Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966  434 KSVSQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCLL---------LWLSVQNQEFEINKDGIPKVDQF--HLDD 502
Cdd:pfam00069 109 EGLESGSSLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILyelltgkppFPGINGNEIYELIIDQPYAFPELpsNLSE 188

                          90       100
                  ....*....|....*....|....*
gi 193785966  503 KVKSLLCSLICYRSS--MTAEQVLN 525
Cdd:pfam00069 189 EAKDLLKKLLKKDPSkrLTATQALQ 213

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 193785966 359 DPMAYLMVPYYPRANLNAV-QANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFTKSV- 436
Cdd:cd14014   72 DGRPYIVMEYVEGGSLADLlRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALg 151

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 193785966 437 -SQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWL 478
Cdd:cd14014  152 dSGLTQTGSVLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYEL 194

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 377 VQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVfaLNREQGI--VGDFDFTKSVSQrASV---NMMVGDLSL 451
Cdd:NF033483  98 IREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNI--LITKDGRvkVTDFGIARALSS-TTMtqtNSVLGTVHY 174

                         90       100
                 ....*....|....*....|....
gi 193785966 452 MSPELKMGKPASPGSDLYAYGCLL 475
Cdd:NF033483 175 LSPEQARGGTVDARSDIYSLGIVL 198

serine/threonine kinase US3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 361 MAYLMVPYYpRANLN---AVQANMPLNseETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFD---FTK 434
Cdd:PHA03212 157 FTCLILPRY-KTDLYcylAAKRNIAIC--DILAIERSVLRAIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGaacFPV 233

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 193785966 435 SVSQRASVNmMVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWLSV-QNQEFEinKDGI 492
Cdd:PHA03212 234 DINANKYYG-WAGTIATNAPELLARDPYGPAVDIWSAGIVLFEMATcHDSLFE--KDGL 289

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 193785966 359 DPMAYLMVPYYPRANLNAV-QANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFTKSV- 436
Cdd:cd14014   72 DGRPYIVMEYVEGGSLADLlRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALg 151

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 193785966 437 -SQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWL 478
Cdd:cd14014  152 dSGLTQTGSVLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYEL 194

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 352 FLFLCKSDPMAYLMVPYYPRANLNAV--QANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGD 429
Cdd:cd13999   55 FIGACLSPPPLCIVTEYMPGGSLYDLlhKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIAD 134

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 193785966 430 FDFTKSVSQRASVNM-MVGDLSLMSPELKMGKPASPGSDLYAYGcLLLW 477
Cdd:cd13999  135 FGLSRIKNSTTEKMTgVVGTPRWMAPEVLRGEPYTEKADVYSFG-IVLW 182

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 352 FLFLCKSDPMAYLMVPYYPRANLNAV--QANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFaLNREQGIV-G 428
Cdd:cd00180   56 LYDVFETENFLYLVMEYCEGGSLKDLlkENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENIL-LDSDGTVKlA 134

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 193785966 429 DFDFTKSV-SQRASVNMMVGDLSL--MSPELKMGKPASPGSDLYAYGCLLLWLS 479
Cdd:cd00180  135 DFGLAKDLdSDDSLLKTTGGTTPPyyAPPELLGGRYYGPKVDIWSLGVILYELE 188

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 354 FLCKSDPMAyLMVPYYPRANL----NAVQANMPLNSEETLKVMKGVAQGLHTLHKAD---IIHGSLHQNNVFaLNRE-QG 425
Cdd:cd14066   58 YCLESDEKL-LVYEYMPNGSLedrlHCHKGSPPLPWPQRLKIAKGIARGLEYLHEECpppIIHGDIKSSNIL-LDEDfEP 135

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 193785966 426 IVGDFDFTK---SVSQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCLLL 476
Cdd:cd14066  136 KLTDFGLARlipPSESVSKTSAVKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLL 189

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 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 193785966 352 FLFLCKSDPMAYLMVPYYPRANL-NAVQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDF 430
Cdd:cd14059   46 FKGVCTQAPCYCILMEYCPYGQLyEVLRAGREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDF 125

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 193785966 431 DFTKSVSQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGcLLLW 477
Cdd:cd14059  126 GTSKELSEKSTKMSFAGTVAWMAPEVIRNEPCSEKVDIWSFG-VVLW 171

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which 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. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf 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 193785966 386 EETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALnrEQGIV--GDFDFTkSVSQRASVNMMV----GDLSLMSPE-LKM 458
Cdd:cd14062   89 LQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLH--EDLTVkiGDFGLA-TVKTRWSGSQQFeqptGSILWMAPEvIRM 165

