NCBI Conserved Domain Search

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Conserved domains on [gi\|117928139\|ref\|YP_872690.1\|]
serine/threonine protein kinase [Acidothermus cellulolyticus 11B]

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List of domain hits		?

References:

Marchler-Bauer A et al. (2009), "CDD: specific functional annotation with the Conserved Domain Database.", Nucleic Acids Res.37(D)205-10.

Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.

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of the residues that compose this conserved feature have been mapped to the query sequence.

Click on the triangle to view details about the feature, including a multiple sequence alignment of your query sequence and the protein sequences used to curate the domain model, where hash marks (#) above the aligned sequences show the location of the conserved feature residues.

The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions. Click on the triangle for interactive 3D structure viewing options.

This image shows a graphical summary of conserved domains identified on the query sequence. The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits (labeled illustration) or all hits (labeled illustration).
Domains are color coded according to superfamilies to which they have been assigned. Hits with scores that pass a domain-specific threshold (specific hits) are drawn in bright colors. Others (non-specific hits) and superfamily placeholders are drawn in pastel colors.
if a domain or superfamily has been annotated with functional sites (conserved features), they are mapped to the query sequence and indicated through sets of triangles with the same color and shade of the domain or superfamily that provides the annotation.
Mouse over the colored bars or triangles to see descriptions of the domains and features. click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.

The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores. Click on the PssmId to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.

To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page, or click on the triangles, if present, that represent functional sites (conserved features) mapped to the query sequence.

Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence. (labeled illustration)
Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance. (labeled illustration)
Four types of hits can be shown, as available, for each region on the query sequence:

specific hits meet or exceed a domain-specific e-value threshold (illustrated example) and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits meet or exceed the RPS-BLAST threshold for statistical significance (default E-value cutoff of 0.01, or an E-value selected by user via the advanced search options)
the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains

The CD-Search help document provides more detail about the tool and its features.

Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool (CDART).

Modify your query to search against a different database and/or use advanced search options

29142

cd00180

S_TKc

Serine/Threonine protein kinases, catalytic domain. Phosphotransferases of the serine or threonine-specific kinase subfamily. The enzymatic activity of these protein kinases is controlled by phosphorylation of specific residues in the activation segment of the catalytic domain, sometimes combined with reversible conformational changes in the C-terminal autoregulatory tail.

Serine/Threonine protein kinases, catalytic domain. Phosphotransferases of the serine...

true

false

256

4e-20

94.89

59.38

3,24,1,30,54,34,37,101,71,82

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALK---RPHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglpc 101
cd00180        2 YELLEKLGKGAFGKVYLARDKKTGELVAIKiikKKKEKKKQVERILREIKILKRLNHPNIVKLYDVFEDE---------- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 102 QCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHARWCDA 181
cd00180       72 DKLYLVMEYMSGGDLFDLLKKRGRLSEDEARFYFRQILSGLEYLHSKGIIHRDLKPENILLDEDGHVKIADFGLAKQLDS 151


                 ..
gi 117928139 182 PQ 183
cd00180      152 GG 153

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

132935

cd05122

PKc_STE

Protein Kinases (PKs), STE family, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The STE family is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). 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), MAPK kinase kinases (MAPKKKs), or MAPK kinase kinase 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.

Protein Kinases (PKs), STE family, catalytic (c) domain. PKs catalyze the transfer of...

false

true

false

253

4e-13

71.42

53.36

5,32,7,3,35,12,20,55,33,31,86,67,6,105,73,69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  33 IGR--YAAVWRARTAVGDRSVALKR-PHATREAAARVVHEAAILRAARHDHVVAFLG---LEREPWrqpapglpcqcpvL 106
cd05122        8 IGKgaFGTVYKARHKKTGELVAVKViKLESDEEQEQILNEIQILKKCKHPNIVKYYGsylKKDELW-------------I 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928139 107 VTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05122       75 VMEYCDGGSLDDLLKSTGPLPESQIAYICREVLQGLEYLHSNGIIHRDIKPANILLTSDGEVKLADFG 142

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132937

cd06606

STKc_MAPKKK

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. 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.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

259

9e-13

70.27

57.92

3,24,1,31,55,35,38,102,73,78

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR---PHATREAAARVVHEAAILRAARHDHVVAFLGLEREPWRqpapglpc 101
cd06606        2 WTRGKLLGRGSFGSVYLALSKDTGELVAVKSvelSSDSEEELESLEREIRILSKLQHPNIVRYYGCEVTEEN-------- 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 102 qCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHARWCD 180
cd06606       74 -TLNIFMEYVSGGSLASLLKKFGKLPEPVIRRYTRQILEGLAYLHSNGIVHRDIKGANILLDSDGVVKLADFGCAKRLA 151

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88470

cd05123

STKc_AGC

STKc_AGC: Serine/Threonine Kinases (STKs), AGC (Protein Kinases A, G and C) family, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AGC 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 (PI3K). 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. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases.

STKc_AGC: Serine/Threonine Kinases (STKs), AGC (Protein Kinases A, G and C) family,...

false

true

false

250

5e-10

61.26

28.80

1,105,69,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05123       70 LVMEYVNGGDLFTHLSKEGRFDEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDADGHIKLTDFGLAK 141

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88482

cd05581

STKc_PDK1

STKc_PDK1: Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PDK1 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 (PI3K). PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. PDK1 is essential for normal embryo development and is important in regulating cell volume.

STKc_PDK1: Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1)...

false

true

false

279

7e-10

60.58

55.20

5,24,2,31,66,33,16,86,49,8,94,59,6,100,73,83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKRphatreaaarvVHEAAILRAARHDHVVaflgLEREPWRQ--PAPGLP-- 100
cd05581        3 FKFGKILGEGSFSTVYLAKEKETNKEYAIKV-----------LDKRHLIKEKKVKYVK----REKEVLTRlnGHPGIVkl 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 101 ------CQCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05581       68 yytfqdEENLYFVLEYAENGELLEYIKKFGSFDEKCTRFYTAEILLALEYLHSKGIIHRDLKPENILLDKDGHIKITDFG 147


                 ....*....
gi 117928139 175 HARWCDAPQ 183
cd05581      148 TAKVLDPNS 156

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132945

cd06614

STKc_PAK

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

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, catalytic (c)...

false

true

false

287

1e-08

56.84

49.83

6,27,21,11,38,34,17,55,52,31,86,86,6,105,92,16,121,109,55

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  28 SELVAIGRYAA--VWRARTAVGDRSVALKR-PHATREAAARVVHEAAILRAARHDHVVAFLG---LEREPWrqpapglpc 101
cd06614       22 DNLEKIGEGASgeVYTATDRATGKEVAIKKmRLRKQPKKELIINEILIMKECKHPNIVNYYDsylVGDELW--------- 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928139 102 qcpvLVTEYAEGGTLAELLA-NRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHA 176
cd06614       93 ----VVMEYMDGGSLTDIITqTFVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFA 164

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88480

cd05579

STKc_MAST_like

STKc_MAST_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. The MAST kinase subfamily includes MAST kinases, MAST-like (MASTL) kinases, 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 also contains an insert relative to MAST kinases like MASTL. 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. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively.

