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 1631970676 131 VQLVQDPATGGTFVVKSLPRCHMVSRERLTIIPHGVPYMTKLLRYFVSEDSIFLHLEHVQG------------------- 191
Cdd:cd05576    15 VLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGgklwsylskflndkeihql 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 192 --------------------------------------------------------HIRLTYFGQWSEVEPQCCGEAVDN 215
Cdd:cd05576    95 fadlderlaaasrfyipeeciqrwaaemvvaldalhregivcrdlnpnnillndrgHIQLTYFSRWSEVEDSCDSDAIEN 174

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1631970676 216 LYSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05576   175 MYCAPEVGGISEETEACDWWSLGALLFELLTGKA 208

Catalytic domain of the Serine/Threonine Kinase, RPK118, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RPK118 contains an N-terminal Phox homology (PX) domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain containing a long uncharacterized insert. Also included in the family is human RPK60 (or ribosomal protein S6 kinase-like 1), which also contains MIT and kinase domains but lacks a PX domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. RPK118 also binds the antioxidant peroxiredoxin-3. RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. The RPK118-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 1631970676 131 VQLVQDPATGGTFVVKSLPRCHMVSRERLTIIPHGVPYMTKLLRYFVSEDSIFLHLEHVQG------------------- 191
Cdd:cd05576    15 VLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGgklwsylskflndkeihql 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 192 --------------------------------------------------------HIRLTYFGQWSEVEPQCCGEAVDN 215
Cdd:cd05576    95 fadlderlaaasrfyipeeciqrwaaemvvaldalhregivcrdlnpnnillndrgHIQLTYFSRWSEVEDSCDSDAIEN 174

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1631970676 216 LYSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05576   175 MYCAPEVGGISEETEACDWWSLGALLFELLTGKA 208

Microtubule Interacting and Trafficking molecule domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676   46 KRDYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQR 120
Cdd:smart00745   1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEIKKSLLER 75

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 117 HLQRPLSSGASpSAVQLVQDPATGGTFVVKSLPRCHMVSRERLTIIP---------HgvPYMTKLLRYFVSEDSIFLHLE 187
Cdd:pfam00069   2 EVLRKLGSGSF-GTVYKAKHRDTGKIVAIKKIKKEKIKKKKDKNILReikilkklnH--PNIVRLYDAFEDKDNLYLVLE 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1631970676 188 HVQG---HIRLTYFGQWSEVEPQ----CCGEAVDN-----------LYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:pfam00069  79 YVEGgslFDLLSEKGAFSEREAKfimkQILEGLESgsslttfvgtpWYMAPEVLGGNPYGPKVDVWSLGCILYELLTG 156

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1631970676 190 QGHIRLTYFGQWSEVEPQC---CGEAVdnlYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:PTZ00263  154 KGHVKVTDFGFAKKVPDRTftlCGTPE---YLAPEVIQSKGHGKAVDWWTMGVLLYEFIAG 211

Catalytic domain of the Serine/Threonine Kinase, RPK118, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RPK118 contains an N-terminal Phox homology (PX) domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain containing a long uncharacterized insert. Also included in the family is human RPK60 (or ribosomal protein S6 kinase-like 1), which also contains MIT and kinase domains but lacks a PX domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. RPK118 also binds the antioxidant peroxiredoxin-3. RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. The RPK118-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 1631970676 131 VQLVQDPATGGTFVVKSLPRCHMVSRERLTIIPHGVPYMTKLLRYFVSEDSIFLHLEHVQG------------------- 191
Cdd:cd05576    15 VLLVMDTRTQETFILKGLRKSSEYSRERKTIIPRCVPNMVCLRKYIISEESVFLVLQHAEGgklwsylskflndkeihql 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 192 --------------------------------------------------------HIRLTYFGQWSEVEPQCCGEAVDN 215
Cdd:cd05576    95 fadlderlaaasrfyipeeciqrwaaemvvaldalhregivcrdlnpnnillndrgHIQLTYFSRWSEVEDSCDSDAIEN 174

