1CKJ,3SV0,4HNI


Conserved Protein Domain Family
STKc_CK1_delta_epsilon

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cd14125: STKc_CK1_delta_epsilon 
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Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 delta and epsilon
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. The delta and epsilon isoforms of CK1 play important roles in circadian rhythm and cell growth. They phosphorylate PERIOD proteins (PER1-3), which are circadian clock proteins that fulfill negative regulatory functions. PER phosphorylation leads to its degradation. However, CRY proteins form a complex with PER and CK1delta/epsilon that protects PER from degradation and leads to nuclear accummulation of the complex, which inhibits BMAL1-CLOCK dependent transcription activation. CK1delta/epsilon also phosphorylate the tumor suppressor p53 and the cellular oncogene Mdm2, which are key regulators of cell growth, genome integrity, and the development of cancer. This subfamily also includes the CK1 fungal proteins Saccharomyces cerevisiae HRR25 and Schizosaccharomyces pombe HHP1. These fungal proteins are involved in DNA repair. The CK1 delta/epsilon 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.
Statistics
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PSSM-Id: 271027
Aligned: 38 rows
Threshold Bit Score: 559.678
Created: 16-Dec-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 20 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:4HNI: Human CK1epsilon binds inhibitor; contacts at 4A.
  • Comment:also based on the structure of Schizosaccharomyces pombe CK1 with bound MgATP
  • Citation:PMID 7889932

