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Reviewed, UniProtKB/Swiss-Prot Q9Y463 (DYR1B_HUMAN)

Last modified February 9, 2010. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Dual specificity tyrosine-phosphorylation-regulated kinase 1B
    EC=2.7.12.1
Alternative name(s):
    Mirk protein kinase
    Minibrain-related kinase
Gene names
Name: DYRK1B
Synonyms: MIRK
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length629 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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. Ref.2 Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Inhibited by RANBP9.

Subunit structure

Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interatcs with WDR68. Ref.5 Ref.6 Ref.7

Subcellular location

Nucleus.

Tissue specificity

Highest expression in skeletal muscle, testis, heart and brain with little expression in colon or lung. Expressed in a variety of tumor cell lines. Ref.2

Post-translational modification

Autophosphorylated on tyrosine residues. Phosphorylated by MAP kinase. Tyrosine phosphorylation may be required for dimerization. Ref.2 Ref.8 Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAC28914.1 differs from that shown. Reason: Erroneous gene model prediction.

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y463-1)

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.
Isoform 2 (identifier: Q9Y463-2)

The sequence of this isoform differs from the canonical sequence as follows:
     366-405: Missing.
Isoform 3 (identifier: Q9Y463-3)

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 629629Dual specificity tyrosine-phosphorylation-regulated kinase 1B
PRO_0000085934

Regions

Domain111 – 431321Protein kinase
Nucleotide binding117 – 1259ATP By similarity
Region480 – 52041Interaction with RANBP9
Motif69 – 8618Bipartite nuclear localization signal Potential
Compositional bias558 – 5614Poly-Pro

Sites

Active site2391Proton acceptor By similarity
Binding site1401ATP By similarity

Amino acid modifications

Modified residue571N6-acetyllysine Ref.13
Modified residue2711Phosphotyrosine; by autocatalysis Ref.10
Modified residue2731Phosphotyrosine; by autocatalysis Ref.8 Ref.9 Ref.10 Ref.11

Natural variations

Alternative sequence366 – 40540Missing in isoform 2.
VSP_004925
Alternative sequence378 – 40528Missing in isoform 3.
VSP_004926
Natural variant281L → P: dbSNP rs34587974. Ref.14
VAR_040454
Natural variant1021R → H: dbSNP rs55687541. Ref.14
VAR_040455
Natural variant2341S → G: dbSNP rs35858874. Ref.14
VAR_040456
Natural variant2751Q → R in a metastatic melanoma sample; somatic mutation. Ref.14
VAR_040457

Experimental info

Mutagenesis1401K → R: Abolishes kinase activity. Ref.2
Mutagenesis2711Y → F: Abolishes kinase activity; when associated with F-273. Ref.2
Mutagenesis2731Y → F: Abolishes kinase activity; when associated with F-271. Ref.2

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: D7C354AC55943A8B

FASTA62969,198
        10         20         30         40         50         60 
MAVPPGHGPF SGFPGPQEHT QVLPDVRLLP RRLPLAFRDA TSAPLRKLSV DLIKTYKHIN 

        70         80         90        100        110        120 
EVYYAKKKRR AQQAPPQDSS NKKEKKVLNH GYDDDNHDYI VRSGERWLER YEIDSLIGKG 

       130        140        150        160        170        180 
SFGQVVKAYD HQTQELVAIK IIKNKKAFLN QAQIELRLLE LMNQHDTEMK YYIVHLKRHF 

       190        200        210        220        230        240 
MFRNHLCLVF ELLSYNLYDL LRNTHFRGVS LNLTRKLAQQ LCTALLFLAT PELSIIHCDL 

       250        260        270        280        290        300 
KPENILLCNP KRSAIKIVDF GSSCQLGQRI YQYIQSRFYR SPEVLLGTPY DLAIDMWSLG 

       310        320        330        340        350        360 
CILVEMHTGE PLFSGSNEVD QMNRIVEVLG IPPAAMLDQA PKARKYFERL PGGGWTLRRT 

       370        380        390        400        410        420 
KELRKDYQGP GTRRLQEVLG VQTGGPGGRR AGEPGHSPAD YLRFQDLVLR MLEYEPAARI 

       430        440        450        460        470        480 
SPLGALQHGF FRRTADEATN TGPAGSSAST SPAPLDTCPS SSTASSISSS GGSSGSSSDN 

       490        500        510        520        530        540 
RTYRYSNRYC GGPGPPITDC EMNSPQVPPS QPLRPWAGGD VPHKTHQAPA SASSLPGTGA 

       550        560        570        580        590        600 
QLPPQPRYLG RPPSPTSPPP PELMDVSLVG GPADCSPPHP APAPQHPAAS ALRTRMTGGR 

       610        620 
PPLPPPDDPA TLGPHLGLRG VPQSTAASS

« Hide

Isoform 2.

