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O43781

- DYRK3_HUMAN

UniProt

O43781 - DYRK3_HUMAN

Protein

Dual specificity tyrosine-phosphorylation-regulated kinase 3

Gene

DYRK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 3 (26 Jun 2007)
      Previous versions | rss
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    Functioni

    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. May act by regulating CREB/CRE signaling.1 Publication

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Inhibited by harmine, leucettamine B and leucettine L41.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei238 – 2381ATPPROSITE-ProRule annotation
    Active sitei335 – 3351Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi215 – 2239ATPPROSITE-ProRule annotation
    Nucleotide bindingi288 – 2914ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. magnesium ion binding Source: UniProtKB
    3. protein kinase activity Source: UniProtKB
    4. protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
    5. protein serine/threonine kinase activity Source: UniProtKB-KW
    6. protein tyrosine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. erythrocyte differentiation Source: UniProtKB
    2. protein phosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.12.1. 2681.
    SignaLinkiO43781.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC:2.7.12.1)
    Alternative name(s):
    Regulatory erythroid kinase
    Short name:
    REDK
    Gene namesi
    Name:DYRK3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:3094. DYRK3.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27551.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 588588Dual specificity tyrosine-phosphorylation-regulated kinase 3PRO_0000085938Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei369 – 3691PhosphotyrosineBy similarity

    Post-translational modificationi

    Autophosphorylated on tyrosine residues.

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiO43781.
    PRIDEiO43781.

    PTM databases

    PhosphoSiteiO43781.

    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

    ArrayExpressiO43781.
    BgeeiO43781.
    CleanExiHS_DYRK3.
    GenevestigatoriO43781.

    Interactioni

    Protein-protein interaction databases

    BioGridi114022. 5 interactions.
    IntActiO43781. 4 interactions.
    STRINGi9606.ENSP00000356076.

    Structurei

    3D structure databases

    ProteinModelPortaliO43781.
    SMRiO43781. Positions 137-522.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini209 – 522314Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000220863.
    HOVERGENiHBG051426.
    InParanoidiO43781.
    KOiK08825.
    OMAiLKQYKHH.
    PhylomeDBiO43781.
    TreeFamiTF314624.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    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

    MGGTARGPGR KDAGPPGAGL PPQQRRLGDG VYDTFMMIDE TKCPPCSNVL    50
    CNPSEPPPPR RLNMTTEQFT GDHTQHFLDG GEMKVEQLFQ EFGNRKSNTI 100
    QSDGISDSEK CSPTVSQGKS SDCLNTVKSN SSSKAPKVVP LTPEQALKQY 150
    KHHLTAYEKL EIINYPEIYF VGPNAKKRHG VIGGPNNGGY DDADGAYIHV 200
    PRDHLAYRYE VLKIIGKGSF GQVARVYDHK LRQYVALKMV RNEKRFHRQA 250
    AEEIRILEHL KKQDKTGSMN VIHMLESFTF RNHVCMAFEL LSIDLYELIK 300
    KNKFQGFSVQ LVRKFAQSIL QSLDALHKNK IIHCDLKPEN ILLKHHGRSS 350
    TKVIDFGSSC FEYQKLYTYI QSRFYRAPEI ILGSRYSTPI DIWSFGCILA 400
    ELLTGQPLFP GEDEGDQLAC MMELLGMPPP KLLEQSKRAK YFINSKGIPR 450
    YCSVTTQADG RVVLVGGRSR RGKKRGPPGS KDWGTALKGC DDYLFIEFLK 500
    RCLHWDPSAR LTPAQALRHP WISKSVPRPL TTIDKVSGKR VVNPASAFQG 550
    LGSKLPPVVG IANKLKANLM SETNGSIPLC SVLPKLIS 588
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti313 – 3131R → H in AAH15501. (PubMed:15489334)Curated
    Sequence conflicti396 – 3961G → R in CAA73266. (PubMed:9748265)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti239 – 2391M → L.1 Publication
    VAR_040464

