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 1278360567   1 MKIISRGAEAILYDV---GDK-IKKERISKTYRLPQIDITLRKTRARKELNNMTRLAAIGVNVPHI-TQD-GDFGLRIDK 74
Cdd:PRK14879    1 MKLIKRGAEAEIYLGdflGIKaVIKWRIPKRYRHPELDERIRRERTRREARIMSRARKAGVNVPAVyFVDpENFIIVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  75 IKGITLQKLIKTNDQNLNVLFQMLGEQIKKIHDFDIIHGDLAPTNMVINNMQPFLIDFGLSYQSKSIEDKATDIVLFLKL 154
Cdd:PRK14879   81 IEGEPLKDLINSNGMEELELSREIGRLVGKLHSAGIIHGDLTTSNMILSGGKIYLIDFGLAEFSKDLEDRAVDLHVLLRS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1278360567 155 LRSLHTN--ENLISAFFKGYLP-----NKLFLDKIEQIKKRARY 191
Cdd:PRK14879  161 LESTHPDwaEELFEAFLEGYREvmgekAEEVLERVKEIRLRGRY 204

Kae1-associated kinase Bud32;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567   1 MKIISRGAEAILYDV---GDK-IKKERISKTYRLPQIDITLRKTRARKELNNMTRLAAIGVNVPHI-TQD-GDFGLRIDK 74
Cdd:PRK14879    1 MKLIKRGAEAEIYLGdflGIKaVIKWRIPKRYRHPELDERIRRERTRREARIMSRARKAGVNVPAVyFVDpENFIIVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  75 IKGITLQKLIKTNDQNLNVLFQMLGEQIKKIHDFDIIHGDLAPTNMVINNMQPFLIDFGLSYQSKSIEDKATDIVLFLKL 154
Cdd:PRK14879   81 IEGEPLKDLINSNGMEELELSREIGRLVGKLHSAGIIHGDLTTSNMILSGGKIYLIDFGLAEFSKDLEDRAVDLHVLLRS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1278360567 155 LRSLHTN--ENLISAFFKGYLP-----NKLFLDKIEQIKKRARY 191
Cdd:PRK14879  161 LESTHPDwaEELFEAFLEGYREvmgekAEEVLERVKEIRLRGRY 204

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 1278360567  40 TRARKELNNMTRLAAIGVNVPHI----TQDGDfgLRIDKIKGITLQKLIKTNDqNLNVLFQMLGEQIKKIHDFDIIHGDL 115
Cdd:COG3642     1 ERTRREARLLRELREAGVPVPKVldvdPDDAD--LVMEYIEGETLADLLEEGE-LPPELLRELGRLLARLHRAGIVHGDL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567 116 APTNMVINNMQPFLIDFGLSYQSKSIEDKATDIVLFLKLLRSLHTN--ENLISAFFKGYLPNKLF---LDKIEQIKKRAR 190
Cdd:COG3642    78 TTSNILVDDGGVYLIDFGLARYSDPLEDKAVDLAVLKRSLESTHPDpaEELWEAFLEGYREVGPAeevLRRLREIELRGR 157

                  ..
gi 1278360567 191 YL 192
Cdd:COG3642   158 YL 159

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 1278360567  42 ARKELNNMTRLAAIGVNVP-------HItqdgdfgLRIDKI--KGITLQKLIKTNDQNL-NVLFQMLGEQIKKIHDFDII 111
Cdd:pfam01163  53 AEKEFRNLKRLYEAGVPVPkpidvnrHV-------LVMEFIgkDGVPAPKLKDVELEEAeEIYDEIIREMRRLYQEAGLV 125

                          90       100
                  ....*....|....*....|..
gi 1278360567 112 HGDLAPTNMVINNMQPFLIDFG 133
Cdd:pfam01163 126 HGDLSEYNILVHDDKPVIIDVP 147