STKc_MAST_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/...

false

true

false

265

1e-08

56.74

26.04

1,105,69,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05579       70 LVMEYLPGGDLASLLENVGSLDEDMARIYIAEIVLALEYLHSNGIIHRDLKPDNILIDSNGHLKLTDFG 138

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133163

cd00192

PTKc

Catalytic Domain of Protein Tyrosine Kinases

false

true

false

261

2e-07

52.90

56.32

6,33,5,10,43,18,11,54,31,32,86,65,5,103,70,17,120,95,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRAR---TAVGDRSVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLG--LEREPwrqpapglpcqcPVL 106
cd00192        6 GAFGEVYKGElkgKGGKKTPVAVKtlKEDASDSEREDFLKEAKIMKKLGHPNIVRLLGvcTEEEP------------LYL 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 107 VTEYAEGGTLAELL--------ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd00192       74 VLEYMEGGDLLDFLrksrpvfsPESSTLSLKDLLSFAYQIASGMEYLASKNFVHRDLAARNVLVGEDLVVKIADFGLSR 152

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132957

cd06626

STKc_MEKK4

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK4 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. MEKK4 is a mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MKKK or MAP3K), that phosphorylates and activates 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. MEKK4 activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 4 (MEKK4) subfamily, catalytic (...

false

true

false

264

2e-07

52.73

35.98

6,71,51,17,88,70,3,104,73,3,107,77,16,124,93,10,134,104,42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGLE--REPwrqpapglpcqcpVLV-TEYAEGGTLAELLANRiRLSPAEVVTL-GVPIARALDLLRR 147
cd06626       52 VLELLKHPNLVKYYGVEvhREK-------------VYIfMEYCSGGTLEELLEHG-RILDEHVIRVyTLQLLEGLAYLHS 117

                         90       100
                 ....*....|....*....|....*....
gi 117928139 148 RGIRHGDLRPANIAFTADGKPLLIDFGHA 176
cd06626      118 HGIVHRDIKPANIFLDHNGVIKLGDFGCA 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132939

cd06608

STKc_myosinIII_like

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The class III myosin-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. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), mitogen-activated protein kinase (MAPK) kinase kinase kinase 4 (MAPKKKK4 or MAP4K4) and MAPKKKK6 (or MAP4K6). MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAPK signaling cascades are important in mediating cellular responses to extracellular signals.

Serine/threonine kinases (STKs), Class III myosin-like subfamily, catalytic (c) domain....

false

true

false

275

3e-07

51.89

54.91

5,24,7,51,75,59,16,94,75,9,104,84,18,122,106,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKRPHATREAAARVVHEAAILRA-ARHDHVVAFLGLEREPwrqPAPGLPCQC 103
cd06608        8 FELVEVIGTGTYGKVYKARHKKTGQLVAIKIMDIIEDEEEEIEEEYNILRKySNHPNIATFYGAFIKK---GPPGSDDQL 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 104 pVLVTEYAEGGTLAELLAN----RIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06608       85 -WLVMELCGGGSVTDLVKGlrkkGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTKEGEVKLVDFG 158

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88481

cd05580

STKc_PKA

STKc_PKA: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA) subfamily, catalytic (c) subunit. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKA 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 (PI3K). This subfamily is composed of the cAMP-dependent proteins kinases, PKA and PRKX. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic (C) 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 C 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.

STKc_PKA: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA)...

false

true

false

290

1e-06

50.13

50.69

3,24,2,31,55,37,37,102,74,75

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR----PHATREAAARVVHEAAILRAARHDHVVAFLGLEREPWrqpapglp 100
cd05580        3 FEFIKTLGTGSFGRVMLVKHKGTGKYYAMKIlskaKIVKLKQVEHVLNEKRILQAVRHPFLVNLLGSFKDNS-------- 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 101 cqCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05580       75 --NLYMVMEFVPGGELFSLLRRSGRFPEPVARFYAAQVVLALEYLHSLDIVYRDLKPENLLLDSDGYIKITDFGFAK 149

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132944

cd06613

STKc_MAP4K3_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3-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. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK).

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

261

1e-06

49.60

54.02

4,24,4,31,55,36,31,86,70,6,105,76,69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR-PHATREAAARVVHEAAILRAARHDHVVAFLG---LEREPWrqpapglp 100
cd06613        5 YELLQRIGSGTYGDVYKARDIATGELAAVKViKLEPGDDFEIIQQEISMLKECRHPNIVAYFGsylRRDKLW-------- 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 101 cqcpvLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06613       77 -----IVMEYCGGGSLQDIYQVTGPLSELQIAYVCRETLKGLAYLHSQGKIHRDIKGANILLTEDGDVKLADFG 145

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132943

cd06612

STKc_MST1_2

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 1 (MST1) and MST2 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST1/2 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. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 (a MAPK kinase) and MEKK1 (a MAPK kinase kinase) by acting as a MAPK kinase kinase kinase (MAPKKKK). Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress.

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 1 (MST1) and MST2...

false

true

false

256

2e-06

49.57

54.69

5,24,4,31,56,35,30,86,68,6,105,74,15,120,90,54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKRpHATREAAARVVHEAAILRAARHDHVVAFLG---LEREPWrqpapglpc 101
cd06612        5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKV-VPVEEDLQEIIKEISILKQCDSPYIVKYYGsyfKNTDLW--------- 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 102 qcpvLVTEYAEGGTLAELL-ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06612       75 ----IVMEYCGAGSVSDIMkITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFG 144

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132958

cd06627

STKc_Cdc7_like

Serine/threonine kinases (STKs), cell division control protein 7 (Cdc7)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Cdc7-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. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane.

Serine/threonine kinases (STKs), cell division control protein 7 (Cdc7)-like subfamily,...

false

true

false

254

2e-06

49.55

57.09

3,24,1,31,55,35,36,101,71,75

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR---PHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglpc 101
cd06627        2 YQLGDLIGKGAFGVVYKGLNLETGDFVAIKQislEKIKEEALKSIMQEIDLLKNLNHPNIVKYIGSVKTS---------- 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 102 QCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHA 176
cd06627       72 DSLYIILEYAENGSLRQIIKKFGKFPESLVAVYVYQVLQGLAYLHEQGVIHRDIKAANILTTKDGVVKLADFGVA 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132979

cd06648

STKc_PAK_II

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group II, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, Group II,...

false

true

false

285

3e-06

48.60

32.28

4,71,68,15,86,86,6,105,92,16,122,108,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLG---LEREPWrqpapglpcqcpvLVTEYAEGGTLAELLAnRIRLSPAEVVTLGVPIARALDLLRRR 148
cd06648       69 IMRDYQHPNIVEMYSsylVGDELW-------------VVMEFLEGGALTDIVT-HTRMNEEQIATVCLAVLKALSFLHAQ 134

                         90       100
                 ....*....|....*....|....*.
gi 117928139 149 GIRHGDLRPANIAFTADGKPLLIDFG 174
cd06648      135 GVIHRDIKSDSILLTSDGRVKLSDFG 160

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132954

cd06623

PKc_MAPKK_plant_like

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis. MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling, MKK2 is involved in cold and salt stress signaling, MKK4/MKK5 participates in innate immunity, and MKK7 regulates basal and systemic acquired resistance.

