Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Dictyostelium discoideum Vasodilator-stimulated phosphoprotein (VASP) and similar proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in Dictyostelium discoideum vasodilator-stimulated phosphoprotein (VASP) and similar proteins. VASP belongs to the Ena/VASP protein family whose members act as actin polymerases that drive the processive elongation of filament barbed ends in membrane protrusions or at the surface of bacterial pathogens. These actin-associated proteins are involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as lamellipodial and filopodial dynamics in migrating cells. VASP plays a crucial role in filopodia formation, cell-substratum adhesion, and proper chemotaxis. It nucleates and bundles actin filaments via oligomers that use their WH2 domains to effect both the tethering of actin filaments and their processive elongation in sites of active actin assembly.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1160595631 529 NGMSRGALLSSIQNFQKGTLRKAKTCDHSAP 559
Cdd:cd22062     1 SPPGRGALLSSIQGFSKGGLKKTVTVDRSAP 31

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1160595631  58 PLPPKKLIGNMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFLDPN 106
Cdd:pfam00787  36 PLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 182 IKLLPSCLHPYIYRVTFATANESSALLIRMFNEKGTLKDLIYKakpkdpflkkycnpkKIQGLELQQIKTYGRQILEVLK 261
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 262 FLHDKGFPYGHLHASNVMLDGD---------TCRLLDLENSLLGLPSFYRSYF----SQFRKINTLESVDVHCFGHLLYE 328
Cdd:cd00180   107 YLHSNGIIHRDLKPENILLDSDgtvkladfgLAKDLDSDDSLLKTTGGTTPPYyappELLGGRYYGPKVDIWSLGVILYE 186

                  .
gi 1160595631 329 M 329
Cdd:cd00180   187 L 187

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  182 IKLLPSCLHPYIYRVTFATANESSALLIrM-FNEKGTLKDLIYKAKPkdpflkkycnpkkiqgLELQQIKTYGRQILEVL 260
Cdd:smart00220  48 IKILKKLKHPNIVRLYDVFEDEDKLYLV-MeYCEGGDLFDLLKKRGR----------------LSEDEARFYLRQILSAL 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  261 KFLHDKGFPYGHLHASNVMLDGDT---------CRLLDLE---NSLLGLPsFYRS-------YFSqfrkintlESVDVHC 321
Cdd:smart00220 111 EYLHSKGIVHRDLKPENILLDEDGhvkladfglARQLDPGeklTTFVGTP-EYMApevllgkGYG--------KAVDIWS 181

                          170
                   ....*....|....
gi 1160595631  322 FGHLLYEMTYGRPP 335
Cdd:smart00220 182 LGVILYELLTGKPP 195

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  31 QSHTEYIIRVQrgISVENSWQI------------------AGLSLP-LPPKKLIGNMDREFIAERQKGLQNYLNVITTNH 91
Cdd:cd06093    15 KKYVVYIIEVT--TQGGEEWTVyrrysdfeelheklkkkfPGVILPpLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNHP 92

                          90
                  ....*....|...
gi 1160595631  92 ILSNCELVKKFLD 104
Cdd:cd06093    93 ELRNSEELKEFLE 105

Wiskott Aldrich syndrome homology region 2 (WH2 motif) found in Dictyostelium discoideum Vasodilator-stimulated phosphoprotein (VASP) and similar proteins; This family contains the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) found in Dictyostelium discoideum vasodilator-stimulated phosphoprotein (VASP) and similar proteins. VASP belongs to the Ena/VASP protein family whose members act as actin polymerases that drive the processive elongation of filament barbed ends in membrane protrusions or at the surface of bacterial pathogens. These actin-associated proteins are involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as lamellipodial and filopodial dynamics in migrating cells. VASP plays a crucial role in filopodia formation, cell-substratum adhesion, and proper chemotaxis. It nucleates and bundles actin filaments via oligomers that use their WH2 domains to effect both the tethering of actin filaments and their processive elongation in sites of active actin assembly.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1160595631 529 NGMSRGALLSSIQNFQKGTLRKAKTCDHSAP 559
Cdd:cd22062     1 SPPGRGALLSSIQGFSKGGLKKTVTVDRSAP 31