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               ####### #            # #                                           ##### 
1CKJ_A         8 RYRLGRKIGSGSFGDIYLGTDIaaGEEVAIKLECVKtKHPQLHIESKIYKMMqgGVGIPTIRWCGAEgDYNVMVMELLGp 87  Norway rat
4HNI_A        10 KYRLGRKIGSGSFGDIYLGANIasGEEVAIKLECVKtKHPQLHIESKFYKMMqgGVGIPSIKWCGAEgDYNVMVMELLGp 89  human
P40235        10 KYRIGRKIGSGSFGDIYLGTNVvsGEEVAIKLESTRaKHPQLEYEYRVYRILsgGVGIPFVRWFGVEcDYNAMVMDLLGp 89  Schizosaccharom...
AAD01192       8 KYRISRKIGGGSFGEIYLGTNIstNEEVAIKLEPAKaIHPQLLFESKLYKIFqgGIGIPAVKWFGFDgDYNIMVMDLLGp 87  Dictyostelium d...
ABV69055      17 KYRLGKKIGSGSFGDIYLGINIisGEEVAIKLESVKaKHPQLEYESKVYKTLagGVGVPFVRWFGTEcDYNAMVIDLLGp 96  Phanerochaete c...
EEY69063      16 KFRLGRKIGSGSFGDIYLGTNMtsGEEVGIKLESVKsKHPQLLYESKIYKILngGLGVPSLRWFGVEgEYNVMVIDLLGp 95  Phytophthora in...
XP_002295127   8 KYRLGRKIGSGSFGDIYLGTNMttGEEVAIKLESVKtKHPQLLYESKIYRILhgGLGIPNVRWYGIEgDYNVMVLDLLGp 87  Thalassiosira p...
EAA36589      11 KYRIGRKIGSGSFGDIYLGTNIisGEEIAIKLESVKaKHPQLEYEARVYKSLagGVGIPFVRWFGTEcDYNAMVLDLLGp 90  Neurospora cras...
CCJ28417      10 KYRIGRKIGSGSFGDIYLGTNIisGEEIAIKLESSKvKHPQLEYEARVYKALagGVGIPFVRWFGTEcDYNAMVMDLLGp 89  Pneumocystis ji...
EKX50959       8 KYRIGRKIGSGSFGDIFLGTNIstSEEVAIKLESVKsKHPQLLYESKVLKILqgGVGLPSVRWYGVEgDYNVMVIDLLGp 87  Guillardia thet...
Feature 1                                                  # ## #             #                  
1CKJ_A        88 SLEDLFNFCsRKFSLKTVLLLADQMISRIEYIHSKNFIHRDVKPDNFLMGLgKKGNLVYIIDFGLAKKYRDaRTHQHIPY 167 Norway rat
4HNI_A        90 SLEDLFNFCsRKFSLKTVLLLADQMISRIEYIHSKNFIHRDVKPDNFLMGLgKKGNLVYIIDFGLAKKYRDaRTHQHIPY 169 human
P40235        90 SLEDLFNFCnRKFSLKTVLLLADQLISRIEFIHSKSFLHRDIKPDNFLMGIgKRGNQVNIIDFGLAKKYRDhKTHLHIPY 169 Schizosaccharom...
AAD01192      88 SLEDLFNYCgRKFSLKTVLMLGDQMLRRIEFIHSNNFIHRDIKPDNFLMGIgKRGHVVNLIDFGLAKRYRDpKTHQHIPY 167 Dictyostelium d...
ABV69055      97 SLEDLFNFCnRKFSLKTVLLLADQLISRIEYIHSRNFIHRDIKPDNFLMGIgKRGNQVNVIDFGLAKKYRDpKTHLHIPY 176 Phanerochaete c...
EEY69063      96 SLEDLFNYCgRRFQLKTVLMIADQLLCRLEYCHSKNFIHRDVKPDNFLIGLgKRAQIVHVIDFGLAKKYRDpKTHQHIPY 175 Phytophthora in...
XP_002295127  88 SLEDLFNYCgRRFQLKTVLMLADQLLGRLEYVHTKSFIHRDVKPDNFLIGLgKRQSVIHIIDFGLAKKYRDpRSHQHIPY 167 Thalassiosira p...
EAA36589      91 SLEDLFNFCnRKFSLKTVLLLADQLISRIEYIHAKSFIHRDIKPDNFLMGIgKRGNQVNVIDFGLAKKYRDpKTHFHIPY 170 Neurospora cras...
CCJ28417      90 SLEDLFNFCnRKFSLKTVLLLADQLISRIEYIHAKSFIHRDIKPDNFLMGIgKRGNQVNVIDFGLAKKFRDpKTHLHIPY 169 Pneumocystis ji...
EKX50959      88 SLEDLFNFCsRKFSLKTVLMLAEQMLSRIEFVHSKSFIHRDIKPDNFLMGLgKKANQVNIIDFGLAKKYRDpKTHQHIPY 167 Guillardia thet...
Feature 1                                                                                        
1CKJ_A       168 RENKNLTGTARYASINTHLgIEQSRRDDLESLGYVLMYFNLgSLPWQGLKAaTKRQKYERISEKKMSTpIEVLCKGyPSE 247 Norway rat
4HNI_A       170 RENKNLTGTARYASINTHLgIEQSRRDDLESLGYVLMYFNLgSLPWQGLKAaTKRQKYERISEKKMSTpIEVLCKGyPSE 249 human
P40235       170 RENKNLTGTARYASINTHLgIEQSRRDDLESLGYVLVYFCRgSLPWQGLKAtTKKQKYEKIMEKKISTpTEVLCRGfPQE 249 Schizosaccharom...
AAD01192     168 REHKNLTGTARYASLNTHQgIEQSRRDDLESLGLVLMYFNRgSLPWQGLKAyTKRDKYEKICDKKAQTkIDTLCQGfPSE 247 Dictyostelium d...
ABV69055     177 RENKNLTGTARYTSINTHLgVEQARRDDLESLAYVLMYFLRgSLPWQGLKAaTKKQKYDRIMEKKMTTpTGLLCRGfPNE 256 Phanerochaete c...
EEY69063     176 RENKNLTGTARYASINTHVgIEQSRRDDLESLGYVYMYFIRgSLPWQGLKAnTKKQKYEKIMEKKMNTpIEVLCKGyPAE 255 Phytophthora in...
XP_002295127 168 RENKNLTGTARYASINTHIgIEQSRRDDLESLGYVLMYFIRgSLPWQGLKAnTKKQKYERIMDRKMSTsTEQLCKGyATE 247 Thalassiosira p...
EAA36589     171 RENKNLTGTARYASINTHLgVEQSRRDDMESLGYVMLYFCRgSLPWQGLKAaTKKQKYDRIMEKKMTTpTEVLCRGfPNE 250 Neurospora cras...
CCJ28417     170 KENKNLTGTARYASINTHLgVEQSRRDDLESLGYVMMYFCRgSLPWQGLKAaTKKQKYDRIMEKKMTTpTEVLTRGfPNE 249 Pneumocystis ji...
EKX50959     168 RENKNLTGTARYASINTHLgIEQSRRDDLESLGYVLMYFNRgSLPWQGLRAaNKKQKYEKISEKKMGTqVEQLCKGfPQE 247 Guillardia thet...
Feature 1                                           
1CKJ_A       248 FATYLNFCRSLRFDDKPDYSYLRQLFRNLFHRQGF 282 Norway rat
4HNI_A       250 FSTYLNFCRSLRFDDKPDYSYLRQLFRNLFHRQGF 284 human
P40235       250 FSIYLNYTRSLRFDDKPDYAYLRKLFRDLFCRQSY 284 Schizosaccharomyces pombe
AAD01192     248 FATFLNYTRFLKFEDKPDFLYLRKLLREMFVREGY 282 Dictyostelium discoideum
ABV69055     257 FGIFLNYTRALRFDDKPDYSYLRKLFRDLFVREGY 291 Phanerochaete chrysosporium
EEY69063     256 FRAYFEYCRALRFDDKPDYAYLKRLFKELFFRKGF 290 Phytophthora infestans T30-4
XP_002295127 248 FRSYFEYCRSLRFEDRPDYAYLKRLFKELFYRKGF 282 Thalassiosira pseudonana CCMP1335
EAA36589     251 FAIYLNYTRSLRFDDKPDYSYLRKIFRDLFVREGF 285 Neurospora crassa OR74A
CCJ28417     250 FAIYLNYTRSLRFDDKPDYSYLRKLFRDLFVREGF 284 Pneumocystis jirovecii
EKX50959     248 FATYLNYVRALRFDDKPDYGYLRKLFRDLFIREGF 282 Guillardia theta CCMP2712

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