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 767985341 1503 GLEHLKPYHVTHCDLRLENLLLvHYQPGGTAQgfgpaepsptssyptrLIVSNFS----------QAKQKSHLVDpeiLR 1572
Cdd:cd14018   150 GVDHLVRHGIAHRDLKSDNILL-ELDFDGCPW----------------LVIADFGccladdsiglQLPFSSWYVD---RG 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1573 DQSRL-APEIITAT-------QYKKCDEFQTGILIYEMLHLPNPF--DENPELKEREYTRADLPRIPFRSPYSrgLQQLA 1642
Cdd:cd14018   210 GNACLmAPEVSTAVpgpgvviNYSKADAWAVGAIAYEIFGLSNPFygLGDTMLESRSYQESQLPALPSAVPPD--VRQVV 287

                         170       180
                  ....*....|....*....|....*.
gi 767985341 1643 SCLLNPNPSERILISDAKGILQCLLW 1668
Cdd:cd14018   288 KDLLQRDPNKRVSARVAANVLHLSLW 313

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 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 767985341 1503 GLEHLKPYHVTHCDLRLENLLLvHYQPGGTAQgfgpaepsptssyptrLIVSNFS----------QAKQKSHLVDpeiLR 1572
Cdd:cd14018   150 GVDHLVRHGIAHRDLKSDNILL-ELDFDGCPW----------------LVIADFGccladdsiglQLPFSSWYVD---RG 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1573 DQSRL-APEIITAT-------QYKKCDEFQTGILIYEMLHLPNPF--DENPELKEREYTRADLPRIPFRSPYSrgLQQLA 1642
Cdd:cd14018   210 GNACLmAPEVSTAVpgpgvviNYSKADAWAVGAIAYEIFGLSNPFygLGDTMLESRSYQESQLPALPSAVPPD--VRQVV 287

                         170       180
                  ....*....|....*....|....*.
gi 767985341 1643 SCLLNPNPSERILISDAKGILQCLLW 1668
Cdd:cd14018   288 KDLLQRDPNKRVSARVAANVLHLSLW 313

Protein kinase domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341  1577 LAPEIITATQY-KKCDEFQTGILIYEML--HLPNPFDENPELKEREYtRADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:pfam00069  127 MAPEVLGGNPYgPKVDVWSLGCILYELLtgKPPFPGINGNEIYELII-DQPYAFPELPSNLSEEAKDLLKKLLKKDPSKR 205

                   ....*..
gi 767985341  1654 ILISDAK 1660
Cdd:pfam00069  206 LTATQAL 212

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 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 767985341 1503 GLEHLKPYHVTHCDLRLENLLLvHYQPGGTAQgfgpaepsptssyptrLIVSNFS----------QAKQKSHLVDpeiLR 1572
Cdd:cd14018   150 GVDHLVRHGIAHRDLKSDNILL-ELDFDGCPW----------------LVIADFGccladdsiglQLPFSSWYVD---RG 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1573 DQSRL-APEIITAT-------QYKKCDEFQTGILIYEMLHLPNPF--DENPELKEREYTRADLPRIPFRSPYSrgLQQLA 1642
Cdd:cd14018   210 GNACLmAPEVSTAVpgpgvviNYSKADAWAVGAIAYEIFGLSNPFygLGDTMLESRSYQESQLPALPSAVPPD--VRQVV 287

                         170       180
                  ....*....|....*....|....*.
gi 767985341 1643 SCLLNPNPSERILISDAKGILQCLLW 1668
Cdd:cd14018   288 KDLLQRDPNKRVSARVAANVLHLSLW 313

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1468 CLTVADFVRDSLAQ----HGKSPdLYERQVCLLLLQLCSGLEHL---KPyHVTHCDLRLENLLLvhyqpggtaqgfgpae 1540
Cdd:cd13985    77 VLLLMEYCPGSLVDilekSPPSP-LSEEEVLRIFYQICQAVGHLhsqSP-PIIHRDIKIENILF---------------- 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1541 psptsSYPTRLIVSNFSQA---------KQKSHLVDPEILRDQSRL--APEIITATQYK----KCDEFQTGILIYEMLHL 1605
Cdd:cd13985   139 -----SNTGRFKLCDFGSAttehyplerAEEVNIIEEEIQKNTTPMyrAPEMIDLYSKKpigeKADIWALGCLLYKLCFF 213

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767985341 1606 PNPFDENPELKereytraDLP---RIPFRSPYSRGLQQLASCLLNPNPSERILISDAKGILQ 1664
Cdd:cd13985   214 KLPFDESSKLA-------IVAgkySIPEQPRYSPELHDLIRHMLTPDPAERPDIFQVINIIT 268

