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 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDKAVTFY---AKKLHKLRHcPILIQYHTQdtirYRQQDVT 101
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPELAEDEEFRERFlreARALARLSH-PNIVRVYDV----GEDDGRP 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2588348413 102 FLVSEYVEGELLSSFIERQpgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLID 174
Cdd:cd14014    76 YIVMEYVEGGSLADLLRER--GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG---RVKLTD 143

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  26 YEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDKAVTFYA--KKLHKLRHCPILIQYHTqdtirYRQQDVTFL 103
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKKKKDKNILReiKILKKLNHPNIVRLYDA-----FEDKDNLYL 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2588348413 104 VSEYVEGELLSSFIERQpgKRLNAFQAIHLLHALVTGMES 143
Cdd:pfam00069  76 VLEYVEGGSLFDLLSEK--GAFSEREAKFIMKQILEGLES 113

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 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDKAVTFY---AKKLHKLRHcPILIQYHTQdtirYRQQDVT 101
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPELAEDEEFRERFlreARALARLSH-PNIVRVYDV----GEDDGRP 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2588348413 102 FLVSEYVEGELLSSFIERQpgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLID 174
Cdd:cd14014    76 YIVMEYVEGGSLADLLRER--GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG---RVKLTD 143

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413   26 YEVLACLGKGWEGEVYHVIEARSGIERAVKFFyPQRNVRDKAVTFYA-KKLHKLRHCPILIQYHtqDTIRYRQQdvTFLV 104
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVI-KKKKIKKDRERILReIKILKKLKHPNIVRLY--DVFEDEDK--LYLV 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  105 SEYVEGELLSSFIERQpgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLID 174
Cdd:smart00220  76 MEYCEGGDLFDLLKKR--GRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDG---HVKLAD 140

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFF--YPQRNVRDKAVTFYAKKLHKLRHcPILIQ----YHTQDTIryrqq 98
Cdd:cd05117     1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkKKLKSEDEEMLRREIEILKRLDH-PNIVKlyevFEDDKNL----- 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2588348413  99 dvtFLVSEYVE-GELLSSFIERqpgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGLGFELKLID 174
Cdd:cd05117    75 ---YLVMELCTgGELFDRIVKK---GSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSPIKIID 145

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK 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 2588348413  26 YEVLACLGKGWEGEVYHVIEARSGIERAVKFF-YPQRNVRDKAVTFYAKKLHKLRHcPILIQYHTQdtirYRQQDVTFLV 104
Cdd:cd13996     8 FEEIELLGSGGFGSVYKVRNKVDGVTYAIKKIrLTEKSSASEKVLREVKALAKLNH-PNIVRYYTA----WVEEPPLYIQ 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2588348413 105 SEYVEGELLSSFIERQPGKR-LNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVIL 161
Cdd:cd13996    83 MELCEGGTLRDWIDRRNSSSkNDRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFL 140

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 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDKAVTFYAKK---LHKLRHcPILIQYH----TQDTIryrq 97
Cdd:cd14663     1 RYELGRTLGEGTFAKVKFARNTKTGESVAIKIIDKEQVAREGMVEQIKREiaiMKLLRH-PNIVELHevmaTKTKI---- 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2588348413  98 qdvtFLVSEYVE-GELLSSFIErqpGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVIL 161
Cdd:cd14663    76 ----FFVMELVTgGELFSKIAK---NGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLL 133

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. 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 CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  26 YEVLACLGKGWEGEVYHVIEARSGIERAVKFF--------YPQRNVRDKAVTfyaKKLHKLRHCPILIQYHTQDTIRYRQ 97
Cdd:cd07838     1 YEEVAEIGEGAYGTVYKARDLQDGRFVALKKVrvplseegIPLSTIREIALL---KQLESFEHPNVVRLLDVCHGPRTDR 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2588348413  98 QDVTFLVSEYVEGElLSSFIERQPGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLID 174
Cdd:cd07838    78 ELKLTLVFEHVDQD-LATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDG---QVKLAD 150

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (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. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 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 2588348413  32 LGKGWEGEVYHVIEARSGIERAVKFFYPQR---------NVRDKAvtfyaKKLHKLRHcPILIQYHtqDTIRYRQQDVTF 102
Cdd:cd14119     1 LGEGSYGKVKEVLDTETLCRRAVKILKKRKlrripngeaNVKREI-----QILRRLNH-RNVIKLV--DVLYNEEKQKLY 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2588348413 103 LVSEYVEGELLSsFIERQPGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVIL 161
Cdd:cd14119    73 MVMEYCVGGLQE-MLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLL 130

