3GNI,2WTK


Conserved Protein Domain Family
PK_STRAD_alpha

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cd08227: PK_STRAD_alpha 
Click on image for an interactive view with Cn3D
Pseudokinase domain of STE20-related kinase adapter protein alpha
The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. The STRAD alpha subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 173767
View PSSM: cd08227
Aligned: 5 rows
Threshold Bit Score: 654.704
Threshold Setting Gi: 47217823
Created: 14-Dec-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
ATP bindingMO25LKB1
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3GNI_B; human STRAD-alpha binds ATP; contacts at 4A.
    View structure with Cn3D
  • Comment:Although STRAD is a pseudokinase without catalytic activity, it binds ATP and this binding enhances the affinity of STRAD to MO25.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             #####   # #            # #                                              ###
3GNI_B        28 ELLTVIGKGFEDLMTVNLARYKPtgEYVTVRRINLEACSNEMVTFLQGELHVSKLFNHPNIVPYRATFIADNeLWVVTSF 107 human
2WTK_B        12 ELLTVIGKGFEDLMTVNLARYKPtgEYVTVRRINLEACSNEMVTFLQGELHVSKLFNHPNIVPYRATFIADNeLWVVTSF 91  human
NP_001012862  12 ELLTIIGRGFEDLMVVNLARYKPsgEYVTVRRVNLEACTNEMVTFLQGELHVSKLFNHPNIVPYKATFIADNeLWVVTSF 91  chicken
CAG07237      40 DLLAVIGRGLDDLMTVNLARYRPtgEHVAIRRIDLESCTNDMVNFLQCELHVSKLFHHPSILPYKSVFIAENeLWVVTPF 119 Tetraodon nigro...
AAH81364      12 ELLTVIGRGFDDLMTVNLARYRPnaEYVCIRRVNLEFCTNDMVTFLQTELHVSKLFNHPNILPYRATFITDNeLWVVTPF 91  western clawed ...
Feature 1        #   #  #                                         ## #            #              
3GNI_B       108 MAyGSAKDLICTHFmdgMNELAIAYILQGVLKALDYIHHMGYVHRSVKASHILISvdGKVYLSGLRSNLSMISHGqRQRV 187 human
2WTK_B        92 MAyGSAKDLICTHFmdgMNELAIAYILQGVLKALDYIHHMGYVHRSVKASHILISvdGKVYLSGLRSNLSMISHGqRQRV 171 human
NP_001012862  92 MAyGSAKDLICTHFmdgMSELAIAYILQGVLKALDYIHHMGYVHRSVKASHILISvdGKVYLSGLRSNLSMINHGqRLKV 171 chicken
CAG07237     120 MAyGSARDLICTHFsdgMSELTIAYIILGMLKALEYIHHMGYVHRSVKASHVLISadGQVCMSGLRSIFSLIRHGqRARV 199 Tetraodon nigro...
AAH81364      92 MAyGSAKDLICTHFtdgLSELAIAYILVGVLKALNYIHHMGYVHRSVKASHILISldGKVYLSGLRSIHSMINHGqRLKM 171 western clawed ...
Feature 1                                                                                        
3GNI_B       188 VHDFPKYSVKVLPWLSPEVLQQNLQGYDAKSDIYSVGITACELANGHVPFKDMPATQMLLEKLn---------------- 251 human
2WTK_B       172 VHDFPKYSVKVLPWLSPEVLQQNLQGYDAKSDIYSVGITACELANGHVPFKDMPATQMLLEKLn---------------- 235 human
NP_001012862 172 VHDFPKYSIKVLPWLSPEVLQQNLQGYDAKSDIYSIGITACELANGHVPFKDMPSTQMLLEKLn---------------- 235 chicken
CAG07237     200 VHDFPRYSVKVLPWLSPEVLQQNLQGYDSRSDIYSLGITACELANGHVPFKDMPATQVRTGGMapagtlwlfnsprllrf 279 Tetraodon nigro...
AAH81364     172 IHDFPKHSARVLPWLSPEVLQQNLQGYDAKSDIYSVGITACELANGHVPFKDMPATQMLLEKLn---------------- 235 western clawed ...
Feature 1                                                                                        
3GNI_B       252 --------GTVPCLLDTSTIPAeELTMSPSRSVANSGLsdsltts--tprpsnGDSPSHPYHRTFSPHFHHFVEQCLQRN 321 human
2WTK_B       236 --------GTVPCLLDTSTIPAeELTMSPSRSVANSGLsdsltts--tprpsnGDSPSHPYHRTFSPHFHHFVEQCLQRN 305 human
NP_001012862 236 --------GTVPCLLDTTTIPAdELTMKTSRSSANYGLgestavs--nvraanGESTLHPYLRTFSSCFHNFVGQCLQRN 305 chicken
CAG07237     280 qmlleklnGTVPCLLDTTTIPPeELALRPSRSGADSGIcegpgvgavrhsngePSSSAHPYNRTFSPHFHAFVELCLQRD 359 Tetraodon nigro...
AAH81364     236 --------GTVPCLLDTATIPAsELTMKTSRSGADSGIgegts-----srpsnGEPSMHPYNRSFSPQFHSLVEQCLQRN 302 western clawed ...
Feature 1                                         
3GNI_B       322 PDARPSASTLLNHSFFKQIKRrASEALPELLRP 354 human
2WTK_B       306 PDARPSASTLLNHSFFKQIKRrASEALPELLRP 338 human
NP_001012862 306 PDFRPSAGALLNHPFFKQIKRrASEALPELLRP 338 chicken
CAG07237     360 PEKRPSASSLTGHPFFKQIKRwPSEALPELLLP 392 Tetraodon nigroviridis
AAH81364     303 PELRPSAGTLLNHSFFKQIKRrACDALPELLCP 335 western clawed frog

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