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 2462514851  79 SLKIIEKQAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVA 158
Cdd:cd14174    31 AVKIIEKNAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLRGGSILAHIQKRKHFNEREASRVVRDIA 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462514851 159 AALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSCTPITTPELTTPEAEA 222
Cdd:cd14174   111 SALDFLHTKGIAHRDLKPENILCESPDKVSPVKICDFDLGSGVKLNSACTPITTPELTTPCGSA 174

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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 2462514851  79 SLKIIEKQAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVA 158
Cdd:cd14174    31 AVKIIEKNAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLRGGSILAHIQKRKHFNEREASRVVRDIA 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462514851 159 AALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSCTPITTPELTTPEAEA 222
Cdd:cd14174   111 SALDFLHTKGIAHRDLKPENILCESPDKVSPVKICDFDLGSGVKLNSACTPITTPELTTPCGSA 174

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  80 LKIIEKQAGHS---RSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRD 156
Cdd:COG0515    37 LKVLRPELAADpeaRERFRREARALARLN-HPNIVRVYDVGEEDGRPYLVMEYVEGESLADLLRRRGPLPPAEALRILAQ 115

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462514851 157 VAAALDFLHTKGIAHRDLKPENILCeSPEKVspVKICDF 195
Cdd:COG0515   116 LAEALAAAHAAGIVHRDIKPANILL-TPDGR--VKLIDF 151

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  80 LKIIEK-QAGHS-RSRVFREVETLYQCQGnKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDV 157
Cdd:pfam00069  29 IKKIKKeKIKKKkDKNILREIKILKKLNH-PNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLSEKGAFSEREAKFIMKQI 107

                  ....*
gi 2462514851 158 AAALD 162
Cdd:pfam00069 108 LEGLE 112

TOMM system kinase/cyclase fusion protein; This model represents proteins of 1350 in length, in multiple species of Burkholderia, in Acidovorax avenae subsp. citrulli AAC00-1 and Delftia acidovorans SPH-1, and in multiple copies in Sorangium cellulosum, in genomic neighborhoods that include a cyclodehydratase/docking scaffold fusion protein (TIGR03882) and a member of the thiazole/oxazole modified metabolite (TOMM) precursor family TIGR03795. It has a kinase domain in the N-terminal 300 amino acids, followed by a cyclase homology domain, followed by regions without named domain definitions. It is a probable bacteriocin-like metabolite biosynthesis protein. [Cellular processes, Toxin production and resistance]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851   80 LKIIEKQAGHSRSRVFREVETLYQCQgNKNILELIEFFE-DDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVA 158
Cdd:TIGR03903   11 LRTDAPEEEHQRARFRRETALCARLY-HPNIVALLDSGEaPPGLLFAVFEYVPGRTLREVLAADGALPAGETGRLMLQVL 89

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2462514851  159 AALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGS 199
Cdd:TIGR03903   90 DALACAHNQGIVHRDLKPQNIMVSQTGVRPHAKVLDFGIGT 130

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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 2462514851  79 SLKIIEKQAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVA 158
Cdd:cd14174    31 AVKIIEKNAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLRGGSILAHIQKRKHFNEREASRVVRDIA 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462514851 159 AALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSCTPITTPELTTPEAEA 222
Cdd:cd14174   111 SALDFLHTKGIAHRDLKPENILCESPDKVSPVKICDFDLGSGVKLNSACTPITTPELTTPCGSA 174

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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 2462514851  73 LTPCQESLKIIEKQAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASR 152
Cdd:cd14173    25 ITNKEYAVKIIEKRPGHSRSRVFREVEMLYQCQGHRNVLELIEFFEEEDKFYLVFEKMRGGSILSHIHRRRHFNELEASV 104

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 153 VVRDVAAALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSCTPITTPELTTPEAEA 222
Cdd:cd14173   105 VVQDIASALDFLHNKGIAHRDLKPENILCEHPNQVSPVKICDFDLGSGIKLNSDCSPISTPELLTPCGSA 174

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK 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 2462514851  81 KIIEKQAGHSRsrvfrEVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVAAA 160
Cdd:cd14092    37 KIVSRRLDTSR-----EVQLLRLCQGHPNIVKLHEVFQDELHTYLVMELLRGGELLERIRKKKRFTESEASRIMRQLVSA 111

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 161 LDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGsgmKLNNSCTPITTPELTTPEA 220
Cdd:cd14092   112 VSFMHSKGVVHRDLKPENLLFTDEDDDAEIKIVDFGFA---RLKPENQPLKTPCFTLPYA 168

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 2462514851  80 LKIIEK----QAGHSRSrVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVR 155
Cdd:cd14007    30 LKVISKsqlqKSGLEHQ-LRREIEIQSHLR-HPNILRLYGYFEDKKRIYLILEYAPNGELYKELKKQKRFDEKEAAKYIY 107

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462514851 156 DVAAALDFLHTKGIAHRDLKPENILCESPEKvspVKICDF 195
Cdd:cd14007   108 QLALALDYLHSKNIIHRDIKPENILLGSNGE---LKLADF 144

