Table 1 Summary of experimental data and classification of p63 DBD mutations.

From: Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree

Mutation

Syndrome

Position

Activity

DNA binding

Zinc loss

Destabilization

Classification

S272N

ELA

L3

   

DNA contact

R279H

ELA

L3

 

R279C

ELA

L3

   

R279Q

ELA

L3

   

R304W

ELA

L3

+

R304Q

ELA

L3

 

+

R304P

ELA

L3

 

++

+

C308S

ELA

S10/H2

+

+++

  

C308Y

ELA

S10/H2

+

  

A315E

ELA

H2

   

Y192C

ELA

S4

+

+

++

+++

Zinc region

Y192D

ELA

S4

   

K193E

SHFM4

S4/Ha

+

++

+

+

V202M

ELA

L2A

+

+

++

+++

R204W

ELA

L2A

+++

+++

R204Q

ELA

L2A

+

+

++

+++

R204L

ELA

L2A

+

+

++

+

H208Y

ELA

H1

 

+++

+++

C269Y

ELA

L3

   

C273Y

ELA

L3

   

R280S

ELA

L3

+

+

R280C

ELA

L3

+

+++

R280H

ELA

L3

+

++

+

+++

154InsP

ELA

S2

+

   

H2 region

L162P

ELA

S2’

   

Y163C

ELA

S2’

   

C306Y

ELA

S10/H2

   

C306R

ELA

S10/H2

   

P309S

ELA

H2

   

D312G

ELA

H2

   

D312N

ELA

H2

   

D312H

ELA

H2

   

R313G

ELA

H2

+

+

G134D

ELA

N-term.

+++

+++

  

Dimer interface

K194E

SHFM4

S4/Ha

+

+

R227Q

ELA

S5

+

++

R298Q

ELA

S10

+++

++

+

R298G

ELA

S10

+++

++

  
  1. The table shows all p63 DBD mutations examined in this study with the associated and summarizes the most important experimentally determined parameters together with the resultant classification (see discussion). The position of the mutated residue is annotated in relation to the secondary structure elements of the DBD (H α-helix, S β-strand, L loop; see Supplementary Fig. S1A for details). The results of the luciferase reporter assays are displayed in the column ‘Activity’ (-: inactive; +: wildtype-like; +++: hyperactive). Data from the DNA pulldown assay, the luciferase reporter displacement assay and SPR measurements are integrated in the column ‘DNA binding’ (-: no DNA binding; +: residual DNA binding; ++: moderate DNA binding; +++: wildtype-like DNA binding). The tendency of the mutant DBDs to lose the zinc ion as a measurement for the destabilization of the zinc finger is stated in the column ‘Zinc loss’ (-: no zinc loss; +: minor zinc loss; ++: moderate zinc loss; +++: strong zinc loss). The destabilization of the mutant DBDs is displayed in the column ‘Destabilization’ (-: no destabilization or stabilization; +: moderate destabilization; +++: strong destabilization).