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 392894720  459 WLVQNIKSGCMCSAKLVSRKNPEhlqlQKNLDKERKILyDLLPELSNPSHIARLVDIGYDDDFK--FLIFEDFGMDLLTL 536
Cdd:cd05118    16 WLARDKVTGEKVAIKKIKNDFRH----PKAALREIKLL-KHLNDVEGHPNIVKLLDVFEHRGGNhlCLVFELMGMNLYEL 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 392894720  537 FDEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSFSVNQHPFNIKITDY 592
Cdd:cd05118    91 IKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQLKLADF 146

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC 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 392894720  459 WLVQNIKSGCMCSAKLVSRKNPEhlqlQKNLDKERKILyDLLPELSNPSHIARLVDIGYDDDFK--FLIFEDFGMDLLTL 536
Cdd:cd05118    16 WLARDKVTGEKVAIKKIKNDFRH----PKAALREIKLL-KHLNDVEGHPNIVKLLDVFEHRGGNhlCLVFELMGMNLYEL 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 392894720  537 FDEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSFSVNQHPFNIKITDY 592
Cdd:cd05118    91 IKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQLKLADF 146

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  473 KLVSRKNPEHLQLQKNLDKERKILYdllpELSNPsHIARLVDIGYDDDFKFLIFEDF-GMDLLTLFDEFGAvLNPTTmfL 551
Cdd:COG0515    38 KVLRPELAADPEARERFRREARALA----RLNHP-NIVRVYDVGEEDGRPYLVMEYVeGESLADLLRRRGP-LPPAE--A 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 392894720  552 ISYFT--FNAIKELHSFDIVHLDIRPSsfsvnqhpfNI--------KITD 591
Cdd:COG0515   110 LRILAqlAEALAAAHAAGIVHRDIKPA---------NIlltpdgrvKLID 150

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC 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 392894720  459 WLVQNIKSGCMCSAKLVSRKNPEhlqlQKNLDKERKILyDLLPELSNPSHIARLVDIGYDDDFK--FLIFEDFGMDLLTL 536
Cdd:cd05118    16 WLARDKVTGEKVAIKKIKNDFRH----PKAALREIKLL-KHLNDVEGHPNIVKLLDVFEHRGGNhlCLVFELMGMNLYEL 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 392894720  537 FDEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSFSVNQHPFNIKITDY 592
Cdd:cd05118    91 IKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQLKLADF 146

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 392894720  466 SGCMCSAKLVSRKNPE------HLQLQKNLDKERKIL--YDLLPELSNPsHIARLVDIGYDDDFKFLIFE--DFGmDLLT 535
Cdd:cd00180     3 KGSFGKVYKARDKETGkkvavkVIPKEKLKKLLEELLreIEILKKLNHP-NIVKLYDVFETENFLYLVMEycEGG-SLKD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392894720  536 LFDEFGAVLNPttMFLISYF--TFNAIKELHSFDIVHLDIRPSSFSVNqHPFNIKITDY--SRCMTRK 599
Cdd:cd00180    81 LLKENKGPLSE--EEALSILrqLLSALEYLHSNGIIHRDLKPENILLD-SDGTVKLADFglAKDLDSD 145

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 392894720  459 WLVQNIKSGCMCSAKLVSRKNPEHLQLQKNLDKERKILYdllpELSNPsHIARLVDIGYDDDFKFLIFE--DFGmDLLTL 536
Cdd:cd14007    17 YLAREKKSGFIVALKVISKSQLQKSGLEHQLRREIEIQS----HLRHP-NILRLYGYFEDKKRIYLILEyaPNG-ELYKE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  537 FDEFGaVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSFSVNQHpFNIKITDY--------SRCMTR-------KPE 601
Cdd:cd14007    91 LKKQK-RFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSN-GELKLADFgwsvhapsNRRKTFcgtldylPPE 168

                  .
gi 392894720  602 M 602
Cdd:cd14007   169 M 169

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. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. 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. The CDKL 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 392894720  499 LLPELSNPsHIARLVDIGYDDDFKFLIFEDFGMDLLTLFDEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSF 578
Cdd:cd07833    53 VLRQLRHE-NIVNLKEAFRRKGRLYLVFEYVERTLLELLEASPGGLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENI 131

                          90       100
                  ....*....|....*....|....*
gi 392894720  579 SVNQHPFnIKITD--YSRCMTRKPE 601
Cdd:cd07833   132 LVSESGV-LKLCDfgFARALTARPA 155

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 392894720  460 LVQNIKSGCMCSAKLVSrKNPEHLQLQKNLDKERKILYDLlpelSNPsHIARLVDIGYDDDFKFLIfedfgMDLLT---L 536
Cdd:cd05117    18 LAVHKKTGEEYAVKIID-KKKLKSEDEEMLRREIEILKRL----DHP-NIVKLYEVFEDDKNLYLV-----MELCTggeL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  537 FDEfgavlnpttmfLISYFTFN-------------AIKELHSFDIVHLDIRPSS--FSVNQHPFNIKITDY--SRCMTRK 599
Cdd:cd05117    87 FDR-----------IVKKGSFSereaakimkqilsAVAYLHSQGIVHRDLKPENilLASKDPDSPIKIIDFglAKIFEEG 155

