Pan3 Pseudokinase domain; This is a pseudokinase (PK) domain found in PAB-dependent poly(A)-specific ribonuclease subunit pan3. PAN3 proteins contain three prominent regions: an unstructured N-terminal region (N-term), a central PK domain, and a highly conserved C-terminal domain (C-term). The PAN3 PK domain has retained its ATP binding capacity, and this function is required for mRNA degradation in vivo. Analysis of Pan3 amino acids sequences show that, despite of retaining the general structural characteriztics of protein kinases, the PK domain has substitutions in all the conserved motifs that are critical for kinase activity, such as in the catalytic VAIK and HRD motifs and in the Mg2+ binding DFG motif. However, the PAN3 PK domain has been shown to bind ATP. Furthermore, similar to other kinases, the ATP-binding site is located in the cleft between the N- and C-lobes of the kinase fold, however, the ATP-binding pocket is wider than that of typical kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926   457 IESFFPIMSSPYV--------ECEKMERKISDAFQHGRFFNILCKIMFIidNNRASREypiaREKEIS------LIYLLR 522
Cdd:pfam18101   1 IDELLPMIGARLLteldaalhYNDELESELSRELENGRLFRLLCKLGFI--NERPEFE----GDPRWSetgdryMLKLFR 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112926   523 DYLFHQIDEDECPVIDLYQVLNRLGKLDAGINQAIALISRDELDCVSVSYGELKAWLDNVYEM 585
Cdd:pfam18101  75 DYVFHQVDEQGRPVLDLGHVLSCLNKLDAGVDEKIMLTSRDEQSCLVVSYKELKKCIESAFGE 137

Pan3 Pseudokinase domain; This is a pseudokinase (PK) domain found in PAB-dependent poly(A)-specific ribonuclease subunit pan3. PAN3 proteins contain three prominent regions: an unstructured N-terminal region (N-term), a central PK domain, and a highly conserved C-terminal domain (C-term). The PAN3 PK domain has retained its ATP binding capacity, and this function is required for mRNA degradation in vivo. Analysis of Pan3 amino acids sequences show that, despite of retaining the general structural characteriztics of protein kinases, the PK domain has substitutions in all the conserved motifs that are critical for kinase activity, such as in the catalytic VAIK and HRD motifs and in the Mg2+ binding DFG motif. However, the PAN3 PK domain has been shown to bind ATP. Furthermore, similar to other kinases, the ATP-binding site is located in the cleft between the N- and C-lobes of the kinase fold, however, the ATP-binding pocket is wider than that of typical kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926   457 IESFFPIMSSPYV--------ECEKMERKISDAFQHGRFFNILCKIMFIidNNRASREypiaREKEIS------LIYLLR 522
Cdd:pfam18101   1 IDELLPMIGARLLteldaalhYNDELESELSRELENGRLFRLLCKLGFI--NERPEFE----GDPRWSetgdryMLKLFR 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112926   523 DYLFHQIDEDECPVIDLYQVLNRLGKLDAGINQAIALISRDELDCVSVSYGELKAWLDNVYEM 585
Cdd:pfam18101  75 DYVFHQVDEQGRPVLDLGHVLSCLNKLDAGVDEKIMLTSRDEQSCLVVSYKELKKCIESAFGE 137

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926 228 YRYKEQIGFS--SWTYKCTSSIDGNAYVLKRLQDcSINIDTSTVDK-------LKNVFHPNIVPFHSAFHtdtfHDSSLL 298
Cdd:COG0515   9 YRILRLLGRGgmGVVYLARDLRLGRPVALKVLRP-ELAADPEARERfrrearaLARLNHPNIVRVYDVGE----EDGRPY 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19112926 299 LIYDFYPcTTTLGELylnnsknsvkLEENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRI 374
Cdd:COG0515  84 LVMEYVE-GESLADL----------LRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKL 148

