ENSG00000143479 [O43781-2]
ENST00000367109; ENSP00000356076; ENSG00000143479 [O43781-1]
GeneIDi8444
KEGGihsa:8444
UCSCiuc001hei.4 human [O43781-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS30999.1 [O43781-1]
CCDS31000.1 [O43781-2]
RefSeqiNP_001004023.1, NM_001004023.1 [O43781-2]
NP_003573.2, NM_003582.2 [O43781-1]
XP_005273372.1, XM_005273315.4 [O43781-2]
UniGeneiHs.164267

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5Y86X-ray1.90A1-588[»]
ProteinModelPortaliO43781
SMRiO43781
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114022, 6 interactors
IntActiO43781, 5 interactors
STRINGi9606.ENSP00000356076

Chemistry databases

BindingDBiO43781
ChEMBLiCHEMBL4575
GuidetoPHARMACOLOGYi2012

PTM databases

iPTMnetiO43781
PhosphoSitePlusiO43781

Polymorphism and mutation databases

BioMutaiDYRK3

Proteomic databases

MaxQBiO43781
PaxDbiO43781
PeptideAtlasiO43781
PRIDEiO43781
ProteomicsDBi49168
49169 [O43781-2]

Protocols and materials databases

DNASUi8444
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367106; ENSP00000356073; ENSG00000143479 [O43781-2]
ENST00000367108; ENSP00000356075; ENSG00000143479 [O43781-2]
ENST00000367109; ENSP00000356076; ENSG00000143479 [O43781-1]
GeneIDi8444
KEGGihsa:8444
UCSCiuc001hei.4 human [O43781-1]

Organism-specific databases

CTDi8444
DisGeNETi8444
EuPathDBiHostDB:ENSG00000143479.15
GeneCardsiDYRK3
HGNCiHGNC:3094 DYRK3
HPAiHPA075041
MIMi603497 gene
neXtProtiNX_O43781
OpenTargetsiENSG00000143479
PharmGKBiPA27551
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000220863
HOVERGENiHBG051426
InParanoidiO43781
KOiK18669
OMAiLKQYKHH
OrthoDBiEOG091G0Q46
PhylomeDBiO43781
TreeFamiTF314624

Enzyme and pathway databases

BRENDAi2.7.12.1 2681
SignaLinkiO43781
SIGNORiO43781

Miscellaneous databases

ChiTaRSiDYRK3 human
GeneWikiiDYRK3
GenomeRNAii8444
PROiPR:O43781
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143479 Expressed in 163 organ(s), highest expression level in testis
CleanExiHS_DYRK3
ExpressionAtlasiO43781 baseline and differential
GenevisibleiO43781 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 nameiDYRK3_HUMAN
AccessioniPrimary (citable) accession number: O43781
Secondary accession number(s): D3DT79
, Q7Z752, Q9HBY6, Q9HBY7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: June 26, 2007
Last modified: September 12, 2018
This is version 168 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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