                  ....
gi 392894720  600 PEMK 603
Cdd:cd05117   156 EKLK 159

Catalytic domain of Fungal Halotolerance protein 4-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 HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-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 392894720  463 NIKSGCMCSAKLVSRKNPEHLQLQ--KNLDKErkilYDLLPELSNPsHIARLVDIGYDDDFKFLIFedfgMDLLTLFDEF 540
Cdd:cd13994    16 NPRSGVLYAVKEYRRRDDESKRKDyvKRLTSE----YIISSKLHHP-NIVKVLDLCQDLHGKWCLV----MEYCPGGDLF 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  541 GAV---LNPTTMFLISYF--TFNAIKELHSFDIVHLDIRPSSFSVNQHpFNIKITDY--SRCMTRKPEMKVPDDARP--- 610
Cdd:cd13994    87 TLIekaDSLSLEEKDCFFkqILRGVAYLHSHGIAHRDLKPENILLDED-GVLKLTDFgtAEVFGMPAEKESPMSAGLcgs 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 392894720  611 DSF-SPRVFHQKdaQFD-EFVDfeAW----VYTMLFLctaEKLPW 649
Cdd:cd13994   166 EPYmAPEVFTSG--SYDgRAVD--VWscgiVLFALFT---GRFPW 203

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 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 392894720  498 DLLPELSNPShIARLVDIGYDDDFKFLIFEDF-GMDLLTLFDEFGAVLNPTTMFLISYFtFNAIKELHSFDIVHLDIRPS 576
Cdd:cd14098    53 NILKSLEHPG-IVRLIDWYEDDQHIYLVMEYVeGGDLMDFIMAWGAIPEQHARELTKQI-LEAMAYTHSMGITHRDLKPE 130

                          90
                  ....*....|....*..
gi 392894720  577 SFSVNQH-PFNIKITDY 592
Cdd:cd14098   131 NILITQDdPVIVKISDF 147

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  473 KLVSRKNPEHLQLQKNLDKERKILYdllpELSNPsHIARLVDIGYDDDFKFLIFEDF-GMDLLTLFDEFGAvLNPTTmfL 551
Cdd:COG0515    38 KVLRPELAADPEARERFRREARALA----RLNHP-NIVRVYDVGEEDGRPYLVMEYVeGESLADLLRRRGP-LPPAE--A 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 392894720  552 ISYFT--FNAIKELHSFDIVHLDIRPSsfsvnqhpfNI--------KITD 591
Cdd:COG0515   110 LRILAqlAEALAAAHAAGIVHRDIKPA---------NIlltpdgrvKLID 150

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. 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. The CDK1 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 392894720  499 LLPELSNPShIARLVDIGYDDDFKFLIFEDFGMDLLTLFDEF--GAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPS 576
Cdd:cd07861    52 LLKELQHPN-IVCLEDVLMQENRLYLVFEFLSMDLKKYLDSLpkGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQ 130

                          90
                  ....*....|....*.
gi 392894720  577 SFSVNQHPfNIKITDY 592
Cdd:cd07861   131 NLLIDNKG-VIKLADF 145

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 392894720  499 LLPELSNPSHIARLVDIGYDDDFKFLIFEDFGMDLLTLF-DEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSS 577
Cdd:cd14129    48 VLKKLQGKDHVCRFIGCGRNDRFNYVVMQLQGRNLADLRrSQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSN 127

                  ....*..
gi 392894720  578 FSVNQHP 584
Cdd:cd14129   128 FAMGRFP 134

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  460 LVQNIKSGCMCSAKLVSRKNPEHLQLQKNLDKERK-ILYDLLPE------LSNPsHIARLVDIGYDDDFK--FLIFE--D 528
Cdd:cd14008    11 LALDTETGQLYAIKIFNKSRLRKRREGKNDRGKIKnALDDVRREiaimkkLDHP-NIVRLYEVIDDPESDklYLVLEycE 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  529 FG--MDLLTlfDEFGAVLNPTTMFLISYFTFNAIKELHSFDIVHLDIRPSSFSVNQHpFNIKITDY--SRCMTRKPEMKV 604
Cdd:cd14008    90 GGpvMELDS--GDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTAD-GTVKISDFgvSEMFEDGNDTLQ 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392894720  605 PDDARPDSFSPRVFHQKDAQFDEF-VDFeaW-----VYTMLFLctaeKLPWFGDaeNMFKLKEVFFNDPLNY-----LYD 673
Cdd:cd14008   167 KTAGTPAFLAPELCDGDSKTYSGKaADI--WalgvtLYCLVFG----RLPFNGD--NILELYEAIQNQNDEFpippeLSP 238

                  ....*
gi 392894720  674 GCADF 678
Cdd:cd14008   239 ELKDL 243