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 3

Gene

DYRK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • 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
  • 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 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

HGNCiHGNC:3094. DYRK3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
  • cytosol Source: HPA
  • intracellular membrane-bounded organelle Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB

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.

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.
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. 5 interactors.
IntActiO43781. 5 interactors.
STRINGi9606.ENSP00000356076.

Chemistry databases

BindingDBiO43781.

Structurei

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.
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

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

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. Translation: CAI13539.1.
AL591846 Genomic DNA. Translation: CAI13541.1.
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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: March 15, 2017
This is version 163 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families