DYRK3_RAT
ID DYRK3_RAT Reviewed; 586 AA.
AC Q4V8A3;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 3;
DE EC=2.7.12.1 {ECO:0000250|UniProtKB:O43781};
GN Name=Dyrk3 {ECO:0000312|RGD:1310924};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:AAH97474.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAH97474.1};
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 TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9748265; DOI=10.1074/jbc.273.40.25893;
RA Becker W., Weber Y., Wetzel K., Eirmbter K., Tejedor F.J., Joost H.-G.;
RT "Sequence characteristics, subcellular localization, and substrate
RT specificity of DYRK-related kinases, a novel family of dual specificity
RT protein kinases.";
RL J. Biol. Chem. 273:25893-25902(1998).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=17292540; DOI=10.1016/j.mce.2006.12.041;
RA Sacher F., Moeller C., Bone W., Gottwald U., Fritsch M.;
RT "The expression of the testis-specific Dyrk4 kinase is highly restricted to
RT step 8 spermatids but is not required for male fertility in mice.";
RL Mol. Cell. Endocrinol. 267:80-88(2007).
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. Dual-
CC 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. Acts as a central
CC dissolvase of membraneless organelles during the G2-to-M transition,
CC after the nuclear-envelope breakdown: acts by mediating phosphorylation
CC of multiple serine and threonine residues in unstructured domains of
CC proteins, such as SRRM1 and PCM1. Does not mediate disassembly of all
CC membraneless organelles: disassembly of P-body and nucleolus is not
CC regulated by DYRK3. Dissolution of membraneless organelles at the onset
CC of mitosis is also required to release mitotic regulators, such as
CC ZNF207, from liquid-unmixed organelles where they are sequestered and
CC keep them dissolved during mitosis. Regulates mTORC1 by mediating the
CC dissolution of stress granules: during stressful conditions, DYRK3
CC partitions from the cytosol to the stress granule, together with mTORC1
CC components, which prevents mTORC1 signaling. When stress signals are
CC gone, the kinase activity of DYRK3 is required for the dissolution of
CC stress granule and mTORC1 relocation to the cytosol: acts by mediating
CC the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full
CC reactivation of mTORC1 signaling. Also acts as a negative regulator of
CC EPO-dependent erythropoiesis: may place an upper limit on red cell
CC production during stress erythropoiesis. Inhibits cell death due to
CC cytokine withdrawal in hematopoietic progenitor cells. Promotes cell
CC survival upon genotoxic stress through phosphorylation of SIRT1: this
CC in turn inhibits p53/TP53 activity and apoptosis.
CC {ECO:0000250|UniProtKB:O43781}.
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:0000250|UniProtKB:O43781};
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:0000250|UniProtKB:O43781};
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:0000250|UniProtKB:O43781};
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:0000250|UniProtKB:O43781}.
CC -!- SUBUNIT: Interacts with SIRT1. {ECO:0000250|UniProtKB:Q922Y0}.
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 -!- TISSUE SPECIFICITY: Expressed predominantly in testis (PubMed:9748265).
CC Expressed in late pachytene spermatocytes (PubMed:17292540).
CC {ECO:0000269|PubMed:17292540, ECO:0000269|PubMed:9748265}.
CC -!- DOMAIN: The N-terminal domain, which is intrinsically disordered, is
CC required for stress granule localization.
CC {ECO:0000250|UniProtKB:O43781}.
CC -!- PTM: Protein kinase activity is activated following autophosphorylation
CC at Tyr-368. {ECO:0000250|UniProtKB:Q922Y0}.
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 -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC097474; AAH97474.1; -; mRNA.
DR RefSeq; NP_001019938.1; NM_001024767.1.
DR AlphaFoldDB; Q4V8A3; -.
DR SMR; Q4V8A3; -.
DR STRING; 10116.ENSRNOP00000006502; -.
DR iPTMnet; Q4V8A3; -.
DR PhosphoSitePlus; Q4V8A3; -.
DR PaxDb; Q4V8A3; -.
DR PRIDE; Q4V8A3; -.
DR Ensembl; ENSRNOT00000006502; ENSRNOP00000006502; ENSRNOG00000004870.
DR GeneID; 304775; -.
DR KEGG; rno:304775; -.
DR UCSC; RGD:1310924; rat.
DR CTD; 8444; -.
DR RGD; 1310924; Dyrk3.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000159878; -.
DR InParanoid; Q4V8A3; -.
DR OrthoDB; 870358at2759; -.
DR PhylomeDB; Q4V8A3; -.
DR PRO; PR:Q4V8A3; -.
DR Proteomes; UP000002494; Chromosome 13.
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; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
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; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
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:1902751; P:positive regulation of cell cycle G2/M phase transition; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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 2: Evidence at transcript 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_0000291538"
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 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:0000250|UniProtKB:Q922Y0,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
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:0000250|UniProtKB:Q922Y0"
SQ SEQUENCE 586 AA; 65511 MW; 9E194D2F960FBE94 CRC64;
MGGAARERGR KDAALPGAGL PPQQRRLGDG VYDTFMMIDE TKCPPYTNTL CNPSEAPVSR
RLNITTEPFT RGHTQHFVSG GVMKVEQLFQ EFGSRRTSTL QSDGVSNSEK SSPASQGKSS
DSLGTVKCSL SSRPSKVLPL TPEQALKQYK HHLTAYEKLE IISYPEIYFV 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
MELLGMPPQK LLEQSKRAKY FINSKGLPRY CSVTTQTDGR VVLLGGRSRR GKKRGPPGSK
DWAAALKGCD DYLFIEFLKR CLQWDPSARL TPAQALRHPW ISKSAPRPLT TDKVSGKRVV
NPTNAFQGLG SKLPPVVGIA SKLKANLMSE TSGSIPLCSV LPKLIS