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1631970676 216 LYSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05576   175 MYCAPEVGGISEETEACDWWSLGALLFELLTGKA 208

Microtubule Interacting and Trafficking molecule domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676   46 KRDYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQR 120
Cdd:smart00745   1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEIKKSLLER 75

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 1631970676 131 VQLVQDPATGGTFVVKSLPRCHMVSR--------ER--LTIIPHgvPYMTKLLRYFVSEDSIFLHLEHV----------- 189
Cdd:cd05123     9 VLLVRKKDTGKLYAMKVLRKKEIIKRkevehtlnERniLERVNH--PFIVKLHYAFQTEEKLYLVLDYVpggelfshlsk 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 190 ------------------------------------------QGHIRLTYFGQWSEVEP---QC---CGEAVdnlYSAPE 221
Cdd:cd05123    87 egrfpeerarfyaaeivlaleylhslgiiyrdlkpenilldsDGHIKLTDFGLAKELSSdgdRTytfCGTPE---YLAPE 163

                         170       180
                  ....*....|....*....|....*...
gi 1631970676 222 VGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05123   164 VLLGKGYGKAVDWWSLGVLLYEMLTGKP 191

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK 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 1631970676 129 SAVQLVQDPATGGTFVVkslprcHMVSRERLTiiPHGVpymtkllRYFVSEdsIFLHLEHV------------------- 189
Cdd:cd05583    72 AKLHLILDYVNGGELFT------HLYQREHFT--ESEV-------RIYIGE--IVLALEHLhklgiiyrdiklenillds 134

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1631970676 190 QGHIRLTYFGQWSEVEPQC-------CG--EavdnlYSAPEV--GGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05583   135 EGHVVLTDFGLSKEFLPGEndraysfCGtiE-----YMAPEVvrGGSDGHDKAVDWWSLGVLTYELLTGAS 200

MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar sorting proteins and others. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676  50 LVDAATQ-IRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEI 113
Cdd:cd02656     2 LLQQAKElIKQAVKEDEDGNYEEALELYKEALDYLLQALKAEKEPKLRKLLRKKVKEYLDRAEFL 66

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676  117 HLQRPLSSGASpSAVQLVQDPATGGTFVVKSLPR------CHMVSRER--LTIIPHgvPYMTKLLRYFVSEDSIFLHLEH 188
Cdd:smart00220   2 EILEKLGEGSF-GKVYLARDKKTGKLVAIKVIKKkkikkdRERILREIkiLKKLKH--PNIVRLYDVFEDEDKLYLVMEY 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676  189 V-----------------------------------------------------QGHIRLTYFGQWSEVEPqccGEAVDN 215
Cdd:smart00220  79 CeggdlfdllkkrgrlsedearfylrqilsaleylhskgivhrdlkpenilldeDGHVKLADFGLARQLDP---GEKLTT 155

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1631970676  216 L-----YSAPEVggISEL--TEACDWWSFGSLLYELLTG 247
Cdd:smart00220 156 FvgtpeYMAPEV--LLGKgyGKAVDIWSLGVILYELLTG 192

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-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 1631970676 131 VQLVQDPATGGTFVVKSLPR----------CHMVSRERLTIIPHGvPYMTKLLRYFVSEDSIFLHLE---------HVQ- 190
Cdd:cd05592    11 VMLAELKGTNQYFAIKALKKdvvledddveCTMIERRVLALASQH-PFLTHLFCTFQTESHLFFVMEylnggdlmfHIQq 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 191 -------------------------------------------GHIRLTYFGQwseVEPQCCGEAVDNL------YSAPE 221
Cdd:cd05592    90 sgrfdedrarfygaeiicglqflhsrgiiyrdlkldnvlldreGHIKIADFGM---CKENIYGENKASTfcgtpdYIAPE 166

                         170       180
                  ....*....|....*....|....*...
gi 1631970676 222 VGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05592   167 ILKGQKYNQSVDWWSFGVLLYEMLIGQS 194

