Table 1 Localization and function of human peptidylarginine deiminase enzymes

PAD1

Epidermis, hair follicles, arrector pili muscles, and sweat glands

Citrullination of filaggrin and keratin, facilitating proteolysis and crosslinking of the proteins and contributing to skin cornification. Maintains hydration of stratum corneum and epidermis barrier function.

Differentiation of hair follicles.

PAD2

Brain astrocytes, sweat glands, arrector pili muscles, skeletal muscle, spleen, macrophages, monocytes, epidermis, synovial tissue, and synovial fluid

Citrullination of myelin basic protein in the brain and spinal cord, promoting electrical insulation of myelin sheaths.

Citrullination of vimentin in apoptotic monocytes and macrophages.

PAD3

Upper layers of epidermis and hair follicles

Citrullination of trichohyalin, contributing to directional hair growth.

PAD4

Hematopoietic cells and inflamed rheumatoid synovium

Citrullination of transcriptional coactivator p300 and histones H2A, H3, and H4, regulating gene expression by chromatin remodelling. Citrullination of fibrin, contributing to chronic inflammation in rheumatoid arthritis.

P53-dependent citrullination of proteins following DNA damage, translocation of histone chaperone nucleophosmin, and p53- mediated inhibition of tumor cell growth.

PAD6

Ovary and testis tissue and peripheral blood leukocytes

Amino acids known to be conserved in PAD enzymatic activity are not conserved in PAD6. Function and enzymatic activity remain Unclear.