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 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCP 80
Cdd:cd14023   71 MHSYVRSCKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSDEERTQLRLESLEDTHIMKGEDDALSDKHGCP 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSER 160
Cdd:cd14023  151 AYVSPEILNTTGTYSGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPDHVSPKARCLIRSLLRREPSER 230

                        170
                 ....*....|..
gi 545477471 161 LTAPEILLHPWF 172
Cdd:cd14023  231 LTAPEILLHPWF 242

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCP 80
Cdd:cd14023   71 MHSYVRSCKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSDEERTQLRLESLEDTHIMKGEDDALSDKHGCP 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSER 160
Cdd:cd14023  151 AYVSPEILNTTGTYSGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPDHVSPKARCLIRSLLRREPSER 230

                        170
                 ....*....|..
gi 545477471 161 LTAPEILLHPWF 172
Cdd:cd14023  231 LTAPEILLHPWF 242

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471    2 HSYVRSRKRLREEEAARLFKQIVSAVAHCHqsaivlgdlKLRKFVfsteertqlrlesledthimkgeddalsdkhGCPA 81
Cdd:pfam00069  86 FDLLSEKGAFSEREAKFIMKQILEGLESGS---------SLTTFV-------------------------------GTPW 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   82 YVSPEILNTTGTysGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRG---QFCIPEHISPKARCLIRSLLRREPS 158
Cdd:pfam00069 126 YMAPEVLGGNPY--GPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQpyaFPELPSNLSEEAKDLLKKLLKKDPS 203

                         170
                  ....*....|....
gi 545477471  159 ERLTAPEILLHPWF 172
Cdd:pfam00069 204 KRLTATQALQHPWF 217

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLrleslEDTHIMKGEDDALSDKHGCP 80
Cdd:PTZ00263 105 LFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKV-----TDFGFAKKVPDRTFTLCGTP 179

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTGtySGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSER 160
Cdd:PTZ00263 180 EYLAPEVIQSKG--HGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNWFDGRARDLVKGLLQTDHTKR 257

                        170       180
                 ....*....|....*....|
gi 545477471 161 LTA-----PEILLHPWFESV 175
Cdd:PTZ00263 258 LGTlkggvADVKNHPYFHGA 277

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCP 80
Cdd:cd14023   71 MHSYVRSCKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSDEERTQLRLESLEDTHIMKGEDDALSDKHGCP 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSER 160
Cdd:cd14023  151 AYVSPEILNTTGTYSGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPDHVSPKARCLIRSLLRREPSER 230

                        170
                 ....*....|..
gi 545477471 161 LTAPEILLHPWF 172
Cdd:cd14023  231 LTAPEILLHPWF 242

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCP 80
Cdd:cd14022   71 MHSFVRTCKKLREEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKDEERTRVKLESLEDAYILRGHDDSLSDKHGCP 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSER 160
Cdd:cd14022  151 AYVSPEILNTSGSYSGKAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIPETLSPKAKCLIRSILRREPSER 230

                        170
                 ....*....|..
gi 545477471 161 LTAPEILLHPWF 172
Cdd:cd14022  231 LTSQEILDHPWF 242

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 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLR----------K---FVFSTEERTQLRLESLedthimk 67
Cdd:cd14003   86 LFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLEnilldkngnlKiidFGLSNEFRGGSLLKTF------- 158

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  68 geddalsdkHGCPAYVSPEILNTTGtYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARC 147
Cdd:cd14003  159 ---------CGTPAYAAPEVLLGRK-YDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPSHLSPDARD 228

                        170       180
                 ....*....|....*....|....
gi 545477471 148 LIRSLLRREPSERLTAPEILLHPW 171
Cdd:cd14003  229 LIRRMLVVDPSKRITIEEILNHPW 252

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK 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 545477471   4 YVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKgEDDALSDKHGCPAYV 83
Cdd:cd13974  122 YVIREKRLSEREALVIFYDVVRVVEALHKKNIVHRDLKLGNMVLNKRTRKITITNFCLGKHLVS-EDDLLKDQRGSPAYI 200