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK 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 2462514851  74 TPCQESLKIIEKqaghSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRV 153
Cdd:cd14091    24 TGKEYAVKIIDK----SKRDPSEEIEILLRYGQHPNIITLRDVYDDGNSVYLVTELLRGGELLDRILRQKFFSEREASAV 99

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462514851 154 VRDVAAALDFLHTKGIAHRDLKPENILCESPE-KVSPVKICDFDLGSGMKLNNSC--TPITTPELTTPE 219
Cdd:cd14091   100 MKTLTKTVEYLHSQGVVHRDLKPSNILYADESgDPESLRICDFGFAKQLRAENGLlmTPCYTANFVAPE 168

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  80 LKIIEKQaghSRSRvfREVETLYQCQGNKNILELIEFFE---DDTRFYL-VFEKLQGGSILAHIQK--QKHFNEREASRV 153
Cdd:cd14089    31 LKVLRDN---PKAR--REVELHWRASGCPHIVRIIDVYEntyQGRKCLLvVMECMEGGELFSRIQEraDSAFTEREAAEI 105

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462514851 154 VRDVAAALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSC-TPITTPELTTPE 219
Cdd:cd14089   106 MRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGPNAILKLTDFGFAKETTTKKSLqTPCYTPYYVAPE 172

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG 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 2462514851  74 TPCQE-SLKII--------EKQAGHSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKH 144
Cdd:cd14093    26 ETGQEfAVKIIditgekssENEAEELREATRREIEILRQVSGHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTEVVT 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462514851 145 FNEREASRVVRDVAAALDFLHTKGIAHRDLKPENILCESPEKvspVKICDF----DLGSGMKLNNSCtpiTTPELTTPE 219
Cdd:cd14093   106 LSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLN---VKISDFgfatRLDEGEKLRELC---GTPGYLAPE 178

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 2462514851  80 LKIIEKQAGH---SRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRD 156
Cdd:cd14014    30 IKVLRPELAEdeeFRERFLREARALARLS-HPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLLRERGPLPPREALRILAQ 108

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462514851 157 VAAALDFLHTKGIAHRDLKPENILcespekVSP---VKICDFDL 197
Cdd:cd14014   109 IADALAAAHRAGIVHRDIKPANIL------LTEdgrVKLTDFGI 146

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  80 LKIIEKQAGHS---RSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRD 156
Cdd:COG0515    37 LKVLRPELAADpeaRERFRREARALARLN-HPNIVRVYDVGEEDGRPYLVMEYVEGESLADLLRRRGPLPPAEALRILAQ 115

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462514851 157 VAAALDFLHTKGIAHRDLKPENILCeSPEKVspVKICDF 195
Cdd:COG0515   116 LAEALAAAHAAGIVHRDIKPANILL-TPDGR--VKLIDF 151

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 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 2462514851  74 TPCQESLKIIEKqaghSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRV 153
Cdd:cd14178    27 TSTEYAVKIIDK----SKRDPSEEIEILLRYGQHPNIITLKDVYDDGKFVYLVMELMRGGELLDRILRQKCFSEREASAV 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 154 VRDVAAALDFLHTKGIAHRDLKPENIL----CESPEKvspVKICDFDLGSGMKLNNSC--TPITTPELTTPEA------E 221
Cdd:cd14178   103 LCTITKTVEYLHSQGVVHRDLKPSNILymdeSGNPES---IRICDFGFAKQLRAENGLlmTPCYTANFVAPEVlkrqgyD 179

                  ....*...
gi 2462514851 222 AGGDSWNF 229
Cdd:cd14178   180 AACDIWSL 187

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 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 2462514851  74 TPCQESLKIIEKqaghSRSRVFREVETLYQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRV 153
Cdd:cd14175    25 TNMEYAVKVIDK----SKRDPSEEIEILLRYGQHPNIITLKDVYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASSV 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 154 VRDVAAALDFLHTKGIAHRDLKPENILC--ES--PEKvspVKICDFDLGSGMKLNNSC--TPITTPELTTPEA------E 221
Cdd:cd14175   101 LHTICKTVEYLHSQGVVHRDLKPSNILYvdESgnPES---LRICDFGFAKQLRAENGLlmTPCYTANFVAPEVlkrqgyD 177

                  ....*...
gi 2462514851 222 AGGDSWNF 229
Cdd:cd14175   178 EGCDIWSL 185

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 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 2462514851  96 REVETLYQCQGNKNILELIEFFEDDTR----FYLVFEKLQGGSILAHIQKQ--KHFNEREASRVVRDVAAALDFLHTKGI 169
Cdd:cd14172    45 REVEHHWRASGGPHIVHILDVYENMHHgkrcLLIIMECMEGGELFSRIQERgdQAFTEREASEIMRDIGTAIQYLHSMNI 124

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462514851 170 AHRDLKPENILCESPEKVSPVKICDFDLGSGMKLNNSC-TPITTPELTTPE 219
Cdd:cd14172   125 AHRDVKPENLLYTSKEKDAVLKLTDFGFAKETTVQNALqTPCYTPYYVAPE 175

