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Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 1B

Gene

DYRK1B

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. Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase (G6PC).4 Publications

Catalytic activityi

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

Enzyme regulationi

Inhibited by RANBP9.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei140ATPPROSITE-ProRule annotation1
Active sitei239Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi117 – 125ATPPROSITE-ProRule annotation9
Nucleotide bindingi190 – 193ATPPROSITE-ProRule annotation4

GO - Molecular functioni

GO - Biological processi

  • adipose tissue development Source: UniProtKB
  • myoblast fusion Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • protein phosphorylation Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

BioCyciMetaCyc:HS02690-MONOMER
BRENDAi2.7.12.1 2681
SignaLinkiQ9Y463
SIGNORiQ9Y463

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity tyrosine-phosphorylation-regulated kinase 1B (EC:2.7.12.1)
Alternative name(s):
Minibrain-related kinase
Mirk protein kinase
Gene namesi
Name:DYRK1B
Synonyms:MIRK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105204.13
HGNCiHGNC:3092 DYRK1B
MIMi604556 gene
neXtProtiNX_Q9Y463

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

Involvement in diseasei

Abdominal obesity-metabolic syndrome 3 (AOMS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of abdominal obesity-metabolic syndrome, a disorder characterized by abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol, high blood pressure, and elevated fasting glucose levels. AOMS3 is characterized by early-onset coronary artery disease, central obesity, hypertension, and diabetes.
See also OMIM:615812
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07177390H → P in AOMS3; expression of glucose-6-phosphatase is significantly higher than wild-type. 1 PublicationCorresponds to variant dbSNP:rs587777380Ensembl.1
Natural variantiVAR_071774102R → C in AOMS3; accumulation of intracellular lipid is significantly greater than with wild-type protein; cells expressing the variant are able to transform into mature adipocytes without requiring adipogenic medium; expression levels of CEBPA, PPARG forms 1 and 2 and PPARGC1A are higher and those of GLI1 and CDKN1B are lower in cells transfected with the mutant protein compared to wild-type; WNT1 signaling activity is lower in mutant cells compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs367643250Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140K → R: Abolishes kinase activity. 1 Publication1
Mutagenesisi271Y → F: Abolishes kinase activity; when associated with F-273. 1 Publication1
Mutagenesisi273Y → F: Abolishes kinase activity; when associated with F-271. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Obesity

Organism-specific databases

DisGeNETi9149
MalaCardsiDYRK1B
MIMi615812 phenotype
OpenTargetsiENSG00000105204
PharmGKBiPA27549

Chemistry databases

ChEMBLiCHEMBL5543
GuidetoPHARMACOLOGYi2010

Polymorphism and mutation databases

BioMutaiDYRK1B
DMDMi9296963

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859341 – 629Dual specificity tyrosine-phosphorylation-regulated kinase 1BAdd BLAST629

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei63PhosphotyrosineBy similarity1
Modified residuei92PhosphotyrosineBy similarity1
Modified residuei111PhosphotyrosineBy similarity1
Modified residuei129PhosphotyrosineBy similarity1
Modified residuei171PhosphotyrosineBy similarity1
Modified residuei262PhosphoserineBy similarity1
Modified residuei271Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei273Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei401PhosphotyrosineBy similarity1
Modified residuei624PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated on tyrosine residues. Phosphorylated by MAP kinase. Tyrosine phosphorylation may be required for dimerization.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Y463
PeptideAtlasiQ9Y463
PRIDEiQ9Y463

PTM databases

iPTMnetiQ9Y463
PhosphoSitePlusiQ9Y463

Expressioni

Tissue specificityi

Highest expression in skeletal muscle, testis, heart and brain with little expression in colon or lung. Expressed in a variety of tumor cell lines.1 Publication

Gene expression databases

BgeeiENSG00000105204
CleanExiHS_DYRK1B
ExpressionAtlasiQ9Y463 baseline and differential
GenevisibleiQ9Y463 HS

Organism-specific databases

HPAiHPA028522
HPA028786

Interactioni

Subunit structurei

Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with DCAF7.3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi114596, 63 interactors
ELMiQ9Y463
IntActiQ9Y463, 54 interactors
MINTiQ9Y463
STRINGi9606.ENSP00000312789

Chemistry databases

BindingDBiQ9Y463

Structurei

3D structure databases

ProteinModelPortaliQ9Y463
SMRiQ9Y463
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini111 – 431Protein kinasePROSITE-ProRule annotationAdd BLAST321

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni480 – 520Interaction with RANBP91 PublicationAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi69 – 86Bipartite nuclear localization signalSequence analysisAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi558 – 561Poly-Pro4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000220863
HOVERGENiHBG051425
InParanoidiQ9Y463
KOiK08825
OMAiDCEMNSP
OrthoDBiEOG091G03J7
PhylomeDBiQ9Y463
TreeFamiTF314624

