UBA domain found in serine/threonine-protein kinase BRSK1, BRSK2 and similar proteins; The family includes brain-specific kinases BRSK1 and BRSK2. They are AMP-activated protein kinase (AMPK)-related kinases that are highly expressed in mammalian forebrain and crucial for establishing neuronal polarity.BRSK1, also called brain-selective kinase 1, brain-specific serine/threonine-protein kinase 1, BR serine/threonine-protein kinase 1, serine/threonine-protein kinase SAD-B, or synapses of Amphids Defective homolog 1 (SAD1 homolog), is associated with synaptic vesicles and is tightly associated with the presynaptic cytomatrix in nerve terminals. It can regulate neurotransmitter release presynaptically. BRSK2, also called brain-selective kinase 2, brain-specific serine/threonine-protein kinase 2, BR serine/threonine-protein kinase 2, serine/threonine-protein kinase 29, or serine/threonine-protein kinase SAD-A is an AMP-activated protein kinase (AMPK)-related kinase exclusively expressed in brain and pancreas. It plays an essential role in neuronal polarization. It interacts with CDK-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release, and further negatively regulates glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells through activation of p21-activated kinase-1 (PAK1). BRSK2 also regulates cell-cycle progression controlled by APC/C(Cdh1) through the ubiquitin-proteasome pathway. Moreover, BRSK2 is regulated by endoplasmic reticulum (ER) stress in protein level and involved in ER stress-induced apoptosis. Both BRSK1 and BRSK2 contain an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039779094 138 ELDPDVLESMASLGCFRDRERLHRELRSEEENQEKMIYYLLLDRKERYPSCEDQ 191
Cdd:cd14340     1 DIDPDVLDSMTSLGCFKDKEKLVQELLSPEHNTEKVIYFLLLDRKERKPSCEDD 54

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  281 PEPGAGDEARGGGSPTSKTQTLPSRGPRGGGAGEQPPPPSARSTPLPGPPGSPRSSGGTPLHSPLHTPRASPTGTPGTTP 360
Cdd:PHA03247  2578 SEPAVTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPA 2657

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039779094  361 PPSPGGGVggaawRSRLNSIRNSFLGSPRFHRRKMQVPTAEEMSSLT----PESSPELAKRSW 419
Cdd:PHA03247  2658 PGRVSRPR-----RARRLGRAAQASSPPQRPRRRAARPTVGSLTSLAdpppPPPTPEPAPHAL 2715

UBA domain found in serine/threonine-protein kinase BRSK1, BRSK2 and similar proteins; The family includes brain-specific kinases BRSK1 and BRSK2. They are AMP-activated protein kinase (AMPK)-related kinases that are highly expressed in mammalian forebrain and crucial for establishing neuronal polarity.BRSK1, also called brain-selective kinase 1, brain-specific serine/threonine-protein kinase 1, BR serine/threonine-protein kinase 1, serine/threonine-protein kinase SAD-B, or synapses of Amphids Defective homolog 1 (SAD1 homolog), is associated with synaptic vesicles and is tightly associated with the presynaptic cytomatrix in nerve terminals. It can regulate neurotransmitter release presynaptically. BRSK2, also called brain-selective kinase 2, brain-specific serine/threonine-protein kinase 2, BR serine/threonine-protein kinase 2, serine/threonine-protein kinase 29, or serine/threonine-protein kinase SAD-A is an AMP-activated protein kinase (AMPK)-related kinase exclusively expressed in brain and pancreas. It plays an essential role in neuronal polarization. It interacts with CDK-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release, and further negatively regulates glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells through activation of p21-activated kinase-1 (PAK1). BRSK2 also regulates cell-cycle progression controlled by APC/C(Cdh1) through the ubiquitin-proteasome pathway. Moreover, BRSK2 is regulated by endoplasmic reticulum (ER) stress in protein level and involved in ER stress-induced apoptosis. Both BRSK1 and BRSK2 contain an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039779094 138 ELDPDVLESMASLGCFRDRERLHRELRSEEENQEKMIYYLLLDRKERYPSCEDQ 191
Cdd:cd14340     1 DIDPDVLDSMTSLGCFKDKEKLVQELLSPEHNTEKVIYFLLLDRKERKPSCEDD 54

