An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

Table 3

Body distribution, target substrates, and normal physiology and pathology of PADs.

Isotype	Expression	Substrates	Biological process	Pathological process
PAD1	Epidermis and uterus	Keratin K1 and filaggrin	Cornification of epidermal tissues	Psoriasis
PAD2	Widely expressed: pituitary gland, brain, uterus, spleen, spinal cord, and skeletal muscle	MBP, GFAP, vimentin, and β and γ-actin histones (H3 and H4)	Plasticity of the CNS, transcription regulation, innate immunity, and female fertility	Multiple sclerosis, rheumatoid arthritis, Alzheimer’s disease, and prion disease
PAD3	Epidermis and hair follicles	Filaggrin and trichohyalin	Regulation of epidermal functions	Unknown
PAD4	Neutrophils, monocytes, macrophages, mammary glands, epithelial cells, and tumors	Histones H2A, H3, and H4; ING4; p300/CBP; nucleophosmin; and nuclear Lamin C	Chromatin decondensation, transcription regulation, tumor formation, innate immune response, and NETosis process	Rheumatoid arthritis, multiple sclerosis, and cancers
PAD6	Eggs, ovary, early fetus, and testis tissues	Protamine	Ovocyte, sperm chromatin decondensation, female productivity, cytoskeleton formation, early fetal growth, and target for contraceptive drugs	Unknown