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 1596252162 217 LGEGASGVIHRVEC--EDQALALKLFKGEVTSDGWPH--SEMAAWLAAgSHPGLIPVTGRLQAHPEGraGLFMPLIP-PS 291
Cdd:cd00180     1 LGKGSFGKVYKARDkeTGKKVAVKVIPKEKLKKLLEEllREIEILKKL-NHPNIVKLYDVFETENFL--YLVMEYCEgGS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 292 FRALagppsLDSCTRdiypealRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFG-AASLFEP 370
Cdd:cd00180    78 LKDL-----LKENKG-------PLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGlAKDLDSD 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1596252162 371 GTAQALALQRLEVRafgYLLEELLARCEGEPPA-------------AWMALMQACLVETPADRPLFAAI 426
Cdd:cd00180   146 DSLLKTTGGTTPPY---YAPPELLGGRYYGPKVdiwslgvilyeleELKDLIRRMLQYDPKKRPSAKEL 211

type III secretion system effector E3 ubiquitin transferase SlrP;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162  26 LTALPPELFEpaiaqTLEVLDVSGNALETLPEALATlpRLRIVFASANRFTVLPEVLGrcAQLEMVGFKSNRIEQVSAAa 105
Cdd:PRK15370  274 ISCLPENLPE-----ELRYLSVYDNSIRTLPAHLPS--GITHLNVQSNSLTALPETLP--PGLKTLEAGENALTSLPAS- 343

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 106 LPPRLRWLILTDNALEQLPEALgeRPRLQKLALAGNRLRALPQSLAQArqLELLRISANRLEALPEGLLRL----PRLAW 181
Cdd:PRK15370  344 LPPELQVLDVSKNQITVLPETL--PPTITTLDVSRNALTNLPENLPAA--LQIMQASRNNLVRLPESLPHFrgegPQPTR 419

                         170
                  ....*....|
gi 1596252162 182 LACGGNPFSE 191
Cdd:PRK15370  420 IIVEYNPFSE 429

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 321 QRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGqAYLGDFGAASLFEPGTAQALALQRLEvRAFGYLLEELlarcege 400
Cdd:COG3642    54 PELLRELGRLLARLHRAGIVHGDLTTSNILVDDGG-VYLIDFGLARYSDPLEDKAVDLAVLK-RSLESTHPDP------- 124

                          90
                  ....*....|.
gi 1596252162 401 PPAAWMALMQA 411
Cdd:COG3642   125 AEELWEAFLEG 135

3-deoxy-D-manno-octulosonic-acid kinase; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 327 VAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAASLFEPGTAQALALQRLEvRAFgylLEELLAR-CEGEPPAAW 405
Cdd:PRK01723  151 IGQLIARFHDAGVYHADLNAHNILLDPDGKFWLIDFDRGELRTPTRWKQANLARLL-RSF---NKEQGKRpILAFSEQDW 226

                  ....*.
gi 1596252162 406 MALMQA 411
Cdd:PRK01723  227 QALLAG 232

Leucine rich repeat;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1596252162 108 PRLRWLILTDNALEQL-PEALGERPRLQKLALAGNRLRAL-PQSLAQARQLELLRISANRL 166
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLdDGAFKGLSNLKVLDLSNNLLTTLsPGAFSGLPSLRYLDLSGNRL 61

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1596252162 323 LAGTVAAALAQLHERGISHGDLYAHNLLHGpGGQAYLGDFG 363
Cdd:TIGR03724  95 LAREIGRLVGKLHKAGIVHGDLTTSNIIVR-DDKVYLIDFG 134

Leucine-rich repeat (LRR) protein [Transcription];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162  18 RISLNGAGLTALPPELFEPaiaQTLEVLDVSGNALETLPEALATLPRLRIVFASANRFTVLPEvLGRCAQLEMVGFKSNR 97
Cdd:COG4886   186 ELDLSNNQITDLPEPLGNL---TNLEELDLSGNQLTDLPEPLANLTNLETLDLSNNQLTDLPE-LGNLTNLEELDLSNNQ 261

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1596252162  98 IEQVSAAALPPRLRWLILTDNALEQLPEALGERPRLQKLALAGNRLRALPQSLAQARQLELLRISANRLEALPEGL 173
Cdd:COG4886   262 LTDLPPLANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTL 337

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 1596252162 217 LGEGASGVIHRVEC--EDQALALKLFKGEVTSDGWPH--SEMAAWLAAgSHPGLIPVTGRLQAHPEGraGLFMPLIP-PS 291
Cdd:cd00180     1 LGKGSFGKVYKARDkeTGKKVAVKVIPKEKLKKLLEEllREIEILKKL-NHPNIVKLYDVFETENFL--YLVMEYCEgGS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 292 FRALagppsLDSCTRdiypealRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFG-AASLFEP 370
Cdd:cd00180    78 LKDL-----LKENKG-------PLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGlAKDLDSD 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1596252162 371 GTAQALALQRLEVRafgYLLEELLARCEGEPPA-------------AWMALMQACLVETPADRPLFAAI 426
Cdd:cd00180   146 DSLLKTTGGTTPPY---YAPPELLGGRYYGPKVdiwslgvilyeleELKDLIRRMLQYDPKKRPSAKEL 211

