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 2414731873 200 SHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLWVGFFGQETAPeidrnFLADL 279
Cdd:cd00180    90 SEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPY-----YAPPE 164

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2414731873 280 ALTQGRHTVKSDVYSLGV---AFRNLVQLLgngnigpedrgavrqdhlelldklsQKMIEEEPGNRPTIEEIMKDP 352
Cdd:cd00180   165 LLGGRYYGPKVDIWSLGVilyELEELKDLI-------------------------RRMLQYDPKKRPSAKELLEHL 215

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 200 SHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLWVGFFGQETAPeidrnFLADL 279
Cdd:cd00180    90 SEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPY-----YAPPE 164

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2414731873 280 ALTQGRHTVKSDVYSLGV---AFRNLVQLLgngnigpedrgavrqdhlelldklsQKMIEEEPGNRPTIEEIMKDP 352
Cdd:cd00180   165 LLGGRYYGPKVDIWSLGVilyELEELKDLI-------------------------RRMLQYDPKKRPSAKELLEHL 215

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 256 TRLWVgffgqetAPEIdrnfladlaLTQGRHTVKSDVYSLGVAFRNLV-----------QLLGNGNIGPEDRGAVRQDHL 324
Cdd:pfam00069 123 TPWYM-------APEV---------LGGNPYGPKVDVWSLGCILYELLtgkppfpgingNEIYELIIDQPYAFPELPSNL 186

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2414731873 325 --ELLDKLSqKMIEEEPGNRPTIEEIMKDPLF 354
Cdd:pfam00069 187 seEAKDLLK-KLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 200 SHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLWVGFFGQETAPeidrnFLADL 279
Cdd:cd00180    90 SEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPY-----YAPPE 164

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2414731873 280 ALTQGRHTVKSDVYSLGV---AFRNLVQLLgngnigpedrgavrqdhlelldklsQKMIEEEPGNRPTIEEIMKDP 352
Cdd:cd00180   165 LLGGRYYGPKVDIWSLGVilyELEELKDLI-------------------------RRMLQYDPKKRPSAKELLEHL 215

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 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 2414731873 211 MVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLwvgffgqeTAPEIDRNFLAdLALTQGRHTVKS 290
Cdd:cd14050   109 LLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLVVELDKEDIH--------DAQEGDPRYMA-PELLQGSFTKAA 179

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2414731873 291 DVYSLGVAFRNLV------------QLLGNGNIGPEDRGAVRQDHLELLdklsQKMIEEEPGNRPTIEEIMKDP 352
Cdd:cd14050   180 DIFSLGITILELAcnlelpsggdgwHQLRQGYLPEEFTAGLSPELRSII----KLMMDPDPERRPTAEDLLALP 249

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; 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. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 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 2414731873 202 PDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLWVGFFGQEtapeidrNFLADLAL 281
Cdd:cd14189   101 PEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICGTP-------NYLAPEVL 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 282 TQGRHTVKSDVYSLGVAFRNLvqLLGNGNIGPEDRG----AVRQDHLELLDKLS---QKMI----EEEPGNRPTIEEIMK 350
Cdd:cd14189   174 LRQGHGPESDVWSLGCVMYTL--LCGNPPFETLDLKetyrCIKQVKYTLPASLSlpaRHLLagilKRNPGDRLTLDQILE 251

                  ....
gi 2414731873 351 DPLF 354
Cdd:cd14189   252 HEFF 255

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 2414731873 203 DVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAP-IGTETRLWVGFFG--QETAPEIDRNfladl 279
Cdd:cd05613   106 EVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEfLLDENERAYSFCGtiEYMAPEIVRG----- 180

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 280 alTQGRHTVKSDVYSLGVAFRNLV------QLLGNGNIGPE-DRGAVR------QDHLELLDKLSQKMIEEEPGNR---- 342
Cdd:cd05613   181 --GDSGHDKAVDWWSLGVLMYELLtgaspfTVDGEKNSQAEiSRRILKseppypQEMSALAKDIIQRLLMKDPKKRlgcg 258

                         170       180       190
                  ....*....|....*....|....*....|.
gi 2414731873 343 PT-IEEIMKDPLFEGLNFEDIEEGKA-RPFR 371
Cdd:cd05613   259 PNgADEIKKHPFFQKINWDDLAAKKVpAPFK 289

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 2414731873 203 DVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLdtaapiGTETRLWVGFFGQE-----TAPEIDRNFLa 277
Cdd:cd13997   104 EVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDF------GLATRLETSGDVEEgdsryLAPELLNENY- 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 278 dlaltqgRHTVKSDVYSLGVAF------------RNLVQLLGNGNIGPEDRGAVRQDhlelLDKLSQKMIEEEPGNRPTI 345
Cdd:cd13997   177 -------THLPKADIFSLGVTVyeaatgeplprnGQQWQQLRQGKLPLPPGLVLSQE----LTRLLKVMLDPDPTRRPTA 245

