Conserved Protein Domain Family
STKc_MSK2_N

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cd05614: STKc_MSK2_N (this model, PSSM-Id:173705 is obsolete and has been replaced by 270765)
N-terminal catalytic domain of the Protein Serine/Threonine Kinase, Mitogen and stress-activated kinase 2
Serine/Threonine Kinases (STKs), Mitogen and stress-activated kinase (MSK) subfamily, MSK2, N-terminal catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MSK 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. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis.
Statistics
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PSSM-Id: 173705
View PSSM: cd05614
Aligned: 3 rows
Threshold Bit Score: 701.708
Threshold Setting Gi: 3411161
Created: 8-Nov-2007
Updated: 17-Jan-2013
Structure
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Aligned Rows:
  next features
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:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #####   #               # #                                 #            
gi 3411161    16 NFELLKVLGTGAYGKVFLVRKAgghdagKLYAMKVLRKAALVQRAKtqEHTRTERSVLELVrqAPFLVTLHYAFQTdaKL 95
gi 117167899  28 DFELLKILGTGAYGKVFLVRKVtgpdtnHLYAMKVLQKCALVKKEKtvEHTKTERNVLEHVreSPFLVTLHYAFQTeaKL 107
gi 123231821   3 NFELLKVLGTGAYGKVFLVRKIsghdkgKLYAMKVLKKAAIVQKAKtaEHTRTERQVLEHIrqSPFLVTLHYAFQTqtKL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           ## #   # #                                    # # ## #         ##  #         
gi 3411161    96 HLILDYVsGGEMFTHLYQrqyFKEAEVRVYGGEIVLALEHLHKLGIIYRDLKLENVLLDseGHIVLTDFGLSKEFLTEEK 175
gi 117167899 108 HLILDYVsGGELFTHLYQrdnFSEDAVRFYSGEVILALEHLHKLGVVYRDIKLENILLDseGHVVLTDFGLSKEFLSEEE 187
gi 123231821  83 HLILDYVsGGEMFTHLYQrdhFSEDEVRIYVGEIILALEHLHKLGIVYRDIKLENILLDsdGHVVLTDFGLSKEFLEEEK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1             ######                           #     #  #                                
gi 3411161   176 ERTFSFCGTIEYMAPEIIRSktghGKAVDWWSLGILLFELLTGASPFTLEgerntQAEVSRRILKCSPPFPPRigPVAQD 255
gi 117167899 188 ERTYSFCGTTEYMAPEIIRGqgghGKIVDWWSLGILIYELLTGASPFTLEgekntQSEVSRRILKMDPSLPSFlsFEARD 267
gi 123231821 163 ERTYSFCGTIEYMAPEIIRGksghGKAVDWWSLGILMFELLTGASPFTLEgernsQSEVSKRILRCEPPFPSIigPLAQD 242
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 3411161   256 LLQRLLCKdPKKRLGAgpqgAQEVRNHPFFQGLDWVALAARKIPAPFRPqirseldvgNFAEEFTRLEPVYSPPGSPppg 335
gi 117167899 268 LLHKLLRKdPKKRLGAa--gASQIKEHPFYKDMDWEALSLRKVNPPFRPsirnetdvsNFAEEFTNLDPVYSPAGTPpsg 345
gi 123231821 243 LLRKLIVKdPHKRLGSgprgAEEIKGHPFFKGLNWSDLAEKKVQSPFRPelrdeldvgNFAEEFTGMEPVYSPASTPpst 322
                        330
                 ....*....|...
Feature 1                     
gi 3411161   336 dprIFQGYSFVAP 348
gi 117167899 346 -apVFQGYSFIAP 357
gi 123231821 323 -drLFQGYSFVAP 334

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