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094   7 GDSLLETSCGSPHYACPEVIKGEKYdGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHF---IPPDCQ 83
Cdd:pfam00069 113 SGSSLTTFVGTPWYMAPEVLGGNPY-GPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELpsnLSEEAK 191

                          90       100
                  ....*....|....*....|....*
gi 1039779094  84 SLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:pfam00069 192 DLLKKLLKKDPSKRLTATQALQHPW 216

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  13 TSCGSPHYACPEVIKGEKYDgRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPH----FIPPDCQSLLRG 88
Cdd:COG0515   167 TVVGTPGYMAPEQARGEPVD-PRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSelrpDLPPALDAIVLR 245

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  89 MIEVEPEKRLS--------LEQIQKHPWYLGGKHEPDPCLEPAPGRRVAMRSLPSNGELDPDVLESMASLGCFRDRERLH 160
Cdd:COG0515   246 ALAKDPEERYQsaaelaaaLRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAA 325

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094 161 RELRSEEENqekmiyYLLLDRKERYPSCEDQDLPPRNDVDPPRKRVDSPMLSRHGKRRPERKSMEVLSITDAGSGGSPVP 240
Cdd:COG0515   326 AAAAAAAAA------ALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAA 399

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094 241 TRRALEMAQHSQRSRSVSGASTGLSSSPLSSPRSPVFSFSPEPGAGDEARGGGSPTSKTQTLPSRGPRGGGAGEQPPPPS 320
Cdd:COG0515   400 LAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAAAAAAAAAPLLAALLAAAALAAAAAAAAL 479

                  ..
gi 1039779094 321 AR 322
Cdd:COG0515   480 AL 481

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  281 PEPGAGDEARGGGSPTSKTQTLPSRGPRGGGAGEQPPPPSARSTPLPGPPGSPRSSGGTPLHSPLHTPRASPTGTPGTTP 360
Cdd:PHA03247  2578 SEPAVTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPA 2657

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039779094  361 PPSPGGGVggaawRSRLNSIRNSFLGSPRFHRRKMQVPTAEEMSSLT----PESSPELAKRSW 419
Cdd:PHA03247  2658 PGRVSRPR-----RARRLGRAAQASSPPQRPRRRAARPTVGSLTSLAdpppPPPTPEPAPHAL 2715

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094   7 GDSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLL 86
Cdd:cd14003   151 GGSLLKTFCGTPAYAAPEVLLGRKYDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPSHLSPDARDLI 230

                          90       100
                  ....*....|....*....|..
gi 1039779094  87 RGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14003   231 RRMLVVDPSKRITIEEILNHPW 252

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK 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 1039779094   8 DSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLR 87
Cdd:cd14078   156 DHHLETCCGSPAYAAPELIQGKPYIGSEADVWSMGVLLYALLCGFLPFDDDNVMALYRKIQSGKYEEPEWLSPSSKLLLD 235

                          90       100
                  ....*....|....*....|.
gi 1039779094  88 GMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14078   236 QMLQVDPKKRITVKELLNHPW 256

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to 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 1039779094   7 GDSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLL 86
Cdd:cd14663   155 QDGLLHTTCGTPNYVAPEVLARRGYDGAKADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEFEYPRWFSPGAKSLI 234

                          90       100
                  ....*....|....*....|..
gi 1039779094  87 RGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14663   235 KRILDPNPSTRITVEQIMASPW 256

UBA domain found in serine/threonine-protein kinase BRSK1, BRSK2 and similar proteins; The family includes brain-specific kinases BRSK1 and BRSK2. They are AMP-activated protein kinase (AMPK)-related kinases that are highly expressed in mammalian forebrain and crucial for establishing neuronal polarity.BRSK1, also called brain-selective kinase 1, brain-specific serine/threonine-protein kinase 1, BR serine/threonine-protein kinase 1, serine/threonine-protein kinase SAD-B, or synapses of Amphids Defective homolog 1 (SAD1 homolog), is associated with synaptic vesicles and is tightly associated with the presynaptic cytomatrix in nerve terminals. It can regulate neurotransmitter release presynaptically. BRSK2, also called brain-selective kinase 2, brain-specific serine/threonine-protein kinase 2, BR serine/threonine-protein kinase 2, serine/threonine-protein kinase 29, or serine/threonine-protein kinase SAD-A is an AMP-activated protein kinase (AMPK)-related kinase exclusively expressed in brain and pancreas. It plays an essential role in neuronal polarization. It interacts with CDK-related protein kinase PCTAIRE1, a kinase involved in neurite outgrowth and neurotransmitter release, and further negatively regulates glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells through activation of p21-activated kinase-1 (PAK1). BRSK2 also regulates cell-cycle progression controlled by APC/C(Cdh1) through the ubiquitin-proteasome pathway. Moreover, BRSK2 is regulated by endoplasmic reticulum (ER) stress in protein level and involved in ER stress-induced apoptosis. Both BRSK1 and BRSK2 contain an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1039779094 138 ELDPDVLESMASLGCFRDRERLHRELRSEEENQEKMIYYLLLDRKERYPSCEDQ 191
Cdd:cd14340     1 DIDPDVLDSMTSLGCFKDKEKLVQELLSPEHNTEKVIYFLLLDRKERKPSCEDD 54