Pan3 Pseudokinase domain; This is a pseudokinase (PK) domain found in PAB-dependent poly(A)-specific ribonuclease subunit pan3. PAN3 proteins contain three prominent regions: an unstructured N-terminal region (N-term), a central PK domain, and a highly conserved C-terminal domain (C-term). The PAN3 PK domain has retained its ATP binding capacity, and this function is required for mRNA degradation in vivo. Analysis of Pan3 amino acids sequences show that, despite of retaining the general structural characteriztics of protein kinases, the PK domain has substitutions in all the conserved motifs that are critical for kinase activity, such as in the catalytic VAIK and HRD motifs and in the Mg2+ binding DFG motif. However, the PAN3 PK domain has been shown to bind ATP. Furthermore, similar to other kinases, the ATP-binding site is located in the cleft between the N- and C-lobes of the kinase fold, however, the ATP-binding pocket is wider than that of typical kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926   457 IESFFPIMSSPYV--------ECEKMERKISDAFQHGRFFNILCKIMFIidNNRASREypiaREKEIS------LIYLLR 522
Cdd:pfam18101   1 IDELLPMIGARLLteldaalhYNDELESELSRELENGRLFRLLCKLGFI--NERPEFE----GDPRWSetgdryMLKLFR 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112926   523 DYLFHQIDEDECPVIDLYQVLNRLGKLDAGINQAIALISRDELDCVSVSYGELKAWLDNVYEM 585
Cdd:pfam18101  75 DYVFHQVDEQGRPVLDLGHVLSCLNKLDAGVDEKIMLTSRDEQSCLVVSYKELKKCIESAFGE 137

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926 228 YRYKEQIGFSSWT--YKCTSSIDGNAYVLKRLQDcSINIDTSTVDKLKNV-------FHPNIVPFHSAFhtdtFHDSSLL 298
Cdd:cd13997   2 FHELEQIGSGSFSevFKVRSKVDGCLYAVKKSKK-PFRGPKERARALREVeahaalgQHPNIVRYYSSW----EEGGHLY 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926 299 LIYdfypctttlgELYLNNSKNSVkLEEN---RKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIS 375
Cdd:cd13997  77 IQM----------ELCENGSLQDA-LEELspiSKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIG 145

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 19112926 376 --GCAD-----------------YELVVSNKPPLeerKKQDFVDLGVVIANLATG 411
Cdd:cd13997 146 dfGLATrletsgdveegdsrylaPELLNENYTHL---PKADIFSLGVTVYEAATG 197

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 19112926 277 HPNIVPFHSAFhtdtFHDSSLLLIYDFYPcTTTLGELYlnnskNSVKlEENRKIPERELWNYFFQLTIALSYLHKS-GFA 355
Cdd:cd08528  68 HPNIVRYYKTF----LENDRLYIVMELIE-GAPLGEHF-----SSLK-EKNEHFTEDRIWNIFVQMVLALRYLHKEkQIV 136

                        90       100
                ....*....|....*....|
gi 19112926 356 CNKLTPSRILVDQTERIRIS 375
Cdd:cd08528 137 HRDLKPNNIMLGEDDKVTIT 156

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 19112926 248 DGNAYVLKRLQDCSInIDTSTVDKLKN-------VFHPNIVPFHSAFHTdtfhDSSLLLIYDFYPCtttlGELYlnnskn 320
Cdd:cd05123  17 TGKLYAMKVLRKKEI-IKRKEVEHTLNernilerVNHPFIVKLHYAFQT----EEKLYLVLDYVPG----GELF------ 81

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 19112926 321 sVKLEENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIS 375
Cdd:cd05123  82 -SHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLT 135

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-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 19112926 271 KLKNvfHPNIVPFHSAFhTDTFHdssLLLIYDFYPCTttlgeLYlnnskNSVKLEENRKIPERELWNYFFQLTIALSYLH 350
Cdd:cd07830  53 KLNE--HPNIVKLKEVF-RENDE---LYFVFEYMEGN-----LY-----QLMKDRKGKPFSESVIRSIIYQILQGLAHIH 116

