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 386779515  37 DWEQLCLHNPLGSGGFGSVYKATYYGSTVAVKQVKKYSKNRlASHQSFWAELNVARLSHSNVVRVIAASACspASQDSLG 116
Cdd:cd13979    1 DWEPLRLQEPLGSGGFGSVYKATYKGETVAVKIVRRRRKNR-ASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLG 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386779515 117 TVIMEYVGNSTLHHVIYGtgsmitkrkdsfvcGYEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd13979   78 LIIMEYCGNGTLQQLIYE--------------GSEPLPLAHRILISLDIARALRFCHSHGIVHLD 128

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 386779515  37 DWEQLCLHNPLGSGGFGSVYKATYYGSTVAVKQVKKYSKNRlASHQSFWAELNVARLSHSNVVRVIAASACspASQDSLG 116
Cdd:cd13979    1 DWEPLRLQEPLGSGGFGSVYKATYKGETVAVKIVRRRRKNR-ASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLG 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386779515 117 TVIMEYVGNSTLHHVIYGtgsmitkrkdsfvcGYEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd13979   78 LIIMEYCGNGTLQQLIYE--------------GSEPLPLAHRILISLDIARALRFCHSHGIVHLD 128

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515   41 LCLHNPLGSGGFGSVYKATYYGS------TVAVKQVKKYSKNRlaSHQSFWAELNV-ARLSHSNVVRVIAASACSPASQd 113
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGEgentkiKVAVKTLKEGADEE--EREDFLEEASImKKLDHPNIVKLLGVCTQGEPLY- 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386779515  114 slgtVIMEYVGNSTLHHVIygtgsmitKRKDsfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:pfam07714  78 ----IVTEYMPGGDLLDFL--------RKHK------RKLTLKDLLSMALQIAKGMEYLESKNFVHRD 127

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  47 LGSGGFGSVYKA--TYYGSTVAVKqVKKYSknrLASHQSFWA----E-LNVARLSHSNVVRVIAASacspaSQDSLGTVI 119
Cdd:NF033483  15 IGRGGMAEVYLAkdTRLDRDVAVK-VLRPD---LARDPEFVArfrrEaQSAASLSHPNIVSVYDVG-----EDGGIPYIV 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386779515 120 MEYVGNSTLHHVIygtgsmitkRKDSfvcgyePLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:NF033483  86 MEYVDGRTLKDYI---------REHG------PLSPEEAVEIMIQILSALEHAHRNGIVHRD 132

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 386779515  37 DWEQLCLHNPLGSGGFGSVYKATYYGSTVAVKQVKKYSKNRlASHQSFWAELNVARLSHSNVVRVIAASACspASQDSLG 116
Cdd:cd13979    1 DWEPLRLQEPLGSGGFGSVYKATYKGETVAVKIVRRRRKNR-ASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLG 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386779515 117 TVIMEYVGNSTLHHVIYGtgsmitkrkdsfvcGYEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd13979   78 LIIMEYCGNGTLQQLIYE--------------GSEPLPLAHRILISLDIARALRFCHSHGIVHLD 128

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase 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 mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  47 LGSGGFGSVYKATYYGSTVAVKQVKKYSKNRLASHQsFWAELNV-ARLSHSNVVRVIAASacspaSQDSLGTVIMEYVGN 125
Cdd:cd13999    1 IGSGSFGEVYKGKWRGTDVAIKKLKVEDDNDELLKE-FRREVSIlSKLRHPNIVQFIGAC-----LSPPPLCIVTEYMPG 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 386779515 126 STLHHVIygtgsmitkRKDSFvcgyePLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd13999   75 GSLYDLL---------HKKKI-----PLSWSLRLKIALDIARGMNYLHSPPIIHRD 116

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  45 NPLGSGGFGSVYKATYYGS-----TVAVKQVKKYSKNrlASHQSFWAELNV-ARLSHSNVVRVIAASAcspaSQDSLgTV 118
Cdd:cd00192    1 KKLGEGAFGEVYKGKLKGGdgktvDVAVKTLKEDASE--SERKDFLKEARVmKKLGHPNVVRLLGVCT----EEEPL-YL 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386779515 119 IMEYVGNSTLHHVIygtgsmITKRKDSFVCGYEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd00192   74 VMEYMEGGDLLDFL------RKSRPVFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRD 130

