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 2667398973  23 PFAVHGRLGAGGMGVVYGAVGP-DGRWAAVKVVRPEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATP 101
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTlLGRPVAIKVLRPELAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVME 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2667398973 102 YLPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd14014    81 YVEGGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG 137

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 2667398973  23 PFAVHGRLGAGGMGVVYGAVGP-DGRWAAVKVVRPEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATP 101
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTlLGRPVAIKVLRPELAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVME 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2667398973 102 YLPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd14014    81 YVEGGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG 137

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2667398973  28 GRLGAGGMGVVYGAVgpD---GRWAAVKVVRPEYAGEPEFRSRFASEvalmhrvrARCIApVLAH-------DTRAE--L 95
Cdd:NF033483   13 ERIGRGGMAEVYLAK--DtrlDRDVAVKVLRPDLARDPEFVARFRRE--------AQSAA-SLSHpnivsvyDVGEDggI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2667398973  96 PWYATPYLPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:NF033483   82 PYIVMEYVDGRTLKDYIREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDG 144

serine/threonine-protein kinase PknD;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2667398973  21 IPPFAVHGRLGAGGMGVVYGAVGPD-GRWAAVKVVRPEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYA 99
Cdd:PRK13184    1 MQRYDIIRLIGKGGMGEVYLAYDPVcSRRVALKKIREDLSENPLLKKRFLREAKIAADLIHPGIVPVYSICSDGDPVYYT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2667398973 100 TPYLPGPTLGA---RVRQGGALA-PHQARV-------VAAGMAEAIAAIHAAGVVHRDLKPANVIL 154
Cdd:PRK13184   81 MPYIEGYTLKSllkSVWQKESLSkELAEKTsvgaflsIFHKICATIEYVHSKGVLHRDLKPDNILL 146

ABC1 atypical kinase-like domain; This family includes ABC1 from yeast and AarF from E. coli. These proteins have a nuclear or mitochondrial subcellular location in eukaryotes. The exact molecular functions of these proteins is not clear, however yeast ABC1 suppresses a cytochrome b mRNA translation defect and is essential for the electron transfer in the bc 1 complex and E. coli AarF is required for ubiquinone production. It has been suggested that members of the ABC1 family are novel chaperonins. These proteins are unrelated to the ABC transporter proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2667398973  30 LGAGGMGVVYGAVGPDGRWAAVKVVRpeyagePEFRSRFASEVALMHRV 78
Cdd:pfam03109  38 IAAASIAQVHRARLKDGEEVAVKVQR------PGVKKRIRSDLLLLRFL 80

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 2667398973  23 PFAVHGRLGAGGMGVVYGAVGP-DGRWAAVKVVRPEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATP 101
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTlLGRPVAIKVLRPELAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVME 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2667398973 102 YLPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd14014    81 YVEGGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG 137

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2667398973  28 GRLGAGGMGVVYGAVgpD---GRWAAVKVVRPEYAGEPEFRSRFASEvalmhrvrARCIApVLAH-------DTRAE--L 95
Cdd:NF033483   13 ERIGRGGMAEVYLAK--DtrlDRDVAVKVLRPDLARDPEFVARFRRE--------AQSAA-SLSHpnivsvyDVGEDggI 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2667398973  96 PWYATPYLPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:NF033483   82 PYIVMEYVDGRTLKDYIREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDG 144

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 2667398973  30 LGAGGMGVVYGAV-GPDGRWAAVKVVRPEYAGEPefRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATPYLPGPTL 108
Cdd:cd00180     1 LGKGSFGKVYKARdKETGKKVAVKVIPKEKLKKL--LEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSL 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2667398973 109 GARVRQ-GGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd00180    79 KDLLKEnKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDG 129

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK 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 2667398973  30 LGAGGMGVVYGAVGPDGRWAAVKVVRPEYAgePEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATPYLPGPTLG 109
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNC--AASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLE 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2667398973 110 ARVRQGGALAPHQ-----------ARVVAAGMAEAIAAihaagVVHRDLKPANVIL 154
Cdd:cd14066    79 DRLHCHKGSPPLPwpqrlkiakgiARGLEYLHEECPPP-----IIHGDIKSSNILL 129

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK 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 (PI3K).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2667398973  30 LGAGGMGVVYGAVGPD-GRWAAVKVVRPEYAGEPEFRSRFASEVALMHR------VRARCIAPVLAHDTRAELPWYATPY 102
Cdd:cd13989     1 LGSGGFGYVTLWKHQDtGEYVAIKKCRQELSPSDKNRERWCLEVQIMKKlnhpnvVSARDVPPELEKLSPNDLPLLAMEY 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2667398973 103 LPGPTLG---ARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd13989    81 CSGGDLRkvlNQPENCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQGG 139

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-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 mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. 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. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2667398973  30 LGAGGMGVVYgavgpDGRWA----AVKVVRPEYaGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATPYLPG 105
Cdd:cd13999     1 IGSGSFGEVY-----KGKWRgtdvAIKKLKVED-DNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPG 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2667398973 106 PTLGARVR-QGGALAPHQ--------ARvvaagmaeaiaaihaaG--------VVHRDLKPANVIL 154
Cdd:cd13999    75 GSLYDLLHkKKIPLSWSLrlkialdiAR----------------GmnylhsppIIHRDLKSLNILL 124