Kae1-associated kinase Bud32;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567   1 MKIISRGAEAILYDV---GDK-IKKERISKTYRLPQIDITLRKTRARKELNNMTRLAAIGVNVPHI-TQD-GDFGLRIDK 74
Cdd:PRK14879    1 MKLIKRGAEAEIYLGdflGIKaVIKWRIPKRYRHPELDERIRRERTRREARIMSRARKAGVNVPAVyFVDpENFIIVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  75 IKGITLQKLIKTNDQNLNVLFQMLGEQIKKIHDFDIIHGDLAPTNMVINNMQPFLIDFGLSYQSKSIEDKATDIVLFLKL 154
Cdd:PRK14879   81 IEGEPLKDLINSNGMEELELSREIGRLVGKLHSAGIIHGDLTTSNMILSGGKIYLIDFGLAEFSKDLEDRAVDLHVLLRS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1278360567 155 LRSLHTN--ENLISAFFKGYLP-----NKLFLDKIEQIKKRARY 191
Cdd:PRK14879  161 LESTHPDwaEELFEAFLEGYREvmgekAEEVLERVKEIRLRGRY 204

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567   3 IISRGAEAIL----YDVGDKIKKERISKTYRLPQIDITLRKTRARKE--LNNMTRLAaiGVNVPHItQDGD---FGLRID 73
Cdd:PRK09605  340 LIGKGAEADIkkgeYLGRDAVIKERVPKGYRHPELDERLRTERTRAEarLLSEARRA--GVPTPVI-YDVDpeeKTIVME 416

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  74 KIKGITLQKLIKTNDQNLNvlfqMLGEQIKKIHDFDIIHGDLAPTNMVINNMQPFLIDFGLSYQSKSIEDKATDIVLFLK 153
Cdd:PRK09605  417 YIGGKDLKDVLEGNPELVR----KVGEIVAKLHKAGIVHGDLTTSNFIVRDDRLYLIDFGLGKYSDLIEDKAVDLHVLKQ 492

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1278360567 154 LLRSLHTN-ENLISAFFKGYLPNKLF---LDKIEQIKKRARYL 192
Cdd:PRK09605  493 SLESTHYDfEELWEAFLEGYRETEGAedvLERLKEIEKRGRYL 535

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  21 KERISKTYrlpqiditLRKTRARKELNNMTRLAAIGVNVP-------HItqdgdfgLRIDKIKGITLQKLIKTNDQnlnV 93
Cdd:COG0478    33 KEHYSWLY--------AARTRAEREFRALERLYPAGLPVPrpiaanrHA-------IVMERIEGVELARLKLEDPE---E 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  94 LFQMLGEQIKKIHDFDIIHGDLAPTN-MVINNMQPFLIDFGlsyQSKSIEDKATDIVlflkLLRSLhtnENLISAFFKGY 172
Cdd:COG0478    95 VLDKILEEIRRAHDAGIVHADLSEYNiLVDDDGGVWIIDWP---QAVPRDHPNAEEL----LERDL---ENLLRSFRKKY 164

                         170
                  ....*....|
gi 1278360567 173 lPNKLFLDKI 182
Cdd:COG0478   165 -GLEVDLDEV 173

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 1278360567  42 ARKELNNMTRLAAIGVNVP-------HItqdgdfgLRIDKI--KGITLQKLIKTNDQNL-NVLFQMLGEQIKKIHDFDII 111
Cdd:pfam01163  53 AEKEFRNLKRLYEAGVPVPkpidvnrHV-------LVMEFIgkDGVPAPKLKDVELEEAeEIYDEIIREMRRLYQEAGLV 125

                          90       100
                  ....*....|....*....|..
gi 1278360567 112 HGDLAPTNMVINNMQPFLIDFG 133
Cdd:pfam01163 126 HGDLSEYNILVHDDKPVIIDVP 147

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 1278360567  29 RLPQIDITLRKTRARKELNNMTRLaaigvNVPHI-------TQDGDFGLRIDKIKGITLQKLIKTNDQNLN------VLF 95
Cdd:cd00180    25 VIPKEKLKKLLEELLREIEILKKL-----NHPNIvklydvfETENFLYLVMEYCEGGSLKDLLKENKGPLSeeealsILR 99