                         90       100
                 ....*....|....*....|..
gi 193785966 459 --GKPASPGSDLYAYGCLLLWL 478
Cdd:cd14062  166 qdENPYSFQSDVYAFGIVLYEL 187

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. 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. The ULK4 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 193785966 395 VAQGLHTLHKADIIHGSLHQNNV------------FALNREQG-----IVGDFDFTKSVSQRASVNMMVGDLSLMSPELK 457
Cdd:cd14010  103 LVRGLHYIHSKGIIYCDLKPSNIlldgngtlklsdFGLARREGeilkeLFGQFSDEGNVNKVSKKQAKRGTPYYMAPELF 182

                         90
                 ....*....|....*...
gi 193785966 458 MGKPASPGSDLYAYGCLL 475
Cdd:cd14010  183 QGGVHSFASDLWALGCVL 200

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 193785966 376 AVQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFTKSVSQRAS-VNMMVGDLSLMSP 454
Cdd:cd08221   91 AQQKNQLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSmAESIVGTPYYMSP 170

                         90       100
                 ....*....|....*....|.
gi 193785966 455 ELKMGKPASPGSDLYAYGCLL 475
Cdd:cd08221  171 ELVQGVKYNFKSDIWAVGCVL 191

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates 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. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf 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 193785966 389 LKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFTkSVSQRASVNMMV----GDLSLMSPE---LKMGKP 461
Cdd:cd14150   99 IDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLA-TVKTRWSGSQQVeqpsGSILWMAPEvirMQDTNP 177

                         90
                 ....*....|....
gi 193785966 462 ASPGSDLYAYGCLL 475
Cdd:cd14150  178 YSFQSDVYAYGVVL 191

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-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 193785966 352 FLFLCKSDPMAYLMVPYYPRANLNAVQANM--PLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNN--VFALNREQ-GI 426
Cdd:cd14065   53 FIGVCVKDNKLNFITEYVNGGTLEELLKSMdeQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNclVREANRGRnAV 132

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 193785966 427 VGDF-------DFTKSVSQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCLL 475
Cdd:cd14065  133 VADFglarempDEKTKKPDRKKRLTVVGSPYWMAPEMLRGESYDEKVDVFSFGIVL 188

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 193785966 363 YLMVPYYPRANL-NAVQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVfaLNREQGIVGDFDFTKSVSQRAS 441
Cdd:cd14007   76 YLILEYAPNGELyKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENI--LLGSNGELKLADFGWSVHAPSN 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 442 VNM-MVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWLSVQNQEFEIN-----KDGIPKVDqFHLDDKV----KSLLCSL 511
Cdd:cd14007  154 RRKtFCGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKshqetYKRIQNVD-IKFPSSVspeaKDLISKL 232

                        170
                 ....*....|....*.
gi 193785966 512 ICYRSS--MTAEQVLN 525
Cdd:cd14007  233 LQKDPSkrLSLEQVLN 248

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates 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. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf 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 193785966 387 ETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFTkSVSQRAS----VNMMVGDLSLMSPE---LKMG 459
Cdd:cd14149  109 QLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLA-TVKSRWSgsqqVEQPTGSILWMAPEvirMQDN 187

                         90
                 ....*....|....*....
gi 193785966 460 KPASPGSDLYAYGCLLLWL 478
Cdd:cd14149  188 NPFSFQSDVYSYGIVLYEL 206

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 193785966 395 VAQGLHTLHKADIIHGSLHQNNVfaLNREQGIV--GDFDFTKSVSQRASVNM---MVGDLSLMSPELKMGKPASPGSDLY 469
Cdd:cd06606  108 ILEGLEYLHSNGIVHRDIKGANI--LVDSDGVVklADFGCAKRLAEIATGEGtksLRGTPYWMAPEVIRGEGYGRAADIW 185

                 ....*..
gi 193785966 470 AYGCLLL 476
Cdd:cd06606  186 SLGCTVI 192

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 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 193785966 377 VQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVG--DFDFTKSVSQRASVNMMVGDLSLMSP 454
Cdd:cd14191   91 IDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKliDFGLARRLENAGSLKVLFGTPEFVAP 170

                         90       100
                 ....*....|....*....|....
gi 193785966 455 ELKMGKPASPGSDLYAYG--CLLL 476
Cdd:cd14191  171 EVINYEPIGYATDMWSIGviCYIL 194

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein 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 193785966 356 CKSDPMAYLMVPYYPRANLNAVQAN--MPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFDFT 433
Cdd:cd14045   71 CIEVPNVAIITEYCPKGSLNDVLLNedIPLNWGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLT 150