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta 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 2667398973  29 RLGAGGMGVVYGAVGPD-GRWAAVKVVRPEYAgePEFRSRFASEVALMHR------VRARCIAPVLAHDTRAELPWYATP 101
Cdd:cd14038     1 RLGTGGFGNVLRWINQEtGEQVAIKQCRQELS--PKNRERWCLEIQIMKRlnhpnvVAARDVPEGLQKLAPNDLPLLAME 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2667398973 102 YLPGPTLGARVRQ---GGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAP 156
Cdd:cd14038    79 YCQGGDLRKYLNQfenCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQ 136

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 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 2667398973  29 RLGAGGMGVVYGAVGPD-GRWAAVK-VVRPEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATPYLPGP 106
Cdd:cd14098     7 RLGSGTFAEVKKAVEVEtGKMRAIKqIVKRKVAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGG 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2667398973 107 TLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDGP 159
Cdd:cd14098    87 DLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDP 139

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to 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 2667398973  28 GR-LGAGGMGVVYGAVG-PDGRWAAVKVVRPEYAGEPEFRSRFASEVALMHRVRARCIA---PVLAHDTRAelpWYATPY 102
Cdd:cd14663     5 GRtLGEGTFAKVKFARNtKTGESVAIKIIDKEQVAREGMVEQIKREIAIMKLLRHPNIVelhEVMATKTKI---FFVMEL 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2667398973 103 LPGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd14663    82 VTGGELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDG 137

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 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 2667398973  30 LGAGGMGVVY-GAVGPDGRWAAVKVVR--PEYAGEPEFRSRFASEVALMHRVRARCIAPVLAHDTRAELPWYATPYLPGP 106
Cdd:cd06632     8 LGSGSFGSVYeGFNGDTGDFFAVKEVSlvDDDKKSRESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGG 87

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2667398973 107 TLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd06632    88 SIHKLLQRYGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNG 139

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 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 2667398973  28 GRLGAGGMGVVYGAVGPD-GRWAAVKVVrpEYAGEPEFRSrFASEVALMHRVRARCIAPVLA---HDTRAelpWYATPYL 103
Cdd:cd06644    18 GELGDGAFGKVYKAKNKEtGALAAAKVI--ETKSEEELED-YMVEIEILATCNHPYIVKLLGafyWDGKL---WIMIEFC 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2667398973 104 PGPTLGARVRQ-GGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd06644    92 PGGAVDAIMLElDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDG 147

Catalytic domain of Fungal Nak1-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 Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 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 2667398973  30 LGAGGMGVVY-GAVGPDGRWAAVKVVRPEyagEPEFR-SRFASEVALMHRVRARCIAPVLAhdtraelpwYATPYLPGPT 107
Cdd:cd06917     9 VGRGSYGAVYrGYHVKTGRVVALKVLNLD---TDDDDvSDIQKEVALLSQLKLGQPKNIIK---------YYGSYLKGPS 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2667398973 108 L--------GARVR---QGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVILAPDG 158
Cdd:cd06917    77 LwiimdyceGGSIRtlmRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTG 138

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK 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 2667398973  28 GRLGAGGMGVVYGAV-GPDGRWAAVKVVRPEyaGEPEFRSRFASEVALMHRvrarCIAPVL-----AHDTRAELpWYATP 101
Cdd:cd06605     7 GELGEGNGGVVSKVRhRPSGQIMAVKVIRLE--IDEALQKQILRELDVLHK----CNSPYIvgfygAFYSEGDI-SICME 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2667398973 102 YLPGPTLGARVRQGGALAPHQ-ARVVAAGMAEAIAAIHAAGVVHRDLKPANVIL 154
Cdd:cd06605    80 YMDGGSLDKILKEVGRIPERIlGKIAVAVVKGLIYLHEKHKIIHRDVKPSNILV 133

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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 2667398973  30 LGAGGMGVVYGAVG-PDGRWAAVKVVRPEYAGEpefRSRFASEVALMHRVRAR-----CIApVLAHDTRAELPWyatPYL 103
Cdd:cd14090    10 LGEGAYASVQTCINlYTGKEYAVKIIEKHPGHS---RSRVFREVETLHQCQGHpnilqLIE-YFEDDERFYLVF---EKM 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2667398973 104 PGPTLGARVRQGGALAPHQARVVAAGMAEAIAAIHAAGVVHRDLKPANVI 153
Cdd:cd14090    83 RGGPLLSHIEKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENIL 132

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. 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 CDK7 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
                  ....*....|....*..
gi 2667398973 142 VVHRDLKPANVILAPDG 158
Cdd:cd07841   123 ILHRDLKPNNLLIASDG 139

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
                  ....*....|....*...
gi 2667398973 141 GVVHRDLKPANVILAPDG 158
Cdd:cd14008   128 GIVHRDIKPENLLLTADG 145