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  46 PLGSGGFGSVYKA--TYYGSTVAVKQVKKYSKNRLASHQSFWAELNV-ARLSHSNVVRVIAAsacspASQDSLGTVIMEY 122
Cdd:COG0515   14 LLGRGGMGVVYLArdLRLGRPVALKVLRPELAADPEARERFRREARAlARLNHPNIVRVYDV-----GEEDGRPYLVMEY 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 386779515 123 VGNSTLHHVIYGTGsmitkrkdsfvcgyePLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:COG0515   89 VEGESLADLLRRRG---------------PLPPAEALRILAQLAEALAAAHAAGIVHRD 132

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515    41 LCLHNPLGSGGFGSVYKATYYGS------TVAVKQVKKYSKNrlASHQSFWAELNV-ARLSHSNVVRVIAAsacspASQD 113
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKggkkkvEVAVKTLKEDASE--QQIEEFLREARImRKLDHPNVVKLLGV-----CTEE 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386779515   114 SLGTVIMEYVGNSTLHHVIygtgsmitkRKDSfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:smart00219  74 EPLYIVMEYMEGGDLLSYL---------RKNR-----PKLSLSDLLSFALQIARGMEYLESKNFIHRD 127

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK 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 386779515  47 LGSGGFGSVYKATY-YGSTVAVKQVKkySKNRLASHQSFWAEL-NVARLSHSNVVRVIAASacspaSQDSLGTVIMEYVG 124
Cdd:cd14066    1 IGSGGFGTVYKGVLeNGTVVAVKRLN--EMNCAASKKEFLTELeMLGRLRHPNLVRLLGYC-----LESDEKLLVYEYMP 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515 125 NSTLHHVIYGTGSMitkrkdsfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQF---IVHLD 181
Cdd:cd14066   74 NGSLEDRLHCHKGS------------PPLPWPQRLKIAKGIARGLEYLHEECpppIIHGD 121

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  43 LHNPLGSGGFGSVYKA--TYYGSTVAVKQVKKYSKNRLASHQSFWAELN-VARLSHSNVVRVIAAsacspASQDSLGTVI 119
Cdd:cd14014    4 LVRLLGRGGMGEVYRArdTLLGRPVAIKVLRPELAEDEEFRERFLREARaLARLSHPNIVRVYDV-----GEDDGRPYIV 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386779515 120 MEYVGNSTLHHVIygtgsmitKRKdsfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd14014   79 MEYVEGGSLADLL--------RER-------GPLPPREALRILAQIADALAAAHRAGIVHRD 125

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515   47 LGSGGFGSVYKATY--YGSTVAVKQVKKySKNRLASHQSFWAELNV-ARLSHSNVVRVIaaSACSpaSQDSLgTVIMEYV 123
Cdd:pfam00069   7 LGSGSFGTVYKAKHrdTGKIVAIKKIKK-EKIKKKKDKNILREIKIlKKLNHPNIVRLY--DAFE--DKDNL-YLVLEYV 80

                  ....*....
gi 386779515  124 GNSTLHHVI 132
Cdd:pfam00069  81 EGGSLFDLL 89

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 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 386779515  47 LGSGGFGSVYKATYYGSTVAVKQVKKysknrLASHQSFWAEL-NVARLSHSNVVRVIAasACSPASQDSLgtvIMEYVGN 125
Cdd:cd14058    1 VGRGSFGVVCKARWRNQIVAVKIIES-----ESEKKAFEVEVrQLSRVDHPNIIKLYG--ACSNQKPVCL---VMEYAEG 70

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515 126 STLHHVIYGTGSmitkrkdsfvcgyEPL-SVMQSLSYSCDIVAGLVFLHS---QFIVHLD 181
Cdd:cd14058   71 GSLYNVLHGKEP-------------KPIyTAAHAMSWALQCAKGVAYLHSmkpKALIHRD 117

