Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806   53 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 132
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  133 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 212
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568918806  213 VDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 262
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806   53 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 132
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  133 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 212
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568918806  213 VDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 262
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  94 RRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIEDsVTVRDYIQSTMETEkdpqcllDLARRMGQVLAGMHDQDL 173
Cdd:COG3642    1 ERTRREARLLRELREAGVPVPKVLDVDPDDADLVMEYIEG-ETLADLLEEGELPP-------ELLRELGRLLARLHRAGI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 174 IHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKGVDLYVLEKAFLSTHP-HTETAFEAFLKSYgASSKKSSPVLK 252
Cdd:COG3642   73 VHGDLTTSNILVDDG----GVYLIDFGLARYSDPLEDKAVDLAVLKRSLESTHPdPAEELWEAFLEGY-REVGPAEEVLR 147

                        170
                 ....*....|
gi 568918806 253 KLDEVRLRGR 262
Cdd:COG3642  148 RLREIELRGR 157

Lipopolysaccharide kinase (Kdo/WaaP) family; These lipopolysaccharide kinases are related to protein kinases pfam00069. This family includes waaP (rfaP) gene product is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region. It has previously been shown that WaaP is necessary for resistance to hydrophobic and polycationic antimicrobials in E. coli and that it is required for virulence in invasive strains of S. enterica.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806   54 VQQGAEARVFRGRFQGRAAvvKHRFPKSYRHPelearLGRRRTVQEARALLRCRRAGIAAP-VVFFVDYASNCLY----- 127
Cdd:pfam06293  22 VVARVGNGVLRKYYRGGMW--GHLNRDLYRYP-----LGRTRAFREFRLIRRLREAGLPVPkPVAAGEVKVGGGYradll 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  128 MEEIEDSVTVRDYIQSTME-TEKDPQCLLdlaRRMGQVLAGMHDQDLIHGDLTTSNMLLRRP-LAQLHIVLIDFGLSfVS 205
Cdd:pfam06293  95 TERLEGAQSLADWLADWAVpSGELRRAIW---EAVGRLIRQMHRAGVQHGDLYAHHILLQQEgDEGFEAWLIDLDKG-RL 170

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 568918806  206 GLPEDKGV--DLYVLEKAFLsTHPHTETAFEAFLKSY 240
Cdd:pfam06293 171 RLPARRWRnkDLARLLRSFL-NIGFTEADWERLLRAY 206

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806   53 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 132
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  133 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 212
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568918806  213 VDLYVLEKAFLSTHPHT-ETAFEAFLKSYGASSKKSSPVLKKLDEVRLRGR 262
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

bifunctional N(6)-L-threonylcarbamoyladenine synthase/serine/threonine protein kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  52 ELVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEI 131
Cdd:PRK09605 339 HLIGKGAEADIKKGEYLGRDAVIKERVPKGYRHPELDERLRTERTRAEARLLSEARRAGVPTPVIYDVDPEEKTIVMEYI 418

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 132 EDsVTVRDYIQSTmetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDK 211
Cdd:PRK09605 419 GG-KDLKDVLEGN----------PELVRKVGEIVAKLHKAGIVHGDLTTSNFIVRDD----RLYLIDFGLGKYSDLIEDK 483

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568918806 212 GVDLYVLEKAFLSTHPHTETAFEAFLKSYGAsSKKSSPVLKKLDEVRLRGR 262
Cdd:PRK09605 484 AVDLHVLKQSLESTHYDFEELWEAFLEGYRE-TEGAEDVLERLKEIEKRGR 533

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  56 QGAEARVFRGR--FQGRAAVVKhRFPKSYRHPELEARLgrrrtvQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIEd 133
Cdd:cd00180    3 KGSFGKVYKARdkETGKKVAVK-VIPKEKLKKLLEELL------REIEILKKLNHPNIVKLYDVFETENFLYLVMEYCE- 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 134 SVTVRDYIQSTMETEKDPQcLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 202
Cdd:cd00180   75 GGSLKDLLKENKGPLSEEE-ALSILRQLLSALEYLHSNGIIHRDLKPENILLDS---DGTVKLADFGLA 139

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  51 LELVQQGAEARVFRGRFQ--GRAAVVKHRFPKSYRHPELearlgRRRTVQEARALLRCRRAGIAApvVFFVDYASNCLY- 127
Cdd:cd14014    5 VRLLGRGGMGEVYRARDTllGRPVAIKVLRPELAEDEEF-----RERFLREARALARLSHPNIVR--VYDVGEDDGRPYi 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568918806 128 -MEEIEdSVTVRDYIQstMETEKDPQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 202
Cdd:cd14014   78 vMEYVE-GGSLADLLR--ERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTE---DGRVKLTDFGIA 147

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  56 QGAEARVFRGRFQGRAAVVkhrfpkSYRHPELEARLGRRRTVQEARALLRCRRAGIaaPVVFFVDYAS----NCLYMEEI 131
Cdd:cd13968    3 EGASAKVFWAEGECTTIGV------AVKIGDDVNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDvdgpNILLMELV 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 132 EDsVTVRDYIQSTMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFG 200
Cdd:cd13968   75 KG-GTLIAYTQEEELDEKDVE---SIMYQLAECMRLLHSFHLIHRDLNNDNILLSE---DGNVKLIDFG 136

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 123 SNCLYMEEIEDSVTvrDYIQSTMETEKDP---QCLLDLARRMGQVLAGMH-DQDLIHGDLTTSNMLLRRPLAQlhIVLID 198
Cdd:cd14001   80 SLCLAMEYGGKSLN--DLIEERYEAGLGPfpaATILKVALSIARALEYLHnEKKILHGDIKSGNVLIKGDFES--VKLCD 155

                         90       100
                 ....*....|....*....|..
gi 568918806 199 FGLSfvsgLPEDKgvDLYVLEK 220
Cdd:cd14001  156 FGVS----LPLTE--NLEVDSD 171

Serine/threonine-protein kinase RIO1 [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  57 GAEARVFRGR-FQGRAAVVK------HRFPKSYRHPELEAR------LGRRRTVQ-----EARALLRCRRAGIAAP--VV 116
Cdd:COG1718   57 GKEANVFLARrPGGELVAAKiyrtatSSFKRMAQYIEGDPRfmgkgsFGRRQLIFawarkEFRNLYRLYEAGVRVPepIA 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 117 FFvdyaSNCLYMEEIEDSVTVRDYIQSTMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVL 196
Cdd:COG1718  137 FY----GNVLLMEFIGDDGVPAPRLKDVELEPEEAE---ELYEQLIEYIVRLYKAGLVHGDLSEYNILVDDG----GPVI 205

                 ....
gi 568918806 197 IDFG 200
Cdd:COG1718  206 IDLP 209

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 568918806 156 DLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 202
Cdd:cd05117  103 KIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSPIKIIDFGLA 149

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 568918806 154 LLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLSF 203
Cdd:cd14015  129 VLQLALRILDVLEYIHENGYVHADIKASNLLLGFGKNKDQVYLVDYGLAS 178

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 123 SNCLYMeeiedsvtVRDYIQ--STMETEKDPQCL---LDLARR-MGQVLAG---MHDQDLIHGDLTTSNMLLRrplAQLH 193
Cdd:cd14008   78 SDKLYL--------VLEYCEggPVMELDSGDRVPplpEETARKyFRDLVLGleyLHENGIVHRDIKPENLLLT---ADGT 146

                         90
                 ....*....|....*..
gi 568918806 194 IVLIDFGLSFVSGLPED 210
Cdd:cd14008  147 VKISDFGVSEMFEDGND 163

RIO-like serine/threonine protein kinase fused to N-terminal HTH domain [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  67 FQGRAAVVKHrfpksYRHPELEARLGRR----------------RTVQEARALLRCRRAGIAAPVVffVDYASNCLYMEE 130
Cdd:COG0478    6 PGGGPVALKF-----HREGRTSFRKVRReradkehyswlyaartRAEREFRALERLYPAGLPVPRP--IAANRHAIVMER 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 131 IEDsVTVRDYIQStmetekDPQCLLDlarRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDF 199
Cdd:COG0478   79 IEG-VELARLKLE------DPEEVLD---KILEEIRRAHDAGIVHADLSEYNILVD---DDGGVWIIDW 134

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 568918806 151 PQCL-LDLAR----RMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQlhIVLIDFGLS 202
Cdd:cd05118   95 PRGLpLDLIKsylyQLLQALDFLHSNGIIHRDLKPENILINLELGQ--LKLADFGLA 149

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806    93 RRRTVQEARALLRCRRAGIaapvVFFVDY--ASNCLY--MEEIeDSVTVRDYIQSTME-TEKDpqclldlARR-MGQVLA 166
Cdd:smart00220  41 RERILREIKILKKLKHPNI----VRLYDVfeDEDKLYlvMEYC-EGGDLFDLLKKRGRlSEDE-------ARFyLRQILS 108

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 568918806   167 G---MHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 202
Cdd:smart00220 109 AleyLHSKGIVHRDLKPENILLDE---DGHVKLADFGLA 144

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  97 VQEARALLRCRRAGIAA--PVVFFVDYASNCLYMEEIE-DSVTVRDYIQSTMeTEKDPQCLldlarrMGQVLAG---MHD 170
Cdd:cd07845   54 LREITLLLNLRHPNIVElkEVVVGKHLDSIFLVMEYCEqDLASLLDNMPTPF-SESQVKCL------MLQLLRGlqyLHE 126

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568918806 171 QDLIHGDLTTSNMLLRRplaQLHIVLIDFGLSFVSGLP 208
Cdd:cd07845  127 NFIIHRDLKVSNLLLTD---KGCLKIADFGLARTYGLP 161

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 126 LY--MEEIEDSvTVRDYIQSTMETEKDPqcLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 202
Cdd:cd14046   79 LYiqMEYCEKS-TLRDLIDSGLFQDTDR--LWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLD---SNGNVKIGDFGLA 151

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568918806 168 MHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLSFVsGLpEDKGVDLYVLEKAFLSTHPHTETAF 233
Cdd:cd05579  109 LHSHGIIHRDLKPDNILID---ANGHLKLTDFGLSKV-GL-VRRQIKLSIQKKSNGAPEKEDRRIV 169

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 164 VLA--GMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLSfvSGLPeDKGVDLYVLEKAFLSTHPHTETAFEAFLKSY 240
Cdd:cd05573  111 VLAldSLHKLGFIHRDIKPDNILLDA---DGHIKLADFGLC--TKMN-KSGDRESYLNDSVNTLFQDNVLARRRPHKQR 183

Phosphotransferase enzyme family; This family consists of bacterial antibiotic resistance proteins, which confer resistance to various aminoglycosides they include: aminoglycoside 3'-phosphotransferase or kanamycin kinase / neomycin-kanamycin phosphotransferase and streptomycin 3''-kinase or streptomycin 3''-phosphotransferase. The aminoglycoside phosphotransferases inactivate aminoglycoside antibiotics via phosphorylation. This family also includes homoserine kinase. This family is related to fructosamine kinase pfam03881.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806   51 LELVQQGAEARVFRGRFQGRAAVVKhRFPKSYRHPELEarlgrrrtvQEARALLRCRRAGI-AAPVVFfvdyaSNCLYME 129
Cdd:pfam01636   2 LRPISSGASNRTYLVTTGDGRYVLR-LPPPGRAAEELR---------RELALLRHLAAAGVpPVPRVL-----AGCTDAE 66

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568918806  130 EIEDSVTVRDYIQ-STMETEKDPQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLH 193
Cdd:pfam01636  67 LLGLPFLLMEYLPgEVLARPLLPEERGALLEALGRALARLHAVDPAALPLAGRLARLLELLRQLE 131

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 568918806 168 MHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 202
Cdd:cd14016  112 LHSKGYIHRDIKPENFLMGLGKNSNKVYLIDFGLA 146

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  77 RFPKSYRHPELEARLGR-----RRTVQEAR--ALLR----CRragiaapvVFFVDYASNCLYME-EIEDSVTVRDYI-QS 143
Cdd:cd14077   36 RASNAGLKKEREKRLEKeisrdIRTIREAAlsSLLNhphiCR--------LRDFLRTPNHYYMLfEYVDGGQLLDYIiSH 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568918806 144 TMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 202
Cdd:cd14077  108 GKLKEKQAR---KFARQIASALDYLHRNSIVHRDLKIENILISK---SGNIKIIDFGLS 160

Catalytic domain of the atypical protein serine kinases, RIO kinases; RIO kinases are atypical protein serine kinases present in archaea, bacteria and eukaryotes. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. RIO kinases contain a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. Most organisms contain at least two RIO kinases, RIO1 and RIO2. A third protein, RIO3, is present in multicellular eukaryotes. In yeast, RIO1 and RIO2 are essential for survival. They function as non-ribosomal factors necessary for late 18S rRNA processing. RIO1 is also required for proper cell cycle progression and chromosome maintenance. The biological substrates for RIO kinases are still unknown. The RIO kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806  53 LVQQGAEARVFR--GRFQGR--AAVVK-HR-----FPKSYRHPELEARLGRRR----------TVQEARALLRCRRAGIA 112
Cdd:cd05119    4 VISTGKEANVFYadGVFDGKpvACAVKiYRietseFDKVDEYLYGDERFDYRRispkekvfiwTEKEFRNLERAKEAGVS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918806 113 APVVFfvDYASNCLYMEEI-EDSVTVRDYIQSTME-TEKDPQCLLDLArrMGQVLAGMHDQDLIHGDLTTSNMLLRRpla 190
Cdd:cd05119   84 VPQPY--TYEKNVLL*EFIgEDELPAPTLVELGRElKELDVEGIFNDV--VENVKRLYQEAELVHADLSEYNILYID--- 156

                        170
                 ....*....|....*...
gi 568918806 191 qlHIVLIDFGLSFVSGLP 208
Cdd:cd05119  157 --KVYFIDFGQAVTLRHP 172

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 568918806 151 PQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIV-LIDFGLS 202
Cdd:cd14017   96 VSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSDERTVyILDFGLA 148