Fig. 2

CKHS profiling facilitates the identification of unannotated essential domains. a The CKHS profile and domain annotation of YAP1. b The 3D structure of the YAP1&TEAD1 interaction (PDBID: 3KYS). Three interfaces of YAP1 interact with TEAD1. The CKHS region (interface 3) is highlighted in red. c The CKHS profile and domain annotation of SMARCB1, aligned with mutation frequency retrieved from the COSMIC database⁴⁷. d A schematic representation of exogenous full-length, a truncated form (Δ2-53), and two small-deletion forms (Δ29-31, Δ150-152) of SMARCB1, as well as the endogenous protein. The CKHS region is highlighted in red. The Myc and 6xHis tag sequences were appended to the C-terminus of exogenous proteins. Three sgRNAs were designed to target the endogenous SMARCB1 DNA sequence coding part of the SNF5_2 domain. Synonymous mutations were introduced into the exogenous proteins, except the bases at the PAM (red) and methionine codon. e Relative proliferation of DLD-1 cells with exogenous expression of full-length or the truncated form of SMARCB1 shown in d, in combination of endogenous SMARCB1 knockout. f Relative proliferation of DLD-1 cells with exogenous expression of SMARCB1 harboring small deletions inside or outside the CKHS region (Δ29-31 or Δ150-152), in combination of endogenous SMARCB1 knockout. The red and black dash lines represent normalized relative viability of vector control cells with AAVS1sg or SMARCB1sg, respectively. All the data points represent the relative viability normalized to the AAVS1 control group. The error bars represent the standard divation of three biological replicates performed at each time point. The star symbols represent statistical significance: p < 0.01 (**) and p < 0.001 (***). The p-values were computed using t-test. Source data are provided as a Source Data file