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs...

false

true

false

264

8e-06

47.20

35.61

5,71,51,11,82,66,2,94,68,7,105,75,40,145,116,29

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVV----AFlglerepwrqPAPGLPCqcpvLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLL-R 146
cd06623       52 TLRSCESPYVVkcygAF----------YKEGEIS----IVLEYMDGGSLADLLKKVGKIPEPVLAYIARQILKGLDYLhT 117

                         90       100
                 ....*....|....*....|....*...
gi 117928139 147 RRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06623      118 KRHIIHRDIKPSNLLINSKGEVKIADFG 145

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88612

cd05120

APH_ChoK_like

Aminoglycoside 3'-phosphotransferase (APH) and Choline Kinase (ChoK) family. The APH/ChoK family is part of a larger superfamily that includes the catalytic domains of other kinases, such as the typical serine/threonine/tyrosine protein kinases (PKs), RIO kinases, actin-fragmin kinase (AFK), and phosphoinositide 3-kinase (PI3K). The family is composed of APH, ChoK, ethanolamine kinase (ETNK), macrolide 2'-phosphotransferase (MPH2'), an unusual homoserine kinase, and uncharacterized proteins with similarity to the N-terminal domain of acyl-CoA dehydrogenase 10 (ACAD10). The members of this family catalyze the transfer of the gamma-phosphoryl group from ATP (or CTP) to small molecule substrates such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine. Phosphorylation of the antibiotics, aminoglycosides and macrolides, leads to their inactivation and to bacterial antibiotic resistance. Phosphorylation of choline, ethanolamine, and homoserine serves as precursors to the synthesis of important biological compounds, such as the major phospholipids, phosphatidylcholine and phosphatidylethanolamine and the amino acids, threonine, methionine, and isoleucine.

Aminoglycoside 3'-phosphotransferase (APH) and Choline Kinase (ChoK) family. The APH/...

false

155

2e-05

45.81

47.10

3,103,67,16,126,83,21,147,107,33

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 104 PVLVTEYAEGGTLAELlanrirlSPAEVVTLGVPIARALDLLRR---RGIRHGDLRPANIAFTADGKPLLIDFGHARWCD 180
cd05120       68 SYLLMEWIEGETLDEV-------SEEEKEDIAEQLAELLAKLHQlplLVLCHGDLHPGNILVDDGKILGIIDWEYAGYGP 140

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88273

cd05119

RIO

RIO kinase family, catalytic domain. The RIO kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). RIO kinases are atypical protein serine kinases present in archaea, bacteria and eukaryotes. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. RIO kinases contain a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. Most organisms contain at least two RIO kinases, RIO1 and RIO2. A third protein, RIO3, is present in multicellular eukaryotes. In yeast, RIO1 and RIO2 are essential for survival. They function as non-ribosomal factors necessary for late 18S rRNA processing. RIO1 is also required for proper cell cycle progression and chromosome maintenance. The biological substrates for RIO kinases are still unknown.

RIO kinase family, catalytic domain. The RIO kinase catalytic domain family is part of...

false

187

1e-04

43.19

48.66

5,97,77,7,104,90,23,127,115,13,142,128,21,164,149,19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  98 GLPCQCP------VLVTEYAEGGTLAELLANRIRLS--PAEVVTLGVPIARalDLLRRRGIRHGDLRPANIAFTaDGKPL 169
cd05119       78 GVPVPKPidlnrhVLVMEFIGGDGIPAPRLKDVRLLedPEELYDQILELMR--KLYREAGLVHGDLSEYNILVD-DGKVY 154

                         90
                 ....*....|....
gi 117928139 170 LIDFGHARWCDAPQ 183
cd05119      155 IIDVPQAVEIDHPN 168

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88275

cd05145

RIO1_like

RIO kinase family; RIO1, RIO3 and similar proteins, catalytic domain. The RIO kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). RIO kinases are atypical protein serine kinases containing a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. RIO1 is present in archaea, bacteria and eukaryotes. In addition, RIO3 is present in multicellular eukaryotes. RIO1 is essential for survival and is required for 18S rRNA processing, proper cell cycle progression and chromosome maintenance. The biological substrates for RIO1 are unknown. The function of RIO3 is also unknown.

RIO kinase family; RIO1, RIO3 and similar proteins, catalytic domain. The RIO kinase...

false

190

0.002

39.74

47.89

6,91,73,13,104,92,6,110,99,12,123,111,19,142,131,21,164,152,12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  92 WRQPAPGLPCQCP------VLVTEY-AEGGTLAELLANrIRLSPAEVVTLGVPIARAL-DLLRRRGIRHGDLRPANIAFT 163
cd05145       74 KRLYEAGVPVPEPillkknVLVMEFiGDDGSPAPRLKD-VPLEEEEAEELYEQVVEQMrRLYQEAGLVHGDLSEYNILYH 152

                         90
                 ....*....|...
gi 117928139 164 aDGKPLLIDFGHA 176
cd05145      153 -DGKPYIIDVSQA 164

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88477

cd05576

STKc_RPK118_like

STKc_RPK118_like: Serine/Threonine Kinases (STKs), RPK118-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The RPK118-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. Members of this subfamily show similarity to human RPK118, which contains an N-terminal Phox homology (PX) domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain containing a long 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 (PRDX3). RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria.

STKc_RPK118_like: Serine/Threonine Kinases (STKs), RPK118-like subfamily, catalytic (c)...

false

237

0.002

39.61

30.80

2,105,61,69,176,130,4

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGhaRWCD 180
cd05576       62 LVLQHAEGGKLWSHISKFLNIPEECVKRWAAEMVVALDALHREGIVCRDLNPNNILLDDRGHIQLTYFS--RWSE 134

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132989

cd06658

STKc_PAK5

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 5, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK5 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 5, catalytic (c) domain....

false

true

false

292

1e-05

46.57

23.29

2,105,95,17,123,112,51

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANrIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06658       96 VVMEFLEGGALTDIVTH-TRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFG 163

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88510

cd05609

STKc_MAST

STKc_MAST: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. 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. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also referred to as syntrophin-associated STK (SAST), while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3.

STKc_MAST: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (...

false

true

false

305

2e-05

46.08

22.62

3,105,77,17,123,94,14,137,109,37

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 106 LVTEYAEGGTLAELLANrIRLSPAEVVTLGVP-IARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05609       78 MVMEYVEGGDCATLLKN-IGPLPVDMARMYFAeTVLALEYLHNYGIVHRDLKPDNLLITSMGHIKLTDFG 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88474

cd05573

STKc_ROCK_NDR_like

STKc_ROCK_NDR_like: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) and Nuclear Dbf2-Related (NDR)-like kinase subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK- and NDR-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. 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.

STKc_ROCK_NDR_like: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil...

false

true

false

354

2e-05

46.00

19.49

1,105,77,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05573       78 LVMEYMPGGDLMTLLIKYDVFPEETARFYIAELVLAIDSVHKLGFIHRDIKPDNILIDADGHIKLADFG 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88473

cd05572

STKc_cGK_PKG

STKc_cGK_PKG: Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or PKG) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cGK 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. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm.