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 19112926 351 KSGFACNKLTPSRILVDQTERIRIsgcADYELV--VSNKPPLEE 392
Cdd:cd07830 117 KHGFFHRDLKPENLLVSGPEVVKI---ADFGLAreIRSRPPYTD 157

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 19112926 272 LKNVFHPNIVPFHSAFHTDTfhdsSLLLIYDFYPCtttlGELYlnnsknsVKLEENRKIPERELWNYFFQLTIALSYLHK 351
Cdd:cd14003  53 MKLLNHPNIIKLYEVIETEN----KIYLVMEYASG----GELF-------DYIVNNGRLSEDEARRFFQQLISAVDYCHS 117

                        90       100
                ....*....|....*....|....
gi 19112926 352 SGFACNKLTPSRILVDQTERIRIS 375
Cdd:cd14003 118 NGIVHRDLKLENILLDKNGNLKII 141

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 19112926 228 YRYKEQIG---FSSwTYKCTSSIDGNAYVLKRLQ-----------DCsinidTSTVDKLKNVFHPNIVPFHSAFhtdtFH 293
Cdd:cd08224   2 YEIEKKIGkgqFSV-VYRARCLLDGRLVALKKVQifemmdakarqDC-----LKEIDLLQQLNHPNIIKYLASF----IE 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 19112926 294 DSSLLLIYDFYPCtttlGEL--YLNNSKnsvklEENRKIPERELWNYFFQLTIALSYLH 350
Cdd:cd08224  72 NNELNIVLELADA----GDLsrLIKHFK-----KQKRLIPERTIWKYFVQLCSALEHMH 121

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 19112926 228 YRYKEQIGFSSWT--YKCTSSIDGNAYVLKRLQ-----DCSINID-TSTVDKLKNVFHPNIVPFHSAFhtdtFHDSSLLL 299
Cdd:cd08229  26 FRIEKKIGRGQFSevYRATCLLDGVPVALKKVQifdlmDAKARADcIKEIDLLKQLNHPNVIKYYASF----IEDNELNI 101

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19112926 300 IYDFYPcTTTLGELYLNNSKnsvkleENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRI 374
Cdd:cd08229 102 VLELAD-AGDLSRMIKHFKK------QKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKL 169

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 19112926 277 HPNIVPFHSAFHTDtfhdSSLLLIYDFypctTTLGELYlnnsknsVKLEENRKIPERELWNYFFQLTIALSYLHKSGFAC 356
Cdd:cd14073  60 HPHIIRIYEVFENK----DKIVIVMEY----ASGGELY-------DYISERRRLPEREARRIFRQIVSAVHYCHKNGVVH 124

                        90       100       110
                ....*....|....*....|....*....|.
gi 19112926 357 NKLTPSRILVDQTERIRIsgcADYELvvSNK 387
Cdd:cd14073 125 RDLKLENILLDQNGNAKI---ADFGL--SNL 150

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 19112926 272 LKNVFHPNIVPFHsafhtDTFHD--SSLLLIYDFYpCTTtlGEL--YLNNSKnsvklEENRKIPERELWNYFFQLTIALS 347
Cdd:cd08217  53 LRELKHPNIVRYY-----DRIVDraNTTLYIVMEY-CEG--GDLaqLIKKCK-----KENQYIPEEFIWKIFTQLLLALY 119

                ...
gi 19112926 348 YLH 350
Cdd:cd08217 120 ECH 122

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR 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 19112926 241 YKCTSSIDGNAYVLKRLQDCSINIDTStVDKLKNVFHPNIVPFHSAFhTDTFHDsslllIYDFYPCTTTLGELYL----- 315
Cdd:cd14047  23 FKAKHRIDGKTYAIKRVKLNNEKAERE-VKALAKLDHPNIVRYNGCW-DGFDYD-----PETSSSNSSRSKTKCLfiqme 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926 316 -------------NNSKNSVKLEENRKiperelwnyFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIsgcADYEL 382
Cdd:cd14047  96 fcekgtleswiekRNGEKLDKVLALEI---------FEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKI---GDFGL 163

