Abstract: BACKGROUND ＆ AIM: We explored the amino acid substitution in ErbB3 tyrosine kinase domain by bioformatics. MATERIALS AND METHODS: ErbB receptor family and tyrosine receptor family sequence alignments were performed to find out the important amino acid substitution sites in ErbB3 kinase domain, these sites was then located on EGFR crystal structure. RESULTS: A total of 54 substitution sites which might be meaningful were identified, in which 17 sites could be more important, R726E，L738T，E740H，D815N，K830Q，L836V，R838D might be the key substitution sites related to tyrosine kinase activity decrease. The tyrosine site near DFG motif in ErbB3 appeared to be ineffective. CONCLUSION: These substitution sites are related to the decrease of tyrosine kinase activity.

Key words: ErbB3, tyrosine kinase domain, amino acid site