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162  31 PELFepAIAQTLEVLDVSGNALE-TLPEALATLPRLRIVFASANRFT-VLPEVLGRCAQLEMVGFKSNRIeqvsAAALPP 108
Cdd:PLN00113  301 PELV--IQLQNLEILHLFSNNFTgKIPVALTSLPRLQVLQLWSNKFSgEIPKNLGKHNNLTVLDLSTNNL----TGEIPE 374

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 109 ------RLRWLILTDNALE-QLPEALG-----ERPRLQKLALAGNrlraLPQSLAQARQLELLRISANRLEA-LPEGLLR 175
Cdd:PLN00113  375 glcssgNLFKLILFSNSLEgEIPKSLGacrslRRVRLQDNSFSGE----LPSEFTKLPLVYFLDISNNNLQGrINSRKWD 450

                         170
                  ....*....|....*
gi 1596252162 176 LPRLAWLACGGNPFS 190
Cdd:PLN00113  451 MPSLQMLSLARNKFF 465

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 321 QRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGqAYLGDFGAASLFEPGTAQALALQRLEvRAFGYLLEELlarcege 400
Cdd:COG3642    54 PELLRELGRLLARLHRAGIVHGDLTTSNILVDDGG-VYLIDFGLARYSDPLEDKAVDLAVLK-RSLESTHPDP------- 124

                          90
                  ....*....|.
gi 1596252162 401 PPAAWMALMQA 411
Cdd:COG3642   125 AEELWEAFLEG 135

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162  29 LPPE---LFEP----AIAQTLEVLDVSGNALETLpEALATLPRLRIVFASANR---FTVLPEVLGRCAQLEMVGFKSNRI 98
Cdd:cd21340   102 LPPGeklTFDPrslaALSNSLRVLNISGNNIDSL-EPLAPLRNLEQLDASNNQisdLEELLDLLSSWPSLRELDLTGNPV 180

                          90       100
                  ....*....|....*....|....*.
gi 1596252162  99 eqvsaaALPPRLR-WLILTDNALEQL 123
Cdd:cd21340   181 ------CKKPKYRdKIILASKSLEVL 200

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 1596252162 217 LGEGASGVIHRVECEDQALALKLFKGEVTSDgwPHSEM----AAWLAAGSHPGLIPVTGRLQAHPegRAGLFMPLIPPSf 292
Cdd:cd13999     1 IGSGSFGEVYKGKWRGTDVAIKKLKVEDDND--ELLKEfrreVSILSKLRHPNIVQFIGACLSPP--PLCIVTEYMPGG- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 293 ralagppSLDSCTRDIYPEalrLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAASLF---- 368
Cdd:cd13999    76 -------SLYDLLHKKKIP---LSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKnstt 145

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 369 -----EPGTAQALA---LQRLE------VRAFGYLLEELLAR-----------------CEGEPPA-------AWMALMQ 410
Cdd:cd13999   146 ekmtgVVGTPRWMApevLRGEPytekadVYSFGIVLWELLTGevpfkelspiqiaaavvQKGLRPPippdcppELSKLIK 225

                         250       260
                  ....*....|....*....|
gi 1596252162 411 ACLVETPADRPLFAAIARAL 430
Cdd:cd13999   226 RCWNEDPEKRPSFSEIVKRL 245

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 322 RLAGTVAAALAQLHER---------GISHGDLYAHNLLHGPGGQAYLGDFGAASLFEP-------------GTAQALA-- 377
Cdd:cd13998    96 RLALSVARGLAHLHSEipgctqgkpAIAHRDLKSKNILVKNDGTCCIADFGLAVRLSPstgeednanngqvGTKRYMApe 175

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1596252162 378 -------------LQRLEVRAFGYLLEELLARCEG 399
Cdd:cd13998   176 vlegainlrdfesFKRVDIYAMGLVLWEMASRCTD 210

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162  42 LEVLDVSGNALETLpEALATLPRLRIVFASANRFTVLpEVLGRCAQLEmvgfksnriE-QVSAAALPPrlrwliltDNAL 120
Cdd:cd21340    48 LTHLYLQNNQIEKI-ENLENLVNLKKLYLGGNRISVV-EGLENLTNLE---------ElHIENQRLPP--------GEKL 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1596252162 121 EQLPEAL-GERPRLQKLALAGNRLRALpQSLAQARQLELLRISANRL---EALPEGLLRLPRLAWLACGGNPFS 190
Cdd:cd21340   109 TFDPRSLaALSNSLRVLNISGNNIDSL-EPLAPLRNLEQLDASNNQIsdlEELLDLLSSWPSLRELDLTGNPVC 181

