DYRK3_MOUSE
ID DYRK3_MOUSE Reviewed; 586 AA.
AC Q922Y0; Q8BM34;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 3;
DE EC=2.7.12.1 {ECO:0000269|PubMed:12356771, ECO:0000269|PubMed:20167603};
GN Name=Dyrk3 {ECO:0000312|MGI:MGI:1330300};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH06704.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH06704.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 49-586.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC28949.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAC28949.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-368, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF LYS-237; TYR-366 AND TYR-368.
RX PubMed=12356771; DOI=10.1074/jbc.m205374200;
RA Li K., Zhao S., Karur V., Wojchowski D.M.;
RT "DYRK3 activation, engagement of protein kinase A/cAMP response element-
RT binding protein, and modulation of progenitor cell survival.";
RL J. Biol. Chem. 277:47052-47060(2002).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=16524748; DOI=10.1016/j.bcmd.2006.01.007;
RA Wojchowski D.M., Menon M.P., Sathyanarayana P., Fang J., Karur V.,
RA Houde E., Kapelle W., Bogachev O.;
RT "Erythropoietin-dependent erythropoiesis: new insights and questions.";
RL Blood Cells Mol. Dis. 36:232-238(2006).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF SIRT1, INTERACTION WITH SIRT1, AND CATALYTIC
RP ACTIVITY.
RX PubMed=20167603; DOI=10.1074/jbc.m110.102574;
RA Guo X., Williams J.G., Schug T.T., Li X.;
RT "DYRK1A and DYRK3 promote cell survival through phosphorylation and
RT activation of SIRT1.";
RL J. Biol. Chem. 285:13223-13232(2010).
CC -!- FUNCTION: Dual-specificity protein kinase that promotes disassembly of
CC several types of membraneless organelles during mitosis, such as stress
CC granules, nuclear speckles and pericentriolar material (By similarity).
CC Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a
CC critical tyrosine residue in their activation loop and phosphorylate
CC their substrate on serine and threonine residues (PubMed:12356771).
CC Acts as a central dissolvase of membraneless organelles during the G2-
CC to-M transition, after the nuclear-envelope breakdown: acts by
CC mediating phosphorylation of multiple serine and threonine residues in
CC unstructured domains of proteins, such as SRRM1 and PCM1 (By
CC similarity). Does not mediate disassembly of all membraneless
CC organelles: disassembly of P-body and nucleolus is not regulated by
CC DYRK3 (By similarity). Dissolution of membraneless organelles at the
CC onset of mitosis is also required to release mitotic regulators, such
CC as ZNF207, from liquid-unmixed organelles where they are sequestered
CC and keep them dissolved during mitosis (By similarity). Regulates
CC mTORC1 by mediating the dissolution of stress granules: during
CC stressful conditions, DYRK3 partitions from the cytosol to the stress
CC granule, together with mTORC1 components, which prevents mTORC1
CC signaling (By similarity). When stress signals are gone, the kinase
CC activity of DYRK3 is required for the dissolution of stress granule and
CC mTORC1 relocation to the cytosol: acts by mediating the phosphorylation
CC of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1
CC signaling (By similarity). Also acts as a negative regulator of EPO-
CC dependent erythropoiesis: may place an upper limit on red cell
CC production during stress erythropoiesis (By similarity). Inhibits cell
CC death due to cytokine withdrawal in hematopoietic progenitor cells (By
CC similarity). Promotes cell survival upon genotoxic stress through
CC phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and
CC apoptosis (PubMed:20167603). {ECO:0000250|UniProtKB:O43781,
CC ECO:0000269|PubMed:12356771, ECO:0000269|PubMed:20167603}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:12356771, ECO:0000269|PubMed:20167603};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.12.1; Evidence={ECO:0000269|PubMed:12356771,
CC ECO:0000269|PubMed:20167603};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC Evidence={ECO:0000269|PubMed:12356771, ECO:0000269|PubMed:20167603};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O43781};
CC -!- ACTIVITY REGULATION: Protein kinase activity is activated following
CC autophosphorylation at Tyr-368. {ECO:0000269|PubMed:12356771}.
CC -!- SUBUNIT: Interacts with SIRT1. {ECO:0000269|PubMed:20167603}.
CC -!- INTERACTION:
CC Q922Y0; Q923E4: Sirt1; NbExp=7; IntAct=EBI-5242007, EBI-1802585;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O43781}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43781}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O43781}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:O43781}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:O43781}.
CC Note=Associates with membraneless organelles in the cytoplasm and
CC nucleus. Shuttles between cytoplasm and stress granules. Localized
CC predominantly on distinct speckles distributed throughout the cytoplasm
CC of the cell. At low concentration, showns a homogeneous distribution
CC throughout the cytoplasm and does not condense in speckles. During
CC oxidative and osmotic stress, localizes to stress granules.
CC {ECO:0000250|UniProtKB:O43781}.
CC -!- DOMAIN: The N-terminal domain, which is intrinsically disordered, is
CC required for stress granule localization.
CC {ECO:0000250|UniProtKB:O43781}.
CC -!- PTM: Ubiquitinated at anaphase by the anaphase-promoting complex
CC (APC/C), leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:O43781}.