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094   7 GDSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEK-VKRGVFHMPH--FIPPDCQ 83
Cdd:cd14080   157 GDVLSKTFCGSAAYAAPEILQGIPYDPKKYDIWSLGVILYIMLCGSMPFDDSNIKKMLKDqQNRKVRFPSSvkKLSPECK 236

                          90       100
                  ....*....|....*....|....*.
gi 1039779094  84 SLLRGMIEVEPEKRLSLEQIQKHPWY 109
Cdd:cd14080   237 DLIDQLLEPDPTKRATIEEILNHPWL 262

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  10 LLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGV-FHMPHFIPPDCQSLLRG 88
Cdd:cd14162   160 LSETYCGSYAYASPEILRGIPYDPFLSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQRRVvFPKNPTVSEECKDLILR 239

                          90       100
                  ....*....|....*....|.
gi 1039779094  89 MIeVEPEKRLSLEQIQKHPWY 109
Cdd:cd14162   240 ML-SPVKKRITIEEIKRDPWF 259

Catalytic domain of Kin1, Kin2, and simlar 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 yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 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 1039779094   8 DSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLR 87
Cdd:cd14077   166 RRLLRTFCGSLYFAAPELLQAQPYTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPSYLSSECKSLIS 245

                          90       100
                  ....*....|....*....|.
gi 1039779094  88 GMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14077   246 RMLVVDPKKRATLEQVLNHPW 266

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK 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 1039779094  11 LETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLRGMI 90
Cdd:cd14074   160 LETSCGSLAYSAPEILLGDEYDAPAVDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDCKYTVPAHVSPECKDLIRRML 239

                          90
                  ....*....|....*...
gi 1039779094  91 EVEPEKRLSLEQIQKHPW 108
Cdd:cd14074   240 IRDPKKRASLEEIENHPW 257

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 1039779094  13 TSCGSPHYACPEVIKGEKYDgRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLRGMIEV 92
Cdd:cd14007   157 TFCGTLDYLPPEMVEGKEYD-YKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPSSVSPEAKDLISKLLQK 235

                          90
                  ....*....|....*.
gi 1039779094  93 EPEKRLSLEQIQKHPW 108
Cdd:cd14007   236 DPSKRLSLEQVLNHPW 251

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK 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 1039779094   8 DSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHfIPPDCQSLLR 87
Cdd:cd14073   154 DKLLQTFCGSPLYASPEIVNGTPYQGPEVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQISSGDYREPT-QPSDASGLIR 232

                          90       100
                  ....*....|....*....|.
gi 1039779094  88 GMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14073   233 WMLTVNPKRRATIEDIANHWW 253

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 1039779094   7 GDSLLETSCGSPHYACPEVIKGEK--YDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRG--VFHMPHFIPPDC 82
Cdd:cd14008   161 GNDTLQKTAGTPAFLAPELCDGDSktYSGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQndEFPIPPELSPEL 240

                          90       100
                  ....*....|....*....|....*.
gi 1039779094  83 QSLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14008   241 KDLLRRMLEKDPEKRITLKEIKEHPW 266

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 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 1039779094   1 MASLQVGDSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFiPP 80
Cdd:cd14161   148 LSNLYNQDKFLQTYCGSPLYASPEIVNGRPYIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSGAYREPTK-PS 226

                          90       100
                  ....*....|....*....|....*...
gi 1039779094  81 DCQSLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14161   227 DACGLIRWLLMVNPERRATLEDVASHWW 254