STKc_cGK_PKG: Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or...

false

true

false

262

3e-05

45.56

45.42

3,72,22,11,84,33,23,107,71,70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  73 LRAARHDHVVAfLGLEREPWRQPAPGLPCQCPVLV---------------TEYAEGGTLAELLANRIRLSPAEVVTLGVP 137
cd05572       23 LKCVKKRHIVE-TGQQEHIFSEKEILEECNSPFIVrlyrtfkdkkyiyflMEYCLGGELWTILRDRGLLDEYTARFYTAC 101

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 117928139 138 IARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05572      102 VVEAFEYLHNRGIIYRDLKPENLLLDSNGYVKLVDFGFAK 141

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132991

cd06917

STKc_NAK1_like

Serine/threonine kinases (STKs), Nak1 subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nak1 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. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also known as N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner.

Serine/threonine kinases (STKs), Nak1 subfamily, catalytic (c) domain. STKs catalyze...

false

true

false

277

3e-05

45.51

51.26

7,28,6,26,54,37,32,90,69,4,95,73,4,104,77,16,120,94,19,141,113,35

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  29 ELVAIGRYAAVWRARTAVGDRSVALK-----RPHATREAAARVVHEAAILRAARHDHVVAFLGlerePWRQpAPGLpcqc 103
cd06917        7 ELIGRGAYGAVYRGKHVPTGRVVALKiinldTPDDDVSDIQREVALLSQLRQSQPPNITKYYG----SYLK-GPRL---- 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 104 pVLVTEYAEGGTLAELL-ANRIRLSPAEVVTLGVPIAraLDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHA 176
cd06917       78 -WIIMEYAEGGSVRTLMkAGPIAEKYISVIIREVLVA--LKYIHKVGVIHRDIKAANILVTNTGNVKLCDFGVA 148

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88512

cd05611

STKc_Rim15_like

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, fungal Rim15-like kinases, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase.

STKc_Rim15_like: Serine/Threonine Kinases (STKs), Microtubule-associated serine/...

false

true

false

260

4e-05

45.31

27.69

1,105,73,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05611       74 LVMEYLNGGDCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSR 145

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88479

cd05578

STKc_Yank1

STKc_Yank1: Serine/Threonine Kinases (STKs), Yank1 or STK32A subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Yank1 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. This subfamily contains uncharacterized STKs with similarity to the human protein designated Yank1 or STK32A.

STKc_Yank1: Serine/Threonine Kinases (STKs), Yank1 or STK32A subfamily, catalytic (c)...

false

true

false

258

4e-05

44.84

27.91

1,105,76,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05578       77 LVVDLLLGGDLRYHLQQKVKFSEEQVKFYVCEIVLALEYLHSKGIIHRDIKPDNILLDEQGHAHLTDFNIAT 148

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88501

cd05600

STKc_Sid2p_Dbf2p

STKc_Sid2p_Dbf2p: Serine/Threonine Kinases (STKs), ROCK- and NDR-like subfamily, fungal Sid2p- and Dbf2p-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Sid2p- and Dbf2p-like group 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. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis.

STKc_Sid2p_Dbf2p: Serine/Threonine Kinases (STKs), ROCK- and NDR-like subfamily, fungal...

false

true

false

333

4e-05

44.90

43.24

3,24,2,31,55,37,36,101,73,73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR----PHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglp 100
cd05600        3 FQILTQVGQGGYGQVFLAKKKDTGEIVALKRmkksLLFKLNEVRHVLTERDILTTTKSEWLVKLLYAFQDD--------- 73

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 101 cQCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05600       74 -EYLYLAMEYVPGGDFRTLLNNLGVLSEDHARFYMAEMFEAVDALHELGYIHRDLKPENFLIDASGHIKLTDFG 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88484

cd05583

STKc_MSK_N

STKc_MSK_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. 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, 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.

STKc_MSK_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

288

4e-05

44.92

23.96

1,105,81,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05583       82 LILDYVNGGELFTHLYQREHFTESEVRVYIAEIVLALDHLHQLGIIYRDIKLENILLDSEGHVVLTDFG 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88514

cd05613

STKc_MSK1_N

STKc_MSK1_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK1, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. 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. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkappaB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MEK1 is associated with the development of cerebral ischemic/hypoxic preconditioning.

STKc_MSK1_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

290

4e-05

44.62

24.83

1,105,81,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05613       82 LILDYINGGELFTHLSQRERFKEQEVQIYSGEIVLALEHLHKLGIIYRDIKLENILLDSNGHVVLTDFGLSK 153

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132988

cd06657

STKc_PAK4

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 4, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK4 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 4, catalytic (c) domain....

false

true

false

292

4e-05

44.63

23.29

2,105,93,17,123,110,51

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANrIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06657       94 VVMEFLEGGALTDIVTH-TRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFG 161

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88274

cd05144

RIO2_C

RIO kinase family; RIO2, C-terminal catalytic domain. The RIO kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). RIO kinases are atypical protein serine kinases containing a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. RIO2 is present in archaea and eukaryotes. It contains an N-terminal winged helix (wHTH) domain and a C-terminal RIO kinase catalytic domain. The wHTH domain is primarily seen in DNA-binding proteins, although some wHTH domains may be involved in RNA recognition. RIO2 is essential for survival and is necessary for rRNA cleavage during 40S ribosomal subunit maturation. The biological substrates of RIO2 are still unknown.

RIO kinase family; RIO2, C-terminal catalytic domain. The RIO kinase catalytic domain...

false

true

false

198

8e-05

43.97

36.87

4,104,106,15,122,121,9,137,130,9,146,142,37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 105 VLVTEYAEGGTLAELlanRIRLSPAEVvtlgvpIARALDLLR---RRGIRHGDLRPANIAFTADGKPLLIDFGHARWCDA 181
cd05144      107 AVVMEYIDGVELYRV---RVLEDPEEV------LDEILEEIVkayKHGIIHGDLSEFNILVDDDEKIYIIDWPQMVSTDH 177


                 ..
gi 117928139 182 PQ 183
cd05144      178 PN 179

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88511

cd05610

STKc_MASTL

STKc_MASTL: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (MAST) kinase subfamily, MAST-like (MASTL) kinases, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAST kinase 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. 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. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. The human MASTL gene has also been labelled FLJ14813. A missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. To date, the function of MASTL is unknown.

STKc_MASTL: Serine/Threonine Kinases (STKs), Microtubule-associated serine/threonine (...

false

true

false

669

1e-04

43.51

10.76

1,105,80,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05610       81 LVMEYLIGGDVKSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSK 152

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132990

cd06659

STKc_PAK6

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 6, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK6 belongs to group II. Group II PAKs contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility.

