DYRK3_MACFA
ID DYRK3_MACFA Reviewed; 568 AA.
AC Q4R6S5;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 3;
DE EC=2.7.12.1 {ECO:0000250|UniProtKB:O43781};
GN Name=DYRK3 {ECO:0000250|UniProtKB:O43781};
GN ORFNames=QtsA-17232 {ECO:0000303|Ref.1};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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-349. {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 -!- 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-349. Autophosphorylation at Ser-330 stabilizes the protein and
CC enhances the protein kinase activity. {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 -!- 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; AB169105; BAE01199.1; -; mRNA.
DR RefSeq; NP_001272176.1; NM_001285247.1.
DR AlphaFoldDB; Q4R6S5; -.
DR SMR; Q4R6S5; -.
DR STRING; 9541.XP_005540700.1; -.
DR GeneID; 101866219; -.
DR CTD; 8444; -.
DR eggNOG; KOG0667; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0035063; P:nuclear speck organization; ISS:UniProtKB.
DR GO; GO:1903008; P:organelle disassembly; ISS:UniProtKB.
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..568
FT /note="Dual specificity tyrosine-phosphorylation-regulated
FT kinase 3"
FT /id="PRO_0000291536"
FT DOMAIN 189..502
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..168
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:O43781"
FT MOTIF 448..461
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O43781"
FT ACT_SITE 315
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 195..203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 218
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q922Y0,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43781"
FT MOD_RES 349
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q922Y0"
SQ SEQUENCE 568 AA; 64088 MW; C7278981ABC34D7C CRC64;
MKWKEKLGDG VYDTFMMIDE TKCPPCSNVL CNPSEPPPPR RLNMTTEKFI RDHTQHFLDG
GEMKVEQLFQ EFGNRKSNTV QSDGISDSEK CSPTVSQGKS SDCLNTVKSN SSSKAPKVVP
LTPEQALKQY KHHLTAYEKL EIINYPEIYF VGPNAKKRHG VIGGPNNGGY DDADGAYIHV
PRDHLAYRYE VLKIIGKGSF GQVARVYDHK LRQYVALKMV RNEKRFHRQA AEEIRILEHL
KKQDKTGSMN VIHMLESFTF RNHVCMAFEL LSIDLYELIK KNKFQGFSVQ LVRKFAQSIL
QSLDALHKNK IIHCDLKPEN ILLKHHGRSS TKVIDFGSSC FEYQKLYTYI QSRFYRAPEI
ILGSRYSTPI DIWSFGCILA ELLTGQPLFP GEDEGDQLAC MMELLGMPPP KLLEQSKRAK
YFINSKGIPR YCSVTTQADG RVVLVGGRSR RGKKRGPPGS KDWGTALKGC DDYLFIEFLK
RCLHWDPSAR LTPAQALRHP WISKSVPRPL TTIDKVSGKR IVNPASAFQG LGSKLPPVVG
IANKLKANLM SETNGSIPLC SVLPKLIS
