PADI3 gene

peptidyl arginine deiminase 3

The PADI3 gene provides instructions for making an enzyme called peptidylarginine deiminase type III. This enzyme modifies proteins by changing certain protein building blocks (amino acids). Specifically, it changes the positively charged amino acid arginine to the neutral amino acid citrulline when positively charged calcium atoms (ions) are present. This process is called deimination. In most cases, deimination alters the protein's interactions with other proteins.

Peptidylarginine deiminase type III is found in the skin's tough outer surface (the stratum corneum), within cells called keratinocytes. The protein also functions in hair follicles, which are specialized structures in the skin where hair growth occurs. In hair follicles, peptidylarginine deiminase type III modifies proteins involved in giving structure to the hair strand (shaft).

At least nine mutations in the PADI3 gene have been found to cause uncombable hair syndrome. This condition is characterized by dry, frizzy, blond scalp hair that cannot be combed flat. This condition usually improves over time, and by adolescence individuals with uncombable hair syndrome have hair that lies flat and has normal or nearly normal texture.

The PADI3 gene mutations likely result in a peptidylarginine deiminase type III enzyme with little or no activity. As a result, the enzyme cannot deiminate other proteins. In particular, peptidylarginine deiminase type III cannot deiminate a protein within the hair shaft called trichohyalin. Trichohyalin needs this modification so that it can attach (bind) to other proteins, giving the hair shaft its cylindrical shape. Without deimination of trichohyalin, the cross-section of the hair shaft becomes triangular, heart-like, or flat. These angular hair shafts result in frizzy hair that will not lie flat, which is typical of uncombable hair syndrome.

Cytogenetic Location: 1p36.13, which is the short (p) arm of chromosome 1 at position 36.13

Molecular Location: base pairs 17,249,079 to 17,284,233 on chromosome 1 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 1p36.13, which is the short (p) arm of chromosome 1 at position 36.13
  • PAD3
  • PDI3
  • peptidyl arginine deiminase, type III
  • peptidylarginine deiminase III
  • protein-arginine deiminase type-3
  • protein-arginine deiminase type III