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 193785966 434 KSVSQRASVNMMVGDLSLM----SPE---LKMGKPASPGsDLYAYGCLLLWLSVQNQ 483
Cdd:cd14045  151 TYRKEDGSENASGYQQRLMqvylPPEnhsNTDTEPTQAT-DVYSYAIILLEIATRND 206

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 348 LPLIFLFLCKSDPMaylmvpyypRANLNAVQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIV 427
Cdd:cd14038   72 LPLLAMEYCQGGDL---------RKYLNQFENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQGEQRLI 142

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 193785966 428 G---DFDFTKSVSQRASVNMMVGDLSLMSPELKMGKPASPGSDLYAYGCL 474
Cdd:cd14038  143 HkiiDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTL 192

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; 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. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 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 193785966 351 IFLFLCKSDPMAYLMvpyypranlnavQANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDF 430
Cdd:cd14189   78 IFLELCSRKSLAHIW------------KARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDF 145

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 193785966 431 DFT---KSVSQRASVnmMVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWLSVQNQEFE 486
Cdd:cd14189  146 GLAarlEPPEQRKKT--ICGTPNYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFE 202

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 193785966 382 PLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVfaLNREQGIVGDFDFTKSV------SQRASVNMMVGDLSLMSPE 455
Cdd:cd13979   99 PLPLAHRILISLDIARALRFCHSHGIVHLDVKPANI--LISEQGVCKLCDFGCSVklgegnEVGTPRSHIGGTYTYRAPE 176

                         90       100
                 ....*....|....*....|..
gi 193785966 456 LKMGKPASPGSDLYAYGcLLLW 477
Cdd:cd13979  177 LLKGERVTPKADIYSFG-ITLW 197

serine/threonine kinase US3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193785966 361 MAYLMVPYYpRANLN---AVQANMPLNseETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFALNREQGIVGDFD---FTK 434
Cdd:PHA03212 157 FTCLILPRY-KTDLYcylAAKRNIAIC--DILAIERSVLRAIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGaacFPV 233

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 193785966 435 SVSQRASVNmMVGDLSLMSPELKMGKPASPGSDLYAYGCLLLWLSV-QNQEFEinKDGI 492
Cdd:PHA03212 234 DINANKYYG-WAGTIATNAPELLARDPYGPAVDIWSAGIVLFEMATcHDSLFE--KDGL 289

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 193785966 395 VAQGLHTLHKADIIHGSLHQNNVF-ALNREQGIVGDFDFTKSVSQRASV-NMMVGDLSLMSPELKMGKPASPGSDLYAYG 472
Cdd:cd08225  110 ISLGLKHIHDRKILHRDIKSQNIFlSKNGMVAKLGDFGIARQLNDSMELaYTCVGTPYYLSPEICQNRPYNNKTDIWSLG 189

                         90
                 ....*....|....*.
gi 193785966 473 CLLLWLSVQNQEFEIN 488
Cdd:cd08225  190 CVLYELCTLKHPFEGN 205

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein 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 193785966 395 VAQGLHTLH-KADIIHGSLHQNNVFaLNrEQG--IVGDFDFTKSVSQRASVNMMVG------------DLSLMSPELKMG 459
Cdd:cd14011  123 ISEALSFLHnDVKLVHGNICPESVV-IN-SNGewKLAGFDFCISSEQATDQFPYFReydpnlpplaqpNLNYLAPEYILS 200

                         90
                 ....*....|....*.
gi 193785966 460 KPASPGSDLYAYGCLL 475
Cdd:cd14011  201 KTCDPASDMFSLGVLI 216

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK 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 193785966 378 QANMPLNSEETLKVMKGVAQGLHTLHKADIIHGSLHQNNVFaLNREQGI-VGDFDF----TKSVSQRASvnmMVGDLSLM 452
Cdd:cd06614   89 QNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNIL-LSKDGSVkLADFGFaaqlTKEKSKRNS---VVGTPYWM 164

                         90       100
                 ....*....|....*....|
gi 193785966 453 SPELKMGKPASPGSDLYAYG 472
Cdd:cd06614  165 APEVIKRKDYGPKVDIWSLG 184

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 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 193785966 385 SEETLKV-MKGVAQGLHTLHKADIIHGSLHQNNV---FALNREQGIVG------DFDFTKSVSQRASVNMMVGDLSLMSP 454
Cdd:cd14201  103 SEDTIRVfLQQIAAAMRILHSKGIIHRDLKPQNIllsYASRKKSSVSGirikiaDFGFARYLQSNMMAATLCGSPMYMAP 182