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  39 EQLCLHNPLGSGGFGSVYKATY------YGSTVAVKQVKKYSKNrlASHQSFWAELNVAR-LSHSNVVRVIAasACSPAS 111
Cdd:cd05038    4 RHLKFIKQLGEGHFGSVELCRYdplgdnTGEQVAVKSLQPSGEE--QHMSDFKREIEILRtLDHEYIVKYKG--VCESPG 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515 112 QDSLGtVIMEYVGNSTLHHVIYGTGSMITKRkdsfvcgyeplsvmQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd05038   80 RRSLR-LIMEYLPSGSLRDYLQRHRDQIDLK--------------RLLLFASQICKGMEYLGSQRYIHRD 134

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 386779515  47 LGSGGFGSVYKA--TYYGSTVAVKQVKKYSKNRLASHQSFWAELNVA------------RLSHSNVVR---VIaasacSP 109
Cdd:cd14008    1 LGRGSFGKVKLAldTETGQLYAIKIFNKSRLRKRREGKNDRGKIKNAlddvrreiaimkKLDHPNIVRlyeVI-----DD 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386779515 110 ASQDSLGTViMEYVGNSTLHHVIYGTGSmitkrkdsfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd14008   76 PESDKLYLV-LEYCEGGPVMELDSGDRV-------------PPLPEETARKYFRDLVLGLEYLHENGIVHRD 133

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 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 386779515  45 NPLGSGGFGSVYKATYYGSTVAVKQVKKYSKNRLAS-HQSFWAELNV-ARLSHSNVVRVIAASACSPASqdslgTVIMEY 122
Cdd:cd14158   21 NKLGEGGFGVVFKGYINDKNVAVKKLAAMVDISTEDlTKQFEQEIQVmAKCQHENLVELLGYSCDGPQL-----CLVYTY 95

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386779515 123 VGNSTLhhviygtgsmitkrKDSFVC--GYEPLSVMQslsySCDIVA----GLVFLHSQFIVHLD 181
Cdd:cd14158   96 MPNGSL--------------LDRLAClnDTPPLSWHM----RCKIAQgtanGINYLHENNHIHRD 142

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 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 386779515  47 LGSGGFGSVYKATYYGSTVAVKqVKKYSknrlaSHQSFWAELNVARLS---HSNVVRVIAASACSPASQDSLGTVIMEYV 123
Cdd:cd14054    3 IGQGRYGTVWKGSLDERPVAVK-VFPAR-----HRQNFQNEKDIYELPlmeHSNILRFIGADERPTADGRMEYLLVLEYA 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 386779515 124 GNSTLHHviygtgsmitkrkdsFVCGYEpLSVMQSLSYSCDIVAGLVFLHS 174
Cdd:cd14054   77 PKGSLCS---------------YLRENT-LDWMSSCRMALSLTRGLAYLHT 111

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  44 HNPLGSGGFGSVYKAT--YYGSTVAVKQVKKYSKNRLASHQSFWAELNV-ARLSHSNVVRVIAASacspasQDSLGT-VI 119
Cdd:cd14099    6 GKFLGKGGFAKCYEVTdmSTGKVYAGKVVPKSSLTKPKQREKLKSEIKIhRSLKHPNIVKFHDCF------EDEENVyIL 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386779515 120 MEYVGNSTLHHviygtgsMITKRKdsfvcgyePLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd14099   80 LELCSNGSLME-------LLKRRK--------ALTEPEVRYFMRQILSGVKYLHSNRIIHRD 126

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK 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 386779515  47 LGSGGFGSVYKATY--YGSTVAVKQVKKYSKNrlaSHQSFWAELNVAR-LSHSNVVRVIAAsacspASQDSLGTVIMEYV 123
Cdd:cd14154    1 LGKGFFGQAIKVTHreTGEVMVMKELIRFDEE---AQRNFLKEVKVMRsLDHPNVLKFIGV-----LYKDKKLNLITEYI 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 386779515 124 GNSTLHHVIygtgsmitKRKDsfvcgyEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd14154   73 PGGTLKDVL--------KDMA------RPLPWAQRVRFAKDIASGMAYLHSMNIIHRD 116

