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 922580708  57 LQLQKDLNKQRKLL--FDLLPELSNPsHIARLVDVGYDDDFKFLIFE--DFGmDFLTLFDEFGPVLNPATLFLISYFTFN 132
Cdd:cd00180   26 IPKEKLKKLLEELLreIEILKKLNHP-NIVKLYDVFETENFLYLVMEycEGG-SLKDLLKENKGPLSEEEALSILRQLLS 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 922580708 133 AIKELHSFDIVHLDIRPSSFSVNqHPFNIKITDY--SRCMTRK 173
Cdd:cd00180  104 ALEYLHSNGIIHRDLKPENILLD-SDGTVKLADFglAKDLDSD 145

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 922580708 134 IKELHSFDIVHLDIRPSS-FSVNQHPFNIKITDYSRCMTRKPEMKVPDD-ARPDSFSPRVFHQkdaqfdEFVDF--EAW- 208
Cdd:cd14192  115 VHYLHQHYILHLDLKPENiLCVNSTGNQIKIIDFGLARRYKPREKLKVNfGTPEFLAPEVVNY------DFVSFptDMWs 188

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 922580708 209 --VYTMLFLCTVEklPWFG--DAENM---LRLKEEFFNDPLNYLYDGCADFV 253
Cdd:cd14192  189 vgVITYMLLSGLS--PFLGetDAETMnniVNCKWDFDAEAFENLSEEAKDFI 238

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 922580708  57 LQLQKDLNKQRKLL--FDLLPELSNPsHIARLVDVGYDDDFKFLIFE--DFGmDFLTLFDEFGPVLNPATLFLISYFTFN 132
Cdd:cd00180   26 IPKEKLKKLLEELLreIEILKKLNHP-NIVKLYDVFETENFLYLVMEycEGG-SLKDLLKENKGPLSEEEALSILRQLLS 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 922580708 133 AIKELHSFDIVHLDIRPSSFSVNqHPFNIKITDY--SRCMTRK 173
Cdd:cd00180  104 ALEYLHSNGIIHRDLKPENILLD-SDGTVKLADFglAKDLDSD 145

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  77 LSNPsHIARLVDVGYDDDFKFLIFEDF-GMDFLTLFDEFGPvLNPATLflISYFT--FNAIKELHSFDIVHLDIRPSsfs 153
Cdd:COG0515   64 LNHP-NIVRVYDVGEEDGRPYLVMEYVeGESLADLLRRRGP-LPPAEA--LRILAqlAEALAAAHAAGIVHRDIKPA--- 136

                         90       100
                 ....*....|....*....|
gi 922580708 154 vnqhpfNI--------KITD 165
Cdd:COG0515  137 ------NIlltpdgrvKLID 150

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 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 922580708 134 IKELHSFDIVHLDIRPSS-FSVNQHPFNIKITDYSRCMTRKPEMKVPDD-ARPDSFSPRVFHQkdaqfdEFVDF--EAW- 208
Cdd:cd14192  115 VHYLHQHYILHLDLKPENiLCVNSTGNQIKIIDFGLARRYKPREKLKVNfGTPEFLAPEVVNY------DFVSFptDMWs 188

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 922580708 209 --VYTMLFLCTVEklPWFG--DAENM---LRLKEEFFNDPLNYLYDGCADFV 253
Cdd:cd14192  189 vgVITYMLLSGLS--PFLGetDAETMnniVNCKWDFDAEAFENLSEEAKDFI 238

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 922580708  57 LQLQKDLNKQRKLL--FDLLPELSNPsHIARLVDVGYDDDFKFLIFE--DFGmDFLTLFDEFGPVLNPATLFLISYFTFN 132
Cdd:cd00180   26 IPKEKLKKLLEELLreIEILKKLNHP-NIVKLYDVFETENFLYLVMEycEGG-SLKDLLKENKGPLSEEEALSILRQLLS 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 922580708 133 AIKELHSFDIVHLDIRPSSFSVNqHPFNIKITDY--SRCMTRK 173
Cdd:cd00180  104 ALEYLHSNGIIHRDLKPENILLD-SDGTVKLADFglAKDLDSD 145