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1477 DSLAQHGKspdLYERQVCLLLLQLCSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTaqgfgpaepsptssyptrLIVSNF 1556
Cdd:cd05117    88 DRIVKKGS---FSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSP------------------IKIIDF 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1557 SQAKqksHLVDPEILRDQ----SRLAPEIITATQY-KKCDEFQTGILIYEML---HlpnPFDEN--PELKER----EYTr 1622
Cdd:cd05117   147 GLAK---IFEEGEKLKTVcgtpYYVAPEVLKGKGYgKKCDIWSLGVILYILLcgyP---PFYGEteQELFEKilkgKYS- 219

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 767985341 1623 adlpripFRSPY----SRGLQQLASCLLNPNPSERILISDA 1659
Cdd:cd05117   220 -------FDSPEwknvSEEAKDLIKRLLVVDPKKRLTAAEA 253

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 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 767985341 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaepspTSSYPTRLIVSNFSQAKQKSHLVDPEILRDqSRL--AP 1579
Cdd:cd14121   106 SALQFLREHNISHMDLKPQNLLL-------------------SSRYNPVLKLADFGFAQHLKPNDEAHSLRG-SPLymAP 165

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767985341 1580 EIITATQY-KKCDEFQTGILIYEMLHLPNPFDENP--ELKEReyTRADLP-RIPFRSPYSRGLQQLASCLLNPNPSERI 1654
Cdd:cd14121   166 EMILKKKYdARVDLWSVGVILYECLFGRAPFASRSfeELEEK--IRSSKPiEIPTRPELSADCRDLLLRLLQRDPDRRI 242

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC 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 767985341 1501 CSGLEHLKPYHVTHCDLRLENLLLvhyqpggTAQGFgpaepsptssyptrLIVSNFSQAKQKSHLVD--------PEILr 1572
Cdd:cd05123   103 VLALEYLHSLGIIYRDLKPENILL-------DSDGH--------------IKLTDFGLAKELSSDGDrtytfcgtPEYL- 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1573 dqsrlAPEIITATQY-KKCDEFQTGILIYEMLH-LPnPF-DENPELKEREYTRADLpRIPFRspYSRGLQQLASCLLNPN 1649
Cdd:cd05123   161 -----APEVLLGKGYgKAVDWWSLGVLLYEMLTgKP-PFyAENRKEIYEKILKSPL-KFPEY--VSPEAKSLISGLLQKD 231

                  ....*
gi 767985341 1650 PSERI 1654
Cdd:cd05123   232 PTKRL 236

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) 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. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 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 767985341 1501 CSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTAqgfgpaepsptssyptrLIVSNFSQAKqksHLVDP--EILRDQSRLA 1578
Cdd:cd14185   108 CEALVYIHSKHIVHRDLKPENLLVQHNPDKSTT-----------------LKLADFGLAK---YVTGPifTVCGTPTYVA 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1579 PEIITATQYK-KCDEFQTGILIYEMLHLPNPFDENPELKEREYTRADLPRIPFRSPY----SRGLQQLASCLLNPNPSER 1653
Cdd:cd14185   168 PEILSEKGYGlEVDMWAAGVILYILLCGFPPFRSPERDQEELFQIIQLGHYEFLPPYwdniSEAAKDLISRLLVVDPEKR 247

                         170
                  ....*....|.
gi 767985341 1654 IlisDAKGILQ 1664
Cdd:cd14185   248 Y---TAKQVLQ 255

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 767985341 1503 GLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaepspTSSYPTRLIvsNFSQAKQKSHLVDpeilRDQ-----SRL 1577
Cdd:cd05122   110 GLEYLHSHGIIHRDIKAANILL-------------------TSDGEVKLI--DFGLSAQLSDGKT----RNTfvgtpYWM 164

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767985341 1578 APEIITATQY-KKCDEFQTGILIYEMLHLPNPFDENPELKEREYT-RADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:cd05122   165 APEVIQGKPYgFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIaTNGPPGLRNPKKWSKEFKDFLKKCLQKDPEKR 242