                  ....*..
gi 2414731873 346 EEIMKDP 352
Cdd:cd13997   246 DQLLAHD 252

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 212 VAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIGTETRLWVGFFGQETAPEIDRNFLADLALTQGRH--TVK 289
Cdd:cd08216   111 LNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLRYAYSMVKHGKRQRVVHDFPKSSEKNLPWLSPEVLQQNLLgyNEK 190

                  ....*...
gi 2414731873 290 SDVYSLGV 297
Cdd:cd08216   191 SDIYSVGI 198

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 187 SKGLVGDMLETGRSHPDVQV--LAANMVAALKSLHNLGLLHRSIELNS---FSVLPDGTVVLGGLDTAAPIGTETRLwvg 261
Cdd:cd14012    87 PGGSLSELLDSVGSVPLDTArrWTLQLLEALEYLHRNGVVHKSLHAGNvllDRDAGTGIVKLTDYSLGKTLLDMCSR--- 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 262 ffGQETAPEIDRNFLADLALTQGRHTVKSDVYSLGVAFRNLVQ--------LLGNGNIGPEDRGAVRQDHLelldklsQK 333
Cdd:cd14012   164 --GSLDEFKQTYWLPPELAQGSKSPTRKTDVWDLGLLFLQMLFgldvlekyTSPNPVLVSLDLSASLQDFL-------SK 234

                         170
                  ....*....|....*
gi 2414731873 334 MIEEEPGNRPTIEEI 348
Cdd:cd14012   235 CLSLDPKKRPTALEL 249

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; 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. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 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 2414731873 200 SHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPI---GTETRLWVGffgqetAPeidrNFL 276
Cdd:cd14187   105 TEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVeydGERKKTLCG------TP----NYI 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 277 ADLALTQGRHTVKSDVYSLGVAFRNLvqLLGNGnigPEDRGAVRQDHLEL--------------LDKLSQKMIEEEPGNR 342
Cdd:cd14187   175 APEVLSKKGHSFEVDIWSIGCIMYTL--LVGKP---PFETSCLKETYLRIkkneysipkhinpvAASLIQKMLQTDPTAR 249

                         170
                  ....*....|..
gi 2414731873 343 PTIEEIMKDPLF 354
Cdd:cd14187   250 PTINELLNDEFF 261

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 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 2414731873 169 PSLGEYRGAFL----TYIFHPLSKGLVGDMLETGR---SHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTV 241
Cdd:cd06634    75 PNTIEYRGCYLrehtAWLVMEYCLGSASDLLEVHKkplQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLV 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 242 VLGGLDTAAPIGTETrlwvGFFGQE--TAPEIDrnfladLALTQGRHTVKSDVYSLGVAFRNLVQL---LGNGN------ 310
Cdd:cd06634   155 KLGDFGSASIMAPAN----SFVGTPywMAPEVI------LAMDEGQYDGKVDVWSLGITCIELAERkppLFNMNamsaly 224

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2414731873 311 -IGPEDRGAVRQDHL-ELLDKLSQKMIEEEPGNRPTIEEIMK 350
Cdd:cd06634   225 hIAQNESPALQSGHWsEYFRNFVDSCLQKIPQDRPTSDVLLK 266

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 207 LAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIG----TETRLWVGffgqeT----APEidrnflad 278
Cdd:COG0515   112 ILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGgatlTQTGTVVG-----TpgymAPE-------- 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 279 laLTQGRH-TVKSDVYSLGVAfrnLVQLL-GNGNIGPEDRGAVRQDHL---------------ELLDKLSQKMIEEEPGN 341
Cdd:COG0515   179 --QARGEPvDPRSDVYSLGVT---LYELLtGRPPFDGDSPAELLRAHLrepppppselrpdlpPALDAIVLRALAKDPEE 253

                         170
                  ....*....|.
gi 2414731873 342 RP-TIEEIMKD 351
Cdd:COG0515   254 RYqSAAELAAA 264

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK 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 2414731873 195 LETGRSHPDVQVLAANMVAALKSLHNLGLLHRSIELNSFSVLPDGTVVLGGLDTAAPIgtETRLWVGFFG--QETAPEId 272
Cdd:cd14004   102 RKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAYI--KSGPFDTFVGtiDYAAPEV- 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2414731873 273 rnfladlaLTQGRHTVKS-DVYSLGVA----------FRNLVQLLgNGNIGPEDrgAVRQDHLELLdklsQKMIEEEPGN 341
Cdd:cd14004   179 --------LRGNPYGGKEqDIWALGVLlytlvfkenpFYNIEEIL-EADLRIPY--AVSEDLIDLI----SRMLNRDVGD 243

                         170
                  ....*....|...
gi 2414731873 342 RPTIEEIMKDPLF 354
Cdd:cd14004   244 RPTIEELLTDPWL 256