Continued from EC 2.7.8 and EC 2.7.9
EC 2.7.10 Protein-tyrosine kinases
EC 2.7.11 Protein-serine/threonine kinases
EC 2.7.12 Dual-specificity kinases (those acting on Ser/Thr and Tyr residues)
EC 2.7.13 Protein-histidine kinases
EC 2.7.14 Protein-arginine kinases
EC 2.7.99 Other protein kinases
EC 2.7.10.3 bacterial tyrosine kinase
Accepted name: receptor protein-tyrosine kinase
Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Other name(s): AATK; AATYK; AATYK2; AATYK3; ACH; ALK; anaplastic lymphoma kinase; ARK; ATP:protein-tyrosine O-phosphotransferase (ambiguous); AXL; Bek; Bfgfr; BRT; Bsk; C-FMS; CAK; CCK4; CD115; CD135; CDw135; Cek1; Cek10; Cek11; Cek2; Cek3; Cek5; Cek6; Cek7; CFD1; CKIT; CSF1R; DAlk; DDR1; DDR2; Dek; DKFZp434C1418; Drosophila Eph kinase; DRT; DTK; Ebk; ECK; EDDR1; Eek; EGFR; Ehk2; Ehk3; Elk; EPH; EPHA1; EPHA2; EPHA6; EPHA7; EPHA8; EPHB1; EPHB2; EPHB3; EPHB4; EphB5; ephrin-B3 receptor tyrosine kinase; EPHT; EPHT2; EPHT3; EPHX; ERBB; ERBB1; ERBB2; ERBB3; ERBB4; ERK; Eyk; FGFR1; FGFR2; FGFR3; FGFR4; FLG; FLK1; FLK2; FLT1; FLT2; FLT3; FLT4; FMS; Fv2; HBGFR; HEK11; HEK2; HEK3; HEK5; HEK6; HEP; HER2; HER3; HER4; HGFR; HSCR1; HTK; IGF1R; INSR; INSRR; insulin receptor protein-tyrosine kinase; IR; IRR; JTK12; JTK13; JTK14; JWS; K-SAM; KDR; KGFR; KIA0641; KIAA1079; KIAA1459; Kil; Kin15; Kin16; KIT; KLG; LTK; MCF3; Mdk1; Mdk2; Mdk5; MEhk1; MEN2A/B; Mep; MER; MERTK; MET; Mlk1; Mlk2; Mrk; MST1R; MTC1; MUSK; Myk1; N-SAM; NEP; NET; Neu; neurite outgrowth regulating kinase; NGL; NOK; nork; novel oncogene with kinase-domain; Nsk2; NTRK1; NTRK2; NTRK3; NTRK4; NTRKR1; NTRKR2; NTRKR3; Nuk; NYK; PCL; PDGFR; PDGFRA; PDGFRB; PHB6; protein-tyrosine kinase (ambiguous); protein tyrosine kinase (ambiguous); PTK; PTK3; PTK7; receptor protein tyrosine kinase; RET; RON; ROR1; ROR2; ROS1; RSE; RTK; RYK; SEA; Sek2; Sek3; Sek4; Sfr; SKY; STK (ambiguous); STK1; TEK; TIE; TIE1; TIE2; TIF; TKT; TRK; TRKA; TRKB; TRKC; TRKE; TYK1; TYRO10; Tyro11; TYRO3; Tyro5; Tyro6; TYRO7; UFO; VEGFR1; VEGFR2; VEGFR3; Vik; YK1; Yrk
Systematic name: ATP:[protein]-L-tyrosine O-phosphotransferase (receptor-type)
Comments: The receptor protein-tyrosine kinases, which can be defined as having a transmembrane domain, are a large and diverse multigene family found only in Metazoans [1]. In the human genome, 58 receptor-type protein-tyrosine kinases have been identified and these are distributed into 20 subfamilies.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Robinson, D.R., Wu, Y.M. and Lin, S.F. The protein tyrosine kinase family of the human genome. Oncogene 19 (2000) 5548-5557. [PMID: 11114734]
2. Iwahara, T., Fujimoto, J., Wen, D., Cupples, R., Bucay, N., Arakawa, T., Mori, S., Ratzkin, B. and Yamamoto, T. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 14 (1997) 439-449. [PMID: 9053841]
3. Lorén, C.E., Scully, A., Grabbe, C., Edeen, P.T., Thomas, J., McKeown, M., Hunter, T. and Palmer, R.H. Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo. Genes Cells 6 (2001) 531-544. [PMID: 11442633]
Accepted name: non-specific protein-tyrosine kinase
Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Other name(s): ABL; ABL1; ABL2; ABLL; ACK1; ACK2; AGMX1; ARG; ATK; ATP:protein-tyrosine O-phosphotransferase (ambiguous); BLK; Bmk; BMX; BRK; Bruton's tyrosine kinase; Bsk; BTK; BTKL; CAKb; Cdgip; CHK; CSK; CTK; CYL; cytoplasmic protein tyrosine kinase; EMT; ETK; Fadk; FAK; FAK2; FER; Fert1/2; FES; FGR; focal adhesion kinase; FPS; FRK; FYN; HCK; HCTK; HYL; IMD1; ITK; IYK; JAK1; JAK2; JAK3; Janus kinase 1; Janus kinase 2; Janus kinase 3; JTK1; JTK9; L-JAK; LCK; LSK; LYN; MATK; Ntk; p60c-src protein tyrosine kinase; PKB; protein-tyrosine kinase (ambiguous); PSCTK; PSCTK1; PSCTK2; PSCTK4; PSCTK5; PTK2; PTK2B; PTK6; PYK2; RAFTK; RAK; Rlk; Sik; SLK; SRC; SRC2; SRK; SRM; SRMS; STD; SYK; SYN; Tck; TEC; TNK1; Tsk; TXK; TYK2; TYK3; YES1; YK2; ZAP70
Systematic name: ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)
Comments: Unlike EC 2.7.10.1, receptor protein-tyrosine kinase, this protein-tyrosine kinase does not have a transmembrane domain. In the human genome, 32 non-specific protein-tyrosine kinases have been identified and these can be divided into ten families [1].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Robinson, D.R., Wu, Y.M. and Lin, S.F. The protein tyrosine kinase family of the human genome. Oncogene 19 (2000) 5548-5557. [PMID: 11114734]
2. Roskoski, R., Jr. Src protein-tyrosine kinase structure and regulation. Biochem. Biophys. Res. Commun. 324 (2004) 1155-1164. [PMID: 15504335]
Accepted name: bacterial tyrosine kinase
Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Other name(s): BY-kinase; bacterial protein tyrosine kinase
Systematic name: ATP:[protein]-L-tyrosine O-phosphotransferase (bacterial-type)
Comments: This family of enzymes includes most of the bacterial tyrosine kinases. These enzymes do not share sequence or structural homology with eukaryotic tyrosine kinases, and exploit ATP/GTP-binding Walker motifs to catalyse autophosphorylation and substrate phosphorylation on tyrosine. Two subfamilies have been defined: P-type enzymes contain an N-terminal transmembrane portion and an extracellular hairpin loop domain. The intracellular portion comprises the catalytic domain and a tyrosine-rich C-terminal domain that contains the site for autophosphorylation. In F-type enzymes the extracellular transmembrane domain and the intracellular catalytic domain are two independent proteins encoded by two separate genes. The majority of characterized bacterial tyrosine kinases regulate the production and export of capsular and extracellular polysaccharides, but other members are involved in many other functions.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Grangeasse, C., Doublet, P., Vaganay, E., Vincent, C., Deleage, G., Duclos, B. and Cozzone, A.J. Characterization of a bacterial gene encoding an autophosphorylating protein tyrosine kinase. Gene 204 (1997) 259-265. [PMID: 9434192]
2. Wugeditsch, T., Paiment, A., Hocking, J., Drummelsmith, J., Forrester, C. and Whitfield, C. Phosphorylation of Wzc, a tyrosine autokinase, is essential for assembly of group 1 capsular polysaccharides in Escherichia coli, J. Biol. Chem. 276 (2001) 2361-2371. [PMID: 11053445]
3. Soulat, D., Jault, J.M., Duclos, B., Geourjon, C., Cozzone, A.J. and Grangeasse, C. Staphylococcus aureus operates protein-tyrosine phosphorylation through a specific mechanism. J. Biol. Chem. 281 (2006) 14048-14056. [PMID: 16565080]
4. Lee, D.C., Zheng, J., She, Y.M. and Jia, Z. Structure of Escherichia coli tyrosine kinase Etk reveals a novel activation mechanism. EMBO J. 27 (2008) 1758-1766. [PMID: 18497741]
5. Chao, J.D., Wong, D. and Av-Gay, Y. Microbial protein-tyrosine kinases. J. Biol. Chem. 289 (2014) 9463-9472. [PMID: 24554699]
EC 2.7.11.32 [pyruvate, phosphate dikinase] kinase
EC 2.7.11.33 [pyruvate, water dikinase] kinase
EC 2.7.11.34 NEK6-subfamily protein kinase
EC 2.7.11.35 CRIK-subfamily protein kinase
EC 2.7.11.36 MASTL-subfamily protein kinase
EC 2.7.11.37 MAST-subfamily kinase
EC 2.7.11.38 NEK9 subfamily protein kinase
EC 2.7.11.39 ROCK-subfamily protein kinase
Accepted name: non-specific serine/threonine protein kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): A-kinase; AP50 kinase; ATP-protein transphosphorylase; calcium-dependent protein kinase C; calcium/phospholipid-dependent protein kinase; cAMP-dependent protein kinase; cAMP-dependent protein kinase A; casein kinase; casein kinase (phosphorylating); casein kinase 2; casein kinase I; casein kinase II; cGMP-dependent protein kinase; CK-2; CKI; CKII; cyclic AMP-dependent protein kinase; cyclic AMP-dependent protein kinase A; cyclic monophosphate-dependent protein kinase; cyclic nucleotide-dependent protein kinase; cyclin-dependent kinase; cytidine 3',5'-cyclic monophosphate-responsive protein kinase; dsk1; glycogen synthase a kinase; glycogen synthase kinase; HIPK2; Hpr kinase; hydroxyalkyl-protein kinase; hydroxyalkyl-protein kinase; M phase-specific cdc2 kinase; mitogen-activated S6 kinase; p82 kinase; phosphorylase b kinase kinase; PKA; protein glutamyl kinase; protein kinase (phosphorylating); protein kinase A; protein kinase CK2; protein kinase p58; protein phosphokinase; protein serine kinase; protein serine-threonine kinase; protein-aspartyl kinase; protein-cysteine kinase; protein-serine kinase; Prp4 protein kinase; Raf kinase; Raf-1; ribosomal protein S6 kinase II; ribosomal S6 protein kinase; serine kinase; serine protein kinase; serine-specific protein kinase; serine(threonine) protein kinase; serine/threonine protein kinase; STK32; T-antigen kinase; threonine-specific protein kinase; twitchin kinase; type-2 casein kinase; βIIPKC; ε PKC; Wee 1-like kinase; Wee-kinase; WEE1Hu
Systematic name: ATP:protein phosphotransferase (non-specific)
Comments: This is a heterogeneous group of serine/threonine protein kinases that do not have an activating compound and are either non-specific or their specificity has not been analysed to date.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Damuni, Z. and Reed, L.J. Purification and properties of a protamine kinase and a type II casein kinase from bovine kidney mitochondria. Arch. Biochem. Biophys. 262 (1988) 574-584. [PMID: 2835010]
2. Baggio, B., Pinna, L.A., Moret, V. and Siliprandi, N. A simple procedure for the purification of rat liver phosvitin kinase. Biochim. Biophys. Acta 212 (1970) 515-517. [PMID: 5456997]
3. Jergil, B. and Dixon, G.H. Protamine kinase from rainbow trout testis. Partial purification and characterization. J. Biol. Chem. 245 (1970) 425-434. [PMID: 4312674]
4. Langan, T.A. Action of adenosine 3',5'-monophosphate-dependent histone kinase in vivo. J. Biol. Chem.244 (1969) 5763-5765. [PMID: 4310608]
5. Takeuchi, M. and Yanagida, M. A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization. Mol. Biol. Cell 4 (1993) 247-260. [PMID: 8485317]
6. Gross, T., Lutzelberger, M., Weigmann, H., Klingenhoff, A., Shenoy, S. and Kaufer, N.F. Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue. Nucleic Acids Res. 25 (1997) 1028-1035. [PMID: 9102632]
7. Wang, Y., Hofmann, T.G., Runkel, L., Haaf, T., Schaller, H., Debatin, K. and Hug, H. Isolation and characterization of cDNAs for the protein kinase HIPK2. Biochim. Biophys. Acta 1518 (2001) 168-172. [PMID: 11267674]
Accepted name: [pyruvate dehydrogenase (acetyl-transferring)] kinase
Reaction: ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate
Glossary: lipoyl group
Other name(s): PDH kinase; PDHK; PDK; PDK1; PDK2; PDK3; PDK4; pyruvate dehydrogenase kinase; pyruvate dehydrogenase kinase (phosphorylating); pyruvate dehydrogenase kinase activator protein; STK1
Systematic name: ATP:[pyruvate dehydrogenase (acetyl-transferring)] phosphotransferase
Comments: The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the pyruvate dehydrogenase complex in mammals. Phosphorylation inactivates EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9074-01-5
References:
1. Linn, T.C., Pelley, J.W., Petit, F.H., Hucho, F., Randall, D.D. and Reed, L.J. α-Keto acid dehydrogenase complexes. XV. Purification and properties of the component enzymes of the pyruvate dehydrogenase complexes from bovine kidney and heart. Arch. Biochem. Biophys. 148 (1972) 327-342. [PMID: 4401694]
2. Reed, L.J., Damuni, Z. and Merryfield, M.L. Regulation of mammalian pyruvate and branched-chain α-keto acid dehydrogenase complexes by phosphorylation-dephosphorylation. Curr. Top. Cell. Regul. 27 (1985) 41-49. [PMID: 3004826]
3. Tovar-Mendez, A., Hirani, T.A., Miernyk, J.A. and Randall, D.D. Analysis of the catalytic mechanism of pyruvate dehydrogenase kinase. Arch. Biochem. Biophys. 434 (2005) 159-168. [PMID: 15629119]
4. Bao, H., Kasten, S.A., Yan, X., Hiromasa, Y. and Roche, T.E. Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADP. Biochemistry 43 (2004) 13442-13451. [PMID: 15491151]
5. Roche, T.E., Hiromasa, Y., Turkan, A., Gong, X., Peng, T., Yan, X., Kasten, S.A., Bao, H. and Dong, J. Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1. Eur. J. Biochem. 270 (2003) 1050-1056. [PMID: 12631265]
Accepted name: dephospho-[reductase kinase] kinase
Reaction: ATP + dephospho-{[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} = ADP + {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase}
Other name(s): AMP-activated kinase; AMP-activated protein kinase kinase; hydroxymethylglutaryl coenzyme A reductase kinase kinase; hydroxymethylglutaryl coenzyme A reductase kinase kinase (phosphorylating); reductase kinase; reductase kinase kinase; STK30
Systematic name: ATP:dephospho-{[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} phosphotransferase
Comments: The enzyme is activated by AMP and is specific for its substrate. Phosphorylates and activates EC 2.7.11.31, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase, that has been inactivated by EC 3.1.3.16, protein-serine/threonine phosphatase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 72060-33-4
References:
1. Beg, Z.H., Stonik, J.A. and Brewer, H.B., Jr. Characterization and regulation of reductase kinase, a protein kinase that modulates the enzymic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc. Natl. Acad. Sci. USA 76 (1979) 4375-4379. [PMID: 291971]
2. Ingebritsen, T.S., Lee, H.-S., Parker, R.A. and Gibson, D.M. Reversible modulation of the activities of both liver microsomal hydroxymethylglutaryl coenzyme A reductase and its inactivating enzyme. Evidence for regulation by phosphorylation-dephosphorylation. Biochem. Biophys. Res. Commun. 81 (1978) 1268-1277. [PMID: 666819]
3. Beg, Z.H., Stonik, J.A. and Brewer, H.B., Jr. Phosphorylation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and modulation of its enzymic activity by calcium-activated and phospholipid-dependent protein kinase. J. Biol. Chem. 260 (1985) 1682-1687. [PMID: 3155737]
4. Clarke, P.R. and Hardie, D.G. Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver. EMBO J. 9 (1990) 2439-2446. [PMID: 2369897]
5. Sato, R., Goldstein, J.L. and Brown, M.S. Replacement of serine-871 of hamster 3-hydroxy-3-methylglutaryl-CoA reductase prevents phosphorylation by AMP-activated kinase and blocks inhibition of sterol synthesis induced by ATP depletion. Proc. Natl. Acad. Sci. USA 90 (1993) 9261-9265. [PMID: 8415689]
Accepted name: [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase
Reaction: ATP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphate
Glossary: lipoyl group
Other name(s): BCK; BCKD kinase; BCODH kinase; branched-chain α-ketoacid dehydrogenase kinase; branched-chain 2-oxo acid dehydrogenase kinase; branched-chain keto acid dehydrogenase kinase; branched-chain oxo acid dehydrogenase kinase (phosphorylating); STK2
Systematic name: ATP:[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] phosphotransferase
Comments: The enzyme has no activating compound but is specific for its substrate. It is a mitochondrial enzyme associated with the branched-chain 2-oxoacid dehydrogenase complex. Phosphorylation inactivates EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 82391-38-6
References:
1. Paxton, R. and Harris, R.A. Isolation of rabbit liver branched chain α-ketoacid dehydrogenase and regulation by phosphorylation. J. Biol. Chem. 257 (1982) 14433-14439. [PMID: 7142221]
2. Wynn, R.M., Chuang, J.L., Cote, C.D. and Chuang, D.T. Tetrameric assembly and conservation in the ATP-binding domain of rat branched-chain α-ketoacid dehydrogenase kinase. J. Biol. Chem. 275 (2000) 30512-30519. [PMID: 10903321]
3. Chuang, J.L., Wynn, R.M. and Chuang, D.T. The C-terminal hinge region of lipoic acid-bearing domain of E2b is essential for domain interaction with branched-chain α-keto acid dehydrogenase kinase. J. Biol. Chem. 277 (2002) 36905-36908. [PMID: 12189132]
4. Popov, K.M., Hawes, J.W. and Harris, R.A. Mitochondrial α-ketoacid dehydrogenase kinases: a new family of protein kinases. Adv. Second Messenger Phosphoprotein Res. 31 (1997) 105-111. [PMID: 9344245]
Accepted name: [isocitrate dehydrogenase (NADP+)] kinase
Reaction: ATP + [isocitrate dehydrogenase (NADP+)] = ADP + [isocitrate dehydrogenase (NADP+)] phosphate
Other name(s): [isocitrate dehydrogenase (NADP)] kinase; ICDH kinase/phosphatase; IDH kinase; IDH kinase/phosphatase; IDH-K/P; IDHK/P; isocitrate dehydrogenase kinase (phosphorylating); isocitrate dehydrogenase kinase/phosphatase; STK3
Systematic name: ATP:[isocitrate dehydrogenase (NADP+)] phosphotransferase
Comments: The enzyme has no activating compound but is specific for its substrate. Phosphorylates and inactivates EC 1.1.1.42, isocitrate dehydrogenase (NADP+).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 83682-93-3
References:
1. Wang, J.Y.J. and Koshland, D.E., Jr. The reversible phosphorylation of isocitrate dehydrogenase of Salmonella typhimurium. Arch. Biochem. Biophys. 218 (1982) 59-67. [PMID: 6756316]
2. Miller, S.P., Karschnia, E.J., Ikeda, T.P. and LaPorte, D.C. Isocitrate dehydrogenase kinase/phosphatase. Kinetic characteristics of the wild-type and two mutant proteins. J. Biol. Chem. 271 (1996) 19124-19128. [PMID: 8702587]
3. Singh, S.K., Matsuno, K., LaPorte, D.C. and Banaszak, L.J. Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 Å. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase. J. Biol. Chem. 276 (2001) 26154-26163. [PMID: 11290745]
4. Oudot, C., Cortay, J.C., Blanchet, C., Laporte, D.C., Di Pietro, A., Cozzone, A.J. and Jault, J.M. The "catalytic" triad of isocitrate dehydrogenase kinase/phosphatase from E. coli and its relationship with that found in eukaryotic protein kinases. Biochemistry 40 (2001) 3047-3055. [PMID: 11258918]
Accepted name: [tyrosine 3-monooxygenase] kinase
Reaction: ATP + [tyrosine-3-monooxygenase] = ADP + phospho-[tyrosine-3-monooxygenase]
Other name(s): pheochromocytoma tyrosine hydroxylase-associated kinase; STK4; tyrosine 3-monooxygenase kinase (phosphorylating)
Systematic name: ATP:[tyrosine-3-monoxygenase] phosphotransferase
Comments: The enzyme has no activating compound but is specific for its substrate, with which it co-purifies. Requires Mg2+. Activates EC 1.14.16.2, tyrosine 3-monooxygenase, by phosphorylation.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 103537-12-8
References:
1. Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification de la tyrosine hydroxylase due phéochromocytome de rat avec une protéine kinase. C.R. Acad. Sci. Paris III 302 (1986) 435-438. [PMID: 2872947]
2. Pigeon, D., Ferrara, P., Gros, F. and Thibault, J. Rat pheochromocytoma tyrosine hydroxylase is phosphorylated on serine 40 by an associated protein kinase. J. Biol. Chem. 262 (1987) 6155-6158. [PMID: 2883182]
Accepted name: myosin-heavy-chain kinase
Reaction: ATP + [myosin heavy-chain] = ADP + [myosin heavy-chain] phosphate
Other name(s): ATP:myosin-heavy-chain O-phosphotransferase; calmodulin-dependent myosin heavy chain kinase; MHCK; MIHC kinase; myosin heavy chain kinase; myosin I heavy-chain kinase; myosin II heavy-chain kinase; [myosin-heavy-chain] kinase; myosin heavy chain kinase A; STK6
Systematic name: ATP:[myosin heavy-chain] O-phosphotransferase
Comments: The enzyme from Dictyostelium sp. (slime moulds) brings about phosphorylation of the heavy chains of Dictyostelium myosin, inhibiting the actin-activated ATPase activity of the myosin. One threonine residue in each heavy chain acts as acceptor. While the enzyme from some species is activated by actin, in other cases Ca2+/calmodulin are required for activity.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 64763-54-8
References:
1. Côté, G.P. and Bukiejko, U. Purification and characterization of a myosin heavy chain kinase from Dictyostelium discoideum. J. Biol. Chem. 262 (1987) 1065-1072. [PMID: 3027076]
2. Hammer, J.A., 3rd, Albanesi, J.P. and Korn, E.D. Purification and characterization of a myosin I heavy chain kinase from Acanthamoeba castellanii. J. Biol. Chem. 258 (1983) 10168-10175. [PMID: 6309772]
3. Rieker, J.P., Swanljung-Collins, H. and Collins, J.H. Purification and characterization of a calmodulin-dependent myosin heavy chain kinase from intestinal brush border. J. Biol. Chem. 262 (1987) 15262-15268. [PMID: 2822719]
4. Ravid, S. and Spudich, J.A. Myosin heavy chain kinase from developed Dictyostelium cells. Purification and characterization. J. Biol. Chem. 264 (1989) 15144-15150. [PMID: 2549052]
5. Brzeska, H., Lynch, T.J., Martin, B., Corigliano-Murphy, A. and Korn, E.D. Substrate specificity of Acanthamoeba myosin I heavy chain kinase as determined with synthetic peptides. J. Biol. Chem. 265 (1990) 16138-16144. [PMID: 2168881]
6. Ravid, S. and Spudich, J.A. Membrane-bound Dictyostelium myosin heavy chain kinase: a developmentally regulated substrate-specific member of the protein kinase C family. Proc. Natl. Acad. Sci. USA 89 (1992) 5877-5881. [PMID: 1321427]
7. Futey, L.M., Medley, Q.G., Côté, G.P. and Egelhoff, T.T. Structural analysis of myosin heavy chain kinase A from Dictyostelium. Evidence for a highly divergent protein kinase domain, an amino-terminal coiled-coil domain, and a domain homologous to the β-subunit of heterotrimeric G proteins. J. Biol. Chem. 270 (1995) 523-529. [PMID: 7822274]
8. Szczepanowska, J., Zhang, X., Herring, C.J., Qin, J., Korn, E.D. and Brzeska, H. Effect of mutating the regulatory phosphoserine and conserved threonine on the activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain kinase. Proc. Natl. Acad. Sci. USA 95 (1998) 4146-4151. [PMID: 9539704]
9. Egelhoff, T.T., Croft, D. and Steimle, P.A. Actin activation of myosin heavy chain kinase A in Dictyostelium: a biochemical mechanism for the spatial regulation of myosin II filament disassembly. J. Biol. Chem. 280 (2005) 2879-2887. [PMID: 15545285]
Accepted name: Fas-activated serine/threonine kinase
Reaction: ATP + [Fas-activated serine/threonine protein] = ADP + [Fas-activated serine/threonine phosphoprotein]
Other name(s): FAST; FASTK; STK10
Systematic name: ATP:[Fas-activated serine/threonine protein] phosphotransferase
Comments: This enzyme is activated during Fas-mediated apoptosis. Following Fas ligation, the enzyme, which is constitutively phosphorylated, is dephosphorylated, and it is the dephosphorylated form that causes phosphorylation of TIA-1, a nuclear RNA-binding protein. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 170347-50-9
References:
1. Tian, Q., Taupin, J., Elledge, S., Robertson, M. and Anderson, P. Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during Fas-mediated apoptosis. J. Exp. Med. 182 (1995) 865-874. [PMID: 7544399]
2. Li, W., Simarro, M., Kedersha, N. and Anderson, P. FAST is a survival protein that senses mitochondrial stress and modulates TIA-1-regulated changes in protein expression. Mol. Cell. Biol. 24 (2004) 10718-10732. [PMID: 15572676]
Accepted name: Goodpasture-antigen-binding protein kinase
Reaction: ATP + [Goodpasture antigen-binding protein] = ADP + [Goodpasture antigen-binding phosphoprotein]
Other name(s): GPBPK; GPBP kinase; STK11; Goodpasture antigen-binding protein kinase
Systematic name: ATP:[Goodpasture antigen-binding protein] phosphotransferase
Comments: This serine/threonine kinase specifically binds to and phosphorylates the N-terminal region of the human Goodpasture antigen, which is located on the α3 chain of collagen IV and is involved in autoimmune disease.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 230316-19-5
References:
1. Raya, A., Revert, F., Navarro, S. and Saus, J. Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human Goodpasture antigen. J. Biol. Chem. 274 (1999) 12642-12649. [PMID: 10212244]
2. Raya, A., Revert-Ros, F., Martinez-Martinez, P., Navarro, S., Rosello, E., Vieites, B., Granero, F., Forteza, J. and Saus, J. Goodpasture antigen-binding protein, the kinase that phosphorylates the Goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis. J. Biol. Chem. 275 (2000) 40392-40399. [PMID: 11007769]
Accepted name: IκB kinase
Reaction: ATP + [IκB protein] = ADP + [IκB phosphoprotein]
Other name(s): CHUK; IKBKA; IKBKB; IKK; IKK-1; IKK-2; inhibitor of NFκB kinase; inhibitor of NF-κB kinase; STK12; TANK-binding kinase 1; TBK1
Systematic name: ATP:[IκB protein] phosphotransferase
Comments: The enzyme phosphorylates IκB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-κB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Regnier, C.H., Song, H.Y., Gao, X., Goeddel, D.V., Cao, Z. and Rothe, M. Identification and characterization of an IκB kinase. Cell 90 (1997) 373-383. [PMID: 9244310]
2. Mercurio, F., Zhu, H., Murray, B.W., Shevchenko, A., Bennett, B.L., Li, J., Young, D.B., Barbosa, M., Mann, M., Manning, A. and Rao, A. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278 (1997) 860-866. [PMID: 9346484]
3. Zandi, E., Rothwarf, D.M., Delhase, M., Hayakawa, M. and Karin, M. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91 (1997) 243-252. [PMID: 9346241]
4. Viatour, P., Merville, M.P., Bours, V. and Chariot, A. Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation. Trends Biochem. Sci. 30 (2005) 43-52. [PMID: 15653325]
Accepted name: cAMP-dependent protein kinase
Reaction: ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
Glossary: 3',5'-cyclic-AMP = cAMP
Other name(s): PKA; protein kinase A; PKA catalytic (C) subunit; A kinase; ATP:protein phosphotransferase (cAMP-dependent)
Systematic name: ATP:protein Ser/Thr-phosphotransferase (3',5'-cAMP-dependent)
Comments: This eukaryotic enzyme recognizes the sequence -Arg-Arg-X-Ser*/Thr*-Hpo, where * indicates the phosphorylated residue and Hpo indicates a hydrophobic residue.The inactive holoenzyme is a heterotetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Each R subunit occludes the active site of a C subunit and contains two binding sites for 3',5'-cyclic-AMP (cAMP). Binding of cAMP activates the enzyme by causing conformational changes that release two free monomeric C subunits from a dimer of the R subunits, i.e. R2C2 + 4 cAMP = R2(cAMP)4 + 2 C. Activity requires phosphorylation of a conserved Thr in the activation loop (T-loop) sequence (Thr198 in human Cα; Thr224 in budding yeast Tpk2), installed by auto-phosphorylation or by the 3-phosphoinositide-dependent protein kinase-1 (PDPK1). Certain R2C2 combinations can be localized to particular subcellular regions by their association with diverse species of 'A Kinase-Anchoring Proteins' (AKAPs). The enzyme has been characterized from many organisms. Humans have three C units (Cα, Cβ, and Cγ) encoded by the paralogous genes PRKACA, PRKACB and PRKACG, respectively, and four R subunits (R1α, RIβ, RIIα and RIIβ), encoded by PKRAR1A, PKRAR1B, PKRAR2A and PKRAR2B, respectively. Yeast (Saccharomyces cerevisiae) has three C subunits (Tpk1, Tpk2, and Tpk3) encoded by the paralogous genes TPK1, TPK2 and TPK3, respectively, and a single R subunit (Bcy1) encoded by the BCY1 gene. Some validated substrates of the enzyme include cAMP-response element-binding protein (CREB), phosphorylase kinase α subunit (PHKA), and tyrosine 3-monooxygenase (TH) in mammals; Adr1, Whi3, Nej1, and Pyk1 in yeast.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 142008-29-5
References:
1. Krebs, E.G. The Albert Lasker Medical Awards. Role of the cyclic AMP-dependent protein kinase in signal transduction. JAMA 262 (1989) 1815-1818. [PMID: 2550680]
2. Technikova-Dobrova, Z., Sardanelli, A.M., Speranza, F., Scacco, S., Signorile, A., Lorusso, V. and Papa, S. Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role. Biochemistry 40 (2001) 13941-13947. [PMID: 11705384]
3. Smith, F.D., Samelson, B.K. and Scott, J.D. Discovery of cellular substrates for protein kinase A using a peptide array screening protocol. Biochem. J. 438 (2011) 103-110. [PMID: 21644927]
4. Broach, J.R. Nutritional control of growth and development in yeast. Genetics 192 (2012) 73-105. [PMID: 22964838]
5. Embogama, D.M. and Pflum, M.K. K-BILDS: A kinase substrate discovery tool. Chembiochem 18 (2017) 136-141. [PMID: 27860220]
6. Taylor, S.S., Wu, J., Bruystens, J.GH., Del Rio, J.C., Lu, T.W., Kornev, A.P. and Ten Eyck, L.F. From structure to the dynamic regulation of a molecular switch: A journey over 3 decades. J. Biol. Chem. 296 (2021) 100746. [PMID: 33957122]
7. Ramms, D.J., Raimondi, F., Arang, N., Herberg, F.W., Taylor, S.S. and Gutkind, J.S. Galphas-protein kinase A (PKA) pathway signalopathies: The emerging genetic landscape and therapeutic potential of human diseases driven by aberrant Galphas-PKA signaling. Pharmacol Rev 73 (2021) 155-197. [PMID: 34663687]
Accepted name: cGMP-dependent protein kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): 3':5'-cyclic GMP-dependent protein kinase; cGMP-dependent protein kinase Iβ; guanosine 3':5'-cyclic monophosphate-dependent protein kinase; PKG; PKG 1α; PKG 1β; PKG II; STK23
Systematic name: ATP:protein phosphotransferase (cGMP-dependent)
Comments: cGMP is required to activate this enzyme. The enzyme occurs as a dimer in higher eukaryotes. The C-terminal region of each polypeptide chain contains the catalytic domain that includes the ATP and protein substrate binding sites. This domain catalyses the phosphorylation by ATP to specific serine or threonine residues in protein substrates [3]. The enzyme also has two allosteric cGMP-binding sites (sites A and B). Binding of cGMP causes a conformational change that is associated with activation of the kinase [4].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 141588-27-4
References:
1. Gill, G.N., Holdy, K.E., Walton, G.M. and Kanstein, C.B. Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 73 (1976) 3918-3922. [PMID: 186778]
2. Murthy, K.S. Modulation of soluble guanylate cyclase activity by phosphorylation. Neurochem. Int. 45 (2004) 845-851. [PMID: 15312978]
3. Richie-Jannetta, R., Francis, S.H. and Corbin, J.D. Dimerization of cGMP-dependent protein kinase Iβ is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function. J. Biol. Chem. 278 (2003) 50070-50079. [PMID: 12933804]
4. Zhao, J., Trewhella, J., Corbin, J., Francis, S., Mitchell, R., Brushia, R. and Walsh, D. Progressive cyclic nucleotide-induced conformational changes in the cGMP-dependent protein kinase studied by small angle X-ray scattering in solution. J. Biol. Chem. 272 (1997) 31929-31936. [PMID: 9395542]
Accepted name: protein kinase C
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): calcium-dependent protein kinase C; calcium-independent protein kinase C; calcium/phospholipid dependent protein kinase; cPKCα; cPKCβ; cPKCγ; nPKCδ; nPKCε; nPKCη; nPKCθ; PKC; PKCα; PKCβ; PKCγ; PKCδ; PKCε; PKCζ; Pkc1p; protein kinase Cε; STK24
Systematic name: ATP:protein phosphotransferase (diacylglycerol-dependent)
Comments: A family of serine- and threonine-specific protein kinases that depend on lipids for activity. They can be activated by calcium but have a requirement for the second messenger diacylglycerol. Members of this group of enzymes phosphorylate a wide variety of protein targets and are known to be involved in diverse cell-signalling pathways. Members of the protein kinase C family also serve as major receptors for phorbol esters, a class of tumour promoters.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Jaken, S. Protein kinase C and tumor promoters. Curr. Opin. Cell Biol. 2 (1990) 192-197. [PMID: 2194521]
2. Parekh, D.B., Ziegler, W. and Parker, P.J. Multiple pathways control protein kinase C phosphorylation. EMBO J. 19 (2000) 496-503. [PMID: 10675318]
3. Valledor, A.F., Xaus, J., Comalada, M., Soler, C. and Celada, A. Protein kinase Cε is required for the induction of mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages. J. Immunol. 164 (2000) 29-37. [PMID: 10604989]
4. Lendenfeld, T. and Kubicek, C.P. Characterization and properties of protein kinase C from the filamentous fungus Trichoderma reesei. Biochem. J. 330 (1998) 689-694. [PMID: 9480876]
5. Brooks, S.P. and Storey, K.B. Protein kinase C from rainbow trout brain: identification and characterization of three isozymes. Biochem. Mol. Biol. Int. 44 (1998) 259-267. [PMID: 9530509]
Accepted name: rhodopsin kinase
Reaction: ATP + rhodopsin = ADP + phosphorhodopsin
Other name(s): cone opsin kinase; G-protein-coupled receptor kinase 1; GPCR kinase 1; GRK1; GRK7; opsin kinase; opsin kinase (phosphorylating); rhodopsin kinase (phosphorylating); RK; STK14
Systematic name: ATP:rhodopsin phosphotransferase
Comments: Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). Acts on the bleached or activated form of rhodopsin; also phosphorylates the β-adrenergic receptor, but more slowly. Does not act on casein, histones or phosphvitin. Inhibited by Zn2+ and digitonin (cf. EC 2.7.11.15, β-adrenergic-receptor kinase and EC 2.7.11.16, G-protein-coupled receptor kinase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 54004-64-7
References:
1. Benovic, J.L., Mayor, F., Jr., Somers, R.L., Caron, M.G. and Lefkowitz, R.J. Light-dependent phosphorylation of rhodopsin by β-adrenergic receptor kinase. Nature 321 (1986) 869-872. [PMID: 3014340]
2. Shichi, H. and Somers, R.L. Light-dependent phosphorylation of rhodopsin. Purification and properties of rhodopsin kinase. J. Biol. Chem. 253 (1978) 7040-7046. [PMID: 690139]
3. Palczewski, K., McDowell, J.H. and Hargrave, P.A. Purification and characterization of rhodopsin kinase. J. Biol. Chem. 263 (1988) 14067-14073. [PMID: 2844754]
4. Weller, M., Virmaux, N. and Mandel, P. Light-stimulated phosphorylation of rhodopsin in the retina: the presence of a protein kinase that is specific for photobleached rhodopsin. Proc. Natl. Acad. Sci. USA 72 (1975) 381-385. [PMID: 164024]
5. Cha, K., Bruel, C., Inglese, J. and Khorana, H.G. Rhodopsin kinase: expression in baculovirus-infected insect cells, and characterization of post-translational modifications. Proc. Natl. Acad. Sci. USA 94 (1997) 10577-10582. [PMID: 9380677]
6. Khani, S.C., Abitbol, M., Yamamoto, S., Maravic-Magovcevic, I. and Dryja, T.P. Characterization and chromosomal localization of the gene for human rhodopsin kinase. Genomics 35 (1996) 571-576. [PMID: 8812493]
7. Chen, C.K., Zhang, K., Church-Kopish, J., Huang, W., Zhang, H., Chen, Y.J., Frederick, J.M. and Baehr, W. Characterization of human GRK7 as a potential cone opsin kinase. Mol. Vis. 7 (2001) 305-313. [PMID: 11754336]
8. Willets, J.M., Challiss, R.A. and Nahorski, S.R. Non-visual GRKs: are we seeing the whole picture? Trends Pharmacol. Sci. 24 (2003) 626-633. [PMID: 14654303]
Accepted name: β-adrenergic-receptor kinase
Reaction: ATP + [β-adrenergic receptor] = ADP + phospho-[β-adrenergic receptor]
Other name(s): ATP:β-adrenergic-receptor phosphotransferase; [β-adrenergic-receptor] kinase; β-adrenergic receptor-specific kinase; β-AR kinase; β-ARK; β-ARK 1; β-ARK 2; β-receptor kinase; GRK2; GRK3; β-adrenergic-receptor kinase (phosphorylating); β2ARK; βARK1; β-adrenoceptor kinase; β-adrenoceptor kinase 1; β-adrenoceptor kinase 2; ADRBK1; BARK1; adrenergic receptor kinase; STK15
Systematic name: ATP:[β-adrenergic receptor] phosphotransferase
Comments: Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). Acts on the agonist-occupied form of the receptor; also phosphorylates rhodopsin, but more slowly. Does not act on casein or histones. The enzyme is inhibited by Zn2+ and digitonin but is unaffected by cyclic-AMP (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.16, G-protein-coupled receptor kinase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 102925-39-3
References:
1. Benovic, J.L., Mayor, F., Jr., Staniszewski, C., Lefkowitz, R.J. and Caron, M.G. Purification and characterization of the β-adrenergic receptor kinase. J. Biol. Chem. 262 (1987) 9026-9032. [PMID: 87250541]
2. Kim, C.M., Dion, S.B., Onorato, J.J. and Benovic, J.L. Expression and characterization of two β-adrenergic receptor kinase isoforms using the baculovirus expression system. Receptor 3 (1993) 39-55. [PMID: 8394172]
3. Laugwitz, K.L., Kronsbein, K., Schmitt, M., Hoffmann, K., Seyfarth, M., Schomig, A. and Ungerer, M. Characterization and inhibition of β-adrenergic receptor kinase in intact myocytes. Cardiovasc. Res. 35 (1997) 324-333. [PMID: 9349395]
4. Ferguson, S.S., Menard, L., Barak, L.S., Koch, W.J., Colapietro, A.M. and Caron, M.G. Role of phosphorylation in agonist-promoted β2-adrenergic receptor sequestration. Rescue of a sequestration-defective mutant receptor by βARK1. J. Biol. Chem. 270 (1995) 24782-24789. [PMID: 7559596]
5. Willets, J.M., Challiss, R.A. and Nahorski, S.R. Non-visual GRKs: are we seeing the whole picture? Trends Pharmacol. Sci. 24 (2003) 626-633. [PMID: 14654303]
Accepted name: G-protein-coupled receptor kinase
Reaction: ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate
Other name(s): G protein-coupled receptor kinase; GPCR kinase; GPCRK; GRK4; GRK5; GRK6; STK16
Systematic name: ATP:[G-protein-coupled receptor] phosphotransferase
Comments: Requires G-protein for activation and therefore belongs to the family of G-protein-dependent receptor kinases (GRKs). All members of this enzyme subfamily possess a highly conserved binding site for 1-phosphatidylinositol 4,5-bisphosphate. (cf. EC 2.7.11.14, rhodopsin kinase and EC 2.7.11.15, β-adrenergic-receptor kinase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Kunapuli, P., Onorato, J.J., Hosey, M.M. and Benovic, J.L. Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5. J. Biol. Chem. 269 (1994) 1099-1105. [PMID: 8288567]
2. Premont, R.T., Koch, W.J., Inglese, J. and Lefkowitz, R.J. Identification, purification, and characterization of GRK5, a member of the family of G protein-coupled receptor kinases. J. Biol. Chem. 269 (1994) 6832-6841. [PMID: 8120045]
3. Willets, J.M., Challiss, R.A. and Nahorski, S.R. Non-visual GRKs: are we seeing the whole picture? Trends Pharmacol. Sci. 24 (2003) 626-633. [PMID: 14654303]
Accepted name: Ca2+/calmodulin-dependent protein kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): ATP:caldesmon O-phosphotransferase; caldesmon kinase; caldesmon kinase (phosphorylating); Ca2+/calmodulin-dependent microtubule-associated protein 2 kinase; Ca2+/calmodulin-dependent protein kinase 1; Ca2+/calmodulin-dependent protein kinase II; Ca2+/calmodulin-dependent protein kinase IV; Ca2+/calmodulin-dependent protein kinase kinase; Ca2+/calmodulin-dependent protein kinase kinase β; calmodulin-dependent kinase II; CaM kinase; CaM kinase II; CAM PKII; CaM-regulated serine/threonine kinase; CaMKI; CaMKII; CaMKIV; CaMKKα; CaMKKβ; microtubule-associated protein 2 kinase; STK20
Systematic name: ATP:protein phosphotransferase (Ca2+/calmodulin-dependent)
Comments: Requires calmodulin and Ca2+ for activity. A wide range of proteins can act as acceptor, including vimentin, synapsin, glycogen synthase, myosin light chains and the microtubule-associated tau protein. Not identical with EC 2.7.11.18 (myosin-light-chain kinase) or EC 2.7.11.26 (tau-protein kinase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 141467-21-2
References:
1. Adlersberg, M., Liu, K.P., Hsiung, S.C., Ehrlich, Y. and Tamir, H. A Ca2+-dependent protein kinase activity associated with serotonin binding protein. J. Neurochem. 49 (1987) 1105-1115. [PMID: 3040904]
2. Baudier, J. and Cole, R.D. Phosphorylation of tau proteins to a state like that in Alzheimer's brain is catalyzed by a calcium/calmodulin-dependent kinase and modulated by phospholipids. J. Biol. Chem. 262 (1987) 17577-17583. [PMID: 3121601]
3. Schulman, H., Kuret, J., Jefferson, A.B., Nose, P.S. and Spitzer, K.H. Ca2+/calmodulin-dependent microtubule-associated protein 2 kinase: broad substrate specificity and multifunctional potential in diverse tissues. Biochemistry 24 (1985) 5320-5327. [PMID: 4074698]
4. Anderson, K.A., Means, R.L., Huang, Q.H., Kemp, B.E., Goldstein, E.G., Selbert, M.A., Edelman, A.M., Fremeau, R.T. and Means, A.R. Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+/calmodulin-dependent protein kinase kinase β. J. Biol. Chem. 273 (1998) 31880-31889. [PMID: 9822657]
5. Matsushita, M. and Nairn, A.C. Characterization of the mechanism of regulation of Ca2+/ calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase. J. Biol. Chem. 273 (1998) 21473-21481. [PMID: 9705275]
6. Ohmstede, C.A., Jensen, K.F. and Sahyoun, N.E. Ca2+/calmodulin-dependent protein kinase enriched in cerebellar granule cells. Identification of a novel neuronal calmodulin-dependent protein kinase. J. Biol. Chem. 264 (1989) 5866-5875. [PMID: 2538431]
7. Rieker, J.P., Swanljung-Collins, H. and Collins, J.H. Purification and characterization of a calmodulin-dependent myosin heavy chain kinase from intestinal brush border. J. Biol. Chem. 262 (1987) 15262-15268. [PMID: 2822719]
8. Iwasa, T., Inoue, N., Fukunaga, K., Isobe, T., Okuyama, T. and Miyamoto, E. Purification and characterization of a multifunctional calmodulin-dependent protein kinase from canine myocardial cytosol. Arch. Biochem. Biophys. 248 (1986) 21-29. [PMID: 3089163]
9. Gomes, A.V., Barnes, J.A. and Vogel, H.J. Spectroscopic characterization of the interaction between calmodulin-dependent protein kinase I and calmodulin. Arch. Biochem. Biophys. 379 (2000) 28-36. [PMID: 10864438]
10. Mal, T.K., Skrynnikov, N.R., Yap, K.L., Kay, L.E. and Ikura, M. Detecting protein kinase recognition modes of calmodulin by residual dipolar couplings in solution NMR. Biochemistry 41 (2002) 12899-12906. [PMID: 12390014]
11. Ngai, P.K. and Walsh, M.P. Inhibition of smooth muscle actin-activated myosin Mg2+-ATPase activity by caldesmon. J. Biol. Chem. 259 (1984) 13656-13659. [PMID: 6150036]
12. Ikebe, M., Reardon, S., Scott-Woo, G.C., Zhou, Z. and Koda, Y. Purification and characterization of calmodulin-dependent multifunctional protein kinase from smooth muscle: isolation of caldesmon kinase. Biochemistry 29 (1990) 11242-11248. [PMID: 2176896]
Accepted name: myosin-light-chain kinase
Reaction: ATP + [myosin light chain] = ADP + [myosin light chain] phosphate
Other name(s): [myosin-light-chain] kinase; ATP:myosin-light-chain O-phosphotransferase; calcium/calmodulin-dependent myosin light chain kinase; MLCK; MLCKase; myosin kinase; myosin light chain kinase; myosin light chain protein kinase; myosin light-chain kinase (phosphorylating); smooth-muscle-myosin-light-chain kinase; STK18
Systematic name: ATP:[myosin light chain] O-phosphotransferase
Comments: Requires Ca2+ and calmodulin for activity. The 20-kDa light chain from smooth muscle myosin is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors, but more slowly.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 51845-53-5
References:
1. Adelstein, R.S. and Klee, C.B. Purification and characterization of smooth muscle myosin light chain kinase. J. Biol. Chem. 256 (1981) 7501-7509. [PMID: 6894756]
2. Hathaway, D.R. and Adelstein, R.S. Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc. Natl. Acad. Sci. USA 76 (1979) 1653-1657. [PMID: 156362]
3. Pires, E., Perry, S.V. and Thomas, M.A.W. Myosin light-chain kinase, a new enzyme from striated muscle. FEBS Lett. 41 (1974) 292-296. [PMID: 4853304]
4. Nunnally, M.H., Rybicki, S.B. and Stull, J.T. Characterization of chicken skeletal muscle myosin light chain kinase. Evidence for muscle-specific isozymes. J. Biol. Chem. 260 (1985) 1020-1026. [PMID: 3881420]
5. Edelman, A.M., Takio, K., Blumenthal, D.K., Hansen, R.S., Walsh, K.A., Titani, K. and Krebs, E.G. Characterization of the calmodulin-binding and catalytic domains in skeletal muscle myosin light chain kinase. J. Biol. Chem. 260 (1985) 11275-11285. [PMID: 3897230]
6. Mal, T.K., Skrynnikov, N.R., Yap, K.L., Kay, L.E. and Ikura, M. Detecting protein kinase recognition modes of calmodulin by residual dipolar couplings in solution NMR. Biochemistry 41 (2002) 12899-12906. [PMID: 12390014]
7. Sobieszek, A. Enzyme kinetic characterization of the smooth muscle myosin phosphorylating system: activation by calcium and calmodulin and possible inhibitory mechanisms of antagonists. Biochim. Biophys. Acta 1450 (1999) 77-91. [PMID: 10231558]
8. Sobieszek, A., Borkowski, J. and Babiychuk, V.S. Purification and characterization of a smooth muscle myosin light chain kinase-phosphatase complex. J. Biol. Chem. 272 (1997) 7034-7041. [PMID: 9054394]
9. Fujita, K., Ye, L.H., Sato, M., Okagaki, T., Nagamachi, Y. and Kohama, K. Myosin light chain kinase from skeletal muscle regulates an ATP-dependent interaction between actin and myosin by binding to actin. Mol. Cell. Biochem. 190 (1999) 85-90. [PMID: 10098974]
Accepted name: phosphorylase kinase
Reaction: 2 ATP + phosphorylase b = 2 ADP + phosphorylase a
Other name(s): dephosphophosphorylase kinase; glycogen phosphorylase kinase; PHK; phosphorylase b kinase; phosphorylase B kinase; phosphorylase kinase (phosphorylating); STK17
Systematic name: ATP:phosphorylase-b phosphotransferase
Comments: Requires Ca2+ and calmodulin for activity. The enzyme phosphorylates a specific serine residue in each of the subunits of the dimeric phosphorylase b. For muscle phosphorylase but not liver phosphorylase, this is accompanied by a further dimerization to form a tetrameric phosphorylase. The enzyme couples muscle contraction with energy production via glycogenolysis—glycolysis by catalysing the Ca2+-dependent phosphorylation and activation of glycogen phosphorylase b [5]. The γ subunit of the tetrameric αβγδ enzyme is the catalytic subunit.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9001-88-1
References:
1. Krebs, E.G. and Fischer, E.H. The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochim. Biophys. Acta 20 (1956) 150-157. [PMID: 13315361]
2. Krebs, E.G., Kent, A.B. and Fischer, E.H. The muscle phosphorylase b kinase reaction. J. Biol. Chem. 231 (1958) 73-83. [PMID: 13538949]
3. Rall, T.W., Wosilait, W.D. and Sutherland, E.W. The interconversion of phosphorylase a and phosphorylase b from dog heart muscle. Biochim. Biophys. Acta 20 (1956) 69-76. [PMID: 13315351]
4. Nikolaropoulos, S. and Sotiroudis, T.G. Phosphorylase kinase from chicken gizzard. Partial purification and characterization. Eur. J. Biochem. 151 (1985) 467-473. [PMID: 4029141]
5. Farrar, Y.J. and Carlson, G.M. Kinetic characterization of the calmodulin-activated catalytic subunit of phosphorylase kinase. Biochemistry 30 (1991) 10274-10279. [PMID: 1931956]
6. Dasgupta, M. and Blumenthal, D.K. Characterization of the regulatory domain of the γ-subunit of phosphorylase kinase. The two noncontiguous calmodulin-binding subdomains are also autoinhibitory. J. Biol. Chem. 270 (1995) 22283-22289. [PMID: 7673209]
7. Lowe, E.D., Noble, M.E., Skamnaki, V.T., Oikonomakos, N.G., Owen, D.J. and Johnson, L.N. The crystal structure of a phosphorylase kinase peptide substrate complex: kinase substrate recognition. EMBO J. 16 (1997) 6646-6658. [PMID: 9362479]
Accepted name: elongation factor 2 kinase
Reaction: ATP + [elongation factor 2] = ADP + [elongation factor 2] phosphate
Other name(s): Ca/CaM-kinase III; calmodulin-dependent protein kinase III; CaM kinase III; eEF2 kinase; eEF2K; EF2K; STK19
Systematic name: ATP:[elongation factor 2] phosphotransferase
Comments: Requires Ca2+ and calmodulin for activity. The enzyme can also be phosphorylated by the catalytic subunit of EC 2.7.11.11, cAMP-dependent protein kinase. Elongation factor 2 is phosphorylated in several cell types in response to various growth factors, hormones and other stimuli that raise intracellular Ca2+ [1,2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 116283-83-1
References:
1. Mitsui, K., Brady, M., Palfrey, H.C. and Nairn, A.C. Purification and characterization of calmodulin-dependent protein kinase III from rabbit reticulocytes and rat pancreas. J. Biol. Chem. 268 (1993) 13422-13433. [PMID: 8514778]
2. Hincke, M.T. and Nairn, A.C. Phosphorylation of elongation factor 2 during Ca2+-mediated secretion from rat parotid acini. Biochem. J. 282 (1992) 877-882. [PMID: 1372803]
3. Knebel, A., Morrice, N. and Cohen, P. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38δ. EMBO J. 20 (2001) 4360-4369. [PMID: 11500363]
4. Sans, M.D., Xie, Q. and Williams, J.A. Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic acini. Biochem. Biophys. Res. Commun. 319 (2004) 144-151. [PMID: 15158453]
5. Browne, G.J., Finn, S.G. and Proud, C.G. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J. Biol. Chem. 279 (2004) 12220-12231. [PMID: 14709557]
6. Ryazanov, A.G. Elongation factor-2 kinase and its newly discovered relatives. FEBS Lett.514 (2002) 26-29. [PMID: 11904175]
Accepted name: polo kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): Cdc5; Cdc5p; Plk; PLK; Plk1; Plo1; POLO kinase; polo serine-threonine kinase; polo-like kinase; polo-like kinase 1; serine/threonine-specific Drosophila kinase polo; STK21
Systematic name: ATP:protein phosphotransferase (spindle-pole-dependent)
Comments: The enzyme associates with the spindle pole during mitosis and is thought to play an important role in the dynamic function of the mitotic spindle during chromosome segregation. The human form of the enzyme, Plk1, does not phosphorylate histone H1, enolase and phosvitin but it can phosphorylate myelin basic protein and microtubule-associated protein MAP-2, although to a lesser extent than casein [2].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 149433-93-2
References:
1. Llamazares, S., Moreira, A., Tavares, A., Girdham, C., Spruce, B.A., Gonzalez, C., Karess, R.E., Glover, D.M. and Sunkel, C.E. polo encodes a protein kinase homolog required for mitosis in Drosophila. Genes Dev. 5 (1991) 2153-2165. [PMID: 1660828]
2. Golsteyn, R.M., Mundt, K.E., Fry, A.M. and Nigg, E.A. Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function. J. Cell Biol. 129 (1995) 1617-1628. [PMID: 7790358]
3. Mulvihill, D.P. and Hyams, J.S. Cytokinetic actomyosin ring formation and septation in fission yeast are dependent on the full recruitment of the polo-like kinase Plo1 to the spindle pole body and a functional spindle assembly checkpoint. J. Cell. Sci. 115 (2002) 3575-3586. [PMID: 12186944]
4. Ohkura, H. Phosphorylation: polo kinase joins an elite club. Curr. Biol. 13 (2003) R912-R914. [PMID: 14654016]
Accepted name: cyclin-dependent kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): Bur1; Bur1 Cdk; Cak1; Cak1p; cdc2; cdc2 kinase; Cdc28p; CDK; cdk-activating kinase; Cdk-activating protein kinase; cdk1; cdk2; Cdk2; cdk3; cdk4; cdk5; cdk6; cdk7; cdk8; cdk9; cyclin A-activated cdc2; cyclin A-activated cdk2; cyclin D-cdk6 kinase; cyclin D-dependent kinase; cyclin E kinase; cyclin-A associated kinase; cyclin-dependent kinase 6; cyclin-dependent kinase-2; cyclin-dependent kinase-4; cyclin-dependent protein kinase activating kinase; cyk; D-type cyclin kinase; nclk; neuronal cdc2-like kinase; PCTAIRE-1; STK25
Systematic name: ATP:cyclin phosphotransferase
Comments: Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Johnson, D.G. and Walker, C.L. Cyclins and cell cycle checkpoints. Annu. Rev. Pharmacol. Toxicol. 39 (1999) 295-312. [PMID: 10331086]
2. Pan, Z.Q., Amin, A. and Hurwitz, J. Characterization of the in vitro reconstituted cyclin A or B1-dependent cdk2 and cdc2 kinase activities. J. Biol. Chem. 268 (1993) 20443-20451. [PMID: 8397207]
3. Yee, A., Wu, L., Liu, L., Kobayashi, R., Xiong, Y. and Hall, F.L. Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel regulatory subunit. J. Biol. Chem. 271 (1996) 471-477. [PMID: 8550604]
Accepted name: [RNA-polymerase]-subunit kinase
Reaction: ATP + [DNA-directed RNA polymerase] = ADP + phospho-[DNA-directed RNA polymerase]
Other name(s): CTD kinase; STK9
Systematic name: ATP:[DNA-directed RNA polymerase] phosphotransferase
Comments: The enzyme appears to be distinct from other protein kinases. It brings about multiple phosphorylations of the unique C-terminal repeat domain of the largest subunit of eukaryotic DNA-directed RNA polymerase (EC 2.7.7.6). The enzyme does not phosphorylate casein, phosvitin or histone.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 122097-00-1
References:
1. Lee, J.M. and Greenleaf, A.L. A protein kinase that phosphorylates the C-terminal repeat domain of the largest subunit of RNA polymerase II. Proc. Natl. Acad. Sci. USA 86 (1989) 3624-3628. [PMID: 2657724]
Accepted name: mitogen-activated protein kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): c-Jun N-terminal kinase; Dp38; ERK; ERK1; ERK2; extracellular signal-regulated kinase; JNK; JNK3α1; LeMPK3; MAP kinase; MAP-2 kinase; MAPK; MBP kinase I; MBP kinase II; microtubule-associated protein 2 kinase; microtubule-associated protein kinase; myelin basic protein kinase; p38δ; p38-2; p42 mitogen-activated protein kinase; p42mapk; PMK-1; PMK-2; PMK-3; pp42; pp44mapk; p44mpk; SAPK; STK26; stress-activated protein kinase
Systematic name: ATP:protein phosphotransferase (MAPKK-activated)
Comments: Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline [6]. A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Ray, L.B. and Sturgill, T.W. Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells. J. Biol. Chem. 263 (25) 12721-12727. [PMID: 2842341]
2. Rossomando, A.J., Sanghera, J.S., Marsden, L.A., Weber, M.J., Pelech, S.L. and Sturgill, T.W. Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylations. J. Biol. Chem. 266 (1991) 20270-20275. [PMID: 1657919]
3. Seger, R., Ahn, N.G., Posada, J., Munar, E.S., Jensen, A.M., Cooper, J.A., Cobb, M.H. and Krebs, E.G. Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. J. Biol. Chem. 267 (1992) 14373-14381. [PMID: 1321146]
4. Stein, B., Yang, M.X., Young, D.B., Janknecht, R., Hunter, T., Murray, B.W. and Barbosa, M.S. p38-2, a novel mitogen-activated protein kinase with distinct properties. J. Biol. Chem. 272 (1997) 19509-19517. [PMID: 9235954]
5. Lisnock, J., Griffin, P., Calaycay, J., Frantz, B., Parsons, J., O'Keefe, S.J. and LoGrasso, P. Activation of JNK3α1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3α1. Biochemistry 39 (2000) 3141-3148. [PMID: 10715136]
6. Roux, P.P. and Blenis, J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68 (2004) 320-344. [PMID: 15187187]
Accepted name: mitogen-activated protein kinase kinase kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): cMos; cRaf; MAPKKK; MAP3K; MAP kinase kinase kinase; MEKK; MEKK1; MEKK2; MEKK3; MEK kinase; Mil/Raf; MLK-like mitogen-activated protein triple kinase; MLTK; MLTKa; MLTKb; REKS; STK28
Systematic name: ATP:protein phosphotransferase (MAPKKKK-activated)
Comments: This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 146702-84-3
References:
1. Wang, X.S., Diener, K., Jannuzzi, D., Trollinger, D., Tan, T.H., Lichenstein, H., Zukowski, M. and Yao, Z. Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase. J. Biol. Chem. 271 (1996) 31607-31611. [PMID: 8940179]
2. Gotoh, I., Adachi, M. and Nishida, E. Identification and characterization of a novel MAP kinase kinase kinase, MLTK. J. Biol. Chem. 276 (2001) 4276-4286. [PMID: 11042189]
3. Vojtek, A.B., Hollenberg, S.M. and Cooper, J.A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74 (1993) 205-214. [PMID: 8334704]
Accepted name: tau-protein kinase
Reaction: ATP + [tau-protein] = ADP + O-phospho-[tau-protein]
Other name(s): ATP:tau-protein O-hosphotransferase; brain protein kinase PK40erk; cdk5/p20; CDK5/p23; glycogen synthase kinase-3β; GSK; protein tau kinase; STK31; tau kinase; [tau-protein] kinase; tau-protein kinase I; tau-protein kinase II; tau-tubulin kinase; TPK; TPK I; TPK II; TTK
Systematic name: ATP:[tau-protein] O-phosphotransferase
Comments: Activated by tubulin. Involved in the formation of paired helical filaments, which are the main fibrous component of all fibrillary lesions in brain and are associated with Alzheimer's disease.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 111694-09-8
References:
1. Ishiguro, K., Ihara, Y., Uchida, T. and Imahori, K. A novel tubulin-dependent protein kinase forming a paired helical filament epitope on tau. J. Biochem. (Tokyo) 104 (1988) 319-321. [PMID: 2467901]
2. Lund, E.T., McKenna, R., Evans, D.B., Sharma, S.K. and Mathews, W.R. Characterization of the in vitro phosphorylation of human tau by tau protein kinase II (cdk5/p20) using mass spectrometry. J. Neurochem. 76 (2001) 1221-1232. [PMID: 11181841]
3. Michel, G., Mercken, M., Murayama, M., Noguchi, K., Ishiguro, K., Imahori, K. and Takashima, A. Characterization of tau phosphorylation in glycogen synthase kinase-3β and cyclin dependent kinase-5 activator (p23) transfected cells. Biochim. Biophys. Acta 1380 (1998) 177-182. [PMID: 9565682]
4. Aoki, M., Iwamoto-Sugai, M., Sugiura, I., Sasaki, C., Hasegawa, T., Okumura, C., Sugio, S., Kohno, T. and Matsuzaki, T. Expression, purification and crystallization of human tau-protein kinase I/glycogen synthase kinase-3β. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 1464-1465. [PMID: 11053853]
[EC 2.7.11.27 Transferred entry: [acetyl-CoA carboxylase] kinase. Now classified under EC 2.7.11.31, 5-AMP-activated protein kinase. (EC 2.7.11.27 created 1990 as EC 2.7.1.128 (EC 2.7.1.111 created 1984, incorporated 1992), transferred 2005 to EC 2.7.11.27, deleted 2022)]
Accepted name: tropomyosin kinase
Reaction: ATP + tropomyosin = ADP + O-phosphotropomyosin
Other name(s): tropomyosin kinase (phosphorylating); STK (ambiguous)
Systematic name: ATP:tropomyosin O-phosphotransferase
Comments: The enzyme phosphorylates casein equally well, and histone and phosvitin to a lesser extent. The acceptor is a serine residue in the protein.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 90804-56-1
References:
1. deBelle, I. and Mak, A.S. Isolation and characterization of tropomyosin kinase from chicken embryo. Biochim. Biophys. Acta 925 (1987) 17-26. [PMID: 3593768]
2. Montgomery, K. and Mak, A.S. In vitro phosphorylation of tropomyosin by a kinase from chicken embryo. J. Biol. Chem. 259 (1984) 5555-5560. [PMID: 6325440]
3. Watson, M.H., Taneja, A.K., Hodges, R.S. and Mak, A.S. Phosphorylation of αα- and ββ-tropomyosin and synthetic peptide analogues. Biochemistry 27 (1988) 4506-4512. [PMID: 3166994]
Accepted name: low-density-lipoprotein-receptor kinase
Reaction: ATP + [low-density-lipoprotein receptor]-L-serine = ADP + [low-density-lipoprotein receptor]-O-phospho-L-serine
Other name(s): ATP:low-density-lipoprotein-L-serine O-phosphotransferase; LDL receptor kinase; [low-density-lipoprotein] kinase; low-density lipoprotein kinase; low-density-lipoprotein receptor kinase (phosphorylating); STK7
Systematic name: ATP:[low-density-lipoprotein receptor]-L-serine O-phosphotransferase
Comments: Phosphorylates the last serine residue (Ser-833) in the cytoplasmic domain of the low-density lipoprotein receptor from bovine adrenal cortex. Casein can also act as a substrate but with lower affinity. GTP can act instead of ATP.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 107445-00-1
References:
1. Kishimoto, A., Brown, M.S., Slaughter, C.A. and Goldstein, J.L. Phosphorylation of serine 833 in cytoplasmic domain of low density lipoprotein receptor by a high molecular weight enzyme resembling casein kinase II. J. Biol. Chem. 262 (1987) 1344-1351. [PMID: 3100530]
2. Kishimoto, A., Goldstein, J.L. and Brown, M.S. Purification of catalytic subunit of low density lipoprotein receptor kinase and identification of heat-stable activator protein. J. Biol. Chem. 262 (1987) 9367-9373. [PMID: 3597414]
Accepted name: receptor protein serine/threonine kinase
Reaction: ATP + [receptor-protein] = ADP + [receptor-protein] phosphate
Other name(s): activin receptor kinase; receptor type I serine/threonine protein kinase; receptor type II serine/threonine protein kinase; STK13; TGF-β kinase; receptor serine/threonine protein kinase
Systematic name: ATP:[receptor-protein] phosphotransferase
Comments: The transforming growth factor β (TGF-β) family of cytokines regulates cell proliferation, differentiation, recognition and death. Signalling occurs by the binding of ligand to the type II receptor, which is the constitutively active kinase. Bound TGF-β is then recognized by receptor I, which is phosphorylated and can propagate the signal to downstream substrates [1,3].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Wrana, J.L., Attisano, L., Wieser, R., Ventura, F. and Massagué, J. Mechanism of activation of the TGF-β receptor. Nature 370 (1994) 341-347. [PMID: 8047140]
2. Massagué, J. and Chen, Y.G. Controlling TGF-β signaling. Genes Dev. 14 (2000) 627-644. [PMID: 10733523]
3. de Caestecker, M.P., Hemmati, P., Larisch-Bloch, S., Ajmera, R., Roberts, A.B. and Lechleider, R.J. Characterization of functional domains within Smad4/DPC4. J. Biol. Chem. 272 (1997) 13690-13696. [PMID: 9153220]
Accepted name: [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase
Reaction: ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
For diagram click here.
Other name(s): AMPK; AMP-activated protein kinase; HMG-CoA reductase kinase; β-hydroxy-β-methylglutaryl-CoA reductase kinase; [hydroxymethylglutaryl-CoA reductase (NADPH2)] kinase; 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase; 3-hydroxy-3-methylglutaryl-CoA reductase kinase; hydroxymethylglutaryl coenzyme A reductase kinase; hydroxymethylglutaryl coenzyme A reductase kinase (phosphorylating); hydroxymethylglutaryl-CoA reductase kinase; reductase kinase; STK29
Systematic name: ATP:[hydroxymethylglutaryl-CoA reductase (NADPH)] phosphotransferase
Comments: The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) [5]. Thr-172 within the catalytic subunit (α-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase [7]. GTP can act instead of ATP [4]
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 172522-01-9
References:
1. Beg, Z.H., Stonik, J.A. and Brewer, H.B., Jr. 3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. USA 75 (1978) 3678-3682. [PMID: 278983]
2. Gibson, D.M. and Ingebritsen, T.S. Reversible modulation of liver hydroxymethylglutaryl CoA reductase. Life Sci. 23 (1978) 2649-2664. [PMID: 216867]
3. Ingebritsen, T.S., Lee, H.-S., Parker, R.A. and Gibson, D.M. Reversible modulation of the activities of both liver microsomal hydroxymethylglutaryl coenzyme A reductase and its inactivating enzyme. Evidence for regulation by phosphorylation-dephosphorylation. Biochem. Biophys. Res. Commun. 81 (1978) 1268-1277. [PMID: 666819]
4. Ferrer, A., Caelles, C., Massot, N. and Hegardt, F.G. Allosteric activation of rat liver microsomal [hydroxymethylglutaryl-CoA reductase (NADPH)]kinase by nucleoside phosphates. Biol. Chem. Hoppe Seyler 368 (1987) 249-257. [PMID: 3689494]
5. Weekes, J., Ball, K.L., Caudwell, F.B. and Hardie, D.G. Specificity determinants for the AMP-activated protein kinase and its plant homologue analysed using synthetic peptides. FEBS Lett. 334 (1993) 335-339. [PMID: 7902296]
6. Crute, B.E., Seefeld, K., Gamble, J., Kemp, B.E. and Witters, L.A. Functional domains of the a1 catalytic subunit of the AMP-activated protein kinase. J. Biol. Chem. 273 (1998) 35347-35354. [PMID: 9857077]
7. Stein, S.C., Woods, A., Jones, N.A., Davison, M.D. and Carling, D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem. J. 345 (2000) 437-443. [PMID: 10642499]
Accepted name: [pyruvate, phosphate dikinase] kinase
Reaction: ADP + [pyruvate, phosphate dikinase] = AMP + [pyruvate, phosphate dikinase] phosphate
Other name(s): PPDK regulatory protein (ambiguous); pyruvate; phosphate dikinase regulatory protein (ambiguous); bifunctional dikinase regulatory protein (ambiguous)
Systematic name: ADP:[pyruvate, phosphate dikinase] phosphotransferase
Comments: The enzymes from the plants Zea mays (maize) and Arabidopsis thaliana are bifunctional and catalyse both the phosphorylation and dephosphorylation of EC 2.7.9.1 (pyruvate, phosphate dikinase). cf. EC 2.7.4.27, [pyruvate, phosphate dikinase]-phosphate phosphotransferase [2-5]. The enzyme is specific for a reaction intermediate form of EC 2.7.9.1EC 2.7.9.1, and phosphorylates a threonine located adjacent to the catalytic histidine. The phosphorylation only takes place if the histidine is already phosphorylated [3-5].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Burnell, J.N. and Hatch, M.D. Regulation of C4 photosynthesis: identification of a catalytically important histidine residue and its role in the regulation of pyruvate,Pi dikinase. Arch. Biochem. Biophys. 231 (1984) 175-182. [PMID: 6326674]
2. Burnell, J.N. and Hatch, M.D. Regulation of C4 photosynthesis: purification and properties of the protein catalyzing ADP-mediated inactivation and Pi-mediated activation of pyruvate,Pi dikinase. Arch. Biochem. Biophys. 237 (1985) 490-503. [PMID: 2983615]
3. Chastain, C.J., Botschner, M., Harrington, G.E., Thompson, B.J., Mills, S.E., Sarath, G. and Chollet, R. Further analysis of maize C4 pyruvate,orthophosphate dikinase phosphorylation by its bifunctional regulatory protein using selective substitutions of the regulatory Thr-456 and catalytic His-458 residues. Arch. Biochem. Biophys. 375 (2000) 165-170. [PMID: 10683263]
4. Burnell, J.N. and Chastain, C.J. Cloning and expression of maize-leaf pyruvate, Pi dikinase regulatory protein gene. Biochem. Biophys. Res. Commun. 345 (2006) 675-680. [PMID: 16696949]
5. Chastain, C.J., Xu, W., Parsley, K., Sarath, G., Hibberd, J.M. and Chollet, R. The pyruvate, orthophosphate dikinase regulatory proteins of Arabidopsis possess a novel, unprecedented Ser/Thr protein kinase primary structure. Plant J. 53 (2008) 854-863. [PMID: 17996018]
Accepted name: [pyruvate, water dikinase] kinase
Reaction: ADP + [pyruvate, water dikinase] = AMP + [pyruvate, water dikinase] phosphate
Other name(s): PSRP (ambiguous); PEPS kinase
Systematic name: ADP:[pyruvate, water dikinase] phosphotransferase
Comments: The enzyme from the bacterium Escherichia coli is bifunctional and catalyses both the phosphorylation and dephosphorylation of EC 2.7.9.2, pyruvate, water dikinase. cf. EC 2.7.4.28, ([pyruvate, water dikinase] phosphate) phosphotransferase [1]. The enzyme is specific for a reaction intermediate form of EC 2.7.9.2, where it phosphorylates an active site histidine [1]. It has no activity toward EC 2.7.9.1 pyruvate, phosphate dikinase (cf. EC 2.7.11.32, [pyruvate, phosphate dikinase] kinase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Burnell, J.N. Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP-dependent kinase—Pi-dependent pyrophosphorylase from bacteria. BMC Biochem. 11 (2010) 1. [PMID: 20044937]
Accepted name: NEK6-subfamily protein kinase
Reaction: ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
Other name(s): NEK6; NEK7; nekl-3
Comments: Requires Mg2+. NEK6 subfamily kinases are present in animals, though lost in insects, and include human NEK6 and NEK7 and C. elegans nekl-3. They are activated in mitosis by phosphorylation by NEK9 [1], and phosphorylate cytoskeletal proteins including EML4, KIF11A and KIF14 [4,2]. In C. elegans, nekl-3 is involved in clathrin-mediated endocytosis [5]. In peptide arrays, NEK6 prefers to phosphorylate Ser residues, with hydrophobic residues at -2 and +1 and charged residues at -1, -2 and +2 [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Belham, C., Roig, J., Caldwell, J.A., Aoyama, Y., Kemp, B.E., Comb, M. and Avruch, J. A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. J. Biol. Chem. 278 (2003) 34897-34909. [PMID: 12840024]
2. Cullati, S.N., Kabeche, L., Kettenbach, A.N. and Gerber, S.A. A bifurcated signaling cascade of NIMA-related kinases controls distinct kinesins in anaphase. J. Cell Biol. 216 (2017) 2339-2354. [PMID: 28630147]
3. van de Kooij, B., Creixell, P., van Vlimmeren, A., Joughin, B.A., Miller, C.J., Haider, N., Simpson, C.D., Linding, R., Stambolic, V., Turk, B.E. and Yaffe, M.B. Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs. Elife 8 (2019) . [PMID: 31124786]
4. Adib, R., Montgomery, J.M., Atherton, J., O'Regan, L., Richards, M.W., Straatman, K.R., Roth, D., Straube, A., Bayliss, R., Moores, C.A. and Fry, A.M. Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. Sci Signal 12 (2019) . [PMID: 31409757]
5. Joseph, B.B., Wang, Y., Edeen, P., Lazetic, V., Grant, B.D. and Fay, D.S. Control of clathrin-mediated endocytosis by NIMA family kinases. PLoS Genet. 16 (2020) e1008633. [PMID: 32069276]
Accepted name: CRIK-subfamily protein kinase
Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
Other name(s): CRIK; CIT; SGK21; Citron; Citron-K; Sticky/Citron Kinase; Citron Rho-Interacting Kinase
Comments: Requires Mg2+. Peptide array data show a preference for phosphorylation of Thr over Ser and a preference for basic residues in the -5 to -1 positions [1]. CRIK is an animal-specific protein kinase that phosphorylates myosin light chain (cf. EC 2.7.11.18, myosin-light-chain kinase) and is involved in cytokinesis in both mammals and Drosophila. Human CRIK phosphorylates myosin light chain, MYL9/MRLC1 on T19/S20 [2] and GLI2 on S149 [3]. Drosophila CRIK (sticky) interacts with the kinesins Nebbish and Pavarotti, and human CRIK interacts with their orthologs, KIF14 and KIF23/MKLP1 to promote midbody formation during cytokinesis [4]. In Drosophila, CRIK/Sticky catalytic activity was required for this function. Human CRIK is mostly highly expressed in brain, and mutations that alter splicing or kinase activity lead to microcephaly [5, 6], as do knockouts in mouse and rat, and mutations in its interacting partner, the kinesin KIF14 [6].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Johnson, J.L., Yaron, T.M., Huntsman, E.M., Kerelsky, A., Song, J., Regev, A., Lin, T.Y., Liberatore, K., Cizin, D.M., Cohen, B.M., Vasan, N., Ma, Y., Krismer, K., Robles, J.T., van de Kooij, B., van Vlimmeren, A.E., Andree-Busch, N., Kaufer, N.F., Dorovkov, M.V., Ryazanov, A.G., Takagi, Y., Kastenhuber, E.R., Goncalves, M.D., Hopkins, B.D., Elemento, O., Taatjes, D.J., Maucuer, A., Yamashita, A., Degterev, A., Uduman, M., Lu, J., Landry, S.D., Zhang, B., Cossentino, I., Linding, R., Blenis, J., Hornbeck, P.V., Turk, B.E., Yaffe, M.B. and Cantley, L.C. An atlas of substrate specificities for the human serine/threonine kinome. Nature 613 (2023) 759-766. [PMID: 36631611]
2. Yamashiro, S., Totsukawa, G., Yamakita, Y., Sasaki, Y., Madaule, P., Ishizaki, T., Narumiya, S. and Matsumura, F. Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. Mol. Biol. Cell 14 (2003) 1745-1756. [PMID: 12802051]
3. Xing, Z., Lin, A., Li, C., Liang, K., Wang, S., Liu, Y., Park, P.K., Qin, L., Wei, Y., Hawke, D.H., Hung, M.C., Lin, C. and Yang, L. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell 159 (2014) 1110-1125. [PMID: 25416949]
4. Bassi, Z.I., Audusseau, M., Riparbelli, M.G., Callaini, G. and D'Avino, P.P. Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc. Natl. Acad. Sci. USA 110 (2013) 9782-9787. [PMID: 23716662]
5. Shaheen, R., Hashem, A., Abdel-Salam, G.M., Al-Fadhli, F., Ewida, N. and Alkuraya, F.S. Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause severe primary microcephaly in humans. Hum Genet 135 (2016) 1191-1197. [PMID: 27503289]
6. Li, H., Bielas, S.L., Zaki, M.S., Ismail, S., Farfara, D., Um, K., Rosti, R.O., Scott, E.C., Tu, S., Chi, N.C., Gabriel, S., Erson-Omay, E.Z., Ercan-Sencicek, A.G., Yasuno, K., Caglayan, A.O., Kaymakcalan, H., Ekici, B., Bilguvar, K., Gunel, M. and Gleeson, J.G. Biallelic mutations in citron kinase link mitotic cytokinesis to human primary microcephaly. Am. J. Hum. Genet. 99 (2016) 501-510. [PMID: 27453578]
Accepted name: MASTL-subfamily protein kinase
Reaction: (1) ATP + [endosulfine family protein]-L-serine = ADP + [endosulfine family protein]-O-phospho-L-serine
(2) ATP + [endosulfine family protein]-L-threonine = ADP + [endosulfine family protein]-O-phospho-L-threonine
Glossary: MASTL = microtubule-associated
Other name(s): MASTL; gwl; greatwall kinase; RIM15; microtubule-associated (MASTL)-subfamily-protein kinase.
Systematic name: ATP:[endosulfine family protein] phosphotransferase (Ser/Thr-phosphorylating)
Comments: Requires Mg2+. Peptide array data suggest that MASTL prefers to phosphorylate Ser over Thr, followed at position +1 by a bulky hydrophobic (Met, Leu, Phe or Tyr) and with an aromatic residue in the -2 position [4]. Its main role in animal systems is in the regulation of mitosis by phosphorylating a conserved site on endosulfine family proteins (ENSA and ARPP-19 in human), causing them to inhibit the protein phosphatase 2A-B55 [protein phosphatase 2A (PP2A) holoenzyme complex containing a B55-family regulatory subunit] [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Pearce, L.R., Komander, D. and Alessi, D.R. The nuts and bolts of AGC protein kinases. Nat. Rev. Mol. Cell. Biol. 11 (2010) 9-22. [PMID: 20027184]
2. Castro, A. and Lorca, T. Greatwall kinase at a glance. J. Cell Sci. 131 (2018) . [PMID: 30355803]
3. Goguet-Rubio, P., Amin, P., Awal, S., Vigneron, S., Charrasse, S., Mechali, F., Labbe, J.C., Lorca, T. and Castro, A. PP2A-B55 holoenzyme regulation and cancer. Biomolecules 10 (2020) . [PMID: 33266510]
4. Johnson, J.L., Yaron, T.M., Huntsman, E.M., Kerelsky, A., Song, J., Regev, A., Lin, T.Y., Liberatore, K., Cizin, D.M., Cohen, B.M., Vasan, N., Ma, Y., Krismer, K., Robles, J.T., van de Kooij, B., van Vlimmeren, A.E., Andree-Busch, N., Kaufer, N.F., Dorovkov, M.V., Ryazanov, A.G., Takagi, Y., Kastenhuber, E.R., Goncalves, M.D., Hopkins, B.D., Elemento, O., Taatjes, D.J., Maucuer, A., Yamashita, A., Degterev, A., Uduman, M., Lu, J., Landry, S.D., Zhang, B., Cossentino, I., Linding, R., Blenis, J., Hornbeck, P.V., Turk, B.E., Yaffe, M.B. and Cantley, L.C. An atlas of substrate specificities for the human serine/threonine kinome. Nature 613 (2023) 759-766. [PMID: 36631611]
Accepted name: MAST-subfamily protein kinase
Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
Other name(s): microtubule-associated serine/threonine-protein kinase; MAST1; MAST2; MAST3; MAST4; MAST205; SAST; IREH1; dop; kin-4
Comments: Requires Mg2+. MAST (Microtubule Associated Serine/Threonine) kinases are eukaryotic-wide kinases with roles in microtubule function, PTEN regulation and a variety of neuronal functions. They are found in most eukaryotes, though lost from most fungi and ciliates. MAST kinases associate with their substrates via their PDZ domains. Substrates include the PTEN phosphatase (EC 3.1.3.67) in human and nematodes, and Dlic (Dynein light intermediate chain) in Drosophila. The latter is phosphorylated on Ser401.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Valiente, M., Andres-Pons, A., Gomar, B., Torres, J., Gil, A., Tapparel, C., Antonarakis, S.E. and Pulido, R. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J. Biol. Chem. 280 (2005) 28936-28943. [PMID: 15951562]
2. An, S.WA., Choi, E.S., Hwang, W., Son, H.G., Yang, J.S., Seo, K., Nam, H.J., Nguyen, N.TH., Kim, E.JE., Suh, B.K., Kim, Y., Nakano, S., Ryu, Y., Man Ha, C., Mori, I., Park, S.K., Yoo, J.Y., Kim, S. and Lee, S.V. KIN-4/MAST kinase promotes PTEN-mediated longevity of Caenorhabditis elegans via binding through a PDZ domain. Aging Cell 18 (2019) e12906. [PMID: 30773781]
Accepted name: NEK9 subfamily protein kinase
Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
Other name(s): NEK9 subfamily kinase (misleading); serine/threonine-protein kinase Nek9; NEK9 (gene name); NERCC1 (gene name)
Systematic name: ATP:protein Ser/(Thr)-phosphotransferase (NEK9 subfamily)
Comments: This enzyme is found in animals and choanoflagellates, although it has been lost in arthropods and nematodes. It is implicated in centrosome separation [1] and cilium formation [6]. In peptide arrays, the enzyme prefers to phosphorylate Ser, with acidic residues at -2 and -4/-5, similar to that of the NEK6 protein kinase subfamily [4]. NEK9 can autophosphorylate. Substrates in humans include the microtubule-associated protein kinases NEK6/7 [1], the microtubule-associated protein spindle assembly protein TPX2 [3], the γ-tubulin associated protein NEDD1, which is required for mitotic spindle assembly and function [2] and the LC3B protein, which is involved in autophagy substrate selection and autophagosome biogenesis [5].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Bertran, M.T., Sdelci, S., Regue, L., Avruch, J., Caelles, C. and Roig, J. Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J. 30 (2011) 2634-2647. [PMID: 21642957]
2. Sdelci, S., Schutz, M., Pinyol, R., Bertran, M.T., Regue, L., Caelles, C., Vernos, I. and Roig, J. Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of γ-tubulin recruitment to the mitotic centrosome. Curr. Biol. 22 (2012) 1516-1523. [PMID: 22818914]
3. Eibes, S., Gallisa-Sune, N., Rosas-Salvans, M., Martinez-Delgado, P., Vernos, I. and Roig, J. Nek9 Phosphorylation Defines a New Role for TPX2 in Eg5-Dependent Centrosome Separation before Nuclear Envelope Breakdown. Curr. Biol. 28 (2018) 121-129.e4. [PMID: 29276125]
4. van de Kooij, B., Creixell, P., van Vlimmeren, A., Joughin, B.A., Miller, C.J., Haider, N., Simpson, C.D., Linding, R., Stambolic, V., Turk, B.E. and Yaffe, M.B. Comprehensive substrate specificity profiling of the human Nek kinome reveals unexpected signaling outputs. Elife 8 (2019) . [PMID: 31124786]
5. Shrestha, B.K., Skytte Rasmussen, M., Abudu, Y.P., Bruun, J.A., Larsen, K.B., Alemu, E.A., Sjottem, E., Lamark, T. and Johansen, T. NIMA-related kinase 9-mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1. J. Biol. Chem. 295 (2020) 1240-1260. [PMID: 31857374]
6. Yamamoto, Y., Chino, H., Tsukamoto, S., Ode, K.L., Ueda, H.R. and Mizushima, N. NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA. Nat. Commun. 12 (2021) 3292. [PMID: 34078910]
Accepted name: ROCK-subfamily protein kinase
Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
The enzyme has wide range known substrates, mostly involved in cytoskeletal regulation, with a preference for positive charges at P1 to P5.
Other name(s): ROCK; Rho Kinase; ROCK1; ROCK2; rok; let-402; ROCK-I (gene name); ROCK-II (gene name)
Systematic name: ATP:cytoskeleton-protein phosphotransferase
Comments: Requires Mg2+. An animal specific kinase that is duplicated in vertebrates (ROCK1, ROCK2), and with homologs in Drosophila (rok) and Caenorhabditis elegans (let-502). They are ~1300 amino-acid proteins, with an N-terminal kinase domain, with the AGC-specific kinase domain tail, followed by a central coiled-coil region, HR1 domain, Rho-binding domain (RBD), and PH domain. The PH domain is split by an inserted CRD (cysteine-rich Zn finger motif). ROCK is activated by the small GTPase Rho and modulates the cytoskeleton by phosphorylation of a wide array of other cytoskeletal proteins. Binding of Rho-GTP to the RBD relieves an intramolecular inhibition and activates the kinase activity. These kinases modulate the cytoskeleton in response to Rho GTPase signalling. Substrates include LIM-kinase (LIMK) which phosphorylates and inhibits cofilin, blocking its actin-depolymerizing function [1], and myosin regulatory light chain (MRLC2/MYL12B) in that regulates Myosin II. In Drosophila is involve in the planar cell polarity pathway, where it is genetically downstream of frizzled and dishevelled gene families, and phosphorylates the non-muscle myosin light chain, regulating Myosin II [2]. It is activated by Rho1, the single homolog of human RhoA/B/C, which also activate ROCK.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Ohashi, K., Nagata, K., Maekawa, M., Ishizaki, T., Narumiya, S. and Mizuno, K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J. Biol. Chem. 275 (2000) 3577-3582. [PMID: 10652353]
2. Winter, C.G., Wang, B., Ballew, A., Royou, A., Karess, R., Axelrod, J.D. and Luo, L. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 105 (2001) 81-91. [PMID: 11301004]
Accepted name: dual-specificity kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): ADK1; Arabidopsis dual specificity kinase 1; CLK1; dDYRK2; Mps1p
Systematic name: ATP:protein phosphotransferase (Ser/Thr- and Tyr-phosphorylating)
Comments: This family of enzymes can phosphorylate both Ser/Thr and Tyr residues.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Ali, N., Halfter, U. and Chua, N.H. Cloning and biochemical characterization of a plant protein kinase that phosphorylates serine, threonine, and tyrosine. J. Biol. Chem. 269 (1994) 31626-31629. [PMID: 7527390]
2. Lauze, E., Stoelcker, B., Luca, F.C., Weiss, E., Schutz, A.R. and Winey, M. Yeast spindle pole body duplication gene MPS1 encodes an essential dual specificity protein kinase. EMBO J. 14 (1995) 1655-1663. [PMID: 7737118]
3. Menegay, H.J., Myers, M.P., Moeslein, F.M. and Landreth, G.E. Biochemical characterization and localization of the dual specificity kinase CLK1. J. Cell Sci. 113 (2000) 3241-3253. [PMID: 10954422]
4. Lochhead, P.A., Sibbet, G., Kinstrie, R., Cleghon, T., Rylatt, M., Morrison, D.K. and Cleghon, V. dDYRK2: a novel dual-specificity tyrosine-phosphorylation-regulated kinase in Drosophila. Biochem. J. 374 (2003) 381-391. [PMID: 12786602]
Accepted name: mitogen-activated protein kinase kinase
Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): MAP kinase kinase; MAP kinase kinase 4; MAP kinase kinase 7; MAP kinase or ERK kinase; MAP2K; MAPKK; MAPKK1; MEK; MEK1; MEK2; MKK; MKK2; MKK4; MKK6; MKK7; STK27
Systematic name: ATP:protein phosphotransferase (MAPKKK-activated)
Comments: This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC 2.7.11.24, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Mordret, G. MAP kinase kinase: a node connecting multiple pathways. Biol. Cell. 79 (1993) 193-207. [PMID: 8004006]
2. Zheng, C.F. and Guan, K.L. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J. Biol. Chem. 268 (1993) 11435-11439. [PMID: 8388392]
3. Wu, J., Harrison, J.K., Dent, P., Lynch, K.R., Weber, M.J. and Sturgill, T.W. Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2. Mol. Cell. Biol. 13 (1993) 4539-4548. [PMID: 8393135]
4. Alessi, D.R., Saito, Y., Campbell, D.G., Cohen, P., Sithanandam, G., Rapp, U., Ashworth, A., Marshall, C,J, and Cowley, S. Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1. EMBO J. 13 (1994) 1610-1619. [PMID: 8157000]
5. Pham, C.D., Arlinghaus, R.B., Zheng, C.F., Guan, K.L. and Singh, B. Characterization of MEK1 phosphorylation by the v-Mos protein. Oncogene 10 (1995) 1683-1688. [PMID: 7731726]
6. Han, J., Lee, J.D., Jiang, Y., Li, Z., Feng, L. and Ulevitch, R.J. Characterization of the structure and function of a novel MAP kinase kinase (MKK6). J. Biol. Chem. 271 (1996) 2886-2891. [PMID: 8621675]
Accepted name: protein-histidine pros-kinase
Reaction: ATP + protein L-histidine = ADP + protein Nπ-phospho-L-histidine
Other name(s): ATP:protein-L-histidine N-pros-phosphotransferase; histidine kinase (ambiguous); histidine protein kinase (ambiguous); protein histidine kinase (ambiguous); protein kinase (histidine) (ambiguous); HK2
Systematic name: ATP:protein-L-histidine Nπ-phosphotransferase
Comments: A number of histones can act as acceptor.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 99283-67-7
References:
1. Fujitaki, J.M., Fung, G., Oh, E.Y. and Smith, R.A. Characterization of chemical and enzymatic acid-labile phosphorylation of histone H4 using phosphorus-31 nuclear magnetic resonance. Biochemistry 20 (1981) 3658-3664. [PMID: 7196259]
2. Huebner, V.D. and Matthews, H.R. Phosphorylation of histidine in proteins by a nuclear extract of Physarum polycephalum plasmodia. J. Biol. Chem. 260 (1985) 16106-16113. [PMID: 4066704]
Accepted name: protein-histidine tele-kinase
Reaction: ATP + protein L-histidine = ADP + protein Nτ-phospho-L-histidine
Other name(s): ATP:protein-L-histidine N-tele-phosphotransferase; histidine kinase (ambiguous); histidine protein kinase (ambiguous); protein histidine kinase (ambiguous); protein kinase (histidine) (ambiguous); HK3
Systematic name: ATP:protein-L-histidine Nτ-phosphotransferase
Comments: A number of histones can act as acceptor.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 99283-67-7
References:
1. Fujitaki, J.M., Fung, G., Oh, E.Y. and Smith, R.A. Characterization of chemical and enzymatic acid-labile phosphorylation of histone H4 using phosphorus-31 nuclear magnetic resonance. Biochemistry 20 (1981) 3658-3664. [PMID: 7196259]
2. Huebner, V.D. and Matthews, H.R. Phosphorylation of histidine in proteins by a nuclear extract of Physarum polycephalum plasmodia.
Accepted name: histidine kinase
Reaction: ATP + protein L-histidine = ADP + protein N-phospho-L-histidine
Other name(s): EnvZ; histidine kinase (ambiguous); histidine protein kinase (ambiguous); protein histidine kinase (ambiguous); protein kinase (histidine) (ambiguous); HK1; HP165; Sln1p
Systematic name: ATP:protein-L-histidine N-phosphotransferase
Comments: This entry has been included to accommodate those protein-histidine kinases for which the phosphorylation site has not been established (i.e. either the pros- or tele-nitrogen of histidine). A number of histones can act as acceptor.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
Metacyc,
PDB,
CAS registry number: 420839-67-4
References:
1. Kowluru, A. Identification and characterization of a novel protein histidine kinase in the islet beta cell: evidence for its regulation by mastoparan, an activator of G-proteins and insulin secretion. Biochem. Pharmacol. 63 (2002) 2091-2100. [PMID: 12110368]
2. Yoshimi, A., Tsuda, M. and Tanaka, C. Cloning and characterization of the histidine kinase gene Dic1 from Cochliobolus heterostrophus that confers dicarboximide resistance and osmotic adaptation. Mol. Genet. Genomics 271 (2004) 228-236. [PMID: 14752661]
3. Beier, D. and Frank, R. Molecular characterization of two-component systems of Helicobacter pylori. J. Bacteriol. 182 (2000) 2068-2076. [PMID: 10735847]
4. Pflock, M., Dietz, P., Schr, J. and Beier, D. Genetic evidence for histidine kinase HP165 being an acid sensor of Helicobacter pylori. FEMS Microbiol. Lett. 34 (2004) 51-61. [PMID: 15109719]
5. Roberts, D.L., Bennett, D.W. and Forst, S.A. Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli. J. Biol. Chem. 269 (1994) 8728-8733. [PMID: 8132603]
Accepted name: protein arginine kinase
Reaction: ATP + a [protein]-L-arginine = ADP + a [protein]-Nω-phospho-L-arginine
Other name(s): McsB
Systematic name: ATP:[protein]-L-arginine Nω-phosphotransferase
Comments: The enzyme, characterized from Gram-positive bacteria, is involved in the regulation of the bacterial stress response.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
Metacyc,
PDB,
CAS registry number:
References:
1. Fuhrmann, J., Schmidt, A., Spiess, S., Lehner, A., Turgay, K., Mechtler, K., Charpentier, E. and Clausen, T. McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR. Science 324 (2009) 1323-1327. [PMID: 19498169]
2. Elsholz, A.K., Turgay, K., Michalik, S., Hessling, B., Gronau, K., Oertel, D., Mader, U., Bernhardt, J., Becher, D., Hecker, M. and Gerth, U. Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis. Proc. Natl. Acad. Sci. USA 109 (2012) 7451-7456. [PMID: 22517742]
3. Schmidt, A., Trentini, D.B., Spiess, S., Fuhrmann, J., Ammerer, G., Mechtler, K. and Clausen, T. Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response. Mol. Cell. Proteomics 13 (2014) 537-550. [PMID: 24263382]
Accepted name: triphosphate—protein phosphotransferase
Reaction: triphosphate + [microsomal-membrane protein] = diphosphate + phospho-[microsomal-membrane protein]
Other name(s): diphosphate:microsomal-membrane-protein O-phosphotransferase (erroneous); DiPPT (erroneous); pyrophosphate:protein phosphotransferase (erroneous); diphosphateŃprotein phosphotransferase (erroneous); diphosphate:[microsomal-membrane-protein] O-phosphotransferase (erroneous)
Systematic name: triphosphate:[microsomal-membrane-protein] phosphotransferase
Comments: This enzyme was originally thought to use diphosphate as substrate [1] but this has since been disproved [2]. The activity is observed as the second part of a biphasic reaction after depletion of ATP. Tripolyphosphate is a contaminant of [γ-32P]ATP.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
Metacyc,
PDB,
CAS registry number: 74092-32-3
References:
1. Lam, K.S. and Kasper, C.B. Pyrophosphate:protein phosphotransferase: a membrane-bound enzyme of endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 77 (1980) 1927-1931. [PMID: 6246514]
2. Tsutsui, K. Tripolyphosphate is an alternative phosphodonor of the selective protein phosphorylation of liver microsomal membrane. J. Biol. Chem. 261 (1986) 2645-2653. [PMID: 3949741]
EC 2.7.14 Protein-arginine kinases
EC 2.7.99 Other protein kinases
Continued with EC 2.8.1 and EC 2.8.2
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