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1631970676 189 VQGHIRLTYFGQWSEVEPQC---CGEAVdnlYSAPEVggISEL--TEACDWWSFGSLLYELLTG 247
Cdd:cd05580   136 SDGHIKITDFGFAKRVKDRTytlCGTPE---YLAPEI--ILSKghGKAVDWWALGILIYEMLAG 194

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1631970676 190 QGHIRLTYFGqwsevepqCCGEAVDN-----------LYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05584   136 QGHVKLTDFG--------LCKESIHDgtvthtfcgtiEYMAPEILTRSGHGKAVDWWSLGALMYDMLTG 196

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1631970676 191 GHIRLTYFGQwsevepqCCGEAVDNL---------YSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05599   138 GHIKLSDFGL-------CTGLKKSHLaystvgtpdYIAPEVFLQKGYGKECDWWSLGVIMYEMLIG 196

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1631970676 180 DSIFLHLEhvqGHIRLTYFGQWSEvepQCCGEAVDNL------YSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05619   135 DNILLDKD---GHIKIADFGMCKE---NMLGDAKTSTfcgtpdYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQS 204

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta 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 1631970676 173 LRYFVSEDSIF--LHLEHV----QGHIRLTYFGQWSE------VEPQCCGEAVdnlYSAPEVGGISELTEACDWWSFGSL 240
Cdd:cd05620   109 LQFLHSKGIIYrdLKLDNVmldrDGHIKIADFGMCKEnvfgdnRASTFCGTPD---YIAPEILQGLKYTFSVDWWSFGVL 185

                  ....*....
gi 1631970676 241 LYELLTGMS 249
Cdd:cd05620   186 LYEMLIGQS 194

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). 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 MSK2 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 1631970676 173 LRYFVSEdsIFLHLEHV-------------------QGHIRLTYFGQWSEVEPQ-------CCGEAVdnlYSAPE-VGGI 225
Cdd:cd05614   107 VRFYSGE--IILALEHLhklgivyrdiklenilldsEGHVVLTDFGLSKEFLTEekertysFCGTIE---YMAPEiIRGK 181

                          90       100
                  ....*....|....*....|....
gi 1631970676 226 SELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05614   182 SGHGKAVDWWSLGILMFELLTGAS 205

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC 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 1631970676 180 DSIFLHLEhvqGHIRLTYFGQwsevepqcCGEAV--DNL---------YSAPEVggISEL--TEACDWWSFGSLLYELLT 246
Cdd:cd05570   125 DNVLLDAE---GHIKIADFGM--------CKEGIwgGNTtstfcgtpdYIAPEI--LREQdyGFSVDWWALGVLLYEMLA 191

                  ...
gi 1631970676 247 GMS 249
Cdd:cd05570   192 GQS 194

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1631970676 190 QGHIRLTYFGQWSE-VEPQ-----CCG--EavdnlYSAPEVGGISELTEACDWWSFGSLLYELLTGM 248
Cdd:cd05575   132 QGHVVLTDFGLCKEgIEPSdttstFCGtpE-----YLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGL 193

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta 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 1631970676 154 VSRERLTIIPHGVPYMTKL---LRYFVSEDSIF--LHLEHV----QGHIRLTYFGqwsevepqCCGEAVDN--------- 215
Cdd:cd05595    86 LSRERVFTEDRARFYGAEIvsaLEYLHSRDVVYrdIKLENLmldkDGHIKITDFG--------LCKEGITDgatmktfcg 157

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1631970676 216 --LYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05595   158 tpEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCG 191

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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 1631970676 189 VQGHIRLTYFG-----QWSEVEPQCCGEAVDNL---------------------------YSAPEVGGISELTEACDWWS 236
Cdd:cd05573   136 ADGHIKLADFGlctkmNKSGDRESYLNDSVNTLfqdnvlarrrphkqrrvraysavgtpdYIAPEVLRGTGYGPECDWWS 215