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 767985341 1501 CSGLEHLKPYHVTHCDLRLENLLLvhyqpggTAQG------FGpaepsptssyptrliVSNFSQAKQKshlvdpeiLRDQ 1574
Cdd:cd14003   109 ISAVDYCHSNGIVHRDLKLENILL-------DKNGnlkiidFG---------------LSNEFRGGSL--------LKTF 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1575 ----SRLAPEIITATQY--KKCDEFQTGILIYEML--HLpnPFDeNPELKEREY--TRADLPRIPFRSPysrGLQQLASC 1644
Cdd:cd14003   159 cgtpAYAAPEVLLGRKYdgPKADVWSLGVILYAMLtgYL--PFD-DDNDSKLFRkiLKGKYPIPSHLSP---DARDLIRR 232

                         170
                  ....*....|....*.
gi 767985341 1645 LLNPNPSERILISDAK 1660
Cdd:cd14003   233 MLVVDPSKRITIEEIL 248

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 767985341 1501 CSGLEHLKPYHVTHCDLRLENLLLvhyqpggTAQG------FGpaepsptssyptrliVSNFSQAKQKSHLV---Dpeil 1571
Cdd:cd14007   110 ALALDYLHSKNIIHRDIKPENILL-------GSNGelkladFG---------------WSVHAPSNRRKTFCgtlD---- 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1572 rdqsRLAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFdENPELKEReYTRADLPRIPFRSPYSRGLQQLASCLLNPNP 1650
Cdd:cd14007   164 ----YLPPEMVEGKEYdYKVDIWSLGVLCYELLVGKPPF-ESKSHQET-YKRIQNVDIKFPSSVSPEAKDLISKLLQKDP 237

                         170
                  ....*....|
gi 767985341 1651 SERILISDAK 1660
Cdd:cd14007   238 SKRLSLEQVL 247

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek 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 767985341 1577 LAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFDEN--PELKEReYTRADLPRIPfrSPYSRGLQQLASCLLNPNPSER 1653
Cdd:cd08215   170 LSPELCENKPYnYKSDIWALGCVLYELCTLKHPFEANnlPALVYK-IVKGQYPPIP--SQYSSELRDLVNSMLQKDPEKR 246

                          90
                  ....*....|.
gi 767985341 1654 ILISDakgILQ 1664
Cdd:cd08215   247 PSANE---ILS 254

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek 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 767985341 1578 APEIITATQY-KKCDEFQTGILIYEMLHLPNPFDE--NPELKEReYTRADLPRIPFRspYSRGLQQLASCLLNPNPSERI 1654
Cdd:cd08217   178 SPELLNEQSYdEKSDIWSLGCLIYELCALHPPFQAanQLELAKK-IKEGKFPRIPSR--YSSELNEVIKSMLNVDPDKRP 254

                  ....
gi 767985341 1655 LISD 1658
Cdd:cd08217   255 SVEE 258

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 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 767985341 1501 CSGLEHL-----KPYhvTHCDLRLENLLLvHYQPGGTAQGFGPAEPSptssyptRLIVSNFSQAKQkshlvdpeiLRDQ- 1574
Cdd:cd13986   116 CRGLKAMhepelVPY--AHRDIKPGNVLL-SEDDEPILMDLGSMNPA-------RIEIEGRREALA---------LQDWa 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1575 ------SRLAPEIIT----ATQYKKCDEFQTGILIYEMLHLPNPFdenpelkEREYTRAD---------LPRIPFRSPYS 1635
Cdd:cd13986   177 aehctmPYRAPELFDvkshCTIDEKTDIWSLGCTLYALMYGESPF-------ERIFQKGDslalavlsgNYSFPDNSRYS 249

                         170       180
                  ....*....|....*....|...
gi 767985341 1636 RGLQQLASCLLNPNPSERILISD 1658
Cdd:cd13986   250 EELHQLVKSMLVVNPAERPSIDD 272

Catalytic domain of Numb-Associated Kinase (NAK)-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 Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1502 SGLEHLKPyHVTHCDLRLENLLLvhyqpggTAQG------FGPAepsptssypTRLIVSnfSQAKQKSHLVDPEILRD-- 1573
Cdd:cd14037   122 AAMHYLKP-PLIHRDLKVENVLI-------SDSGnyklcdFGSA---------TTKILP--PQTKQGVTYVEEDIKKYtt 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1574 -QSRlAPEIITATQYK----KCDEFQTGILIYEMLHLPNPFDENPEL--KEREYTradlprIPFRSPYSRGLQQLASCLL 1646
Cdd:cd14037   183 lQYR-APEMIDLYRGKpiteKSDIWALGCLLYKLCFYTTPFEESGQLaiLNGNFT------FPDNSRYSKRLHKLIRYML 255