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like 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 2462514851  81 KIIEKQAGhSRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVAAA 160
Cdd:cd14006    24 KFIPKRDK-KKEAVLREISILNQLQ-HPRIIQLHEAYESPTELVLILELCSGGELLDRLAERGSLSEEEVRTYMRQLLEG 101

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462514851 161 LDFLHTKGIAHRDLKPENILCESPeKVSPVKICDFdlGSGMKLNNSC---TPITTPELTTPE 219
Cdd:cd14006   102 LQYLHNHHILHLDLKPENILLADR-PSPQIKIIDF--GLARKLNPGEelkEIFGTPEFVAPE 160

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  91 RSRVFREVETLYQCQGNKNILELIEFFEDD----------TRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVAAA 160
Cdd:cd14171    42 RPKARTEVRLHMMCSGHPNIVQIYDVYANSvqfpgessprARLLIVMELMEGGELFDRISQHRHFTEKQAAQYTKQIALA 121

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462514851 161 LDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDLGsgmKLNNS--CTPITTPELTTPE 219
Cdd:cd14171   122 VQHCHSLNIAHRDLKPENLLLKDNSEDAPIKLCDFGFA---KVDQGdlMTPQFTPYYVAPQ 179

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 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 2462514851  79 SLKIIEKQAGHSRSRVFR-EVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDV 157
Cdd:cd14184    30 ALKIIDKAKCCGKEHLIEnEVSILRRVK-HPNIIMLIEEMDTPAELYLVMELVKGGDLFDAITSSTKYTERDASAMVYNL 108

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462514851 158 AAALDFLHTKGIAHRDLKPENIL-CESPEKVSPVKICDFDLGSGMK--LNNSCtpiTTPELTTPE--AEAG 223
Cdd:cd14184   109 ASALKYLHGLCIVHRDIKPENLLvCEYPDGTKSLKLGDFGLATVVEgpLYTVC---GTPTYVAPEiiAETG 176

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 109 NILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVAAALDFLHTKGIAHRDLKPENILCESPEKvs 188
Cdd:cd14081    62 NVLKLYDVYENKKYLYLVLEYVSGGELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNN-- 139

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462514851 189 pVKICDFDLGS----GMKLNNSCtpiTTPELTTPE 219
Cdd:cd14081   140 -IKIADFGMASlqpeGSLLETSC---GSPHYACPE 170

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851  79 SLKIIEKQAGHSR-SRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDV 157
Cdd:cd14167    32 AIKCIAKKALEGKeTSIENEIAVLHKIK-HPNIVALDDIYESGGHLYLIMQLVSGGELFDRIVEKGFYTERDASKLIFQI 110

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462514851 158 AAALDFLHTKGIAHRDLKPENILCESPEKVSPVKICDFDL----GSGMKLNNSCtpiTTPELTTPEAEA 222
Cdd:cd14167   111 LDAVKYLHDMGIVHRDLKPENLLYYSLDEDSKIMISDFGLskieGSGSVMSTAC---GTPGYVAPEVLA 176

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; 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. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462514851 109 NILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREASRVVRDVAAALDFLHTKGIAHRDLKPENILCESPEKVS 188
Cdd:cd14085    59 NIIKLKEIFETPTEISLVLELVTGGELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDA 138

                  ....*....
gi 2462514851 189 PVKICDFDL 197
Cdd:cd14085   139 PLKIADFGL 147

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 2462514851  92 SRVFREVETLYQCQgNKNILELIEFFEDDTR--FYLVFEKLQGGSILAHIQKQKH--FNEREASRVVRDVAAALDFLHTK 167
Cdd:cd14008    49 DDVRREIAIMKKLD-HPNIVRLYEVIDDPESdkLYLVLEYCEGGPVMELDSGDRVppLPEETARKYFRDLVLGLEYLHEN 127

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462514851 168 GIAHRDLKPENILCESPEKvspVKICDFdlGSGMKLNNSCTPIT----TPELTTPEAEAGGDS 226
Cdd:cd14008   128 GIVHRDIKPENLLLTADGT---VKISDF--GVSEMFEDGNDTLQktagTPAFLAPELCDGDSK 185

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE 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 2462514851  80 LKIIEKQAGHSRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKH-FNEREASRVVRDVA 158
Cdd:cd05122    30 IKKINLESKEKKESILNEIAILKKCK-HPNIVKYYGSYLKKDELWIVMEFCSGGSLKDLLKNTNKtLTEQQIAYVCKEVL 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462514851 159 AALDFLHTKGIAHRDLKPENILCESPEKvspVKICDFdlGSGMKLNNSCTPIT---TPELTTPE 219
Cdd:cd05122   109 KGLEYLHSHGIIHRDIKAANILLTSDGE---VKLIDF--GLSAQLSDGKTRNTfvgTPYWMAPE 167

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK 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 2462514851  73 LTPCQESLKIIEKQA--GHSRSRVFREVETLyQCQGNKNILELIEFFEDDTRFYLVFEKLQGGSILAHIQKQKHFNEREA 150
Cdd:cd14072    23 LTGREVAIKIIDKTQlnPSSLQKLFREVRIM-KILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRMKEKEA 101