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2020Missing in isoform 2. 3 PublicationsVSP_026178Add
    BLAST
    Alternative sequencei21 – 266PPQQRR → MKWKEK in isoform 2. 3 PublicationsVSP_026179

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_005273315.2. [O43781-2]
    XP_005273373.1. XM_005273316.2. [O43781-2]
    XP_006711639.1. XM_006711576.1. [O43781-2]
    XP_006711640.1. XM_006711577.1. [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.3. human. [O43781-2]
    uc001hej.3. human. [O43781-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    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_005273315.2. [O43781-2 ]
    XP_005273373.1. XM_005273316.2. [O43781-2 ]
    XP_006711639.1. XM_006711576.1. [O43781-2 ]
    XP_006711640.1. XM_006711577.1. [O43781-2 ]
    UniGenei Hs.164267.

    3D structure databases

    ProteinModelPortali O43781.
    SMRi O43781. Positions 137-522.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114022. 5 interactions.
    IntActi O43781. 4 interactions.
    STRINGi 9606.ENSP00000356076.

    Chemistry

    BindingDBi O43781.
    ChEMBLi CHEMBL4575.
    GuidetoPHARMACOLOGYi 2012.

    PTM databases

    PhosphoSitei O43781.

    Proteomic databases

    PaxDbi O43781.
    PRIDEi O43781.

    Protocols and materials databases

    DNASUi 8444.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000367106 ; ENSP00000356073 ; ENSG00000143479 . [O43781-2 ]
    ENST00000367108 ; ENSP00000356075 ; ENSG00000143479 . [O43781-2 ]
    ENST00000367109 ; ENSP00000356076 ; ENSG00000143479 . [O43781-1 ]
    GeneIDi 8444.
    KEGGi hsa:8444.
    UCSCi uc001hei.3. human. [O43781-2 ]
    uc001hej.3. human. [O43781-1 ]

    Organism-specific databases

    CTDi 8444.
    GeneCardsi GC01P206800.
    HGNCi HGNC:3094. DYRK3.
    MIMi 603497. gene.
    neXtProti NX_O43781.
    PharmGKBi PA27551.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000220863.
    HOVERGENi HBG051426.
    InParanoidi O43781.
    KOi K08825.
    OMAi LKQYKHH.
    PhylomeDBi O43781.
    TreeFami TF314624.

    Enzyme and pathway databases

    BRENDAi 2.7.12.1. 2681.
    SignaLinki O43781.

    Miscellaneous databases

    GeneWikii DYRK3.
    GenomeRNAii 8444.
    NextBioi 31590.
    PROi O43781.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43781.
    Bgeei O43781.
    CleanExi HS_DYRK3.
    Genevestigatori O43781.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases."
      Becker W., Weber Y., Wetzel K., Eirmbter K., Tejedor F.J., Joost H.-G.
      J. Biol. Chem. 273:25893-25902(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal brain.
    2. Becker W.
      Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO N-TERMINUS.
    3. "Molecular cloning and characterization of novel protein kinase gene DYRK3."
      Xia J., Yang X., Ruan Q., Pan Q., Liu C., Xie W., Deng H.
      Zhonghua Yi Xue Yi Chuan Xue Za Zhi 15:327-332(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "REDK, a novel human regulatory erythroid kinase."
      Lord K.A., Creasy C.L., King A.G., King C., Burns B.M., Lee J.C., Dillon S.B.
      Blood 95:2838-2846(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
      Tissue: Skeletal muscle.
    5. "Cloning of the human testis-specific dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 5 (DYRK5) gene."
      Zhou Z.M.
      Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Testis.
    6. Raya A., de la Luna S.
      Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    7. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Uterus.
    10. "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.
      , 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] [Europe PMC] [Abstract]
      Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-239.

    Entry informationi

    Entry nameiDYRK3_HUMAN
    AccessioniPrimary (citable) accession number: O43781
    Secondary accession number(s): D3DT79
    , Q7Z752, Q9HBY6, Q9HBY7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: June 26, 2007
    Last modified: October 1, 2014
    This is version 141 of the entry and version 3 of the sequence. [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

    External Data

    Dasty 3