3KVW,4AZF


Conserved Protein Domain Family
PKc_DYRK2_3

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cd14224: PKc_DYRK2_3 
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Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3
Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 271126
Aligned: 13 rows
Threshold Bit Score: 764.675
Created: 16-Aug-2010
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:3KVW; Human DYRK2 binds indirubin; contacts at 4A.
  • Structure:4AZF: Human DYRK2 binds Leucettine L41; contacts at 4A
  • Comment:Leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B
  • Comment:also based on structures of other CMGC kinases bound with ATP or ATP analogs
  • Citation:PMID 9739089

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                #####   
3KVW_A        33 PEQAMKQYMQKLTAFeHHEIFSYPEIYFLglNAKKRQGMTGGPNNggYDDDQGSYVQVPHDHvaYRYEVLKVIGKGSFGQ 112 human
4AZF_A        33 PEQAMKQYMQKLTAFeHHEIFSYPEIYFLglNAKKRQGMTGGPNNggYDDDQGSYVQVPHDHvaYRYEVLKVIGKGSFGQ 112 human
P83102       211 PQQVMILYMNKLTPYeRTEILTYPQIYFIgaNAKKRPGVYGPNNSe-YDNEQGAYIHVPHDHvaYRYEMLKIIGKGSFGQ 289 fruit fly
AAL56407      44 QALKNFMHKLTNFEHhEIYNYPNVYFVGQgaRKKTPSSHNATNNNdgYDDEQGTYLLVAHDHiaYRYEIIKVIGKGSFGQ 123 Oikopleura dioica
XP_002602784 146 PEQAMKTFMHKLTPFeHHEIFNYPEVYFSgpNAKKRQGVIGGANNngFDDEQGSYIHVPHDHicYRFEVLKVLGKGSFGQ 225 Florida lancelet
XP_001638207 101 AEVAMKQYMHKLSGYeTHEIFNYSQIYFVgeAAKKRQGVVGGANNcgYDDEQGSYIHVPKDHiaYRYEVLKIIGKGSFGQ 180 starlet sea ane...
XP_002108931  18 PEQAMKLYMHKLSSFeHHEIFNYPQVFFVgaNSKKRQGLVGAPSNngYDDESGNYLPEVHDHiaYRYEILKVLGKGSFGQ 97  Trichoplax adha...
XP_002582131 186 PEMAMKLYFHKLSAYeHQEILNYPYVYFVghNAKKRNGILGTGNNcgYDDDQGSYIHTAHDHvaYRYEVLKILGRGSFGQ 265 Schistosoma man...
A8WJR8       394 PEDAVQTFGAKLVPYeKNEIYNYTRVFFVgsHAKKQPGVIGGANNggYDDENGSYQLVVHDHiaYRYEVLKVIGKGSFGQ 473 Caenorhabditis ...
NP_001026651  81 PEQAMKQYMQKLTTFeHNEIFGYTEIYFLgpNAKKRQGVIGGPNNcgYDDDQGSYIQVPHDHiaYRYEVLKVIGKGSFGQ 160 chicken
NP_001108400 134 PEQALKQHRQQMTTLeQQEIHNYSEIYFLgpNAKKRQAVAGGTNNsgYDDDQGGYIHVPHDHlaYRYEFLKVIGKGSFGQ 213 zebrafish
XP_417975    107 PEQAVKQYKHQLSAYeQQEIFNFSEIYFVgpAAKKRQGVIGGPNNggYDDDQGSYIHVPHDHlaYRYEVLKIIGKGSFGQ 186 chicken
NP_001008158 123 PDQAVKQYKHQLSAYeLQEISSFSEIYFVgpNAKKRQGVVGGPNNggYDDDQGGYNLVPHDHvaYRYEVLKVIGKGSFGQ 202 western clawed ...
Feature 1        #            # #                                 #               ####  #        
3KVW_A       113 VVKAYDHKvHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDkdnTMNVIHMLENFTFRNHICMTFELLSMNLYELIKKN 192 human
4AZF_A       113 VVKAYDHKvHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDkdnTMNVIHMLENFTFRNHICMTFELLSMNLYELIKKN 192 human
P83102       290 VIKAYDHKtHEHVALKIVRNEKRFHRQAQEEIRILHHLRRHDkynTMNIIHMFDYFTFRNHTCITFELLSINLYELIKKN 369 fruit fly
AAL56407     124 VVKAFDHKtQSHVALKIVRNEKRFHRQAQEEIAILEALRRQDrdnNMNLVHMLESFVFRNHVCMTFELLSMNLYELIKKN 203 Oikopleura dioica
XP_002602784 226 VVKVYDHKnHVHTALKMVRNEKRFHRQAQEEIRILEHLKKQDkdnNMNIVHMGESFTFRNHICITFELLSMNLYELIKKN 305 Florida lancelet
XP_001638207 181 VVKALDHKtNTHVALKMVRNEKRFHRQAQEEIRILEHLKKQDkdnTHNIIHMLEHFTFRNHVCMTFELLSMNLYELIKKN 260 starlet sea ane...