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-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 922580708  73 LLPELSNPsHIARLVDVGYDDDFKFLIFEDFGMDFLTLFDEFGPVLNPATLFLISYFTFNAIKELHSFDIVHLDIRPSSF 152
Cdd:cd07829   51 LLKELKHP-NIVKLLDVIHTENKLYLVFEYCDQDLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNL 129

                         90
                 ....*....|...
gi 922580708 153 SVNQHPfNIKITD 165
Cdd:cd07829  130 LINRDG-VLKLAD 141

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708    72 DLLPELSNPsHIARLVDVGYDDDFKFLIFEdF--GMDFLTLFDEFGPvLNPATLFLISYFTFNAIKELHSFDIVHLDIRP 149
Cdd:smart00220  49 KILKKLKHP-NIVRLYDVFEDEDKLYLVME-YceGGDLFDLLKKRGR-LSEDEARFYLRQILSALEYLHSKGIVHRDLKP 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708   150 SSFSVNQHPfNIKITDY--SRCMTRKPEMKvpddarpdSF-------SPRVFHQKdaQFDEFVDFeaW-----VYTMLFL 215
Cdd:smart00220 126 ENILLDEDG-HVKLADFglARQLDPGEKLT--------TFvgtpeymAPEVLLGK--GYGKAVDI--WslgviLYELLTG 192

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 922580708   216 ctveKLPWFGDAE-----NMLRLKEEFFNDPLNYLYDGCADFV 253
Cdd:smart00220 193 ----KPPFPGDDQllelfKKIGKPKPPFPPPEWDISPEAKDLI 231

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 922580708  73 LLPELSNPSH--IARLVDVGYDDDFKFLIFEDFG--MDfltLFD--EFGPVLNPatlFLISYFTFN---AIKELHSFDIV 143
Cdd:cd14004   58 ILDTLNKRSHpnIVKLLDFFEDDEFYYLVMEKHGsgMD---LFDfiERKPNMDE---KEAKYIFRQvadAVKHLHDQGIV 131

                         90       100
                 ....*....|....*....|...
gi 922580708 144 HLDIRPSSFSVNQHpFNIKITDY 166
Cdd:cd14004  132 HRDIKDENVILDGN-GTIKLIDF 153

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins (VRK1, VRK2, and VRK3) while invertebrates, specifically fruit flies and nematodes, seem to carry only a single ortholog. Mutations of VRK in Drosophila and Caenorhabditis elegans showed varying phenotypes ranging from embryonic lethality to mitotic and meiotic defects resulting in sterility. In vertebrates, VRK1 is implicated in cell cycle progression and proliferation, nuclear envelope assembly, and chromatin condensation. VRK2 is involved in modulating JNK signaling. VRK3 is an inactive pseudokinase that inhibits ERK signaling. The VRK 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 922580708  74 LPELSNPSHIARLVDVGYDDDFKFLIFEDFGMDFLTLFDEFGPVLNPATLFLISYFTFNAIKELHSFDIVHLDIRPSSFS 153
Cdd:cd14015   80 LKHLGIPRYIGSGSHEYKGEKYRFLVMPRFGRDLQKIFEKNGKRFPEKTVLQLALRILDVLEYIHENGYVHADIKASNLL 159

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708 154 V--NQHPFNIKITDY---SRCMTRkpemKVPDDARPDsfsPRVFHQKDAQF---DEFV--------DFEAWVYTML-FLC 216
Cdd:cd14015  160 LgfGKNKDQVYLVDYglaSRYCPN----GKHKEYKED---PRKAHNGTIEFtsrDAHKgvapsrrgDLEILGYNMLqWLC 232

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 922580708 217 TveKLPW---FGDAENMLRLKEEFFNDPLNYLYDGCAD---FVPLVACFIADKKLTYDT 269
Cdd:cd14015  233 G--KLPWednLKNPEYVQKQKEKYMDDIPLLLKKCFPGkdvPEELQKYLKYVASLEYEE 289