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 315 LSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAASLF--EPGTAQA-------------LALQ 379
Cdd:cd05052   101 LNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtgDTYTAHAgakfpikwtapesLAYN 180

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 380 RL----EVRAFGYLLEEL-------------------------LARCEGEPPAAWmALMQACLVETPADRPLFAAIARAL 430
Cdd:cd05052   181 KFsiksDVWAFGVLLWEIatygmspypgidlsqvyellekgyrMERPEGCPPKVY-ELMRACWQWNPSDRPSFAEIHQAL 259

Lipopolysaccharide kinase (Kdo/WaaP) family; These lipopolysaccharide kinases are related to protein kinases pfam00069. This family includes waaP (rfaP) gene product is required for the addition of phosphate to O-4 of the first heptose residue of the lipopolysaccharide (LPS) inner core region. It has previously been shown that WaaP is necessary for resistance to hydrophobic and polycationic antimicrobials in E. coli and that it is required for virulence in invasive strains of S. enterica.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 293 RALAGPPSLDSCTRDIYPEALRLSPAALQRlagtVAAALAQLHERGISHGDLYAHN-LLHGPGG---QAYLGDFGAASLF 368
Cdd:pfam06293  96 ERLEGAQSLADWLADWAVPSGELRRAIWEA----VGRLIRQMHRAGVQHGDLYAHHiLLQQEGDegfEAWLIDLDKGRLR 171

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1596252162 369 EPGTaqalalqRLEVRAFGYLLEELLArcEGEPPAAWMALMQA 411
Cdd:pfam06293 172 LPAR-------RWRNKDLARLLRSFLN--IGFTEADWERLLRA 205

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK 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 1596252162 215 ERLGEGASGVIHRVECED--QALALKLfkgeVTSDGWP--HSEMAAWLAAG---SHPGLIPVTGRLQAHPEGRAGLFMpl 287
Cdd:cd06621     7 SSLGEGAGGSVTKCRLRNtkTIFALKT----ITTDPNPdvQKQILRELEINkscASPYIVKYYGAFLDEQDSSIGIAM-- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 288 ippsfrALAGPPSLDSCTRDIYPEALRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGA--- 364
Cdd:cd06621    81 ------EYCEGGSLDSIYKKVKKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVsge 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1596252162 365 -----ASLFEpGTAQALALQRL---------EVRAFGYLLEELLARC-----EGEPPAA 404
Cdd:cd06621   155 lvnslAGTFT-GTSYYMAPERIqggpysitsDVWSLGLTLLEVAQNRfpfppEGEPPLG 212

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1596252162 314 RLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAA 365
Cdd:cd06606    95 KLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCA 146

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1596252162 295 LAGPPSLDSCTRDIYPEAlRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAASLFEPG 371
Cdd:cd13997    81 LCENGSLQDALEELSPIS-KLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLETS 156

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK 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 1596252162 217 LGEGASGVIHRVECEDQALALKLFKGEVTSDGWPHSEM---------------------AAWLAAGSHPGLIPVTGrLQA 275
Cdd:cd14000     2 LGDGGFGSVYRASYKGEPVAVKIFNKHTSSNFANVPADtmlrhlratdamknfrllrqeLTVLSHLHHPSIVYLLG-IGI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1596252162 276 HPegrAGLFMPLIPPSfralagppSLDSCTRDIYPEALRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLL 350
Cdd:cd14000    81 HP---LMLVLELAPLG--------SLDHLLQQDSRSFASLGRTLQQRIALQVADGLRYLHSAMIIYRDLKSHNVL 144

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK 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 1596252162 215 ERLGEGASGVIHRVE--CEDQALALKLFKGEVTSDGWPHS---EMAAWLAAGSHPGLIPVtgrLQAHPEG-RAGLFMPLI 288
Cdd:cd07832     6 GRIGEGAHGIVFKAKdrETGETVALKKVALRKLEGGIPNQalrEIKALQACQGHPYVVKL---RDVFPHGtGFVLVFEYM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1596252162 289 PPSfralagppsLDSCTRDiypEALRLSPAALQRLAGTVAAALAQLHERGISHGDLYAHNLLHGPGGQAYLGDFGAASLF 368
Cdd:cd07832    83 LSS---------LSEVLRD---EERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLF 150

                  ....
gi 1596252162 369 EPGT 372
Cdd:cd07832   151 SEED 154

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK 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 1596252162 217 LGEGASG----VIHRVECEdqALALKLFKgeVTSDGWPHSEMAA---WLAAGSHPGLIpvtgRLQA--HPEGRAGLFMPL 287
Cdd:cd06623     9 LGQGSSGvvykVRHKPTGK--IYALKKIH--VDGDEEFRKQLLRelkTLRSCESPYVV----KCYGafYKEGEISIVLEY 80