Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK)
1_MGGTA 6_ RGPGR 11_ KDAGP 16_ PGAGL 21_ PPQQR 26_ RLGDG 31_ VYDTF 36_ MMIDE 41_ TKCPP 46_ CSNVL 51_ CNPSE 56_ PPPPR 61_ RLNMT 66_ TEQFT 71_ GDHTQ 76_ HFLDG 81_ GEMKV 86_ EQLFQ 91_ EFGNR 96_ KSNTI 101_ QSDGI 106_ SDSEK 111_ CSPTV 116_ SQGKS 121_ SDCLN 126_ TVKSN 131_ SSSKA 136_ PKVVP 141_ LTPEQ 146_ ALKQY 151_ KHHLT 156_ AYEKL 161_ EIINY 166_ PEIYF 171_ VGPNA 176_ KKRHG 181_ VIGGP 186_ NNGGY 191_ DDADG 196_ AYIHV 201_ PRDHL 206_ AYRYE 211_ VLKII 216_ GKGSF 221_ GQVAR 226_ VYDHK 231_ LRQYV 236_ ALKMV 241_ RNEKR 246_ FHRQA 251_ AEEIR 256_ ILEHL 261_ KKQDK 266_ TGSMN 271_ VIHML 276_ ESFTF 281_ RNHVC 286_ MAFEL 291_ LSIDL 296_ YELIK 301_ KNKFQ 306_ GFSVQ 311_ LVRKF 316_ AQSIL 321_ QSLDA 326_ LHKNK 331_ IIHCD 336_ LKPEN 341_ ILLKH 346_ HGRSS 351_ TKVID 356_ FGSSC 361_ FEYQK 366_ LYTYI 371_ QSRFY 376_ RAPEI 381_ ILGSR 386_ YSTPI 391_ DIWSF 396_ GCILA 401_ ELLTG 406_ QPLFP 411_ GEDEG 416_ DQLAC 421_ MMELL 426_ GMPPP 431_ KLLEQ 436_ SKRAK 441_ YFINS 446_ KGIPR 451_ YCSVT 456_ TQADG 461_ RVVLV 466_ GGRSR 471_ RGKKR 476_ GPPGS 481_ KDWGT 486_ ALKGC 491_ DDYLF 496_ IEFLK 501_ RCLHW 506_ DPSAR 511_ LTPAQ 516_ ALRHP 521_ WISKS 526_ VPRPL 531_ TTIDK 536_ VSGKR 541_ VVNPA 546_ SAFQG 551_ LGSKL 556_ PPVVG 561_ IANKL 566_ KANLM 571_ SETNG 576_ SIPLC 581_SVLPK
1: Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603)