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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPSLE 82
Cdd:cd14100  167 GTRVYSPPEWIRFHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIKWCLALRPSDRPSFE 246

                 ....*...
gi 677477730  83 DIFNHSWL 90
Cdd:cd14100  247 DIQNHPWM 254

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPSLE 82
Cdd:cd14100  167 GTRVYSPPEWIRFHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIKWCLALRPSDRPSFE 246

                 ....*...
gi 677477730  83 DIFNHSWL 90
Cdd:cd14100  247 DIQNHPWM 254

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677477730     2 VGTRVYSPPEWIRYHRYhGRSATIWSLGVLLYDMVCGDVPFEQDDD-------IVQGQLFFRRR---VSLECQDLIRWCL 71
Cdd:smart00220 157 VGTPEYMAPEVLLGKGY-GKAVDIWSLGVILYELLTGKPPFPGDDQllelfkkIGKPKPPFPPPewdISPEAKDLIRKLL 235

                           90
                   ....*....|....*....
gi 677477730    72 SMRPSDRPSLEDIFNHSWL 90
Cdd:smart00220 236 VKDPEKRLTAEEALQHPFF 254

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677477730   3 GTRVYSPPEWIRyHRYHGRSATIWSLGVLLYDMVCG------DVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPS 76
Cdd:PTZ00263 177 GTPEYLAPEVIQ-SKGHGKAVDWWTMGVLLYEFIAGyppffdDTPFRIYEKILAGRLKFPNWFDGRARDLVKGLLQTDHT 255

                         90
                 ....*....|....*...
gi 677477730  77 DR-----PSLEDIFNHSW 89
Cdd:PTZ00263 256 KRlgtlkGGVADVKNHPY 273

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPSLE 82
Cdd:cd14100  167 GTRVYSPPEWIRFHRYHGRSAAVWSLGILLYDMVCGDIPFEHDEEIIRGQVFFRQRVSSECQHLIKWCLALRPSDRPSFE 246

                 ....*...
gi 677477730  83 DIFNHSWL 90
Cdd:cd14100  247 DIQNHPWM 254

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM 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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPSLE 82
Cdd:cd14005  168 GTRVYSPPEWIRHGRYHGRPATVWSLGILLYDMLCGDIPFENDEQILRGNVLFRPRLSKECCDLISRCLQFDPSKRPSLE 247

                 ....*...
gi 677477730  83 DIFNHSWL 90
Cdd:cd14005  248 QILSHPWF 255

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 677477730   1 PVGTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDD------IVQGQLFFRRRVSLECQDLIRWCLSMR 74
Cdd:cd14003  158 FCGTPAYAAPEVLLGRKYDGPKADVWSLGVILYAMLTGYLPFDDDNDsklfrkILKGKYPIPSHLSPDARDLIRRMLVVD 237

                         90
                 ....*....|....*
gi 677477730  75 PSDRPSLEDIFNHSW 89
Cdd:cd14003  238 PSKRITIEEILNHPW 252

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677477730     2 VGTRVYSPPEWIRYHRYhGRSATIWSLGVLLYDMVCGDVPFEQDDD-------IVQGQLFFRRR---VSLECQDLIRWCL 71
Cdd:smart00220 157 VGTPEYMAPEVLLGKGY-GKAVDIWSLGVILYELLTGKPPFPGDDQllelfkkIGKPKPPFPPPewdISPEAKDLIRKLL 235

                           90
                   ....*....|....*....
gi 677477730    72 SMRPSDRPSLEDIFNHSWL 90
Cdd:smart00220 236 VKDPEKRLTAEEALQHPFF 254

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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRRV---SLECQDLIRWCLSM 73
Cdd:cd14080  166 GSAAYAAPEILQGIPYDPKKYDIWSLGVILYIMLCGSMPFDDSNikkmlkDQQNRKVRFPSSVkklSPECKDLIDQLLEP 245