                       170
                ....*....|....
gi 19112926 383 VVSNKPPLEERKKQ 396
Cdd:cd14047 164 VTSLKNDGKRTKSK 177

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 19112926 272 LKNVFHPNIVPFHSAFHtDTFHDSsLLLIYDFYPCtttlGELYLNNSKnsvklEENRKIPERELWNYFFQLTIALSYLHK 351
Cdd:cd14008  58 MKKLDHPNIVRLYEVID-DPESDK-LYLVLEYCEG----GPVMELDSG-----DRVPPLPEETARKYFRDLVLGLEYLHE 126

                        90       100
                ....*....|....*....|....*....
gi 19112926 352 SGFACNKLTPSRILVDQTERIRIS--GCA 378
Cdd:cd14008 127 NGIVHRDIKPENLLLTADGTVKISdfGVS 155

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19112926 228 YRYKEQIGFS--SWTYKCTSSIDGNAYVLKRLQDcSINIDTSTVDK-------LKNVFHPNIVPFHSAFHtdtfHDSSLL 298
Cdd:COG0515   9 YRILRLLGRGgmGVVYLARDLRLGRPVALKVLRP-ELAADPEARERfrrearaLARLNHPNIVRVYDVGE----EDGRPY 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19112926 299 LIYDFYPcTTTLGELylnnsknsvkLEENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRI 374
Cdd:COG0515  84 LVMEYVE-GESLADL----------LRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKL 148

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. 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. The ULK4 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 19112926 277 HPNIVPFHSAFHTdTFHdssLLLIYDFypCT-TTLGELylnnsknsvkLEENRKIPERELWNYFFQLTIALSYLHKSGFA 355
Cdd:cd14010  53 HPNVLKFYEWYET-SNH---LWLVVEY--CTgGDLETL----------LRQDGNLPESSVRKFGRDLVRGLHYIHSKGII 116

                        90       100
                ....*....|....*....|.
gi 19112926 356 CNKLTPSRILVDQTERIRISG 376
Cdd:cd14010 117 YCDLKPSNILLDGNGTLKLSD 137

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 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 19112926 248 DGNAYVLKRLQDCSI-------NIDTSTVDKLKNVFHPNIVPFHSAFHTDtfhdSSLLLIYDFypctTTLGELYLNnskn 320
Cdd:cd05603  19 DGKFYAVKVLQKKTIlkkkeqnHIMAERNVLLKNLKHPFLVGLHYSFQTS----EKLYFVLDY----VNGGELFFH---- 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 19112926 321 svkLEENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVD 367
Cdd:cd05603  87 ---LQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLD 130

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC 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 19112926 265 DTSTVDKLKNVF-----HPNIVPFHSAFHTDtfhdSSLLLIYDfypctttlgelYLNNSKNSVKLEENRKIPERELWNYF 339
Cdd:cd05618  63 DIDWVQTEKHVFeqasnHPFLVGLHSCFQTE----SRLFFVIE-----------YVNGGDLMFHMQRQRKLPEEHARFYS 127

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 19112926 340 FQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIS 375
Cdd:cd05618 128 AEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLT 163

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 19112926 272 LKNVFHPNIVPFHsafhtDTFHDSS-LLLIYDFYPCtttlGEL--YLNnsknsvkleENRKIPERELWNYFFQLTIALSY 348
Cdd:cd14081  55 MKLIEHPNVLKLY-----DVYENKKyLYLVLEYVSG----GELfdYLV---------KKGRLTEKEARKFFRQIISALDY 116