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 182 IKLLPSCLHPYIYRVTFATANESSALLIRMFNEKGTLKDLIYKakpkdpflkkycnpkKIQGLELQQIKTYGRQILEVLK 261
Cdd:cd00180    42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 262 FLHDKGFPYGHLHASNVMLDGD---------TCRLLDLENSLLGLPSFYRSYF----SQFRKINTLESVDVHCFGHLLYE 328
Cdd:cd00180   107 YLHSNGIIHRDLKPENILLDSDgtvkladfgLAKDLDSDDSLLKTTGGTTPPYyappELLGGRYYGPKVDIWSLGVILYE 186

                  .
gi 1160595631 329 M 329
Cdd:cd00180   187 L 187

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  34 TEYIIRVQRgiSVENSW------------------QIAGLSLPLPPKKLIG-NMDREFIAERQKGLQNYLNVITTNHILS 94
Cdd:cd07276    21 TVYKIRVEN--KVGDSWfvfrrytdfvrlndklkqMFPGFRLSLPPKRWFKdNFDPDFLEERQLGLQAFVNNIMAHKDIA 98

                  ....*....
gi 1160595631  95 NCELVKKFL 103
Cdd:cd07276    99 KCKLVREFF 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 173 LSDKDFQCLIKLL-PSCLHPYIYRVTFATanESSALLIRMFNE---KGTLKDLIYKAKPkdpflkkycnpkkiqgLELQQ 248
Cdd:cd14012    44 LLEKELESLKKLRhPNLVSYLAFSIERRG--RSDGWKVYLLTEyapGGSLSELLDSVGS----------------VPLDT 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 249 IKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGD----TCRLLD------------------LENSLLGLPSFYRSYFS 306
Cdd:cd14012   106 ARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDagtgIVKLTDyslgktlldmcsrgsldeFKQTYWLPPELAQGSKS 185

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1160595631 307 QFRKintlesVDVHCFGHLLYEMTYGRP-------PDSVPVdsfPPAPSMAVVAVLESTLSCEACKNgmPTISRLLQMP 378
Cdd:cd14012   186 PTRK------TDVWDLGLLFLQMLFGLDvlekytsPNPVLV---SLDLSASLQDFLSKCLSLDPKKR--PTALELLPHE 253

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                          10        20
                  ....*....|....*....|....*..
gi 1160595631  59 LPPKKLIGNMDREFIAERQKGLQNYLN 85
Cdd:cd06875    58 LPPKKLIGNKSPSFVEKRRKELEIYLQ 84

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 182 IKLLPSCLHPYI--YRVTFATANEssaLLIRM-FNEKGTLKDLiykakpkdpfLKKYCNPkkiqgLELQQIKTYGRQILE 258
Cdd:cd05122    48 IAILKKCKHPNIvkYYGSYLKKDE---LWIVMeFCSGGSLKDL----------LKNTNKT-----LTEQQIAYVCKEVLK 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 259 VLKFLHDKGFPYGHLHASNVML--DGDTcRLLD-----------LENSLLGLPsfyrSYFS--QFRKINTLESVDVHCFG 323
Cdd:cd05122   110 GLEYLHSHGIIHRDIKAANILLtsDGEV-KLIDfglsaqlsdgkTRNTFVGTP----YWMApeVIQGKPYGFKADIWSLG 184

                         170
                  ....*....|..
gi 1160595631 324 HLLYEMTYGRPP 335
Cdd:cd05122   185 ITAIEMAEGKPP 196

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  182 IKLLPSCLHPYIYRVTFATANESSALLIrM-FNEKGTLKDLIYKAKPkdpflkkycnpkkiqgLELQQIKTYGRQILEVL 260
Cdd:smart00220  48 IKILKKLKHPNIVRLYDVFEDEDKLYLV-MeYCEGGDLFDLLKKRGR----------------LSEDEARFYLRQILSAL 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  261 KFLHDKGFPYGHLHASNVMLDGDT---------CRLLDLE---NSLLGLPsFYRS-------YFSqfrkintlESVDVHC 321
Cdd:smart00220 111 EYLHSKGIVHRDLKPENILLDEDGhvkladfglARQLDPGeklTTFVGTP-EYMApevllgkGYG--------KAVDIWS 181