                         90
                 ....*....|....*..
gi 677477730  74 RPSDRPSLEDIFNHSWL 90
Cdd:cd14080  246 DPTKRATIEEILNHPWL 262

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 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 677477730   7 YSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDD------IVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPS 80
Cdd:cd14081  166 YACPEVIKGEKYDGRKADIWSCGVILYALLVGALPFDDDNLrqllekVKRGVFHIPHFISPDAQDLLRRMLEVNPEKRIT 245

                         90
                 ....*....|
gi 677477730  81 LEDIFNHSWL 90
Cdd:cd14081  246 IEEIKKHPWF 255

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK 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 677477730   2 VGTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDDIVQGQLFFRRRVSLECQDLIRWCLSMRPSDRPSL 81
Cdd:cd14004  168 VGTIDYAAPEVLRGNPYGGKEQDIWALGVLLYTLVFKENPFYNIEEILEADLRIPYAVSEDLIDLISRMLNRDVGDRPTI 247

                 ....*....
gi 677477730  82 EDIFNHSWL 90
Cdd:cd14004  248 EELLTDPWL 256

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 677477730   3 GTRVYSPPEWIRYHRY--HGRSATIWSLGVLLYDMVCGDVPF-------EQDDDIVQGQLFF----RRRVSLECQDLIRW 69
Cdd:cd14084  175 GTPTYLAPEVLRSFGTegYTRAVDCWSLGVILFICLSGYPPFseeytqmSLKEQILSGKYTFipkaWKNVSEEAKDLVKK 254

                         90       100
                 ....*....|....*....|.
gi 677477730  70 CLSMRPSDRPSLEDIFNHSWL 90
Cdd:cd14084  255 MLVVDPSRRPSIEEALEHPWL 275

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRR--VSLECQDLIRWCLSMR 74
Cdd:cd14099  163 GTPNYIAPEVLEKKKGHSFEVDIWSLGVILYTLLVGKPPFETSDvketykRIKKNEYSFPSHlsISDEAKDLIRSMLQPD 242

                         90
                 ....*....|....*.
gi 677477730  75 PSDRPSLEDIFNHSWL 90
Cdd:cd14099  243 PTKRPSLDEILSHPFF 258

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 677477730   2 VGTRVYSPPE--WIRYHRYHGRSATIWSLGVLLYDMVCGDVPF------EQDDDIVQGQLFFRRR--VSLECQDLIRWCL 71
Cdd:cd14008  169 AGTPAFLAPElcDGDSKTYSGKAADIWALGVTLYCLVFGRLPFngdnilELYEAIQNQNDEFPIPpeLSPELKDLLRRML 248

                         90
                 ....*....|....*....
gi 677477730  72 SMRPSDRPSLEDIFNHSWL 90
Cdd:cd14008  249 EKDPEKRITLKEIKEHPWV 267

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 677477730   3 GTRVYSPPEWIR-YHRYHGRSATIWSLGVLLYDMVCGDVPFEQD------DDIVQGQLFFRRRVSLECQDLIRWCLSMRP 75
Cdd:cd14119  161 GSPAFQPPEIANgQDSFSGFKVDIWSAGVTLYNMTTGKYPFEGDniyklfENIGKGEYTIPDDVDPDLQDLLRGMLEKDP 240

                         90
                 ....*....|....*
gi 677477730  76 SDRPSLEDIFNHSWL 90
Cdd:cd14119  241 EKRFTIEQIRQHPWF 255

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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRRVSLECQDLIRWCLSMRPS 76
Cdd:cd14077  174 GSLYFAAPELLQAQPYTGPEVDVWSFGVVLYVLVCGKVPFDDENmpalhaKIKKGKVEYPSYLSSECKSLISRMLVVDPK 253

                         90
                 ....*....|....
gi 677477730  77 DRPSLEDIFNHSWL 90
Cdd:cd14077  254 KRATLEQVLNHPWM 267

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK 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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQD------DDIVQGQL---FFrrrVSLECQDLIRWCLSM 73
Cdd:cd14071  160 GSPPYAAPEVFEGKEYEGPQLDIWSLGVVLYVLVCGALPFDGStlqtlrDRVLSGRFripFF---MSTDCEHLIRRMLVL 236