Family and domain databases

InterProiView protein in InterPro
IPR033565 DYRK1B
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR24058:SF27 PTHR24058:SF27, 1 hit
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y463-1) [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
MAVPPGHGPF SGFPGPQEHT QVLPDVRLLP RRLPLAFRDA TSAPLRKLSV
60 70 80 90 100
DLIKTYKHIN EVYYAKKKRR AQQAPPQDSS NKKEKKVLNH GYDDDNHDYI
110 120 130 140 150
VRSGERWLER YEIDSLIGKG SFGQVVKAYD HQTQELVAIK IIKNKKAFLN
160 170 180 190 200
QAQIELRLLE LMNQHDTEMK YYIVHLKRHF MFRNHLCLVF ELLSYNLYDL
210 220 230 240 250
LRNTHFRGVS LNLTRKLAQQ LCTALLFLAT PELSIIHCDL KPENILLCNP
260 270 280 290 300
KRSAIKIVDF GSSCQLGQRI YQYIQSRFYR SPEVLLGTPY DLAIDMWSLG
310 320 330 340 350
CILVEMHTGE PLFSGSNEVD QMNRIVEVLG IPPAAMLDQA PKARKYFERL
360 370 380 390 400
PGGGWTLRRT KELRKDYQGP GTRRLQEVLG VQTGGPGGRR AGEPGHSPAD
410 420 430 440 450
YLRFQDLVLR MLEYEPAARI SPLGALQHGF FRRTADEATN TGPAGSSAST
460 470 480 490 500
SPAPLDTCPS SSTASSISSS GGSSGSSSDN RTYRYSNRYC GGPGPPITDC
510 520 530 540 550
EMNSPQVPPS QPLRPWAGGD VPHKTHQAPA SASSLPGTGA QLPPQPRYLG
560 570 580 590 600
RPPSPTSPPP PELMDVSLVG GPADCSPPHP APAPQHPAAS ALRTRMTGGR
610 620
PPLPPPDDPA TLGPHLGLRG VPQSTAASS
Length:629
Mass (Da):69,198
Last modified:November 1, 1999 - v1
Checksum:iD7C354AC55943A8B
GO
Isoform 2 (identifier: Q9Y463-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-405: Missing.

Show »
Length:589
Mass (Da):64,934
Checksum:iE98BF9B257237A9D
GO
Isoform 3 (identifier: Q9Y463-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     378-405: Missing.

Show »
Length:601
Mass (Da):66,336
Checksum:i8601907D9652274B
GO

Sequence cautioni

The sequence AAC28914 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04045428L → P1 PublicationCorresponds to variant dbSNP:rs34587974Ensembl.1
Natural variantiVAR_07177390H → P in AOMS3; expression of glucose-6-phosphatase is significantly higher than wild-type. 1 PublicationCorresponds to variant dbSNP:rs587777380Ensembl.1
Natural variantiVAR_071774102R → C in AOMS3; accumulation of intracellular lipid is significantly greater than with wild-type protein; cells expressing the variant are able to transform into mature adipocytes without requiring adipogenic medium; expression levels of CEBPA, PPARG forms 1 and 2 and PPARGC1A are higher and those of GLI1 and CDKN1B are lower in cells transfected with the mutant protein compared to wild-type; WNT1 signaling activity is lower in mutant cells compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs367643250Ensembl.1
Natural variantiVAR_040455102R → H1 PublicationCorresponds to variant dbSNP:rs55687541Ensembl.1
Natural variantiVAR_040456234S → G1 PublicationCorresponds to variant dbSNP:rs35858874Ensembl.1
Natural variantiVAR_040457275Q → R in a metastatic melanoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004925366 – 405Missing in isoform 2. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_004926378 – 405Missing in isoform 3. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y17999 mRNA Translation: CAA76991.1
Y17999 mRNA Translation: CAA76990.1
Y17999 mRNA Translation: CAA76989.1
AF205861 mRNA Translation: AAF15893.1
AC005393 Genomic DNA Translation: AAC28914.1 Sequence problems.
BC018751 mRNA Translation: AAH18751.1
BC025291 mRNA Translation: AAH25291.1
CCDSiCCDS12543.1 [Q9Y463-1]
CCDS12544.1 [Q9Y463-3]
CCDS46075.1 [Q9Y463-2]
PIRiJG0195
RefSeqiNP_004705.1, NM_004714.2 [Q9Y463-1]
NP_006474.1, NM_006483.2 [Q9Y463-2]
NP_006475.1, NM_006484.2 [Q9Y463-3]
XP_005259455.1, XM_005259398.4 [Q9Y463-1]
UniGeneiHs.130988

Genome annotation databases

EnsembliENST00000323039; ENSP00000312789; ENSG00000105204 [Q9Y463-1]
ENST00000348817; ENSP00000221803; ENSG00000105204 [Q9Y463-3]
ENST00000430012; ENSP00000403182; ENSG00000105204 [Q9Y463-2]
ENST00000593685; ENSP00000469863; ENSG00000105204 [Q9Y463-1]
ENST00000597639; ENSP00000472941; ENSG00000105204 [Q9Y463-3]
ENST00000625388; ENSP00000486839; ENSG00000281320 [Q9Y463-3]
ENST00000625438; ENSP00000487313; ENSG00000281320 [Q9Y463-3]
ENST00000625757; ENSP00000485915; ENSG00000281320 [Q9Y463-1]
ENST00000627034; ENSP00000487539; ENSG00000281320 [Q9Y463-2]
ENST00000631090; ENSP00000486377; ENSG00000281320 [Q9Y463-1]
GeneIDi9149
KEGGihsa:9149
UCSCiuc002omi.4 human [Q9Y463-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDYR1B_HUMAN
AccessioniPrimary (citable) accession number: Q9Y463
Secondary accession number(s): O75258, O75788, O75789
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: February 28, 2018
This is version 178 of the entry and version 1 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health