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  84 SPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPE--HISPKARCLIRSLLRREPSERL 161
Cdd:cd13974  201 SPDVLSGK-PYLGKPSDMWALGVVLFTMLYGQFPFYDSIPQELFRKIKAAEYTIPEdgRVSENTVCLIRKLLVLNPQKRL 279

                 ....*.
gi 545477471 162 TAPEIL 167
Cdd:cd13974  280 TASEVL 285

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK 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 545477471   4 YVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFstEERTQLRLESLEDTHIMKgEDDALSDKHGCPAYV 83
Cdd:cd14079   92 YIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLL--DSNMNVKIADFGLSNIMR-DGEFLKTSCGSPNYA 168

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  84 SPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSERLTA 163
Cdd:cd14079  169 APEVISGK-LYAGPEVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSGIYTIPSHLSPGARDLIKRMLVVDPLKRITI 247

                 ....*....
gi 545477471 164 PEILLHPWF 172
Cdd:cd14079  248 PEIRQHPWF 256

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 545477471   3 SYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALSDKHGCPAY 82
Cdd:cd14663   89 SKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALSEQFRQDGLLHTTCGTPNY 168

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  83 VSPEILNTTGtYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREPSERLT 162
Cdd:cd14663  169 VAPEVLARRG-YDGAKADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEFEYPRWFSPGAKSLIKRILDPNPSTRIT 247

                 ....*....
gi 545477471 163 APEILLHPW 171
Cdd:cd14663  248 VEQIMASPW 256

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; 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. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. 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. The NUAK 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 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVfsteertqlrlesLEDTHIMKGEDDALSDKH--- 77
Cdd:cd14073   88 LYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENIL-------------LDQNGNAKIADFGLSNLYskd 154

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  78 -------GCPAYVSPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISpKARCLIR 150
Cdd:cd14073  155 kllqtfcGSPLYASPEIVNGT-PYQGPEVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQISSGDYREPTQPS-DASGLIR 232

                        170       180
                 ....*....|....*....|.
gi 545477471 151 SLLRREPSERLTAPEILLHPW 171
Cdd:cd14073  233 WMLTVNPKRRATIEDIANHWW 253

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   8 RKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLrleslED---THIMKGEDDALSDKHGCPAYVS 84
Cdd:cd14008  102 VPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKI-----SDfgvSEMFEDGNDTLQKTAGTPAFLA 176

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  85 PEILNTT-GTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQ--FCIPEHISPKARCLIRSLLRREPSERL 161
Cdd:cd14008  177 PELCDGDsKTYSGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNdeFPIPPELSPELKDLLRRMLEKDPEKRI 256

                        170
                 ....*....|.
gi 545477471 162 TAPEILLHPWF 172
Cdd:cd14008  257 TLKEIKEHPWV 267

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-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 545477471   4 YVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLK-------------LRKFVFSTeertqlrlesledtHIMKGED 70
Cdd:cd14080   92 YIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKcenilldsnnnvkLSDFGFAR--------------LCPDDDG 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  71 DALSDKH-GCPAYVSPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIP---EHISPKAR 146
Cdd:cd14080  158 DVLSKTFcGSAAYAAPEILQGI-PYDPKKYDIWSLGVILYIMLCGSMPFDDSNIKKMLKDQQNRKVRFPssvKKLSPECK 236

                        170       180
                 ....*....|....*....|....*.
gi 545477471 147 CLIRSLLRREPSERLTAPEILLHPWF 172
Cdd:cd14080  237 DLIDQLLEPDPTKRATIEEILNHPWL 262

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora 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 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIV-------------LGDLKLRKFVFSTEERTQLRLESLedthimk 67
Cdd:cd14007   87 LYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIhrdikpenillgsNGELKLADFGWSVHAPSNRRKTFC------- 159

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  68 geddalsdkhGCPAYVSPEILNttGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARC 147
Cdd:cd14007  160 ----------GTLDYLPPEMVE--GKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPSSVSPEAKD 227

                        170       180
                 ....*....|....*....|....
gi 545477471 148 LIRSLLRREPSERLTAPEILLHPW 171
Cdd:cd14007  228 LISKLLQKDPSKRLSLEQVLNHPW 251