Serine/threonine kinases (STKs), p21-activated kinase (PAK) 6, catalytic (c) domain....

false

true

false

297

1e-04

43.48

22.90

2,105,94,16,122,110,52

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLAnRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06659       95 VLMEFLQGGALTDIVS-QTRLNEEQIATVCESVLQALCYLHSQGVIHRDIKSDSILLTLDGRVKLSDFG 162

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132960

cd06629

STKc_MAPKKK_Bck1_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Bck1-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

272

1e-04

43.25

33.09

2,77,66,14,101,80,76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  78 HDHVVAFLGLEREPwrqpapglpcQCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRP 157
cd06629       67 HLNIVQYLGFETTE----------EYLSIFLEYVPGGSIGSCLRTYGRFEEQLVRFFTEQVLEGLAYLHSKGILHRDLKA 136

                         90       100
                 ....*....|....*....|
gi 117928139 158 ANIAFTADGKPLLIDFGHAR 177
cd06629      137 DNLLVDADGICKISDFGISK 156

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133170

cd05038

PTKc_Jak_rpt2

Catalytic (Repeat 2) Domain of the Protein Tyrosine Kinases, Janus kinases

false

true

false

279

2e-04

43.11

35.48

3,71,58,24,103,82,18,121,101,56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGLEREPWRQPapglpcqcPVLVTEYAEGGTLAELLA-NRIRLSPAEVVTLGVPIARALDLLRRRGI 150
cd05038       59 IMRTLDHENIVKYKGVSEEPGGRS--------LSLIMEYLPSGSLRDYLRrHRDQLNLKRLLLFALQIAKGMDYLGSKRL 130

                         90       100
                 ....*....|....*....|....*..
gi 117928139 151 RHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05038      131 IHRDLAARNILVDSEDLVKISDFGLAK 157

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88475

cd05574

STKc_phototropin_like

STKc_phototropin_like: Serine/Threonine Kinases (STKs), Phototropin-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The phototropin-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. Included in this subfamily are plant phototropins and predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2. 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. N. crassa nrc-2 plays a role in growth and development by controlling entry into the conidiation program.

STKc_phototropin_like: Serine/Threonine Kinases (STKs), Phototropin-like subfamily,...

false

true

false

315

2e-04

42.93

22.22

3,105,77,18,123,104,10,140,114,33

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 106 LVTEYAEGGTLAELLANR---------IRLSPAEVVTlgvpiarALDLLRRRGIRHGDLRPANIAFTADGKPLLIDF 173
cd05574       78 LVMDYCPGGELFRLLQRQpgkcfpeevARFYAAEVLL-------ALEYLHLLGIVYRDLKPENILLHEDGHIMLSDF 147

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132952

cd06621

PKc_MAPKK_Pek1_like

Protein kinases (PKs), MAP kinase kinase(MAPKK) subfamily, fungal Pek1-like proteins, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates the MAPK Pmk1/Spm1 and is regulated by the MAPKKK Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKKK Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis.

Protein kinases (PKs), MAP kinase kinase(MAPKK) subfamily, fungal Pek1-like proteins,...

false

true

false

287

3e-04

42.03

34.49

4,71,51,15,95,66,10,105,77,11,116,92,58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGlerepwrqpAPGLPCQCPV-LVTEYAEGGTL----AELLANRIRLSPAEVVTLGVPIARALDLLR 146
cd06621       52 INKSCKSPYIVKYYG---------AFLDESSSSIgIAMEYCEGGSLdsiyKKVKKRGGRIGEKVLGKIAESVLKGLSYLH 122

                         90       100
                 ....*....|....*....|....*...
gi 117928139 147 RRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06621      123 SRKIIHRDIKPSNILLTRKGQVKLCDFG 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88513

cd05612

STKc_PRKX_like

STKc_PRKX_like: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA) subfamily, PRKX-like kinases, catalytic (c) subunit. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKA 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. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney.

STKc_PRKX_like: Serine/Threonine Kinases (STKs), cAMP-dependent protein kinase (PKA)...

false

true

false

291

7e-04

41.00

24.74

1,105,77,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05612       78 MLMEYVPGGELFSYLRKAGKFSNSTARFYAAEIVCALEYLHSKEIVYRDLKPENLLLDKEGHIKITDFGFAK 149

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133204

cd05073

PTKc_Hck

Catalytic Domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase

false

true

false

260

7e-04

40.78

51.54

6,33,16,9,43,25,44,87,70,5,104,75,16,120,95,7,129,102,48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRArTAVGDRSVALKRPHATREAAARVVHEAAILRAARHDHVVAFLGL-EREPWrqpapglpcqcpVLVTEYAE 112
cd05073       17 GQFGEVWMA-TYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVvTKEPI------------YIITEFMA 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 113 GGTLAELL----ANRIRLSpaEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05073       84 KGSLLDFLksdeGSKQPLP--KLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLAR 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132977

cd06646

STKc_MAP4K5

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 5 (MAPKKKK5 or MAP4K5) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K5 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

267

8e-04

40.40

53.56

5,24,10,31,55,42,31,86,75,5,91,81,1,105,82,71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKR-PHATREAAARVVHEAAILRAARHDHVVAFLG--LEREP-Wrqpapglp 100
cd06646       11 YELIQRVGSGTYGDVYKARNLHTGELAAVKIiKLEPGDDFSLIQQEIFMVKECKHCNIVAYFGsyLSREKlW-------- 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928139 101 cqcpvLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHA 176
cd06646       83 -----ICMEYCGGGSLQDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVA 153

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132936

cd06605

PKc_MAPKK

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK or MAP3K). MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs.

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. PKs...

false

true

false

265

9e-04

40.38

34.34

5,100,55,8,108,78,23,133,101,2,135,106,12,147,119,27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 101 CQCPVLVT---------------EYAEGGTLAELLANRIRLSPAEVvtLG---VPIARALDLLRR-RGIRHGDLRPANIA 161
cd06605       56 CNSPYIVGfygafynngdisicmEYMDGGSLDKILKEVQGRIPERI--LGkiaVAVLKGLTYLHEkHKIIHRDVKPSNIL 133

                         90
                 ....*....|...
gi 117928139 162 FTADGKPLLIDFG 174
cd06605      134 VNSRGEIKLCDFG 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88515

cd05614

STKc_MSK2_N

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK2, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. 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. 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.

STKc_MSK2_N: Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK)...

false

true

false

332

0.001

40.40

21.69

1,105,81,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05614       82 LILDYVSGGEMFTHLYQRDNFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSK 153

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133172

cd05040

PTKc_Ack_like

Catalytic Domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase

false

true

false

257

0.001

40.06

54.47

8,33,5,9,42,16,7,49,24,5,54,31,36,93,67,3,104,70,19,124,89,10,134,102,43

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRA--RTAVGDR-SVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLGLEREpwrQPApglpcqcpVLVT 108
cd05040        6 GSFGVVRRGewSTSGGKViPVAVKclKSDKLSDIMDDFLKEAAIMHSLDHENLIRLYGVVLT---HPL--------MMVT 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 109 EYAEGGTLAELLANRiRLSPAEVVTL---GVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05040       75 ELAPLGSLLDRLRKD-ALGHFLISTLcdyAVQIANGMRYLESKRFIHRDLAARNILLASDDKVKIGDFGLMR 145

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88483

cd05582

STKc_RSK_N

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK) subfamily, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The RSK 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. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks.