                  ....*..
gi 767985341 1647 NPNPSER 1653
Cdd:cd14037   256 EEDPEKR 262

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 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. 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 767985341 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgPAEPSPtssyptRLIVSNFSQAKQKSHLVDPE-ILRDQSRLAPE 1580
Cdd:cd14665   107 SGVSYCHSMQICHRDLKLENTLL-------------DGSPAP------RLKICDFGYSKSSVLHSQPKsTVGTPAYIAPE 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1581 IITATQY--KKCDEFQTGILIYEMLHLPNPFDENPELKEREYTRADLPRIPFRSP----YSRGLQQLASCLLNPNPSERI 1654
Cdd:cd14665   168 VLLKKEYdgKIADVWSCGVTLYVMLVGAYPFEDPEEPRNFRKTIQRILSVQYSIPdyvhISPECRHLISRIFVADPATRI 247

                  ....*.
gi 767985341 1655 LISDAK 1660
Cdd:cd14665   248 TIPEIR 253

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 767985341 1477 DSLAQHGKSPDLYERQVcllLLQLCSGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaepspTSSYPTRLIVSNF 1556
Cdd:cd14098    90 DFIMAWGAIPEQHAREL---TKQILEAMAYTHSMGITHRDLKPENILI-------------------TQDDPVIVKISDF 147

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1557 SQAK-QKSHLVDPEILRDQSRLAPEIITATQYK-------KCDEFQTGILIYEMLHLPNPFDENPELK-EREYTRADLPR 1627
Cdd:cd14098   148 GLAKvIHTGTFLVTFCGTMAYLAPEILMSKEQNlqggysnLVDMWSVGCLVYVMLTGALPFDGSSQLPvEKRIRKGRYTQ 227

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 767985341 1628 IPFR----SPYSRglqQLASCLLNPNPSERILISDA 1659
Cdd:cd14098   228 PPLVdfniSEEAI---DFILRLLDVDPEKRMTAAQA 260

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM 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 767985341 1457 SHVVVITREVPCLTVADFVRDSLAQHGKSPDLYERQVCLLLLQLCSGlehlkpyHVTHCDLRLENLL---------LVHy 1527
Cdd:cd14005    80 GFLLIMERPEPCQDLFDFITERGALSENLARIIFRQVVEAVRHCHQR-------GVLHRDIKDENLLinlrtgevkLID- 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1528 qpggtaqgFGPAEPSPTSSYptrlivSNFSQAKQKShlvDPEILRDQSRLAPEiitATQykkcdeFQTGILIYEMLHLPN 1607
Cdd:cd14005   152 --------FGCGALLKDSVY------TDFDGTRVYS---PPEWIRHGRYHGRP---ATV------WSLGILLYDMLCGDI 205

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 767985341 1608 PFDENPELKEREytradlprIPFRSPYSRGLQQLASCLLNPNPSERI 1654
Cdd:cd14005   206 PFENDEQILRGN--------VLFRPRLSKECCDLISRCLQFDPSKRP 244

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 767985341 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaepsptSSYPTRLIVSNFSQAKQKShlvDPEILR-----DQSR 1576
Cdd:cd14164   111 GAVNYLHDMNIVHRDLKCENILL--------------------SADDRKIKIADFGFARFVE---DYPELSttfcgSRAY 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1577 LAPEIITATQY--KKCDEFQTGILIYEMLHLPNPFDEnpelkereyTRADLPRIPFRS-PYSRGLQQLASC------LLN 1647
Cdd:cd14164   168 TPPEVILGTPYdpKKYDVWSLGVVLYVMVTGTMPFDE---------TNVRRLRLQQRGvLYPSGVALEEPCralirtLLQ 238

                  ....*.
gi 767985341 1648 PNPSER 1653
Cdd:cd14164   239 FNPSTR 244

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 767985341 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgPAEPSPtssyptRLIVSNFSQAKQ-------KSHLVDPeilrdq 1574
Cdd:cd14662   107 SGVSYCHSMQICHRDLKLENTLL-------------DGSPAP------RLKICDFGYSKSsvlhsqpKSTVGTP------ 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767985341 1575 SRLAPEIITATQY--KKCDEFQTGILIYEMLHLPNPFDENPELKEREYTRADLPRIPFRSP----YSRGLQQLASCLLNP 1648
Cdd:cd14662   162 AYIAPEVLSRKEYdgKVADVWSCGVTLYVMLVGAYPFEDPDDPKNFRKTIQRIMSVQYKIPdyvrVSQDCRHLLSRIFVA 241

                         170
                  ....*....|..
gi 767985341 1649 NPSERILISDAK 1660
Cdd:cd14662   242 NPAKRITIPEIK 253