1F3M,4DN5,1L3R,1O6K,1MRY,1MRU,2PHK,2BUJ,3FBV,2ZV2,3GNI,1QMZ,1ZYD,1X8B,1JST,1PW2,2W5A,1FGI,2EVA,1K3A,1MQ4,2V62,1IR3,1M7N,3E7E,1CSN,1IG1,1VJY,3FPQ,3QA8,3DLS,2FH9,2BZK,3LL6,3OTV,4F99,4EUT,2V5Q,4FVR


Conserved Protein Domain Family
PKc

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cd00180: PKc 
Click on image for an interactive view with Cn3D
Catalytic domain of Protein Kinases
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.
Statistics
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PSSM-Id: 270622
Aligned: 151 rows
Threshold Bit Score: 88.8667
Threshold Setting Gi: 48428484
Created: 1-Nov-2000
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1L3R; mouse PKA binds 20-aa peptide substrate and ADP-Mg-AlF3; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1O6K; human PKB-beta binds GSK3 peptide substrate and AMP-PNP; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1K3A; human IGF-1R tyr kinase binds AMP-PCP and substrate IRS-1 peptide; defined at 4A contacts.
    View structure with Cn3D
  • Structure:1QMZ; human CDK2 binds MgATP and substrate p107 peptide; defined at 4A contacts.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1      #####      #                                   # #                              
1F3M_C      28 IGQGAS---GTVYTAMDva-----------------------tgQEVAIRQMNlqqqp-----------kkeliINEILV 70   human
1L3R_E      49 LGTGSF---GRVMLVKHke-----------------------sgNHYAMKILDkqkvvkl--------kqiehtLNEKRI 94   house mouse
3OTV_A      35 LIFHGGvppLQFWQALDta-----------------------ldRQVALTFVDpqgvl-----------pddvlQETLSR 80   Mycobacterium tu...
AAX79064   111 ELVGAY---CVVKELPGgt-----------------------vgRSFLVKAVDdsgpptptvt-tpevedsgkrEFVFKV 163  Trypanosoma brucei
CAJ07932    52 YNAGTI---GRSYFATRdiaalssrctpphgssdcvsddagkgpVFRILKVISfvlr--------------rrlLEEITA 114  Leishmania major
Q9UVG6      33 LGTSRF---LKTVKGLNd-------------------------qGSIVVKVLVkpnsgld--------lsewveKLEFLR 76   Pichia pastoris
AAH27484    74 LEPEEG---GRAYRALHcp-----------------------tgTEYTCKVYPvq-----------------eaLAVLEP 110  human
NP_114406   41 LGNSPV---PSIVQCLArkd---------------------gtdDFYQLKILTleergdqgiesqeerqgkmllHTEYSL 96   human
BAE65613    61 EYKGTY---GRVCRSILtvg---------------------eetIVVARKEMRlsevs------------eekvNREVKI 104  Aspergillus oryzae
EAQ82952   536 LGSGAM---GYVDMVESra-----------------------sgSLCVRKTIRpgsae-----------erqrlVQVVQL 578  Chaetomium globo...
Feature 1                   #                                 ####             # #             
1F3M_C      71 MRENkn----pNIVNYLDSYlvg------------------deLWVVMEYLag----------gSLTDVVtet------- 111  human
1L3R_E      95 LQAVnf----pFLVKLEFSFkdn------------------snLYMVMEYVag----------gEMFSHLrri------- 135  house mouse
3OTV_A      81 TLRLsri-dkpGVARVLDVVhtr------------------agGLVVAEWIrg----------gSLQEVAdt-------- 123  Mycobacterium tu...
AAX79064   164 MTFInr----kNLVEPVLDDkralmnlt--------gdgllrpVHLLLDEGnet--------viSVTPFLkegsca---- 219  Trypanosoma brucei
CAJ07932   115 EQRVlvnivhqNVLHISDVLndea----------------kenMIVITNYHak----------gNIGNYAgrl------- 161  Leishmania major
Q9UVG6      77 LKLLdv----pNVIPYNLVIdsv------------------raGYLIRPFQq-----------rTLYERVsiq------- 116  Pichia pastoris
AAH27484   111 YARLpp---hkHVARPTEVLa---------------------gTQLLYAFFtrt--------hgDMHSLVrsr------- 151  human
NP_114406   97 LSLLht---qdGVVHHHGLFqdrtceivedtessrmvkkmkkrICLVLDCLcahdfsdktadliNLQHYVike------- 166  human
BAE65613   105 LQSLrh----rHLVTFIGSFtar-----------------gfaSILVYPFAt-----------cDLEKLLeeldyaqyhe 152  Aspergillus oryzae
EAQ82952   579 METLnh----vHIVNVLGSYsir------------------peFYILMNPVaq----------wDLKRYMagqg------ 620  Chaetomium globo...
