2FH9,2H6D,2Y94,3H4J


Conserved Protein Domain Family
STKc_AMPK_alpha

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cd14079: STKc_AMPK_alpha 
Click on image for an interactive view with Cn3D
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 270981
Aligned: 29 rows
Threshold Bit Score: 481.383
Created: 9-Aug-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:2Y94: Rattus norvegicus AMPK binds the inhibitor, staurosporine; contacts at 4A.
  • Comment:also based on structures of other members of the CAMK family bound with ATP or ATP analogs or inhibitors
  • Citation:PMID 9362479

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1              ####    #            # #                               #               
2FH9_A      7 IGNYQIVKtLGEGSFGKVKLAYHTtTGQKVALKIINKKVLaksdMQGRIEREISYLRLLrHPHIIKLYDVIKskdEIIMV 86  baker's yeast
2Y94_A     15 IGHYILGDtLGVGTFGKVKVGKHElTGHKVAVKILNRQKIrsldVVGKIRREIQNLKLFrHPHIIKLYQVIStpsDIFMV 94  Norway rat
AAZ10489    8 IGNYVIGKtIGKGSFGKVKEATHIpTGHTVAVKMINRDRLehakMDEKVAREIKILQLFsHPNICRLYEVIYtttEIFLI 87  Trypanosoma brucei
Q95ZQ4     84 IGHYILKEtLGVGTFGKVKVGIHEtTQYKVAVKILNRQKIksldVVGKIRREIQNLSLFrHPHIIRLYQVIStpsDIFMI 163 nematode
CAF97108   11 IGHYILGDtLGVGTFGKVKVGQHElTKHQVAVKILNRQKIrsldVVGKIRREIQNLKLFrHPHIIKLYQVIStptDIFMV 90  Tetraodon nigrovir...
CAA19653   25 IGHYLLGAtLGTGTFGKVKIGEHQiTRVKVAVKILNRQKIksldVVGKIRREIQNLKLFrHPHIIKLYQVIStpsDIFMI 104 fruit fly
XP_764455   7 LRGYTIGTtLGVGSFAKVKLGVDKrTGKQVAIKIIDKTRMatmgLIGKLSREISALQGSyHRNIIQLYDIIDtpdTIFLI 86  Theileria parva st...
CAK80136   11 IEHYIIGKtLGVGAFGKVKLAKHNiTNTQVAIKIINKRKMknsrMGTKIRREIRLLRYFnHPNVIKLYEVLDtpgDIFVV 90  Paramecium tetraur...
CAX69715   17 IGNYIIGEtLGVGTFGKVKVGIHKsTGVQVAVKIVNRDKIkaldVAGKLRREILNLWLFrHPHIIKLYQVIStptDIFMI 96  Schistosoma japonicum
CBZ53562   56 IGPYRLGStLGVGTFGKVKLGYHNvTGQKVAVKIINKAKMemmeMYEKIRREINILQCLhHPHVIRLYELIDtptDIFMV 135 Neospora caninum L...
Feature 1     ####   #                                          ## #         ##               
2FH9_A     87 IEYAG-NELFDYIVqrdkMSEQEARRFFQQIISAVEYCHRHKIVHRDLKPENLLLDehLNVKIADFGLSNIMTDGNFLKT 165 baker's yeast
2Y94_A     95 MEYVSgGELFDYICkngrLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDahMNAKIADFGLSNMMSDGEFLRX 174 Norway rat
AAZ10489   88 MEYVEcGELFQHIVnqgkLRENEARYIFQQIICAVNYCHNFLVAHRDLKPENILLGpgLQVKLIDFGLSNIAKDGEFLQT 167 Trypanosoma brucei
Q95ZQ4    164 MEHVSgGELFDYIVkhgrLKTAEARRFFQQIISGVDYCHRHMVVHRDLKPENLLLDeqNNVKIADFGLSNIMTDGDFLRT 243 nematode
CAF97108   91 MEYVSgGELFDYICkngkLDEKESRRLFQQIISAVDYCHRHMVVHRDLKPENVLLDahMNAKIADFGLSNMMSDGEFLRT 170 Tetraodon nigrovir...