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYpqrnvRDKAVTFYAKKL------HK-LRHCPILIQYHTQDTIRYrq 97
Cdd:cd14003     1 NYELGKTLGEGSFGKVKLARHKLTGEKVAIKIID-----KSKLKEEIEEKIkreieiMKlLNHPNIIKLYEVIETENK-- 73

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2588348413  98 qdvTFLVSEYVE-GELLSSFIERqpgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLID 174
Cdd:cd14003    74 ---IYLVMEYASgGELFDYIVNN---GRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNG---NLKIID 142

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 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 2588348413  22 LAGKYEVLACLGKGWEGEVYHVIEaRSGIERAVKFFYPQRnVRDKAVTFYAKK----LHKLRHCPILIQYHTqdtirYRQ 97
Cdd:cd14161     1 LKHRYEFLETLGKGTYGRVKKARD-SSGRLVAIKSIRKDR-IKDEQDLLHIRReieiMSSLNHPHIISVYEV-----FEN 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2588348413  98 QDVTFLVSEYV-EGELLSSFIERQpgkRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVIL 161
Cdd:cd14161    74 SSKIVIVMEYAsRGDLYDYISERQ---RLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILL 135

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 2588348413  32 LGKGWEGEV--YHVIEARSGIERAVKFFYP------QRNVRDKAVTFY--AKKLHklrHCPILiqyHTQDtIRYRQQDVT 101
Cdd:cd13994     1 IGKGATSVVriVTKKNPRSGVLYAVKEYRRrddeskRKDYVKRLTSEYiiSSKLH---HPNIV---KVLD-LCQDLHGKW 73

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2588348413 102 FLVSEYVEGELLSSFIERqpGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGLgfeLKLID 174
Cdd:cd13994    74 CLVMEYCPGGDLFTLIEK--ADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGV---LKLTD 141

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 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 2588348413  20 RMLAGKYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVR--DKAVTFYAKKLHKLRHCPILIQ--YHTQDTiRY 95
Cdd:cd05622    69 RMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKrsDSAFFWEERDIMAFANSPWVVQlfYAFQDD-RY 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  96 rqqdvTFLVSEYVEGELLSSFIERQ--PGKRLNAFQAihllhALVTGMESIHALGEYHGDLHTDNVILMRYGlgfELKLI 173
Cdd:cd05622   148 -----LYMVMEYMPGGDLVNLMSNYdvPEKWARFYTA-----EVVLALDAIHSMGFIHRDVKPDNMLLDKSG---HLKLA 214

                  .
gi 2588348413 174 D 174
Cdd:cd05622   215 D 215

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  25 KYEVLACLGKGWEGEVYhVIEARSGIERAV-------KFFYPQRNVRDKAVTFyakkLHKLRHCPILIQYHTqdtirYRQ 97
Cdd:cd08225     1 RYEIIKKIGEGSFGKIY-LAKAKSDSEHCVikeidltKMPVKEKEASKKEVIL----LAKMKHPNIVTFFAS-----FQE 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  98 QDVTFLVSEYVEGELLSSFIERQPGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYGL-------GFEL 170
Cdd:cd08225    71 NGRLFIVMEYCDGGDLMKRINRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMvaklgdfGIAR 150

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2588348413 171 KLIDMYHW-----GAP----------RRENIQDDICDLVRIFYDAVGGKKHYA--NQHRVVKEICRG 220
Cdd:cd08225   151 QLNDSMELaytcvGTPyylspeicqnRPYNNKTDIWSLGCVLYELCTLKHPFEgnNLHQLVLKICQG 217

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  32 LGKGWEGEVYHVIEARSGIERAVKffypqrnVRDKAVTFYAKKLHK----------LRHCPILIQYHTQDTiryrqQDVT 101
Cdd:cd05574     9 LGKGDVGRVYLVRLKGTGKLFAMK-------VLDKEEMIKRNKVKRvltereilatLDHPFLPTLYASFQT-----STHL 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2588348413 102 FLVSEYVEGELLSSFIERQPGKRLNA----FQAIHLLHALvtgmESIHALGEYHGDLHTDNVIL 161
Cdd:cd05574    77 CFVMDYCPGGELFRLLQKQPGKRLPEevarFYAAEVLLAL----EYLHLLGFVYRDLKPENILL 136