                          170
                   ....*....|....
gi 1160595631  322 FGHLLYEMTYGRPP 335
Cdd:smart00220 182 LGVILYELLTGKPP 195

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 1160595631 176 KDFQCLIKLLPSCLHPYIYRV-TFATANESSALLIRMFnEKGTLKDLIykakpkdpflkkycnpKKIQGLELQQIKTYGR 254
Cdd:cd14014    45 ERFLREARALARLSHPNIVRVyDVGEDDGRPYIVMEYV-EGGSLADLL----------------RERGPLPPREALRILA 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 255 QILEVLKFLHDKGFpyghLHA----SNVMLDGD-TCRLLDL-ENSLLGLPSFYRS--------YFS--QFRKINTLESVD 318
Cdd:cd14014   108 QIADALAAAHRAGI----VHRdikpANILLTEDgRVKLTDFgIARALGDSGLTQTgsvlgtpaYMApeQARGGPVDPRSD 183

                         170
                  ....*....|....*..
gi 1160595631 319 VHCFGHLLYEMTYGRPP 335
Cdd:cd14014   184 IYSLGVVLYELLTGRPP 200

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 1160595631 244 LELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGD-TCRLLDL----EN--------SLLGLPSFYRSYFSQFRK 310
Cdd:cd05620    93 FDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDgHIKIADFgmckENvfgdnrasTFCGTPDYIAPEILQGLK 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 311 INTleSVDVHCFGHLLYEMTYGRPP----------DSVPVDS--FPPAPSMAVVAVLESTLSCEACKNgMPTISRLLQMP 378
Cdd:cd05620   173 YTF--SVDWWSFGVLLYEMLIGQSPfhgddedelfESIRVDTphYPRWITKESKDILEKLFERDPTRR-LGVVGNIRGHP 249

                         170       180
                  ....*....|....*....|..
gi 1160595631 379 LFSDVLLTTSEKPQFKIPTKLK 400
Cdd:cd05620   250 FFKTINWTALEKRELDPPFKPK 271

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK 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 1160595631 127 EPKWEVVEPLKDigwrirkKYFLMKIKNQPKERLVLSWADLGPDKYLSD-KDFQCLIKLLPSCLHPYIYRVTFATANESS 205
Cdd:cd06643     4 EDFWEIVGELGD-------GAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENN 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 206 ALLIRMFNEKGTLKDLIYKAKpkdpflkkycnpkkiQGLELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVM--LDGD 283
Cdd:cd06643    77 LWILIEFCAGGAVDAVMLELE---------------RPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILftLDGD 141

                         170       180
                  ....*....|....*....|....*.
gi 1160595631 284 -----------TCRLLDLENSLLGLP 298
Cdd:cd06643   142 ikladfgvsakNTRTLQRRDSFIGTP 167

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1160595631  58 PLPPKKLIGNM-DREFIAERQKGLQNYLN-VITTNHILSNCEL 98
Cdd:cd06898    64 SLPPKNLFGRFnNEGFIEERQQGLQDFLEkVLQTPLLLSDSRL 106

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 1160595631 182 IKLLPSCLHPYI--YRVTFataNESSALLIRM-FNEKGTLKDLIYKAKPKDPFLKKycnpkkiqglelQQIKTYGRQILE 258
Cdd:cd08215    50 VKLLSKLKHPNIvkYYESF---EENGKLCIVMeYADGGDLAQKIKKQKKKGQPFPE------------EQILDWFVQICL 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 259 VLKFLHDKGFpyghLH----ASNVMLD-------GD--TCRLL----DLENSLLGLPsfYrsYFS----QFRKINtlESV 317
Cdd:cd08215   115 ALKYLHSRKI----LHrdlkTQNIFLTkdgvvklGDfgISKVLesttDLAKTVVGTP--Y--YLSpelcENKPYN--YKS 184