                         90
                 ....*....|....*..
gi 677477730  74 RPSDRPSLEDIFNHSWL 90
Cdd:cd14071  237 DPSKRLTIEQIKKHKWM 253

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK 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 677477730   3 GTRVYSPPEWIRYHRYHGRsATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFR----RRVSLECQDLIRWCLS 72
Cdd:cd14009  156 GSPLYMAPEILQFQKYDAK-ADLWSVGAILFEMLVGKPPFRGSNhvqllrNIERSDAVIPfpiaAQLSPDCKDLLRRLLR 234

                         90
                 ....*....|....*..
gi 677477730  73 MRPSDRPSLEDIFNHSW 89
Cdd:cd14009  235 RDPAERISFEEFFAHPF 251

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK 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 677477730   2 VGTRVYSPPEWIRyHRYHGRSATIWSLGVLLYDMVCGDVPFEQDDD--------IVQG--QLFFRRRVSLECQDLIRWCL 71
Cdd:cd05572  153 CGTPEYVAPEIIL-NKGYDFSVDYWSLGILLYELLTGRPPFGGDDEdpmkiyniILKGidKIEFPKYIDKNAKNLIKQLL 231

                         90       100
                 ....*....|....*....|...
gi 677477730  72 SMRPSDR-----PSLEDIFNHSW 89
Cdd:cd05572  232 RRNPEERlgylkGGIRDIKKHKW 254

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK 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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFeqDDD--------IVQGQLFFRRRVSLECQDLIRWCLSMR 74
Cdd:cd14078  164 GSPAYAAPELIQGKPYIGSEADVWSMGVLLYALLCGFLPF--DDDnvmalyrkIQSGKYEEPEWLSPSSKLLLDQMLQVD 241

                         90
                 ....*....|....*.
gi 677477730  75 PSDRPSLEDIFNHSWL 90
Cdd:cd14078  242 PKKRITVKELLNHPWV 257

Catalytic domain of testis-specific serine/threonine kinase 3 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. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEqDDDIVQGQLFFRRRVSL--------ECQDLIRWCLSMR 74
Cdd:cd14163  163 GSTAYAAPEVLQGVPHDSRKGDIWSMGVVLYVMLCAQLPFD-DTDIPKMLCQQQKGVSLpghlgvsrTCQDLLKRLLEPD 241

                         90
                 ....*....|....*.
gi 677477730  75 PSDRPSLEDIFNHSWL 90
Cdd:cd14163  242 MVLRPSIEEVSWHPWL 257

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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRRVSLECqDLIRWCLSMRPS 76
Cdd:cd14161  163 GSPLYASPEIVNGRPYIGPEVDSWSLGVLLYILVHGTMPFDGHDykilvkQISSGAYREPTKPSDAC-GLIRWLLMVNPE 241

                         90
                 ....*....|....
gi 677477730  77 DRPSLEDIFNHSWL 90
Cdd:cd14161  242 RRATLEDVASHWWV 255

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It 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 677477730   2 VGTRVYSPPEWIRYHRYHGRSaTIWSLGVLLYDMVCGDVPFE---QDD---DIVQGQlfFRR---RVSLECQDLIRWCLS 72
Cdd:cd08217  171 VGTPYYMSPELLNEQSYDEKS-DIWSLGCLIYELCALHPPFQaanQLElakKIKEGK--FPRipsRYSSELNEVIKSMLN 247

                         90
                 ....*....|....*.
gi 677477730  73 MRPSDRPSLEDIFNHS 88
Cdd:cd08217  248 VDPDKRPSVEELLQLP 263

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 677477730   1 PVGTRVYSPPEWIRYHRYHGRSaTIWSLGVLLYDMVCGDVPFEQDD--DIVQGQLF--------FRRRVSLECQDLIRWC 70
Cdd:COG0515  168 VVGTPGYMAPEQARGEPVDPRS-DVYSLGVTLYELLTGRPPFDGDSpaELLRAHLRepppppseLRPDLPPALDAIVLRA 246