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  26 YEVLACLGKGWEGEVYHVIEARSGIERAVKFFypqrnVRDKAVTFYA----KKLHKLR----HCPILiqyHTQDTIRYRQ 97
Cdd:cd05118     1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKI-----KNDFRHPKAAlreiKLLKHLNdvegHPNIV---KLLDVFEHRG 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2588348413  98 QDVTFLVSEYVeGELLSSFIERQPgKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNvILMRYGLgFELKLIDM 175
Cdd:cd05118    73 GNHLCLVFELM-GMNLYELIKDYP-RGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPEN-ILINLEL-GQLKLADF 146

serine/threonine-protein kinase PknD;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  24 GKYEVLACLGKGWEGEVYHVIEARSGIERAVKffypqrNVRDKAVTFyaKKLHK--LRHCPIliqyhTQDTIR------- 94
Cdd:PRK13184    2 QRYDIIRLIGKGGMGEVYLAYDPVCSRRVALK------KIREDLSEN--PLLKKrfLREAKI-----AADLIHpgivpvy 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  95 --YRQQDVTFLVSEYVEGELLSSFI-----------ERQPGKRLNAFQAIhlLHALVTGMESIHALGEYHGDLHTDNVIL 161
Cdd:PRK13184   69 siCSDGDPVYYTMPYIEGYTLKSLLksvwqkeslskELAEKTSVGAFLSI--FHKICATIEYVHSKGVLHRDLKPDNILL 146

                         170       180
                  ....*....|....*....|....*...
gi 2588348413 162 MRYGlgfELKLIDmyhWGAPRRENIQDD 189
Cdd:PRK13184  147 GLFG---EVVILD---WGAAIFKKLEEE 168

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 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVK--FFYPQRNV--RDKAVTfyaKKLHKLRHCPILIqyhtqdtIRYRQQDV 100
Cdd:cd14017     1 RWKVVKKIGGGGFGEIYKVRDVVDGEEVAMKveSKSQPKQVlkMEVAVL---KKLQGKPHFCRLI-------GCGRTERY 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2588348413 101 TFLVSEYVeGELLSSFIERQPGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMRYG 165
Cdd:cd14017    71 NYIVMTLL-GPNLAELRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGP 134

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They 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. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 2588348413  31 CLGKGWEGEVYHVIEARSGIERAVKffypQRNVRDKAVTFYA------KKLHKLRHcPILIQY----HTQDTIRyrqqdv 100
Cdd:cd06606     7 LLGKGSFGSVYLALNLDTGELMAVK----EVELSGDSEEELEalereiRILSSLKH-PNIVRYlgteRTENTLN------ 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2588348413 101 TFLvsEYVEGELLSSFIERqpGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILmryGLGFELKLID 174
Cdd:cd06606    76 IFL--EYVPGGSLASLLKK--FGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILV---DSDGVVKLAD 142

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 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 2588348413  32 LGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDkavtFYAKKLHKL------RHCPILIQYHTQdtirYRQQDVTFLVS 105
Cdd:cd14198    16 LGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGQD----CRAEILHEIavlelaKSNPRVVNLHEV----YETTSEIILIL 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2588348413 106 EYVEGELLSSFIERQPGKRLNAFQAIHLLHALVTGMESIHALGEYHGDLHTDNVILMR-YGLGfELKLIDmyhWGAPRR 183
Cdd:cd14198    88 EYAAGGEIFNLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSiYPLG-DIKIVD---FGMSRK 162

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 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 2588348413  25 KYEVLACLGKGWEGEVYHVIEARSGIERAVKFFYPQRNVRDKAVTFY--------AKKLHKLRHcPILIQYHTQdtirYR 96
Cdd:cd14084     7 KYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIINKRKFTIGSRREINkprnieteIEILKKLSH-PCIIKIEDF----FD 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2588348413  97 QQDVTFLVSEYVE-GELLSSFIE----RQPGKRLNAFQAIHllhalvtGMESIHALGEYHGDLHTDNVIL 161
Cdd:cd14084    82 AEDDYYIVLELMEgGELFDRVVSnkrlKEAICKLYFYQMLL-------AVKYLHSNGIIHRDLKPENVLL 144