CC -!- PTM: Protein kinase activity is activated following autophosphorylation
CC at Tyr-368. {ECO:0000269|PubMed:12356771}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit unperturbed steady-state
CC erythropoiesis but significantly increased reticulocyte production
CC during stress erythropoiesis and appear to be partially protected
CC against anemia. {ECO:0000269|PubMed:16524748}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
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DR EMBL; BC006704; AAH06704.1; -; mRNA.
DR EMBL; AK035114; BAC28949.1; -; mRNA.
DR CCDS; CCDS15267.1; -.
DR RefSeq; NP_663483.1; NM_145508.2.
DR AlphaFoldDB; Q922Y0; -.
DR SMR; Q922Y0; -.
DR BioGRID; 230510; 3.
DR IntAct; Q922Y0; 2.
DR STRING; 10090.ENSMUSP00000016670; -.
DR iPTMnet; Q922Y0; -.
DR PhosphoSitePlus; Q922Y0; -.
DR PaxDb; Q922Y0; -.
DR PRIDE; Q922Y0; -.
DR ProteomicsDB; 277620; -.
DR Antibodypedia; 34587; 238 antibodies from 29 providers.
DR DNASU; 226419; -.
DR Ensembl; ENSMUST00000016670; ENSMUSP00000016670; ENSMUSG00000016526.
DR GeneID; 226419; -.
DR KEGG; mmu:226419; -.
DR UCSC; uc007cmw.1; mouse.
DR CTD; 8444; -.
DR MGI; MGI:1330300; Dyrk3.
DR VEuPathDB; HostDB:ENSMUSG00000016526; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000159878; -.
DR HOGENOM; CLU_000288_5_13_1; -.
DR InParanoid; Q922Y0; -.
DR OMA; CDDPTFI; -.
DR OrthoDB; 870358at2759; -.
DR PhylomeDB; Q922Y0; -.
DR TreeFam; TF314624; -.
DR BRENDA; 2.7.12.1; 3474.
DR BioGRID-ORCS; 226419; 0 hits in 75 CRISPR screens.
DR PRO; PR:Q922Y0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q922Y0; protein.
DR Bgee; ENSMUSG00000016526; Expressed in seminiferous tubule of testis and 170 other tissues.
DR ExpressionAtlas; Q922Y0; baseline and differential.
DR Genevisible; Q922Y0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0035063; P:nuclear speck organization; ISS:UniProtKB.
DR GO; GO:1903008; P:organelle disassembly; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:1902751; P:positive regulation of cell cycle G2/M phase transition; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0080135; P:regulation of cellular response to stress; ISS:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0035617; P:stress granule disassembly; ISS:UniProtKB.
DR Gene3D; 3.30.10.30; -; 1.
DR InterPro; IPR042521; DYRK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Kinase;
KW Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..586
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 3"
FT /id="PRO_0000291537"
FT DOMAIN 208..521
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..187
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:O43781"
FT MOTIF 467..480
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O43781"
FT COMPBIAS 45..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 334
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 214..222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 237
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:12356771"
FT BINDING 287..290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 368
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12356771"
FT MUTAGEN 237
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12356771"
FT MUTAGEN 366
FT /note="Y->A: Minimal loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12356771"
FT MUTAGEN 366
FT /note="Y->E: Minimal loss of kinase activity; when
FT associated with E-368."
FT /evidence="ECO:0000269|PubMed:12356771"
FT MUTAGEN 368
FT /note="Y->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12356771"
FT MUTAGEN 368
FT /note="Y->E: Minimal loss of kinase activity; when
FT associated with E-366."
FT /evidence="ECO:0000269|PubMed:12356771"
SQ SEQUENCE 586 AA; 65572 MW; 0097F7584726AB55 CRC64;
MGGAARDRGR KDAALPGAGL PPQQRRLGDG VYDTFMMIDE TKGPPYSDTF SNPSEAPVSR
RLNITTEPLT RGHTQHFVNG SEMKVEQLFQ EFGNRRSNTL QSDGISNSEK SSPASQGKSS
ESLSAVKCNL SSRPSKVLPL TPEQALKQYK HHLTAYEKLE IVSYPEIYFV GPNAKKRQGV
IGGPNNGGYD DADGAYIHVP RDHLAYRYEV LKIIGKGSFG QVARVYDHKL RQYVALKMVR
NEKRFHRQAA EEIRILEHLK KQDKTGSMNV IHMLESFTFR NHVCMAFELL SIDLYELIKK
NKFQGFSVQL VRKFAQSILQ SLDALHKNKI IHCDLKPENI LLKHHGRSAT KVIDFGSSCF
EYQKLYTYIQ SRFYRAPEII LGCRYSTPID IWSFGCILAE LLTGQPLFPG EDEGDQLACM
IELLGMPPQK LLEQSKRAKY FINSKGLPRY CSVSTQTDGR VVLLGGRSRR GKKRGPPGSK
DWATALKGCG DYLFIEFLKR CLQWDPSARL TPAQALRHPW ISKSTPKPLT MDKVPGKRVV
NPTNAFQGLG SKLPPVVGIA SKLKANLMSE TSGSIPLCSV LPKLIS