XP_002108931  98 VLKAYDHKsRMHVALKIIRNERRFHRQAAEEIKILEHLKRQDkdnTFNIVHILDHFQFRNHVCLPFELLSINLYELIKKN 177 Trichoplax adha...
XP_002582131 266 VVKAYDHKdGVYVALKMVRNERRFTNQATEEIRILEQLKKQDvdnTRNVVHISEHFTFRGHVCITFELLSINLYELIKRS 345 Schistosoma man...
A8WJR8       474 VIKAFDHKyQQYVALKLVRNEKRFHRQADEEIRILDHLRRQDsdgTHNIIHMLDYFNFRNHKCITFELLSINLYELIKRN 553 Caenorhabditis ...
NP_001026651 161 VVKAYDHKmHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDkdnNMNVIHMLENFTFRSHICMTFELLSMNLYELIKKN 240 chicken
NP_001108400 214 VAKVYDHKlQQHVALKIVRNEKRFHRQAAEEIRILEHLKKQDktgSMNVVHMLENFTFRNHICMTFELLSMNLYELIKRN 293 zebrafish
XP_417975    187 VAKVYDHKlHQHLALKMVRNEKRFHRQAAEEIRILEHLKKQDktgSMNVIHMLESFTFRNHICMTFELLSMNLYELIKRN 266 chicken
NP_001008158 203 VAKVYDHKlHQHLALKMVRNEKRFHRQAAEEIRILEHLKKQDktgSMNVIHMLESFTFRNHICMTFELLSMNLYELIKRN 282 western clawed ...
Feature 1                                        # # ## #            #                           
3KVW_A       193 kfQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQgrSGIKVIDFGSSCYEHQRVYTXIQSRFYRAPEVIL 272 human
4AZF_A       193 kfQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQgrSGIKVIDFGSSCYEHQRVYTXIQSRFYRAPEVIL 272 human
P83102       370 gfKGFSLQLVRKFAHSLLQCLDALYKNDIIHCDMKPENVLLKQQgrSGIKVIDFGSSCFENQRIYTYIQSRFYRAPEVIL 449 fruit fly
AAL56407     204 rfQGFSLQLVRKFAHSILQCLEVLSRNKIIHCDLKPENILLKQQgrSGLKVIDFGSSCYEKKKIYTYIQSRFYRAPEVIL 283 Oikopleura dioica
XP_002602784 306 kfQGFSLQLVRKFAHSLLQCLEALYRNRIIHCDLKPENVLLKQQgrSGIKVIDFGSSCYEHQRVYTYIQSRFYRAPEVIL 385 Florida lancelet
XP_001638207 261 kfQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQgrSGIKVIDFGSSCYEHQRIYTYIQSRFYRAPEVIL 340 starlet sea ane...
XP_002108931 178 kfQGFNLQLVRKFAFSILQCLDALYRNKIIHCDLKPENILLKQHgrSGIKVIDFGSSCFEHQRIYTYIQSRFYRAPEVIL 257 Trichoplax adha...
XP_002582131 346 kfQGFPLPLVRKFAHSILVCLDMLHRNKIIHCDLKPENILLKQQgrSGIKVIDFGSSCYESQRLYTYIQSRFYRAPEVIL 425 Schistosoma man...
A8WJR8       554 kfQGFSLMLVRKFAYSMLLCLDLLQKNRLIHCDLKPENVLLKQQgrSGIKVIDFGSSCFDDQRIYTYIQSRFYRAPEVIL 633 Caenorhabditis ...
NP_001026651 241 kfQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQgrSGIKVIDFGSSCYEHQRVYTYIQSRFYRAPEVIL 320 chicken
NP_001108400 294 kfQGFSLPLVRKFAHSILQCLEALHRHKIIHCDLKPENILLKQQgrSGIKVIDFGSSCFDHQRVYTYIQSRFYRAPEVIL 373 zebrafish
XP_417975    267 kfQGFSVQLVRKFAHSILQCLDALYRNKIIHCDLKPENILLKQQgrSGIKVIDFGSSCFEHQRVYTYIQSRFYRAPEVIL 346 chicken
NP_001008158 283 kfQGFSLQLVRKFAHSILQCLEALYRNKIIHCDLKPENILLKQQgrSGIKVIDFGSSCFDHQRVYTYIQSRFYRAPEVIL 362 western clawed ...