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the 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: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK 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 386779515  47 LGSGGFGSVYKATYY--GSTVAVKQVKkysknrlaSHQSFWAELNV-------ARLSHSNVVRVIAAsacspASQDSLGT 117
Cdd:cd13996   14 LGSGGFGSVYKVRNKvdGVTYAIKKIR--------LTEKSSASEKVlrevkalAKLNHPNIVRYYTA-----WVEEPPLY 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386779515 118 VIMEYVGNSTLHHVIygtgsmitKRKDSFVCGYEPLsvmqSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd13996   81 IQMELCEGGTLRDWI--------DRRNSSSKNDRKL----ALELFKQILKGVSYIHSKGIVHRD 132

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 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 386779515  47 LGSGGFGSVYKATY--YGSTVAVKQVKKYSKNrlaSHQSFWAELNVAR-LSHSNVVRVIAAsacspASQDSLGTVIMEYV 123
Cdd:cd14221    1 LGKGCFGQAIKVTHreTGEVMVMKELIRFDEE---TQRTFLKEVKVMRcLEHPNVLKFIGV-----LYKDKRLNFITEYI 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 386779515 124 GNSTLHHVIygtgsmitKRKDSfvcgYEPLSvmQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd14221   73 KGGTLRGII--------KSMDS----HYPWS--QRVSFAKDIASGMAYLHSMNIIHRD 116

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K 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 386779515  47 LGSGGFGSVYKATYYGSTVAvkqVKKYSKNRLASHQS---FWAELNV-ARLSHSNVVRVIAASACSPasqdSLGTVIMEY 122
Cdd:cd14064    1 IGSGSFGKVYKGRCRNKIVA---IKRYRANTYCSKSDvdmFCREVSIlCRLNHPCVIQFVGACLDDP----SQFAIVTQY 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386779515 123 VGNSTLHHVIYGTGSMITkrkdsfvcgyeplsvMQS-LSYSCDIVAGLVFLH--SQFIVHLD 181
Cdd:cd14064   74 VSGGSLFSLLHEQKRVID---------------LQSkLIIAVDVAKGMEYLHnlTQPIIHRD 120

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 386779515  47 LGSGGFGSVYKAT--YYGSTVAVKQV---KKYSKNRLASHQsfwaELNV-ARLSHSNVVRVIAasacSPASQDSLgTVIM 120
Cdd:cd08215    8 IGKGSFGSAYLVRrkSDGKLYVLKEIdlsNMSEKEREEALN----EVKLlSKLKHPNIVKYYE----SFEENGKL-CIVM 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386779515 121 EYVGNSTLHHviygtgsMITKRKDsfvcGYEPLSVMQSLSYSCDIVAGLVFLHSQFIVHLD 181
Cdd:cd08215   79 EYADGGDLAQ-------KIKKQKK----KGQPFPEEQILDWFVQICLALKYLHSRKILHRD 128

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  27 LPPHLAWcSIDWEQLCLHNPLGSGGFGSVYKATYYG--------STVAVKQVKKYSKNRLAShqSFWAELNVARL--SHS 96
Cdd:cd05053    1 LPLDPEW-ELPRDRLTLGKPLGEGAFGQVVKAEAVGldnkpnevVTVAVKMLKDDATEKDLS--DLVSEMEMMKMigKHK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386779515  97 NVVRVIAASacspaSQDSLGTVIMEYVGNSTLHHVIYGTGSMITK-RKDSFVCGYEPLSVMQSLSYSCDIVAGLVFLHSQ 175
Cdd:cd05053   78 NIINLLGAC-----TQDGPLYVVVEYASKGNLREFLRARRPPGEEaSPDDPRVPEEQLTQKDLVSFAYQVARGMEYLASK 152

                 ....*.
gi 386779515 176 FIVHLD 181
Cdd:cd05053  153 KCIHRD 158

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK 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 386779515  47 LGSGGFGSVYKATY--YGSTVAVKQVK--KYSKNRLASHQSFWAELNvarlsHSNVVRVIAASACspasQDSLgTVIMEY 122
Cdd:cd06614    8 IGEGASGEVYKATDraTGKEVAIKKMRlrKQNKELIINEILIMKECK-----HPNIVDYYDSYLV----GDEL-WVVMEY 77