STKc_RSK_N: Serine/Threonine Kinases (STKs), 90 kDa ribosomal protein S6 kinase (RSK)...

false

true

false

318

0.001

39.95

21.70

1,105,74,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05582       75 LILDFLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEEGHIKLTDFG 143

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133198

cd05067

PTKc_Lck_Blk

Catalytic Domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk

false

true

false

260

0.001

39.81

28.46

2,105,76,18,123,96,54

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 106 LVTEYAEGGTLAELLANR--IRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05067       77 IVTEYMENGSLVDFLKTPegIKLTINKLIDMAAQIAEGMAYIERKNYIHRDLRAANILVSETLCCKIADFGLAR 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88471

cd05570

STKc_PKC

STKc_PKC: Serine/Threonine Kinases (STKs), Protein Kinase C (PKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC 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. 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.

STKc_PKC: Serine/Threonine Kinases (STKs), Protein Kinase C (PKC) subfamily, catalytic (..

false

true

false

318

0.002

39.45

21.70

1,105,72,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05570       73 FVMEYVNGGDLMYHIQQQGRFPEPRARFYAAEIVLGLQFLHERGIIYRDLKLDNVLLDAEGHIKIADFG 141

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132940

cd06609

STKc_MST3_like

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 3 (MST3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MST3-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. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization.

Serine/threonine kinases (STKs), mammalian Ste20-like protein kinase 3 (MST3)-like...

false

true

false

274

0.002

39.52

24.45

2,106,76,14,121,90,53

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928139 107 VTEYAEGGTLAELLaNRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06609       77 IMEYCGGGSCLDLL-KPGKLDETYIAFILREVLLGLEYLHEEGKIHRDIKAANILLSEEGDVKLADFG 143

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132959

cd06628

STKc_MAPKKK_Byr2_like

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) subfamily, fungal Byr2-like proteins, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPKKK 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. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase (..

false

true

false

267

0.002

39.44

34.83

3,71,58,19,95,77,5,105,82,69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGLEREpwrqpAPGLPcqcpvLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIR 151
cd06628       59 LLKELHHENIVQYLGSSQD-----AGHLN-----IFLEYVPGGSVAALLNNYGAFEESLVRNFVRQILKGLNYLHNRGII 128

                         90       100
                 ....*....|....*....|...
gi 117928139 152 HGDLRPANIAFTADGKPLLIDFG 174
cd06628      129 HRDIKGANILVDNKGGIKISDFG 151

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88518

cd05617

STKc_aPKC_zeta

STKc_aPKC_zeta: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC) subfamily, zeta isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The aPKC 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. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. There are two aPKC isoforms, zeta and iota. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells.

STKc_aPKC_zeta: Serine/Threonine Kinases (STKs), Atypical Protein Kinase C (aPKC)...

false

true

false

327

0.002

39.27

22.02

1,105,72,72

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05617       73 LVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCK 144

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133242

cd05111

PTK_HER3

Pseudokinase Domain of the Protein Tyrosine Kinase, HER3

false

true

false

279

0.002

39.13

31.90

4,77,67,10,95,77,7,105,84,13,118,98,58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  78 HDHVVAFLGLerepwrqpAPGLPCQcpvLVTEYAEGGTLAE-LLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLR 156
cd05111       68 HAYIVRLLGI--------CPGASLQ---LVTQLSPLGSLLDhVRQHRGSLDPQRLLNWCVQIAKGMYYLEEHRMVHRNLA 136

                         90       100
                 ....*....|....*....|
gi 117928139 157 PANIAFTADGKPLLIDFGHA 176
cd05111      137 ARNILLKSDSQVQIADFGVA 156

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133166

cd05034

PTKc_Src_like

Catalytic Domain of Src kinase-like Protein Tyrosine Kinases

false

true

false

261

0.003

38.82

51.72

8,33,16,9,43,25,44,87,71,5,104,76,18,122,98,5,129,103,31,161,134,10,171,145,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRArTAVGDRSVALKRPHATREAAARVVHEAAILRAARHDHVVAFLGL--EREPWrqpapglpcqcpVLVTEYA 111
cd05034       17 GQFGEVWMG-TWNGTTKVAVKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLYAVcsEEEPI------------YIVTEYM 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117928139 112 EGGTLAELLAN----RIRLSpaEVVTLGVPIARALDLLRRRGIRHGDLRPANIaFTADGKPLLI-DFGHAR 177
cd05034       84 SKGSLLDFLKSgegkKLRLP--QLVDMAAQIAEGMAYLESRNYIHRDLAARNV-LVGENLVCKVaDFGLAR 151

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133201

cd05070

PTKc_Fyn_Yrk

Catalytic Domain of the Protein Tyrosine Kinases, Fyn and Yrk

false

true

false

260

0.003

38.83

51.54

7,33,16,9,43,25,44,87,70,5,104,75,16,120,93,40,161,133,10,171,144,6

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRArTAVGDRSVALKRPHATREAAARVVHEAAILRAARHDHVVAFLGL-EREPWrqpapglpcqcpVLVTEYAE 112
cd05070       17 GQFGEVWMG-TWNGNTKVAVKTLKPGTMSPESFLEEAQIMKKLRHDKLVQLYAVvSEEPI------------YIVTEYMS 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928139 113 GGTLAELL--ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIaFTADGKPLLI-DFGHAR 177
cd05070       84 KGSLLDFLkdGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANI-LVGDGLVCKIaDFGLAR 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88523

cd05622

STKc_ROCK1

STKc_ROCK1: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta) isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK 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. 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. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring.

STKc_ROCK1: Serine/Threonine Kinases (STKs), ROCK subfamily, ROCK1 (or ROK-beta)...

false

true

false

371

0.004

38.50

18.33

3,105,119,18,123,143,10,140,153,34

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 106 LVTEYAEGGTLAELLANR------IRLSPAEVVTlgvpiarALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05622      120 MVMEYMPGGDLVNLMSNYdvpekwARFYTAEVVL-------ALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG 187

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132968

cd06637

STKc_TNIK

Serine/threonine kinases (STKs),Traf2- and Nck-interacting kinase (TNIK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The TNIK 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to mitogen-activated protein kinase (MAPK), kinase kinase kinase 4 (MAP4K4), and MAP4K6. MAP4Ks participate in some MAPK signaling pathways by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton.

Serine/threonine kinases (STKs),Traf2- and Nck-interacting kinase (TNIK) subfamily,...

false

true

false

272

0.004

38.54

54.78

6,24,7,51,75,59,11,86,72,5,96,77,7,104,84,20,124,106,50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKRPHATREAAARVVHEAAILRA-ARHDHVVAFLG--LEREPwrqpaPGLPC 101
cd06637        8 FELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKySHHRNIATYYGafIKKNP-----PGMDD 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 102 QCpVLVTEYAEGGTLAELLANRI--RLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06637       83 QL-WLVMEFCGAGSVTDLIKNTKgnTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFG 156

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132976

cd06645

STKc_MAP4K3

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase kinase 3 (MAPKKKK3 or MAP4K3) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAP4K3 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain, similar to MAP4K4/6. MAP4Ks are involved in some MAPK signaling pathways that are important in mediating cellular responses to extracellular signals by activating a MAPK kinase kinase (MAPKKK or MAP3K or MKKK). 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer.