Feature 1                                                                                        
3KVW_A       273 GaRYGMPIDMWSLGCILAELLTgYPLLPGedEGDQLACMIELLGMPSQKLLDASKrAKNFVSXK-GYPRYCTVTTLSDgs 351 human
4AZF_A       273 GaRYGMPIDMWSLGCILAELLTgYPLLPGedEGDQLACMIELLGMPSQKLLDASKrAKNFVSXK-GYPRYCTVTTLSDgs 351 human
P83102       450 GgKYGRAIDMWSLGCILAELLSgHALFPGenESDQLACIIEVLGMPNKNILASSKrSKSFFSPK-GYPRYCTVRTMSDgm 528 fruit fly
AAL56407     284 GaEYSTAIDMWSFGCILAELLTgYPLLPGddEGDQLACMIELLGMPPKRMIETAKrTKNFISSR-GHPRYCTQTTMPDgt 362 Oikopleura dioica
XP_002602784 386 GaKYGMAIDMWSLGCILAELLTgYPLLPGedEGDQLACMIELQGMPPQKLLDVSKrAKNFISSK-GYPRYCSVKTLSDgt 464 Florida lancelet
XP_001638207 341 GaRYGMPIDMWSFGCILAELLTgYPLFPGedEGDQLACNMELLGYIPEKLRETSKrAKNFINSK-GYPRYCTITTLPDgs 419 starlet sea ane...
XP_002108931 258 GnRYGMSIDMWSFGCILAELLTgYPLFPGedEGDQLACIMELLGMPTTRLLETAKrGKNFISSK-GHPRYCTVTNAPDgs 336 Trichoplax adha...
XP_002582131 426 GcKYGLPIDMWSFGCILAELLTgAPIFPGedEGDQLACIIELLGMPPQKLLDQCRrVRSFFSATyGYPRYCMAMDANGc- 504 Schistosoma man...
A8WJR8       634 GtKYGMPIDMWSLGCILAELLTgYPLLPGedENDQLALIIELLGMPPPKSLETAKrARTFITSK-GYPRYCTATSMPDgs 712 Caenorhabditis ...
NP_001026651 321 GaRYGMPIDMWSLGCILAELLTgYPLLPGedEGDQLACMIELLGMPSPKLLDSSKrAKNFVSSK-GYPRYCTITTLSDgs 399 chicken
NP_001108400 374 GsRYGMPIDMWSFGCILAELLTgYPLFPGedEGDQLACMMELLGMPPSKLLEQAKrAKNFISSK-GHPRYCTVSTLSNgt 452 zebrafish
XP_417975    347 GsRYGMPIDMWSFGCILVELLTgYPLFPGedEGDQLACMMELLGMPPQKLLDQSKrAKNFINSK-GHPRYCTVTTHADgr 425 chicken
NP_001008158 363 GsRYGMPIDMWSFGCILVELLTgYPLFPGedEGDQLACMMELLGAPPPKLLEQAKrAKNFINSK-GYPRYCTVTTLPNgt 441 western clawed ...
Feature 1                                                                     
3KVW_A       352 VVLNGGRSRrGKLRGPPESREWGnalKGCDDPLFLDFLKQCLEWDPAVRMTpGQALRHPWL 412 human
4AZF_A       352 VVLNGGRSRrGKLRGPPESREWGnalKGCDDPLFLDFLKQCLEWDPAVRMTpGQALRHPWL 412 human
P83102       529 VVLIGGQSRrGKQRGPPCSKSLSkalDGCKDPLFLNFIRGCLEWDADKRLTpSEALKHPWL 589 fruit fly
AAL56407     363 VVLNGGRSKrGKQRGPPGSKDWStalKGCDDSLFIDFLRRCLAWDPQERMTpGQALRHTWL 423 Oikopleura dioica
XP_002602784 465 TVLDGSRSRrGKWRGPPGSKDWVtalKGCDDPLFIDFLKRCLEWDPAARMTpAAALRHAWL 525 Florida lancelet
XP_001638207 420 VAVSGGRSRrGKTRGAPNSKTFVqalKGCDDAMFIDFLKRCLEWDPSARMTpSQALRHPWL 480 starlet sea anemone
XP_002108931 337 VILSGGRSRrGKFRGPPKSKHLVdalKGCDDSLFLDFLSRCLEWDPAQRMTpPQALRHAWL 397 Trichoplax adhaerens
XP_002582131 505 VVLRSSNTKrGKIRGTPGSRSLVtalKGCEDTVFLDFIRKCLRWTPEERMTpREAFKHEWL 565 Schistosoma mansoni
A8WJR8       713 VVLAGARSKrGKMRGPPESRSWStalKNMGDELFVDFLKRCLDWDPETRMTpAQALKHKWL 773 Caenorhabditis briggsae
NP_001026651 400 IILNGGRSRrGKLRGPPESREWGnalKGCDDPLFLDFLKQCLEWDPAIRMTpSQALRHPWL 460 chicken
NP_001108400 453 IVLNGSRSRrGKMRGAPGSKEWGtalKGCEDATFIDFLKKCLDWDPSTRMTpVQALRHPWL 513 zebrafish
XP_417975    426 VTLNGSRSRrGKVRGAPGNKDWVtalKGCDDPLFIEFLKECLSWDPAVRMTpSQALRHPWI 486 chicken
NP_001008158 442 TVLNGSRSRrGKMRGAPGSKDWVaalKGCEDSLFIDFLKGCLTWDPVARMTpSQALRHQWI 502 western clawed frog

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