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  77 LSNPsHIARLVDVGYDDDFKFLIFEDF-GMDFLTLFDEFGPvLNPATLflISYFT--FNAIKELHSFDIVHLDIRPSsfs 153
Cdd:COG0515   64 LNHP-NIVRVYDVGEEDGRPYLVMEYVeGESLADLLRRRGP-LPPAEA--LRILAqlAEALAAAHAAGIVHRDIKPA--- 136

                         90       100
                 ....*....|....*....|
gi 922580708 154 vnqhpfNI--------KITD 165
Cdd:COG0515  137 ------NIlltpdgrvKLID 150

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  270 FMEEMNLIFSVDVMQYSDKEQPRLYTMKELEEVKKTRRAPDFYTNNAIDIAESHWHAADDSDH------------DNLRT 337
Cdd:PTZ00121 1257 FEEARMAHFARRQAAIKAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEEAKKADEakkkaeeakkkaDAAKK 1336

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  338 SDEENEQKSETKKDSCERSSAEVSSSTEQTSApmSEASSSDGRKKPKNAGKSAERKGKPAEKNPSSEKDDDGATEPMSGV 417
Cdd:PTZ00121 1337 KAEEAKKAAEAAKAEAEAAADEAEAAEEKAEA--AEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKKAA 1414

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 922580708  418 ERRSTPSDVVNEKGRVKGDPEKQKQDRKENKTEEQNSK 455
Cdd:PTZ00121 1415 AAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKK 1452

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 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 922580708  73 LLPELSNPSHIARLVDVGYDDDFKFLIFEDFGMDFLTLFDEFGPVLNPATLFLISYFTFNAIKELHSFDIVHLDIRPSSF 152
Cdd:cd14016   48 VYKLLQGGPGIPRLYWFGQEGDYNVMVMDLLGPSLEDLFNKCGRKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENF 127

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 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 922580708 134 IKELHSFDIVHLDIRPSS-FSVNQHPFNIKITDYSRCMTRKPEMKVPDD-ARPDSFSPRVFHQkdaqfdEFVDF--EAW- 208
Cdd:cd14192  115 VHYLHQHYILHLDLKPENiLCVNSTGNQIKIIDFGLARRYKPREKLKVNfGTPEFLAPEVVNY------DFVSFptDMWs 188

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 922580708 209 --VYTMLFLCTVEklPWFG--DAENM---LRLKEEFFNDPLNYLYDGCADFV 253
Cdd:cd14192  189 vgVITYMLLSGLS--PFLGetDAETMnniVNCKWDFDAEAFENLSEEAKDFI 238

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 922580708 120 PATLFLISYFTFN---AIKELHSFDIVHLDIRPSSFSVNQHpFNIKITDY--SRCMTRKPE 175
Cdd:cd07855  105 PLTLEHIRYFLYQllrGLKYIHSANVIHRDLKPSNLLVNEN-CELKIGDFgmARGLCTSPE 164

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 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 922580708  68 KLLFDLLPELSNPSHIARLVDVGYDDDFKFLIFEDFGMDFLTLF-DEFGPVLNPATLFLISYFTFNAIKELHSFDIVHLD 146
Cdd:cd14129   43 KMEVAVLKKLQGKDHVCRFIGCGRNDRFNYVVMQLQGRNLADLRrSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRD 122

                         90
                 ....*....|..
gi 922580708 147 IRPSSFSVNQHP 158
Cdd:cd14129  123 IKPSNFAMGRFP 134

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  288 KEQPRLYTMKELEEVKK----TRRAPDFYTNNAIDIAESHWHAaddsdHDNLRTSDEENEQKsetkkdsceRSSAEVSSS 363
Cdd:PTZ00121 1221 EDAKKAEAVKKAEEAKKdaeeAKKAEEERNNEEIRKFEEARMA-----HFARRQAAIKAEEA---------RKADELKKA 1286

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580708  364 TEQTSApmSEASSSDGRKKPKNAGKSAERKGKPAEKNPSSEKDDDGATEPMSGVERRSTPSDVVNEKGRVKGDPEKQKQD 443
Cdd:PTZ00121 1287 EEKKKA--DEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEE 1364

                         170
                  ....*....|....*...
gi 922580708  444 RK---ENKTEEQNSKISA 458
Cdd:PTZ00121 1365 KAeaaEKKKEEAKKKADA 1382