Checksum: E98BF9B257237A9D
Show »

FASTA58964,934
Isoform 3.

Checksum: 8601907D9652274B
Show »

FASTA60166,336

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References

« Hide 'large scale' references
[1]"Cloning and characterization of DYRK1B, a novel member of the DYRK family of protein kinases."
Leder S., Weber Y., Altafaj X., Estivill X., Joost H.-G., Becker W.
Biochem. Biophys. Res. Commun. 254:474-479(1999) [PubMed: 9918863] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Testis.
[2]"Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates survival of colon cancer cells."
Lee K., Deng X., Friedman E.
Cancer Res. 60:3631-3637(2000) [PubMed: 10910078] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, MUTAGENESIS OF LYS-140; TYR-271 AND TYR-273.
Tissue: Colon carcinoma.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed: 15057824] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[5]"Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha."
Lim S., Jin K., Friedman E.
J. Biol. Chem. 277:25040-25046(2002) [PubMed: 11980910] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DCOHM; MAP2K3 AND TCF1.
Tissue: Muscle.
[6]"Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M."
Zou Y., Lim S., Lee K., Deng X., Friedman E.
J. Biol. Chem. 278:49573-49581(2003) [PubMed: 14500717] [Abstract]
Cited for: FUNCTION, DIMERIZATION, INTERACTION WITH RANBP9, IDENTIFICATION IN A COMPLEX WITH RAN; RANBP9 AND COPS5.
[7]"Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases."
Skurat A.V., Dietrich A.D.
J. Biol. Chem. 279:2490-2498(2004) [PubMed: 14593110] [Abstract]
Cited for: INTERACTION WITH WDR68.
[8]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-273, MASS SPECTROMETRY.
[9]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-273, MASS SPECTROMETRY.
Tissue: Platelet.
[10]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-271 AND TYR-273, MASS SPECTROMETRY.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-273, MASS SPECTROMETRY.
[12]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-273, MASS SPECTROMETRY.
[13]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57, MASS SPECTROMETRY.
[14]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-28; HIS-102; GLY-234 AND ARG-275.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00000352.
IPI00215873.
IPI00332215.
PIRJG0195.
RefSeqNP_004705.1.
NP_006474.1.
NP_006475.1.
UniGeneHs.130988

3D structure databases

SMRQ9Y463. Positions 92-437.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9Y463. 4 interactions.
STRINGQ9Y463.

PTM databases

PhosphoSiteQ9Y463.

Proteomic databases

PRIDEQ9Y463.

Genome annotation databases

EnsemblENST00000323039; ENSP00000312789; ENSG00000105204; Homo sapiens. [Genome view]
GeneID9149.
KEGGhsa:9149.
UCSCuc002omi.1. human.
uc002omj.1. human.
uc002omk.1. human.

Organism-specific databases

CTD9149.
GeneCardsGC19M045007.
H-InvDBHIX0015125.
HGNCHGNC:3092. DYRK1B.
MIM604556. gene.
PharmGKBPA27549.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14617.
HOGENOMHBG755340.
HOVERGENQ9Y463.
InParanoidQ9Y463.
OMALVGGPPD.
OrthoDBEOG9GMXG8.
PhylomeDBQ9Y463.

Enzyme and pathway databases

BRENDA2.7.12.1. 247.

Gene expression databases

ArrayExpressQ9Y463.
BgeeQ9Y463.
CleanExHS_DYRK1B.
GenevestigatorQ9Y463.
GermOnlineENSG00000105204. Homo sapiens.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio34319.
SOURCESearch...

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Entry information

Entry nameDYR1B_HUMAN
AccessionPrimary (citable) accession number: Q9Y463
Secondary accession number(s): O75258, O75788, O75789
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: February 9, 2010
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Human chromosome 19: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

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Index of human polymorphisms and disease mutations

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Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents