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 62510085    29 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 108
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085   109 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 188
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 62510085   189 VDLYVLEKAFLSTHPHT-ETVFEAFLKSYGASTQKSSPVLKKLDEVRLRGR 238
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 62510085    29 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 108
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085   109 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 188
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 62510085   189 VDLYVLEKAFLSTHPHT-ETVFEAFLKSYGASTQKSSPVLKKLDEVRLRGR 238
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 62510085  70 RRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIEDsVTVRDYIQSTMETEkdpqcllDLARRMGQVLAGMHDQDL 149
Cdd:COG3642   1 ERTRREARLLRELREAGVPVPKVLDVDPDDADLVMEYIEG-ETLADLLEEGELPP-------ELLRELGRLLARLHRAGI 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085 150 IHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKGVDLYVLEKAFLSTHP-HTETVFEAFLKSYgASTQKSSPVLK 228
Cdd:COG3642  73 VHGDLTTSNILVDDG----GVYLIDFGLARYSDPLEDKAVDLAVLKRSLESTHPdPAEELWEAFLEGY-REVGPAEEVLR 147

                       170
                ....*....|
gi 62510085 229 KLDEVRLRGR 238
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 62510085    30 VQQGAEARVFRGRFQGRAAvvKHRFPKSYRHPelearLGRRRTVQEARALLRCRRAGIAAP-VVFFVDYASNCLY----- 103
Cdd:pfam06293  22 VVARVGNGVLRKYYRGGMW--GHLNRDLYRYP-----LGRTRAFREFRLIRRLREAGLPVPkPVAAGEVKVGGGYradll 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085   104 MEEIEDSVTVRDYIQSTME-TEKDPQCLLdlaRRMGQVLAGMHDQDLIHGDLTTSNMLLRRP-LAQLHIVLIDFGLSfVS 181
Cdd:pfam06293  95 TERLEGAQSLADWLADWAVpSGELRRAIW---EAVGRLIRQMHRAGVQHGDLYAHHILLQQEgDEGFEAWLIDLDKG-RL 170

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 62510085   182 GLPEDKGV--DLYVLEKAFLsTHPHTETVFEAFLKSY 216
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 62510085    29 LVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIE 108
Cdd:TIGR03724   1 LIAKGAEAIIYLGDFLGRKAVIKERVPKSYRHPELDERLRKERTRREARLLSRARKAGVNTPVIYDVDPDNKTIVMEYIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085   109 DsVTVRDYIQSTMetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDKG 188
Cdd:TIGR03724  81 G-KPLKDVIEENG---------DELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD----KVYLIDFGLGKYSDEIEDKA 146

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 62510085   189 VDLYVLEKAFLSTHPHT-ETVFEAFLKSYGASTQKSSPVLKKLDEVRLRGR 238
Cdd:TIGR03724 147 VDLHVLKRSLESTHPDKaEELFEAFLEGYREVFGEAKDVLERVKEIELRGR 197

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085   28 ELVQQGAEARVFRGRFQGRAAVVKHRFPKSYRHPELEARLGRRRTVQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEI 107
Cdd:PRK09605 339 HLIGKGAEADIKKGEYLGRDAVIKERVPKGYRHPELDERLRTERTRAEARLLSEARRAGVPTPVIYDVDPEEKTIVMEYI 418

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085  108 EDsVTVRDYIQSTmetekdpqclLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPlaqlHIVLIDFGLSFVSGLPEDK 187
Cdd:PRK09605 419 GG-KDLKDVLEGN----------PELVRKVGEIVAKLHKAGIVHGDLTTSNFIVRDD----RLYLIDFGLGKYSDLIEDK 483

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62510085  188 GVDLYVLEKAFLSTHPHTETVFEAFLKSYGASTQKSSpVLKKLDEVRLRGR 238
Cdd:PRK09605 484 AVDLHVLKQSLESTHYDFEELWEAFLEGYRETEGAED-VLERLKEIEKRGR 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 62510085  32 QGAEARVFRGR--FQGRAAVVKhRFPKSYRHPELEARLgrrrtvQEARALLRCRRAGIAAPVVFFVDYASNCLYMEEIEd 109
Cdd:cd00180   3 KGSFGKVYKARdkETGKKVAVK-VIPKEKLKKLLEELL------REIEILKKLNHPNIVKLYDVFETENFLYLVMEYCE- 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62510085 110 SVTVRDYIQSTMETEKDPQcLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 178
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 62510085  27 LELVQQGAEARVFRGRFQ--GRAAVVKHRFPKSYRHPELearlgRRRTVQEARALLRCRRAGIAApvVFFVDYASNCLY- 103
Cdd:cd14014   5 VRLLGRGGMGEVYRARDTllGRPVAIKVLRPELAEDEEF-----RERFLREARALARLSHPNIVR--VYDVGEDDGRPYi 77

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 62510085 104 -MEEIEdSVTVRDYIQstMETEKDPQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 178
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 62510085  32 QGAEARVFRGRFQGRAAVVkhrfpkSYRHPELEARLGRRRTVQEARALLRCRRAGIaaPVVFFVDYAS----NCLYMEEI 107
Cdd:cd13968   3 EGASAKVFWAEGECTTIGV------AVKIGDDVNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDvdgpNILLMELV 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62510085 108 EDsVTVRDYIQSTMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFG 176
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 62510085  99 SNCLYMEEIEDSVTvrDYIQSTMETEKDP---QCLLDLARRMGQVLAGMH-DQDLIHGDLTTSNMLLRRPLAQlhIVLID 174
Cdd:cd14001  80 SLCLAMEYGGKSLN--DLIEERYEAGLGPfpaATILKVALSIARALEYLHnEKKILHGDIKSGNVLIKGDFES--VKLCD 155

                        90       100
                ....*....|....*....|..
gi 62510085 175 FGLSfvsgLPEDKgvDLYVLEK 196
Cdd:cd14001 156 FGVS----LPLTE--NLEVDSD 171

RIO1 family; This is a family of atypical serine kinases which are found in archaea, bacteria and eukaryotes. Activity of Rio1 is vital in Saccharomyces cerevisiae for the processing of ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance. The structure of RIO1 has been determined.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085    75 EARALLRCRRAGIAAPVVffVDYASNCLYMEEIED----SVTVRDyiqstMETEKDPQCLLDLARRMGQVLAGMHdqdLI 150
Cdd:pfam01163  56 EFRNLKRLYEAGVPVPKP--IDVNRHVLVMEFIGKdgvpAPKLKD-----VELEEAEEIYDEIIREMRRLYQEAG---LV 125

                          90       100
                  ....*....|....*....|....*.
gi 62510085   151 HGDLTTSNMLLRRPlaqlHIVLIDFG 176
Cdd:pfam01163 126 HGDLSEYNILVHDD----KPVIIDVP 147

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 62510085 132 DLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 178
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 62510085 130 LLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLSF 179
Cdd:cd14015 129 VLQLALRILDVLEYIHENGYVHADIKASNLLLGFGKNKDQVYLVDYGLAS 178

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; 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. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085 123 TEKDPQCLldlarrMGQVLAG---MHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLSFVsglpEDKGV 189
Cdd:cd14083  99 TEKDASHL------IRQVLEAvdyLHSLGIVHRDLKPENLLYYSPDEDSKIMISDFGLSKM----EDSGV 158

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085  43 FQGRAAVVKHrfpksYRHPELEARLGRR----------------RTVQEARALLRCRRAGIAAPVVffVDYASNCLYMEE 106
Cdd:COG0478   6 PGGGPVALKF-----HREGRTSFRKVRReradkehyswlyaartRAEREFRALERLYPAGLPVPRP--IAANRHAIVMER 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62510085 107 IEDsVTVRDYIQStmetekDPQCLLDlarRMGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDF 175
Cdd:COG0478  79 IEG-VELARLKLE------DPEEVLD---KILEEIRRAHDAGIVHADLSEYNILVD---DDGGVWIIDW 134

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL 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 62510085 102 LYMEEIEDSVTVRDYIQSTMETEKDPQCLLdlaRRMGQVLAGMHDQDLIHGDLTTSNMLLRR-PLAQLHIVLIDFGLSFV 180
Cdd:cd14095  75 LVMELVKGGDLFDAITSSTKFTERDASRMV---TDLAQALKYLHSLSIVHRDIKPENLLVVEhEDGSKSLKLADFGLATE 151

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085     69 RRRTVQEARALLRCRRAGIaapvVFFVDY--ASNCLY--MEEIeDSVTVRDYIQSTME-TEKDpqclldlARR-MGQVLA 142
Cdd:smart00220  41 RERILREIKILKKLKHPNI----VRLYDVfeDEDKLYlvMEYC-EGGDLFDLLKKRGRlSEDE-------ARFyLRQILS 108

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 62510085    143 G---MHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 178
Cdd:smart00220 109 AleyLHSKGIVHRDLKPENILLDE---DGHVKLADFGLA 144

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 62510085 144 MHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLSFVsGLpEDKGVDLYVLEKAFLSTHPHTETVF 209
Cdd:cd05579 109 LHSHGIIHRDLKPDNILID---ANGHLKLTDFGLSKV-GL-VRRQIKLSIQKKSNGAPEKEDRRIV 169

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 62510085  73 VQEARALLRCRRAGIAA--PVVFFVDYASNCLYMEEIE-DSVTVRDYIQSTMeTEKDPQCLldlarrMGQVLAG---MHD 146
Cdd:cd07845  54 LREITLLLNLRHPNIVElkEVVVGKHLDSIFLVMEYCEqDLASLLDNMPTPF-SESQVKCL------MLQLLRGlqyLHE 126

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 62510085 147 QDLIHGDLTTSNMLLRRplaQLHIVLIDFGLSFVSGLP 184
Cdd:cd07845 127 NFIIHRDLKVSNLLLTD---KGCLKIADFGLARTYGLP 161

Catalytic domain of Fungal Halotolerance protein 4-like 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 HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like 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 62510085 111 VTVRDYIQS-------TME--TEKDPQCLLDLARRMG---------QVLAG---MHDQDLIHGDLTTSNMLLRrplAQLH 169
Cdd:cd13994  60 VKVLDLCQDlhgkwclVMEycPGGDLFTLIEKADSLSleekdcffkQILRGvayLHSHGIAHRDLKPENILLD---EDGV 136

                        90
                ....*....|....*...
gi 62510085 170 IVLIDFGLSFVSGLPEDK 187
Cdd:cd13994 137 LKLTDFGTAEVFGMPAEK 154

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 62510085  29 LVQQGAEARVFR--GRFQGR--AAVVK-HR-----FPKSYRHPELEARLGRRR----------TVQEARALLRCRRAGIA 88
Cdd:cd05119   4 VISTGKEANVFYadGVFDGKpvACAVKiYRietseFDKVDEYLYGDERFDYRRispkekvfiwTEKEFRNLERAKEAGVS 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62510085  89 APVVFfvDYASNCLYMEEI-EDSVTVRDYIQSTME-TEKDPQCLLDLArrMGQVLAGMHDQDLIHGDLTTSNMLLRRpla 166
Cdd:cd05119  84 VPQPY--TYEKNVLL*EFIgEDELPAPTLVELGRElKELDVEGIFNDV--VENVKRLYQEAELVHADLSEYNILYID--- 156

                       170
                ....*....|....*...
gi 62510085 167 qlHIVLIDFGLSFVSGLP 184
Cdd:cd05119 157 --KVYFIDFGQAVTLRHP 172

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-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
                ....*....|....*....|....*....|....*....|....*....|.
gi 62510085 132 DLARR-MGQVLAG---MHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 178
Cdd:cd14003  99 DEARRfFQQLISAvdyCHSNGIVHRDLKLENILLD---KNGNLKIIDFGLS 146

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC 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
                ....*....|....*....|....*....|....*....|..
gi 62510085 137 MGQVLAGMHDQDLIHGDLTTSNMLLRrplAQLHIVLIDFGLS 178
Cdd:cd05123 102 IVLALEYLHSLGIIYRDLKPENILLD---SDGHIKLTDFGLA 140

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 62510085  53 RFPKSYRHPELEARLGR-----RRTVQEAR--ALLR----CRragiaapvVFFVDYASNCLYME-EIEDSVTVRDYI-QS 119
Cdd:cd14077  36 RASNAGLKKEREKRLEKeisrdIRTIREAAlsSLLNhphiCR--------LRDFLRTPNHYYMLfEYVDGGQLLDYIiSH 107

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 62510085 120 TMETEKDPQcllDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRplaQLHIVLIDFGLS 178
Cdd:cd14077 108 GKLKEKQAR---KFARQIASALDYLHRNSIVHRDLKIENILISK---SGNIKIIDFGLS 160

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-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
                ....*....|....*....|....*....|....*....|....*...
gi 62510085 131 LDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIVLIDFGLS 178
Cdd:cd14065  92 VSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRNAVVADFGLA 139

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 62510085 127 PQCLLDLARRMGQVLAGMHDQDLIHGDLTTSNMLLRRPLAQLHIV-LIDFGLS 178
Cdd:cd14017  96 VSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSDERTVyILDFGLA 148