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1278360567  96 QMLgEQIKKIHDFDIIHGDLAPTNMVI-NNMQPFLIDFGLSYQSKSIEDKATD 147
Cdd:cd00180   100 QLL-SALEYLHSNGIIHRDLKPENILLdSDGTVKLADFGLAKDLDSDDSLLKT 151

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1278360567  78 ITLQKLIKT-NDQNLNVLF------QMLgEQIKKIHDFDIIHGDLAPTNMVINNMQPFLIDFGLsyqSKSIEDKATDIV 149
Cdd:cd14131    86 IDLATILKKkRPKPIDPNFiryywkQML-EAVHTIHEEGIVHSDLKPANFLLVKGRLKLIDFGI---AKAIQNDTTSIV 160

Aminoglycoside 3'-phosphotransferase and Choline Kinase family; This family is composed of APH, ChoK, ethanolamine kinase (ETNK), macrolide 2'-phosphotransferase (MPH2'), an unusual homoserine kinase, and uncharacterized proteins with similarity to the N-terminal domain of acyl-CoA dehydrogenase 10 (ACAD10). The members of this family catalyze the transfer of the gamma-phosphoryl group from ATP (or CTP) to small molecule substrates such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine. Phosphorylation of the antibiotics, aminoglycosides and macrolides, leads to their inactivation and to bacterial antibiotic resistance. Phosphorylation of choline, ethanolamine, and homoserine serves as precursors to the synthesis of important biological compounds, such as the major phospholipids, phosphatidylcholine and phosphatidylethanolamine and the amino acids, threonine, methionine, and isoleucine. The APH/ChoK 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), RIO kinases, actin-fragmin kinase (AFK), and phosphoinositide 3-kinase (PI3K).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  18 KIKKERISKTYRL-PQIDITLRKTRAR------KELNNMTRLAA-IGVNVPHI----TQDGDFGLRIDKIKGITLQKLIK 85
Cdd:cd05120     5 LIKEGGDNKVYLLgDPREYVLKIGPPRlkkdleKEAAMLQLLAGkLSLPVPKVygfgESDGWEYLLMERIEGETLSEVWP 84

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1278360567  86 T-NDQNLNVLFQMLGEQIKKIHDFDI---IHGDLAPTNMVINNMQPF--LIDFGLS 135
Cdd:cd05120    85 RlSEEEKEKIADQLAEILAALHRIDSsvlTHGDLHPGNILVKPDGKLsgIIDWEFA 140

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1278360567  77 GITLQKLIKTNDQNLN------VLFQMLgEQIKKIHDFDIIHGDLAPTNMVINNM--QPFLIDFGLSYQSKS 140
Cdd:cd05118    84 GMNLYELIKDYPRGLPldliksYLYQLL-QALDFLHSNGIIHRDLKPENILINLElgQLKLADFGLARSFTS 154

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha 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 1278360567  78 ITLQKLikTNDQNLNVLFQMLgEQIKKIHDFDIIHGDLAPTNMVIN-NMQPFLIDFGLS 135
Cdd:cd07877   112 VKCQKL--TDDHVQFLIYQIL-RGLKYIHSADIIHRDLKPSNLAVNeDCELKILDFGLA 167

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta 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 1278360567  13 YDVG--DKIKKERISKTYR-LPQIDITLRKTRARKELNNMTRLAAIGVNVPHITQDgDFG--LRIDKIKGITLQKLIKT- 86
Cdd:cd07878    35 YDTRlrQKVAVKKLSRPFQsLIHARRTYRELRLLKHMKHENVIGLLDVFTPATSIE-NFNevYLVTNLMGADLNNIVKCq 113

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1278360567  87 --NDQNLNVLFQMLGEQIKKIHDFDIIHGDLAPTNMVIN-NMQPFLIDFGLSYQSksiEDKATDIV 149
Cdd:cd07878   114 klSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNeDCELRILDFGLARQA---DDEMTGYV 176

