Conserved Protein Domain Family
STKc_GRK4

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cd05631: STKc_GRK4 
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 173720
View PSSM: cd05631
Aligned: 4 rows
Threshold Bit Score: 592.352
Threshold Setting Gi: 121582340
Created: 22-Oct-2007
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:
  • Comment:Based on the binding of peptide substrates and ATP analogs to the AGC kinases, PKA and PKB.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               #####   #            # #                               #               ##
NP_001004056 154 TFRHYRVLGKGGFGEVCACQVRATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVqSRFVVSLAYAYETKDALCLVLT 233 human
NP_001087932 185 TFRHYRVLGKGGFGEVCACQVRATGKMYACKKLEKKRIKKRKGESMALNEKQILEKVnSRFVVSLGYTYETKDALCLVLT 264 African clawed ...
NP_001006459 182 TFRHYRVLGKGGFGEVCACQVRATGKMYACKKLEKKRIKKRKGESMALNEKRILEKVnSRFVVSLSYTYETKDALCLVLT 261 chicken
NP_001073455 185 TFRHYRVLGKGGFGEVCACQVRATGKMYACKKLEKKRVKKRKGEAMALNEKRILEKVnSSFVVSLAYAYETKDALCLVLT 264 zebrafish
Feature 1         #   # #                                      # # ## #         ##  #            
NP_001004056 234 IMNGGDLKFHIYNLGNpGFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDrGHIRISDLGLATEIPEGQRVRG 313 human
NP_001087932 265 IMNGGDLKFHIYNMGNpGFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDrGHIRISDLGLAVQIPEGETIRG 344 African clawed ...
NP_001006459 262 IMNGGDLKFHIYNMGNpGFDEERAIFYAAELCCGLEDLQKERIVYRDLKPENILLDDcGHIRISDLGLAVQIPEGETVRG 341 chicken
NP_001073455 265 IMNGGDLKFHIYNMGNsGFDEQRAIFYAAEICCGLEDLHRERIVYRDLKPENILLDDrGHIRISDLGLAVQIPEGETIRG 344 zebrafish
Feature 1        ######                          #     #  #                                      
NP_001004056 314 RVGTVGYMAPEVVNNEkytFSPDWWGLGCLIYEMIQGHSPFKKYKEKVKWEEVDQRIKNDTEEYSEKFSEDAKSICRMLL 393 human
NP_001087932 345 RVGTVGYMAPEVINNEsyaFSPDWWGLGCLIYEMIQGQSPFRKRKEKVKRDEVDRRVREDEEEYSEKFSEDAKSICRMLL 424 African clawed ...
NP_001006459 342 RVGTVGYMAPEVLKNEkytFSPDWWGLGCLIYEMIEGQSPFRKHKERVKRDEIDRRVKEDQETYSDKFSEEAKSICRMLL 421 chicken
NP_001073455 345 RVGTVGYMAPEVIQNEsytFSPDWWGLGCLIYEMIQGQSPFRRRKERVKREEVDRRVCEDQEEYTEKFSEDAKDICRQLL 424 zebrafish
Feature 1                                                     
NP_001004056 394 TKnPSKRLGCRgeGAAGVKQHPVFKDINFRRLEANMLEPPFCPDP 438 human
NP_001087932 425 SKdPKQRLGCTgnGASDVKQHPIFKSINFKRLEANILEPPFVPDP 469 African clawed frog
NP_001006459 422 AKnPGERLGCTenGAAIVKQHPIFKNINFKRLEANMLEPPFLPDP 466 chicken
NP_001073455 425 CKdPKERLGCRgsGAAEVKLHPIFRNINFKRLEANMLDPPFCPDP 469 zebrafish

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