                          90       100
                  ....*....|....*....|.
gi 1631970676 237 FGSLLYELLTG----MSSSST 253
Cdd:cd05573   216 LGVILYEMLYGfppfYSDSLV 236

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1631970676 190 QGHIRLTYFGQWSEVEPQC---CGEAVdnlYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:PTZ00263  154 KGHVKVTDFGFAKKVPDRTftlCGTPE---YLAPEVIQSKGHGKAVDWWTMGVLLYEFIAG 211

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1631970676 190 QGHIRLTYFGqWSE---VEPQC--CGEAVDNL--------------YSAPEVGGISELTEACDWWSFGSLLYELLTGM 248
Cdd:cd05579   129 NGHLKLTDFG-LSKvglVRRQIklSIQKKSNGapekedrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLVGI 205

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676 190 QGHIRLTYFGQWSEVePQccGEAVDNL-----YSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05631   138 RGHIRISDLGLAVQI-PE--GETVRGRvgtvgYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQS 199

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676 190 QGHIRLTYFGQWSEVEPqccGEAVDNL-----YSAPEVGGISELTEACDWWSFGSLLYELLTGMS 249
Cdd:cd05605   138 HGHVRISDLGLAVEIPE---GETIRGRvgtvgYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQA 199

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-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
                  ....*....|....*....|....*....|.
gi 1631970676 217 YSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05574   198 YIAPEVIKGDGHGSAVDWWTLGILLYEMLYG 228

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676 190 QGHIRLTYFG------QWSEVEPQCCGEAVdnlYSAPEVGGISELTEACDWWSFGSLLYELLTGM 248
Cdd:cd05585   130 TGHIALCDFGlcklnmKDDDKTNTFCGTPE---YLAPELLLGHGYTKAVDWWTLGVLLYEMLTGL 191

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in the AAA protein spastin, a probable ATPase involved in the assembly or function of nuclear protein complexes; spastins might also be involved in microtubule dynamics. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1631970676  47 RDYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERR 96
Cdd:cd02679     2 RGYYKQAFEEISKALRADEWGDKEQALAHYRKGLRELEEGIAVPVPSAGV 51

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta 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. This alignment model includes the dimerization domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1631970676 177 VSEDSIFLHlehVQGHIRLTYFG------QWSEVEPQCCGEAVDnlYSAPEV-----GGISELTEACDWWSFGSLLYELL 245
Cdd:cd05624   199 IKPDNVLLD---MNGHIRLADFGsclkmnDDGTVQSSVAVGTPD--YISPEIlqameDGMGKYGPECDWWSLGVCMYEML 273

                  ..
gi 1631970676 246 TG 247
Cdd:cd05624   274 YG 275

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1631970676 191 GHIRLTYFGQWSEVEPQC---CGEAVDNL-YSAPEV----GGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05621   188 GHLKLADFGTCMKMDETGmvhCDTAVGTPdYISPEVlksqGGDGYYGRECDWWSVGVFLFEMLVG 252

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1631970676 191 GHIRLTYFG---QWSEVEP--QCCGEAvdnLYSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05117   139 SPIKIIDFGlakIFEEGEKlkTVCGTP---YYVAPEVLKGKGYGKKCDIWSLGVILYILLCG 197

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
                  ....*....|....*....|....*....|.
gi 1631970676 217 YSAPEVGGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd14014   167 YMAPEQARGGPVDPRSDIYSLGVVLYELLTG 197

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-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 1631970676 172 LLRYFVSE-----DSIF-LHLEH-----------VQGHIRLTYFGQ----------WSEVepqccgeAV---DnlYSAPE 221
Cdd:cd05597   103 MARFYLAEmvlaiDSIHqLGYVHrdikpdnvlldRNGHIRLADFGSclklredgtvQSSV-------AVgtpD--YISPE 173

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1631970676 222 V-----GGISELTEACDWWSFGSLLYELLTG 247
Cdd:cd05597   174 IlqameDGKGRYGPECDWWSLGVCMYEMLYG 204