                         90
                 ....*....|
gi 677477730  71 LSMRPSDRPS 80
Cdd:COG0515  247 LAKDPEERYQ 256

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK 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 677477730   1 PVGTRVYSPPEWIRYHRYHgRSATIWSLGVLLYDMVCGDVPFEQDDD----------IVQGQLFFR----RRVSLECQDL 66
Cdd:cd14089  162 PCYTPYYVAPEVLGPEKYD-KSCDMWSLGVIMYILLCGYPPFYSNHGlaispgmkkrIRNGQYEFPnpewSNVSEEAKDL 240

                         90       100
                 ....*....|....*....|...
gi 677477730  67 IRWCLSMRPSDRPSLEDIFNHSW 89
Cdd:cd14089  241 IRGLLKTDPSERLTIEEVMNHPW 263

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, 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. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK 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 677477730   2 VGTRVYSPPEWIRYHRYhGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRR----VSLECQDLIRWCL 71
Cdd:cd14106  171 LGTPDYVAPEILSYEPI-SLATDMWSIGVLTYVLLTGHSPFGGDDkqetflNISQCNLDFPEElfkdVSPLAIDFIKRLL 249

                         90
                 ....*....|....*....
gi 677477730  72 SMRPSDRPSLEDIFNHSWL 90
Cdd:cd14106  250 VKDPEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC 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 677477730   3 GTRVYSPPEWIRYHRYhGRSATIWSLGVLLYDMVCGDVPFEQDDD------IVQGQLFFRRRVSLECQDLIRWCLSMRPS 76
Cdd:cd05570  158 GTPDYIAPEILREQDY-GFSVDWWALGVLLYEMLAGQSPFEGDDEdelfeaILNDEVLYPRWLSREAVSILKGLLTKDPA 236

                         90
                 ....*....|....*.
gi 677477730  77 DR----PSLE-DIFNH 87
Cdd:cd05570  237 RRlgcgPKGEaDIKAH 252

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 677477730  25 IWSLGVLLYDMVCGDVPFEQD---DDIVQ---------GQLFFRRRVSLECQDLIRWCLSMRPSDRPSLEDIFNH 87
Cdd:cd13990  203 VWSVGVIFYQMLYGRKPFGHNqsqEAILEentilkateVEFPSKPVVSSEAKDFIRRCLTYRKEDRPDVLQLAND 277

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB 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 677477730   3 GTRVYSPPEWIRYHR-YHGRSATIWSLGVLLYDMVCGDVPFEQDDD------IVQGQLFFRRRVSLECQDLIRWCLSMRP 75
Cdd:cd13976  148 GCPAYVSPEILNSGAtYSGKAADVWSLGVILYTMLVGRYPFHDSEPaslfakIRRGQFAIPETLSPRARCLIRSLLRREP 227

                         90
                 ....*....|....*
gi 677477730  76 SDRPSLEDIFNHSWL 90
Cdd:cd13976  228 SERLTAEDILLHPWL 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 677477730   3 GTRVYSPPEWIRYH-RYHGRSATIWSLGVLLYDMVCGDVPFEQDD------DIVQGQLFFRRRVSLECQDLIRWCLSMRP 75
Cdd:cd14023  148 GCPAYVSPEILNTTgTYSGKSADVWSLGVMLYTLLVGRYPFHDSDpsalfsKIRRGQFCIPDHVSPKARCLIRSLLRREP 227

                         90
                 ....*....|....*
gi 677477730  76 SDRPSLEDIFNHSWL 90
Cdd:cd14023  228 SERLTAPEILLHPWF 242

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 677477730   3 GTRVYSPPEWIRYHRYHGRSATIWSLGVLLYDMVCGDVPFEqDDDIvqgQLFFRR----------RVSLECQDLIRWCLS 72
Cdd:cd14079  163 GSPNYAAPEVISGKLYAGPEVDVWSCGVILYALLCGSLPFD-DEHI---PNLFKKiksgiytipsHLSPGARDLIKRMLV 238

                         90
                 ....*....|....*...
gi 677477730  73 MRPSDRPSLEDIFNHSWL 90
Cdd:cd14079  239 VDPLKRITIPEIRQHPWF 256