                        90       100       110
                ....*....|....*....|....*....|..
gi 19112926 349 LHKSGFACNKLTPSRILVDQTERIRIsgcADY 380
Cdd:cd14081 117 CHSHSICHRDLKPENLLLDEKNNIKI---ADF 145

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 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 19112926 241 YKCTSSIDGNAYVLKRL----QDCSINIDTSTVDKLKNVFHPNIVPFHSAFHTdtfhDSSLLLIYDFYpcTTTLGElYLN 316
Cdd:cd07873  19 YKGRSKLTDNLVALKEIrlehEEGAPCTAIREVSLLKDLKHANIVTLHDIIHT----EKSLTLVFEYL--DKDLKQ-YLD 91

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19112926 317 NSKNSVKLeENRKIperelwnYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIsgcADYELVVSNKPP 389
Cdd:cd07873  92 DCGNSINM-HNVKL-------FLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKL---ADFGLARAKSIP 153

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 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 19112926 262 INIDTStVDKLKNVFHPNIVPFHSAFhtDTFHDSSLLLIYdfypctTTLGELYlNNSKNSVKLEEnrkiPERELwnYFFQ 341
Cdd:cd14084  56 RNIETE-IEILKKLSHPCIIKIEDFF--DAEDDYYIVLEL------MEGGELF-DRVVSNKRLKE----AICKL--YFYQ 119

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 19112926 342 LTIALSYLHKSGFACNKLTPSRILV---DQTERIRIS 375
Cdd:cd14084 120 MLLAVKYLHSNGIIHRDLKPENVLLssqEEECLIKIT 156

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. 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, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 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 19112926 249 GNAYVLKRLQDCSInidtstVDKLKNVFH--------------PNIVPFHSAFHTDTfhdsSLLLIYDfypctttlgelY 314
Cdd:cd05613  28 GKLYAMKVLKKATI------VQKAKTAEHtrterqvlehirqsPFLVTLHYAFQTDT----KLHLILD-----------Y 86

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 19112926 315 LNNSKNSVKLEENRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERI 372
Cdd:cd05613  87 INGGELFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHV 144

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-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 19112926 241 YKCTSSIDGNAYVLKRlqdcsINID------TST----VDKLKNVFHPNIVPFHSAFHTDtfhdSSLLLIYDFypCTTTL 310
Cdd:cd07829  16 YKAKDKKTGEIVALKK-----IRLDneeegiPSTalreISLLKELKHPNIVKLLDVIHTE----NKLYLVFEY--CDQDL 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19112926 311 GElYLNNSknsvkleeNRKIPERELWNYFFQLTIALSYLHKSGFACNKLTPSRILVDQTERIRIsgcADYEL 382
Cdd:cd07829  85 KK-YLDKR--------PGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKL---ADFGL 144

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (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. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 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 19112926 272 LKNVFHPNIVPFHsafhtDTFHDSSLLLIYDFYP-CTTTLGELyLNNSKNsvkleenRKIPERELWNYFFQLTIALSYLH 350
Cdd:cd14119  48 LRRLNHRNVIKLV-----DVLYNEEKQKLYMVMEyCVGGLQEM-LDSAPD-------KRLPIWQAHGYFVQLIDGLEYLH 114

                        90       100       110
                ....*....|....*....|....*....|.
gi 19112926 351 KSGFACNKLTPSRILVDQTERIRIS--GCAD 379
Cdd:cd14119 115 SQGIIHKDIKPGNLLLTTDGTLKISdfGVAE 145

Catalytic domain of Fungal Nak1-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 Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 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 19112926 227 LYRYKEQIGFSSW--TYKCTSSIDGNAYVLKrlqdcSINIDTSTVD------------KLKNVFHPNIVPFHSAFHTDTf 292
Cdd:cd06917   2 LYRRLELVGRGSYgaVYRGYHVKTGRVVALK-----VLNLDTDDDDvsdiqkevallsQLKLGQPKNIIKYYGSYLKGP- 75