Kin-Driver - A human kinase database with driver mutations



EGFR_HUMAN G719A  

UniProt Pfam

Validation Status: Activating

Relative Frequency: 6.82671

Reference : EGFR database

View Mutation in MSA

View All Samples for this mutation


Central Moving Average Plot

Marked in green is the current mutation location in the central moving average plot of the normalized frequencies of activating mutations in human kinases using EGFR_HUMAN as the reference sequence.

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First, a multiple sequence alignment for the tyrosine kinase domain was obtained from Pfam and additional refinements were done using Muscle. All mutations were then mapped onto the MSA as can be seen here

Second, we computationally calculated a relative frequency for each mutation by dividing the number of samples carrying the mutation by the total number of samples where the corresponding gene has been sequenced (according to COSMIC) and then multiplying the resulting figure by 1,000. The graph below was constructed using the relative frequency of all mutations. For each position of the MSA an accumulated relative frequency was computed by adding the individual relative frequencies of all activating mutations in all human kinases affecting that column of the alignment and a normalized frequency of activating mutations per column was obtained using the formula:

Normalized frequencies were used to calculate central moving averages with a window size of n=13. Values per position of the moving average window are plotted below.

Activating mutations cluster in two hypermutated segments of the kinase domain. The image above show the distribution of mutations in the kinase domain of Tyrosin Kinases, depicted in the ribbon representation of the human EGFR structure (pdb code 1M14). Mutated positions are shown in orange, and the diameter of the ribbon is proportional to the normalized frequency of mutations affecting each position.

For more information, please refer to Molina-Vila et al, 2014

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3D Structures - Mapping the mutation onto a PDB structure

PDB idDescriptionResolutionSPACI Score
3POZ_Aegfr kinase domain complexed with tak-2851.50.598043
2RGP_Astructure of egfr in complex with hydrazone, a potent dual inhibitor20.398807
3VJN_Acrystal structure of the mutated egfr kinase domain (g719s/t complex with amppnp.2.340.357415
1XKK_Aegfr kinase domain complexed with a quinazoline inhibitor- gw5720162.40.349657
3BEL_Ax-ray structure of egfr in complex with oxime inhibitor2.30.334124
3UG2_Acrystal structure of the mutated egfr kinase domain (g719s/t complex with gefitinib2.50.32858
2EB2_Acrystal structure of mutated egfr kinase domain (g719s)2.50.326237
2ITV_Acrystal structure of egfr kinase domain l858r mutation in complex with amp-pnp2.470.319794
2ITN_Acrystal structure of egfr kinase domain g719s mutation in complex with amp-pnp2.470.319681
3VJO_Acrystal structure of the wild-type egfr kinase domain in com amppnp.2.640.304627
2GS6_Acrystal structure of the active egfr kinase domain in complex with an atp analog-peptide conjugate2.60.296067
4G5J_Acrystal structure of egfr kinase in complex with bibw29922.80.292509
2ITQ_Acrystal structure of egfr kinase domain g719s mutation in complex with afn9412.680.282167
2EB3_Acrystal structure of mutated egfr kinase domain (l858r) in c with amppnp2.840.281051
4HJO_Acrystal structure of the inactive egfr tyrosine kinase domai erlotinib2.750.277641
2ITZ_Acrystal structure of egfr kinase domain l858r mutation in complex with iressa2.720.273453
2ITP_Acrystal structure of egfr kinase domain g719s mutation in complex with aee7882.740.27047
2GS2_Acrystal structure of the active egfr kinase domain2.80.267665
3GOP_Acrystal structure of the egf receptor juxtamembrane and kina2.80.267089
2GS7_Acrystal structure of the inactive egfr kinase domain in complex with amp-pnp2.60.265955
2GS7_Bcrystal structure of the inactive egfr kinase domain in complex with amp-pnp2.60.265955
2ITW_Acrystal structure of egfr kinase domain in complex with afn9412.880.264271
1M14_Atyrosine kinase domain from epidermal growth factor receptor2.60.262527
3UG1_Acrystal structure of the mutated egfr kinase domain (g719s/t the apo form2.750.262309
2ITT_Acrystal structure of egfr kinase domain l858r mutation in complex with aee7882.730.261026
2ITU_Acrystal structure of egfr kinase domain l858r mutation in complex with afn9412.80.258994
3LZB_Aegfr kinase domain complexed with an imidazo[2,1-b]thiazole2.70.258584
3LZB_Begfr kinase domain complexed with an imidazo[2,1-b]thiazole2.70.258584
3LZB_Cegfr kinase domain complexed with an imidazo[2,1-b]thiazole2.70.258584
3LZB_Degfr kinase domain complexed with an imidazo[2,1-b]thiazole2.70.258584
1M17_Aepidermal growth factor receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib2.60.249629
2ITX_Acrystal structure of egfr kinase domain in complex with amp- pnp2.980.24909
2J5F_Acrystal structure of egfr kinase domain in complex with an irreversible inhibitor 34-jab30.242153
3GT8_Dcrystal structure of the inactive egfr kinase domain in complex with amp-pnp2.960.225998
3GT8_Acrystal structure of the inactive egfr kinase domain in complex with amp-pnp2.960.225998
3GT8_Bcrystal structure of the inactive egfr kinase domain in complex with amp-pnp2.960.225998
3IKA_Acrystal structure of egfr 696-1022 t790m mutant covalently binding to wz40022.90.224373
2RFE_Acrystal structure of the complex between the egfr kinase domain and a mig6 peptide2.90.22286
2RFE_Dcrystal structure of the complex between the egfr kinase domain and a mig6 peptide2.90.22286
2JIT_Bcrystal structure of egfr kinase domain t790m mutation3.10.216522
2J5E_Acrystal structure of egfr kinase domain in complex with an irreversible inhibitor 13-jab3.10.21627
2J6M_Acrystal structure of egfr kinase domain in complex with aee7883.10.209579
2JIU_Bcrystal structure of egfr kinase domain t790m mutation in complex with aee7883.050.198567
2ITO_Acrystal structure of egfr kinase domain g719s mutation in complex with iressa3.250.193627
4G5P_Acrystal structure of egfr kinase t790m in complex with bibw23.170.181471
4G5P_Bcrystal structure of egfr kinase t790m in complex with bibw23.170.181471
2ITY_Acrystal structure of egfr kinase domain in complex with iressa3.420.177366
2RFD_Acrystal structure of the complex between the egfr kinase domain and a mig6 peptide3.60.133577
2RF9_Acrystal structure of the complex between the egfr kinase domain and a mig6 peptide3.50.0714469
2JIV_Acrystal structure of egfr kinase domain t790m mutation in compex with hki-2723.50.0126281
2JIV_Bcrystal structure of egfr kinase domain t790m mutation in compex with hki-2723.50.0126281
1Z9I_Aa structural model for the membrane-bound form of the juxtamembrane domain of the epidermal growth factor receptor0.00122381
4I1Z_A
4I20_A
4I21_A
4I21_B
4I22_A
4I23_A
4I24_A
3W2O_A
4I24_B
3W2P_A
3W2Q_A
3W2R_A
3W2S_A

PDB: 3POZ_A

Resolution: 1.5 Å
"egfr kinase domain complexed with tak-285"
UniProt residue Number PDB residue Number
719719
   Current Mutation
  Heteroatoms
  Hypermutated Segments