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1160595631 318 DVHCFGHLLYEMTYGRPP---DSVPV-------DSFPPAP---SMAVVAVLESTLSCEACKNgmPTISRLLQMPLF 380
Cdd:cd08215   185 DIWALGCVLYELCTLKHPfeaNNLPAlvykivkGQYPPIPsqySSELRDLVNSMLQKDPEKR--PSANEILSSPFI 258

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK 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 1160595631 176 KDFQCLIKLLPSCLHPYIyrVTFATA----NESSALLIRMFNEKGTLKDLIykakpkdpflkkycnpKKIQGLELQQIKT 251
Cdd:cd13983    45 QRFKQEIEILKSLKHPNI--IKFYDSweskSKKEVIFITELMTSGTLKQYL----------------KRFKRLKLKVIKS 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 252 YGRQILEVLKFLHDKGFPYGH--LHASNVMLDGDT--CRLLDL----------ENSLLGLPSF-----YRSYFSqfrkin 312
Cdd:cd13983   107 WCRQILEGLNYLHTRDPPIIHrdLKCDNIFINGNTgeVKIGDLglatllrqsfAKSVIGTPEFmapemYEEHYD------ 180

                         170       180
                  ....*....|....*....|...
gi 1160595631 313 tlESVDVHCFGHLLYEMTYGRPP 335
Cdd:cd13983   181 --EKVDIYAFGMCLLEMATGEYP 201

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They 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. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 1160595631 182 IKLLPSCLHPYIYRVtFATANESSALLIRM-FNEKGTLKDLIykakpkdpflkkycnpKKIQGLELQQIKTYGRQILEVL 260
Cdd:cd06606    50 IRILSSLKHPNIVRY-LGTERTENTLNIFLeYVPGGSLASLL----------------KKFGKLPEPVVRKYTRQILEGL 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 261 KFLHDKGFPYGHLHASNVMLDGD---------TCRLLDLENSLLGLPSFYRS-YF---------SQFRKintlesVDVHC 321
Cdd:cd06606   113 EYLHSNGIVHRDIKGANILVDSDgvvkladfgCAKRLAEIATGEGTKSLRGTpYWmapevirgeGYGRA------ADIWS 186

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 322 FGHLLYEMTYGRPP-----DSVPV-------DSFPPAPsmavvavleSTLSCEA------C----KNGMPTISRLLQMPL 379
Cdd:cd06606   187 LGCTVIEMATGKPPwselgNPVAAlfkigssGEPPPIP---------EHLSEEAkdflrkClqrdPKKRPTADELLQHPF 257

                  .
gi 1160595631 380 F 380
Cdd:cd06606   258 L 258

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 244 LELQQIKTYGRQILEVLKFLHDKGFPYGHLHASNVMLDGDT-CRLLDL------------ENSLLGLPSFYRSYFSQFRK 310
Cdd:cd05619   103 FDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGhIKIADFgmckenmlgdakTSTFCGTPDYIAPEILLGQK 182

                          90       100
                  ....*....|....*....|....*
gi 1160595631 311 INTleSVDVHCFGHLLYEMTYGRPP 335
Cdd:cd05619   183 YNT--SVDWWSFGVLLYEMLIGQSP 205

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631  36 YIIRVQR--GISVENSWQI------------------AGLS-LPLPPKKLIGNMDREFIAERQKGLQNYLNVITTNHILS 94
Cdd:cd06873    25 YAISVTRiyPNGQEESWHVyrrysdfhdlhmrlkekfPNLSkLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLD 104

                          90
                  ....*....|....*
gi 1160595631  95 NC----ELVKKFLDP 105
Cdd:cd06873   105 ANpglqEIVLDFLEP 119