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-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 545477471   3 SYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERtqLRLESL---EDTHIMKGEDDALSDKH-G 78
Cdd:cd14162   89 DYIRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNN--LKITDFgfaRGVMKTKDGKPKLSETYcG 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  79 CPAYVSPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRG-QFCIPEHISPKARCLIRSLLRREP 157
Cdd:cd14162  167 SYAYASPEILRGI-PYDPFLSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQRRvVFPKNPTVSEECKDLILRMLSPVK 245

                        170
                 ....*....|....*
gi 545477471 158 sERLTAPEILLHPWF 172
Cdd:cd14162  246 -KRITIEEIKRDPWF 259

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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 AMP-activated protein kinase (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 CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   5 VRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSteERTQLRLESLEDTHIMKGEDDALSDKHGCPAYVS 84
Cdd:cd14118  106 VPTDNPLSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLG--DDGHVKIADFGVSNEFEGDDALLSSTAGTPAFMA 183

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  85 PEILNTTGT-YSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEH--ISPKARCLIRSLLRREPSERL 161
Cdd:cd14118  184 PEALSESRKkFSGKALDIWAMGVTLYCFVFGRCPFEDDHILGLHEKIKTDPVVFPDDpvVSEQLKDLILRMLDKNPSERI 263

                        170
                 ....*....|
gi 545477471 162 TAPEILLHPW 171
Cdd:cd14118  264 TLPEIKEHPW 273

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQL---RLESLEDthimkgEDDALSDKH 77
Cdd:cd14077  100 LLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIidfGLSNLYD------PRRLLRTFC 173

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  78 GCPAYVSPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISPKARCLIRSLLRREP 157
Cdd:cd14077  174 GSLYFAAPELLQAQ-PYTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPSYLSSECKSLISRMLVVDP 252

                        170
                 ....*....|....
gi 545477471 158 SERLTAPEILLHPW 171
Cdd:cd14077  253 KKRATLEQVLNHPW 266

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 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. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. 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 545477471  10 RLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESL--EDTHIMKGEDDALSdkhGCPAYVSPEI 87
Cdd:cd14665   92 RFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPRLKICDFgySKSSVLHSQPKSTV---GTPAYIAPEV 168

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  88 LnTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSK----IRRGQFCIPE--HISPKARCLIRSLLRREPSERL 161
Cdd:cd14665  169 L-LKKEYDGKIADVWSCGVTLYVMLVGAYPFEDPEEPRNFRKtiqrILSVQYSIPDyvHISPECRHLISRIFVADPATRI 247

                        170
                 ....*....|
gi 545477471 162 TAPEILLHPW 171
Cdd:cd14665  248 TIPEIRNHEW 257

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 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 545477471   4 YVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDThIMKGEDDALSDKHGCPAYV 83
Cdd:cd14076   96 YILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANT-FDHFNGDLMSTSCGSPCYA 174

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  84 SPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFhDSDPS--------ALFSKIRRGQFCIPEHISPKARCLIRSLLRR 155
Cdd:cd14076  175 APELVVSDSMYAGRKADIWSCGVILYAMLAGYLPF-DDDPHnpngdnvpRLYRYICNTPLIFPEYVTPKARDLLRRILVP 253

                        170
                 ....*....|....*.
gi 545477471 156 EPSERLTAPEILLHPW 171
Cdd:cd14076  254 NPRKRIRLSAIMRHAW 269

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 545477471   1 MHSYVRSRKRLREEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFstEERTQLRLESLEDTHIMKGeDDALSDKHGCP 80
Cdd:cd14161   89 LYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILL--DANGNIKIADFGLSNLYNQ-DKFLQTYCGSP 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 545477471  81 AYVSPEILNTTgTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPEHISpKARCLIRSLLRREPSER 160
Cdd:cd14161  166 LYASPEIVNGR-PYIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSGAYREPTKPS-DACGLIRWLLMVNPERR 243

                        170
                 ....*....|.
gi 545477471 161 LTAPEILLHPW 171
Cdd:cd14161  244 ATLEDVASHWW 254