Serine/threonine kinases (STKs), mitogen-activated protein kinase (MAPK) kinase kinase...

false

true

false

267

0.004

38.11

52.81

5,24,10,49,73,60,13,86,75,5,91,81,1,105,82,69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALKRPHATREAAARVVHEAAIL-RAARHDHVVAFLG--LEREP-Wrqpapglp 100
cd06645       11 FELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPGEDFAVVQQEIIMmKDCKHSNIVAYFGsyLRRDKlW-------- 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 101 cqcpvLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06645       83 -----ICMEFCGGGSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFG 151

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88497

cd05596

STKc_ROCK

STKc_ROCK: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing protein kinase (ROCK) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ROCK 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. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long 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. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development.

STKc_ROCK: Serine/Threonine Kinases (STKs), Rho-associated coiled-coil containing...

false

true

false

370

0.004

37.99

18.38

3,105,119,18,123,143,10,140,153,34

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 106 LVTEYAEGGTLAELLANR------IRLSPAEVVTlgvpiarALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05596      120 MVMEYMPGGDLVNLMSNYdipekwARFYTAEVVL-------ALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG 187

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133183

cd05052

PTKc_Abl

Catalytic Domain of the Protein Tyrosine Kinase, Abelson kinase

false

true

false

263

0.005

37.89

49.43

6,35,22,8,47,30,40,87,71,4,103,75,2,105,78,15,120,95,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  36 YAAVWRARtavgDRSVALKRPHATREAAARVVHEAAILRAARHDHVVAFLGL-EREPwrqpapglpcqcPV-LVTEYAEG 113
cd05052       23 YEGVWKKY----SLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVcTREP------------PFyIITEFMTY 86

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928139 114 GTLAELL--ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05052       87 GNLLDYLreCNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 152

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132956

cd06625

STKc_MEKK3_like

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MEKK3-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. This subfamily is composed of MEKK3, MEKK2, and related proteins, all containing an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks), proteins that 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. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates extracellular signal-regulated kinase 5 (ERK5). The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs.

Serine/threonine kinases (STKs), MAP/ERK kinase kinase 3 (MEKK3)-like subfamily,...

false

true

false

263

0.005

37.87

36.50

2,71,56,20,101,76,76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGLEREPwrqpapglpcQCPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIR 151
cd06625       57 LLKNLQHERIVQYYGCLRDD----------ETLSIFMEYMPGGSVKDQLKAYGALTETVTRKYTRQILEGVEYLHSNMIV 126

                         90       100
                 ....*....|....*....|....*.
gi 117928139 152 HGDLRPANIAFTADGKPLLIDFGHAR 177
cd06625      127 HRDIKGANILRDSAGNVKLGDFGASK 152

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88487

cd05586

STKc_Sck1_like

STKc_Sck1_like: Serine/Threonine Kinases (STKs), Fission yeast Suppressor of loss of cAMP-dependent protein kinase (Sck1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Sck1-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. This subfamily is composed of fungal proteins with similarity to the Schizosaccharomyces pombe STK Sck1. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes.

STKc_Sck1_like: Serine/Threonine Kinases (STKs), Fission yeast Suppressor of loss of...

false

true

false

330

0.005

37.70

20.91

1,105,72,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05586       73 LVTDYMSGGELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKYDIVYRDLKPENILLDATGHIALCDFG 141

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

133202

cd05071

PTKc_Src

Catalytic Domain of the Protein Tyrosine Kinase, Src

false

true

false

262

0.005

37.72

51.15

5,33,16,9,43,25,48,103,73,2,105,76,20,125,98,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  34 GRYAAVWRArTAVGDRSVALKRPHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglpcqcPV-LVTEYAE 112
cd05071       17 GCFGEVWMG-TWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEE------------PIyIVTEYMS 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 113 GGTLAELLANRIR--LSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
cd05071       84 KGSLLDFLKGEMGkyLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLAR 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132949

cd06618

PKc_MKK7

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK). MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 (not included in this subfamily) and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade.

Protein kinases (PKs), MAP kinase kinase 7 (MKK7) subfamily, catalytic (c) domain. PKs...

false

true

false

296

0.006

37.74

21.62

4,113,96,19,133,115,2,135,120,11,146,132,28

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 117928139 114 GTLAELLANRIRLSPAEVVtLG---VPIARALDLLR-RRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd06618       97 STCLDKLLKRIQGPIPEDI-LGkmtVAIVKALHYLKeKHGVIHRDVKPSNILLDASGNVKLCDFG 160

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

88528

cd05627

STKc_NDR2

STKc_NDR2: Serine/Threonine Kinases (STKs), NDR kinase subfamily, NDR2 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The NDR 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. 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. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. Both isoforms play a role in proper centrosome duplication. In addition, NDR2 plays a role in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. It is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR2 is also referred to as STK38-like.

STKc_NDR2: Serine/Threonine Kinases (STKs), NDR kinase subfamily, NDR2 isoform,...

false

true

false

360

0.006

37.75

19.17

1,105,77,69

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 106 LVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
cd05627       78 LIMEFLPGGDMMTLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLLDAKGHVKLSDFG 146

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

132963

cd06632

STKc_MEKK1_plant

Serine/threonine kinases (STKs), plant MAP/ERK kinase kinase 1 (MEKK1)-like subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant MEKK1 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. This subfamily is composed of plant mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs or MAP3Ks) including Arabidopsis thaliana MEKK1 and MAPKKK3. MEKK1 is a MAPKKK that phosphorylates and activates 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. 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.

Serine/threonine kinases (STKs), plant MAP/ERK kinase kinase 1 (MEKK1)-like subfamily,...

false

true

false

258

0.007

37.40

37.21

4,71,54,23,104,77,17,122,94,14,136,109,41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  72 ILRAARHDHVVAFLGLEREPWRQpapglpcqcpVLVTEYAEGGTLAELLAnRIRLSPAEVVTLGV-PIARALDLLRRRGI 150
cd06632       55 LLSKLQHPNIVQYLGTEREEDNL----------YIFLELVPGGSLAKLLK-KYGSFPEPVIRLYTrQILLGLEYLHDRNT 123

                         90       100
                 ....*....|....*....|....*..
gi 117928139 151 RHGDLRPANIAFTADGKPLLIDFGHAR 177
cd06632      124 VHRDIKGANILVDTNGVVKLADFGMAK 150

cl09925

142329

PKc_like

Protein Kinases, catalytic domain

-1

128517

smart00221

STYKc

Protein kinase; unclassified specificity.

false

true

false

225

2e-18

89.32

64.89

4,24,0,30,54,32,37,101,69,19,120,89,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglpcQ 102
smart00221     1 YELGKKLGEGAFGKVYLARDKGTGELVAVKvlKKEKTEKQREEFLREIRILKKLKHPNIVKLYGVFEDP----------E 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 117928139 103 CPVLVTEYAEGGTLAELL-ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
smart00221    71 PLYLVMEYCEGGDLFDYLrKKGGKLSEEEARFYLRQILEALEYLHSLGIVHRDLKPENILLGMDGLVKLADFGLAR 146