Feature 1                                                             # # ## #            #  # 
1F3M_C     112 --------------------------cmDEGQIAAVCRECLQALEFLHsnqVIHRDIKSDNILLGm--dGSVKLTDFGFC 163  human
1L3R_E     136 -------------------------grfXEPHARFYAAQIVLTFEYLHsldLIYRDLKPENLLIDq--qGYIQVTDFGFA 188  house mouse
3OTV_A     124 --------------------------spSPVGAIRAMQSLAAAADAAHragVALSIDHPSRVRVSi--dGDVVLAYPATM 175  Mycobacterium tu...
AAX79064   220 ----------------------rlagklEEDRLLSILRDVASALRLLHshnIYHCNLKLENVLLRe--dGKACLADAALW 275  Trypanosoma brucei
CAJ07932   162 --------------------------shDSDKLRRILVEVAVGLRILHshrVYHHNLKLDNVLENs--eGHFCIADAGFW 213  Leishmania major
Q9UVG6     117 -------------------------pylEPIEKKWIAFQLIHAVMECHergQYHGDIKSENVLLTs--wDMVFLTDFAPF 169  Pichia pastoris
AAH27484   152 -------------------------hriPEPEAAVLFRQMATALAHCHqhgLVLRDLKLCRFVFAdrerKKLVLENLEDS 206  human
NP_114406  167 -------------------------krlSERETVVIFYDVVRVVEALHqknIVHRDLKLGNMVLNkr-tHRITITNFCLG 220  human
BAE65613   153 qkdtvstllaelgwiptttkaaqwkpgdIFPNLRRICGCVCSALLYLHqhrIRHKDIKPSNVLVGk---DGVYITDFNIS 229  Aspergillus oryzae
EAQ82952   621 ------------------------gavvNPRNLARWIGCLARGLSYIHrkrVKHKDIKPSNLLVDg---DNILYTDFDLA 673  Chaetomium globo...
Feature 1                                                                                      
1F3M_C     164 Aqitpeqskrstmvgt-----------------pywmapevvtrkaygPKVDIWSLGIMAIEMiegeppylnenplraly 226  human
1L3R_E     189 Krvkgrtwxlcgtpe--------------------ylapeiilskgynKAVDWWALGVLIYEMaagyppffadqpiqiy- 247  house mouse
3OTV_A     176 Pda--------------------------------------------nPQDDIRGIGASLYALlvnrwplpeagvrsgla 211  Mycobacterium tu...
AAX79064   276 Rifstqsrdcllfngelac-----------mppemfmideadnqskdaSKVDIWGFGLFMYRLaygrepfdiegkaleqv 344  Trypanosoma brucei
CAJ07932   214 Rlfavqcpedlvfngelaclppev-fdpegpyatgevnvvsdegaagvAAVDIWGFGVLMYRLaygcdpveiaecsyaqv 292  Leishmania major
Q9UVG6     170 KpiylpgnnpsqfsfyfdtsrrnvcyvaperflgegtptqyqevdkltSSMDIFSLGCTVAELflegsvlftlpqlfk-- 247  Pichia pastoris
AAH27484   207 Cvltgpddslwdkhacp---------------ayvgpeilssrasysgKAADVWSLGVALFTMlaghypfqdsepvllf- 270  human
NP_114406  221 Khlvsegdllkdqrgsp----------------ayispdvlsgrpyrgKPSDMWALGVVLFTMlygqfpfydsipqelfr 284  human
BAE65613   230 Kafendrssrtmgpyag----------------trvysapecvydarsYPSDVYSLGLIFMEIytyilgrprsemgeytr 293  Aspergillus oryzae
EAQ82952   674 Hrfqslddvttgrtsqt----------------vsysapevaeggertPATDVFSLGCVYVEMltvitgsrvfdifhklp 737  Chaetomium globo...
Feature 1                                                                           
1F3M_C     227 -------------------liatngtpelqnpeklsAIFRDFLNRcldmdVEKRGSa-----kELLQHQ 271  human
1L3R_E     248 ---------------------ekivsgkvrfpshfsSDLKDLLRNllqvdLTKRFGnlkngvnDIKNHK 295  house mouse
3OTV_A     212 pa---------------erdtagqpiepadidrdipFQISAVAARsv-qgDGGIRSa-----sTLLNLM 259  Mycobacterium tuberculosis ...
AAX79064   345 c-----------------elvsvdrlqfpqrnwsiaSSLEDAIRVcldddPERRPTv-----pGLFSFS 391  Trypanosoma brucei
CAJ07932   293 he----------------rlmgfdlsfpprphwsfaYDIEDAIRLclqkePSKRPSv-----lRLLQHT 340  Leishmania major
Q9UVG6     248 ---------------------ykkgeytpslsgivdNDLRNMIQEmidldPRKRISa-----hDCLRKH 290  Pichia pastoris
AAH27484   271 ---------------------gkirrgayalpaglsAPARCLVRCllrrePAERLTa-----tGILLHP 313  human
NP_114406  285 --------------------kikaaeytipedgrvsENTVCLIRKllvldPQQRLAa-----aDVLEAL 328  human
BAE65613   294 snlslskdsqirhaalrvlwvrvifdgagrgdfgmsSGMQELILRmisenQDARPDa-----fEVLSGL 357  Aspergillus oryzae
EAQ82952   738 gergyn--------frghnnavavawleglsfgneqEKYGEAVRLtrqmiSEVRPDa------ETLSRR 792  Chaetomium globosum CBS 148.51

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