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 1160595631 174 SDKDFQCLIKLLPSCLHPYIYRV-TFATANESSaLLIRMFNEKGTLKDLIYKAKPKDPflkkycnpkkiqgLELQQIKTY 252
Cdd:cd14066    33 SKKEFLTELEMLGRLRHPNLVRLlGYCLESDEK-LLVYEYMPNGSLEDRLHCHKGSPP-------------LPWPQRLKI 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 253 GRQILEVLKFLHDKGFP---YGHLHASNVMLD-------GD--TCRLLDLENSLL------GLPSFYRSYFSQFRKINTl 314
Cdd:cd14066    99 AKGIARGLEYLHEECPPpiiHGDIKSSNILLDedfepklTDfgLARLIPPSESVSktsavkGTIGYLAPEYIRTGRVST- 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 315 eSVDVHCFGHLLYEMTYGRPpdsvPVDSFPPAPSmavvavlESTLSCEACKNGMPTISRLLQMPLFSDVLLTTSEkpqfk 394
Cdd:cd14066   178 -KSDVYSFGVVLLELLTGKP----AVDENRENAS-------RKDLVEWVESKGKEELEDILDKRLVDDDGVEEEE----- 240

                         250
                  ....*....|....*.
gi 1160595631 395 iptkLKEALRIAKECI 410
Cdd:cd14066   241 ----VEALLRLALLCT 252

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1160595631  58 PLPPKKLIG--NMDREFIAERQKGLQNYLNVITTNHILSNCELVKKFL 103
Cdd:cd06859    64 PPPEKQAVGrfKVKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFL 111

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 162 LSWADLGPDKY--LSDKDFQCLIKLLPSCLHPYIYRvtFATANESSA------LLIRMFNEKGTLKDLIYKAKPKDPflk 233
Cdd:cd14032    29 VAWCELQDRKLtkVERQRFKEEAEMLKGLQHPNIVR--FYDFWESCAkgkrciVLVTELMTSGTLKTYLKRFKVMKP--- 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 234 kycnpkkiqglelQQIKTYGRQILEVLKFLHDKGFPYGH--LHASNVMLDGDT--CRLLDLENSLLGLPSFYRSYFS--- 306
Cdd:cd14032   104 -------------KVLRSWCRQILKGLLFLHTRTPPIIHrdLKCDNIFITGPTgsVKIGDLGLATLKRASFAKSVIGtpe 170

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1160595631 307 ----QFRKINTLESVDVHCFGHLLYEMTYGRPPDS 337
Cdd:cd14032   171 fmapEMYEEHYDESVDVYAFGMCMLEMATSEYPYS 205

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 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 1160595631 182 IKLLPSCLHPYIYRVtFATANESSALLIRM-FNEKGTLKDLiykakpkdpfLKKYcnpkkiQGLELQQIKTYGRQILEVL 260
Cdd:cd06632    53 IALLSKLRHPNIVQY-YGTEREEDNLYIFLeYVPGGSIHKL----------LQRY------GAFEEPVIRLYTRQILSGL 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 261 KFLHDKGFPYGHLHASNVMLDGD-TCRLLD------LENSLLGLpSFYRSYF-------SQFRKINTLEsVDVHCFGHLL 326
Cdd:cd06632   116 AYLHSRNTVHRDIKGANILVDTNgVVKLADfgmakhVEAFSFAK-SFKGSPYwmapeviMQKNSGYGLA-VDIWSLGCTV 193

                  ....*....
gi 1160595631 327 YEMTYGRPP 335
Cdd:cd06632   194 LEMATGKPP 202

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. 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-epsilon 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 1160595631 252 YGRQILEVLKFLHDKGFPYGHLHASNVMLDGDT-CRLLD------------LENSLLGLPSFYRSYFSQfrKINTLESVD 318
Cdd:cd05591   101 YAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGhCKLADfgmckegilngkTTTTFCGTPDYIAPEILQ--ELEYGPSVD 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1160595631 319 VHCFGHLLYEMTYGRPP----------DSVPVDS--FPPAPSMAVVAVLES--------TLSCEACKNGMPTIsrlLQMP 378
Cdd:cd05591   179 WWALGVLMYEMMAGQPPfeadneddlfESILHDDvlYPVWLSKEAVSILKAfmtknpakRLGCVASQGGEDAI---RQHP 255

                         170       180
                  ....*....|....*....|..
gi 1160595631 379 LFSDVLLTTSEKPQFKIPTKLK 400
Cdd:cd05591   256 FFREIDWEALEQRKVKPPFKPK 277