-1

128516

smart00220

S_TKc

Serine/Threonine protein kinases, catalytic domain

false

true

false

244

2e-17

86.05

54.92

3,35,1,19,54,22,37,101,59,76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  36 YAAVWRARTAVGDRSVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLGLEREPwrqpapglpcQCPVLVTEYAEG 113
smart00220     2 FGKVYLARDKKTGKLVAIKviKKEKIKKKRERILREISILKKLKHPNIVRLYDVFEDE----------DKLYLVMEYCDG 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 117928139 114 GTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
smart00220    72 GDLFDLLKKRGRLSEDEARFYARQILSALEYLHSNGIIHRDLKPENILLDEDGHVKLADFGLAR 135

-1

109137

pfam00069

Pkinase

Protein kinase domain

false

true

false

260

1e-16

83.07

58.46

3,24,0,30,54,33,39,103,72,80

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  25 YDVSELVAIGRYAAVWRARTAVGDRSVALK---RPHATREAAARVVHEAAILRAARHDHVVAFLGLEREPWRqpapglpc 101
pfam00069      1 YELLRKLGSGSFGTVYKAKHKGTGKIVAVKilkKRSEKSKKDQTARREIRILRRLSHPNIVRLIDAFEDKDH-------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139 102 qcPVLVTEYAEGGTLAELLANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHARWCDA 181
pfam00069     73 --LYLVMEYCEGGDLFDYLSRGGPLSEDEAKKIALQILRGLEYLHSNGIIHRDLKPENILLDNNGVVKIADFGLAKKLTK 150


                 ..
gi 117928139 182 PQ 183
pfam00069    151 SS 152

-1

30861

COG0515

SPS1

Serine/threonine protein kinase [General function prediction only / Signal transduction mechanisms / Transcription / DNA replication, recombination, and repair]

Serine/threonine protein kinase [General function prediction only / Signal transduction...

false

true

false

384

6e-12

67.49

39.32

7,23,0,22,48,22,7,55,33,23,78,57,13,101,70,24,125,97,41,166,139,12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  24 GYDVSELVAIGRYAAVWRARTAvgdRSVALKR----PHATREAAARVVHEAAILRAARH-DHVVAFLGLEREPwrqpapg 98
COG0515        1 SYRILRKLGEGSFGEVYLARDR---KLVALKVlakkLESKSKEVERFLREIQILASLNHpPNIVKLYDFFQDE------- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  99 lpcQCPVLVTEYAEGGTLAELLANRIR---LSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADG-KPLLIDFG 174
COG0515       71 ---GSLYLVMEYVDGGSLEDLLKKIGRkgpLSESEALFILAQILSALEYLHSKGIIHRDIKPENILLDRDGrVVKLIDFG 147


                 ....
gi 117928139 175 HARW 178
COG0515      148 LAKL 151

-1

116328

pfam07714

Pkinase_Tyr

Protein tyrosine kinase

false

true

false

258

7e-10

60.59

52.33

5,35,15,19,54,36,32,86,70,7,105,77,15,120,93,57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  36 YAAVWRARTAVGDRSVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLG--LEREPWRqpapglpcqcpvLVTEYA 111
pfam07714     16 YKGTLKGDGEGTETKVAVKtlKEGASEEEREEFLEEASIMKKLSHPNIVRLLGvcTQGEPLY------------IVTEYM 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 112 EGGTLAELL-ANRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
pfam07714     84 PGGDLLDFLrKHGEKLTLKDLLQMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSR 150

-1

128515

smart00219

TyrKc

Tyrosine kinase, catalytic domain

false

true

false

258

5e-08

54.86

52.71

5,35,15,19,54,36,32,86,70,5,103,75,22,125,99,52

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 117928139  36 YAAVWRARTAVGDRSVALK--RPHATREAAARVVHEAAILRAARHDHVVAFLG--LEREPwrqpapglpcqcPVLVTEYA 111
smart00219    16 YKGTLKGLSGEKEVEVAVKtlKEDADEQQIEEFLREARIMRKLDHPNIVKLLGvcTEEEP------------LMIVMEYM 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928139 112 EGGTLAELLANRIR--LSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
smart00219    84 EGGDLLDYLRKNRPkeLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSR 151

-1

31005

COG0661

AarF

Predicted unusual protein kinase [General function prediction only]

false

true

false

517

4e-05

44.94

13.35

3,104,241,21,125,263,14,141,277,33

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 117928139 105 VLVTEYAEGGTLAELLANRIR-LSPAEVVTLGVPIAraLDLLRRRGIRHGDLRPANIAFTADGKPLLIDFG 174
COG0661      242 VLTMEWIDGIKISDIAALKSAgIDRKELAELLVRAF--LRQLLRDGFFHADPHPGNILVRSDGRIVLLDFG 310

-1

30826

COG0478

RIO-like serine/threonine protein kinase fused to N-terminal HTH domain [Signal transduction mechanisms]

RIO-like serine/threonine protein kinase fused to N-terminal HTH domain [Signal...

false

true

false

304

5e-05

44.85

24.01

2,104,182,13,122,195,60

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 117928139 105 VLVTEYAEGGTLAellanRIRLSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHARWCDAP 182
COG0478      183 AVVMEYIEGVELY-----RLRLDVENPDEILDKILEEVRKAYRRGIVHGDLSEFNILVTEDGDIVVIDWPQAVPISHP 255

-1

33440

COG3642

Mn2+-dependent serine/threonine protein kinase [Signal transduction mechanisms]

false

true

false

204

7e-04

40.99

34.80

4,104,74,16,123,90,17,144,107,19,164,126,19

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 117928139 105 VLVTEYAEGGTLAELLanrIRLSPAEVVTLGVPIARaldlLRRRGIRHGDLRPANIAFTaDGKPLLIDFGHARWCDAPQ 183
COG3642       75 LIVMEYIEGELLKDAL---EEARPDLLREVGRLVGK----LHKAGIVHGDLTTSNIILS-GGRIYFIDFGLGEFSDEVE 145

-1

140293

PTZ00267

NIMA-related protein kinase; Provisional

false

true

false

478

0.004

38.46

16.11

2,104,140,21,125,165,52

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 105 VLVTEYAEGGTLAELLANRIR----LSPAEVVTLGVPIARALDLLRRRGIRHGDLRPANIAFTADGKPLLIDFGHAR 177
PTZ00267     141 LLIMEYGSGGDLNKQIKQRLKehlpFQEYEVGLLFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSK 217

-1

137418

PRK09605

O-sialoglycoprotein endopeptidase/protein kinase; Reviewed

false

true

false

536

0.005

38.01

12.31

4,104,413,16,126,429,14,144,443,18,163,461,18

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 117928139 105 VLVTEYAEGGTLAELLanrirlSPAEVVTLGVPIARaldlLRRRGIRHGDLRPANIAFtADGKPLLIDFGHARWCDA 181
PRK09605     414 TITMEYIGGKDLKDVI------SEELCEKVGEMVGK----LHSAGIVHGDLTTSNIIV-RSDRTYLIDFGLGKYSDL 479

-1

catalytic loop	0	10	10	false	29142	cd00180	S_TKc
activation loop	1	10	24	false	29142	cd00180	S_TKc
ATP binding pocket	2	13	13	false	29142	cd00180	S_TKc
substrate binding pocket	3	2	7	false	29142	cd00180	S_TKc