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1278360567  91 LNVLFQMLgEQIKKIHDFDIIHGDLAPTNMVI----NNMQPF-LIDFGLSYQ----SKSIEDKATDIVLFLKLLR----S 157
Cdd:cd14017   100 LRLGIQIL-KAIEDIHEVGFLHRDVKPSNFAIgrgpSDERTVyILDFGLARQytnkDGEVERPPRNAAGFRGTVRyasvN 178

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1278360567 158 LHTNEN------LISAF------FKGYLPNKLFLDKIE--QIKKRARY 191
Cdd:cd14017   179 AHRNKEqgrrddLWSWFymliefVTGQLPWRKLKDKEEvgKMKEKIDH 226

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK 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 1278360567  80 LQKLIK-----TNDQNLNVLFQMLgEQIKKIHDFDIIHGDLAPTNMVIN-NMQPFLIDFGLSYQSKSIEDKATDIV 149
Cdd:cd07858    95 LHQIIRssqtlSDDHCQYFLYQLL-RGLKYIHSANVLHRDLKPSNLLLNaNCDLKICDFGLARTTSEKGDFMTEYV 169

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 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 1278360567 105 IHDFDIIHGDLAPTNMVINNMQPFLIDFGLSYQsksiedkATDIVLFLKLLR 156
Cdd:cd13995   112 LHSKNIIHHDIKPSNIVFMSTKAVLVDFGLSVQ-------MTEDVYVPKDLR 156

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
                  ....*....|....*....|....*....|...
gi 1278360567 105 IHDFDIIHGDLAPTNMVINNM-QPFLIDFGLSY 136
Cdd:cd05579   109 LHSHGIIHRDLKPDNILIDANgHLKLTDFGLSK 141

Catalytic domain of the atypical protein serine kinase, RIO3 kinase; RIO3 is present only in multicellular eukaryotes. It is associated with precursors of 40S ribosomal subunits, just like RIO1 and RIO2. Its specific function is still unknown. Like RIO1 and RIO2, it may be involved in ribosomal subunit processing and maturation. RIO kinases are atypical protein serine kinases containing a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. The RIO3 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 1278360567  42 ARKELNNMTRLAAIGVNVP-------HI---TQDGDFGLRIDKIKGITL--QKLIKTNDQNLNVLFQMLgeqikkiHDFD 109
Cdd:cd05146    72 AEKEMHNLKRMQKAGIPCPevvllkkHVlvmSFIGKDQVPAPKLKDAKLssADLKLAYEQVVQMMKTMY-------NECH 144

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1278360567 110 IIHGDLAPTNMVINNMQPFLIDFglsyqSKSIEDKATDIVLFlkLLRSLHTnenlISAFFK 170
Cdd:cd05146   145 LVHADLSEYNILWHEGKVWFIDV-----SQSVEPTHPHALEF--LLRDCRN----VSNFFQ 194

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1278360567  70 LRIDKIKGITLQKLIKtndqnlnVLFQMLgEQIKKIHDFDIIHGDLAPTNMVINNMQPF---LIDFGLS 135
Cdd:cd14133    91 LKQNKFQYLSLPRIRK-------IAQQIL-EALVFLHSLGLIHCDLKPENILLASYSRCqikIIDFGSS 151

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1278360567  77 GITLQKLIKTNDQNL---NVLfqMLGEQI----KKIHDFDIIHGDLAPTNMVI----NNMQPFLIDFGLSY 136
Cdd:cd14015   110 GRDLQKIFEKNGKRFpekTVL--QLALRIldvlEYIHENGYVHADIKASNLLLgfgkNKDQVYLVDYGLAS 178

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 1278360567  42 ARKELNNMTRLAAIGVNVPHI-TQDGDFGLR----IDKIKGITLQKL-IKTNDQNLNVLFQMLGEQIKKI-HDFDIIHGD 114
Cdd:cd05119    67 TEKEFRNLERAKEAGVSVPQPyTYEKNVLL*efigEDELPAPTLVELgRELKELDVEGIFNDVVENVKRLyQEAELVHAD 146

                          90       100
                  ....*....|....*....|..
gi 1278360567 115 LAPTN-MVINNMqpFLIDFGLS 135
Cdd:cd05119   147 LSEYNiLYIDKV--YFIDFGQA 166