CAA19653  105 MEYVSgGELFDYIVkhgkLQEHQARRFFQQIISGVDYCHRHMIVHRDLKPENLLLDhnMHVKIADFGLSNMMLDGEFLRT 184 fruit fly
XP_764455  87 MEYVDgGELFDYISqnsrLSEVEAIRIFRQILSAVDFCHRKMLCHRDLKPENILIDryMNIKLGDFGLSNFMRDGECLKT 166 Theileria parva st...
CAK80136   91 MEYAErGELFDLIAqrgkLPESEARNFFLQILSGVEYCHNNLVAHRDLKPENILMThnYVVKIADFGLSNLMKDGKYLKT 170 Paramecium tetraur...
CAX69715   97 MEYVSgGELFDFIVksgrLSEKEARKFFQQIISGVAYCHRHKVVHRDLKPENLLLDsnQNVKIADFGLSNIMQDGEFLRT 176 Schistosoma japonicum
CBZ53562  136 MEYVQgGELFDHIVqksrLPEHEARRFFQQIVSGVDYCHRHMICHRDLKPENVLLDtnMNVKVGDFGLSNFMRDGDFLKT 215 Neospora caninum L...
Feature 1                                                                                     
2FH9_A    166 SCGSPNYAAPEVISGKLYAGPEVDVWSCGVILYVMLCRRLPFDDeSIPVLFKNISNGVYTLPKFlsPGAAGLIKRMLIVn 245 baker's yeast
2Y94_A    175 SCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDdHVPTLFKKICDGIFYTPQYlnPSVISLLKHMLQVd 254 Norway rat
AAZ10489  168 SCGSPNYAAPEVIDGRYYVGSNTDIWSCGVILYALLCGSLPFDEsDTPSLFRKIKSGSYKIPAHvsSGARDLIEKILVVd 247 Trypanosoma brucei
Q95ZQ4    244 SCGSPNYAAPEVISGKLYAGPEVDVWSCGVILYALLCGTLPFDDeHVPSLFRKIKSGVFPTPDFleRPIVNLLHHMLCVd 323 nematode
CAF97108  171 SCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDdHVPTLFKKICDGIFFTPQYlnPSVISLLKHMLQVd 250 Tetraodon nigrovir...
CAA19653  185 SCGSPNYAAPEVISGKLYAGPEVDIWSCGVILYALLCGTLPFDDeHVPTLFRKIKSGIFPIPEYlnKQVVNLVCQMLQVd 264 fruit fly
XP_764455 167 PCGSPNYASPEVICGKSYAGPEIDIWSCGIILYVLLCGSLPFDDdEIPALFGKIKLGKFYVPGHltSDSRWLLQRMLDVn 246 Theileria parva st...
CAK80136  171 SCGSPNYAAPEVISGKTYCGSDADVWSCGVILYALLAGFLPFDEeTTQALFKKIKSADYTIPSSfsPQVRDLINRMLTPd 250 Paramecium tetraur...
CAX69715  177 SCGSPNYAAPEVISGKLYAGPEVDVWSCGVILYALLCGTLPFDDeHIPTLFKKIKAGYFHLPETlsAGVRDLLRRMITVd 256 Schistosoma japonicum
CBZ53562  216 SCGSPNYASPEVVSGKAYAGPEVDVWSCGVILYALLCGSLPFDDeHVPNLFKKIKHGNFILPGHlsEASRNLIVRMLVVd 295 Neospora caninum L...
Feature 1                     
2FH9_A    246 PLNRISIHEIMQDDWF 261 baker's yeast
2Y94_A    255 PMKRATIKDIREHEWF 270 Norway rat
AAZ10489  248 PVHRLTIPQIYNHQWF 263 Trypanosoma brucei
Q95ZQ4    324 PMKRATIKDVIAHEWF 339 nematode
CAF97108  251 PMKRATIREIREDEWF 266 Tetraodon nigroviridis
CAA19653  265 PLKRANIEEIKKHEWF 280 fruit fly
XP_764455 247 PQTRITMKELLSHYLL 262 Theileria parva strain Muguga
CAK80136  251 PLKRIKFHEIHLHPYM 266 Paramecium tetraurelia
CAX69715  257 PIKRATIEEIRRHPWF 272 Schistosoma japonicum
CBZ53562  296 PAKRISLSEIRQHPWF 311 Neospora caninum Liverpool

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