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 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 1039779094   8 DSLLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHFIPPDCQSLLR 87
Cdd:cd14075   154 GETLNTFCGSPPYAAPELFKDEHYIGIYVDIWALGVLLYFMVTGVMPFRAETVAKLKKCILEGTYTIPSYVSEPCQELIR 233

                          90       100
                  ....*....|....*....|.
gi 1039779094  88 GMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14075   234 GILQPVPSDRYSIDEIKNSEW 254

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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 AMP-activated protein kinase (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 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 1039779094   7 GDSLLETSCGSPHYACPEVIKGE--KYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMP--HFIPPDC 82
Cdd:cd14118   168 DDALLSSTAGTPAFMAPEALSESrkKFSGKALDIWAMGVTLYCFVFGRCPFEDDHILGLHEKIKTDPVVFPddPVVSEQL 247

                          90       100
                  ....*....|....*....|....*.
gi 1039779094  83 QSLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14118   248 KDLILRMLDKNPSERITLPEIKEHPW 273

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to 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 1039779094  12 ETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDD----DNLRQLLEKVKRGVFHMPHF--IPPDCQSL 85
Cdd:cd14662   155 KSTVGTPAYIAPEVLSRKEYDGKVADVWSCGVTLYVMLVGAYPFEDpddpKNFRKTIQRIMSVQYKIPDYvrVSQDCRHL 234

                          90       100
                  ....*....|....*....|...
gi 1039779094  86 LRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14662   235 LSRIFVANPAKRITIPEIKNHPW 257

Catalytic domain of RCK1-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 fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094   3 SLQVGDSLLETSCGSPHYACPEVIKGEKYDgRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRG--VFHMPHF--I 78
Cdd:cd14096   186 SKQVWDSNTKTPCGTVGYTAPEVVKDERYS-KKVDMWALGCVLYTLLCGFPPFYDESIETLTEKISRGdyTFLSPWWdeI 264

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039779094  79 PPDCQSLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14096   265 SKSAKDLISHLLTVDPAKRYDIDEFLAHPW 294

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 1039779094   1 MASLQVGDSLLETSCGSPHYACPEVIKGEKYDGR-----RADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMP 75
Cdd:cd14098   149 LAKVIHTGTFLVTFCGTMAYLAPEILMSKEQNLQggysnLVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQP 228

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1039779094  76 HF----IPPDCQSLLRGMIEVEPEKRLSLEQIQKHPW 108
Cdd:cd14098   229 PLvdfnISEEAIDFILRLLDVDPEKRMTAAQALDHPW 265

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  13 TSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHF--IPPDCQSLLRGMI 90
Cdd:cd14099   160 TLCGTPNYIAPEVLEKKKGHSFEVDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEYSFPSHlsISDEAKDLIRSML 239

                          90
                  ....*....|....*...
gi 1039779094  91 EVEPEKRLSLEQIQKHPW 108
Cdd:cd14099   240 QPDPTKRPSLDEILSHPF 257

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase 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 1039779094  15 CGSPHYACPEVIKGEKYdGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPHF--IPPDCQSLLRGMIEV 92
Cdd:cd05579   169 VGTPDYLAPEILLGQGH-GKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWPEDpeVSDEAKDLISKLLTP 247

                          90       100
                  ....*....|....*....|..
gi 1039779094  93 EPEKRL---SLEQIQKHPWYLG 111
Cdd:cd05579   248 DPEKRLgakGIEEIKNHPFFKG 269

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; 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 followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. 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. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII 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 1039779094  16 GSPHYACPEVIKGEKYdGRRADMWSCGVILFALLVGALPFDDDNLRQLLEKVKRGVFHMPH----FIPPDCQSLLRGMIE 91
Cdd:cd14086   165 GTPGYLSPEVLRKDPY-GKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYPSpewdTVTPEAKDLINQMLT 243

                          90
                  ....*....|....*..
gi 1039779094  92 VEPEKRLSLEQIQKHPW 108
Cdd:cd14086   244 VNPAKRITAAEALKHPW 260

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039779094  10 LLETSCGSPHYACPEVIKGEKYDGRRADMWSCGVILFALLVGALPFDDDNLRqLLEKVKRGVFHMPHF-IPPDCQSLLRG 88
Cdd:cd14164   157 LSTTFCGSRAYTPPEVILGTPYDPKKYDVWSLGVVLYVMVTGTMPFDETNVR-RLRLQQRGVLYPSGVaLEEPCRALIRT 235