protein-arginine deiminase-4 (peptidylarginine deiminase 4, HL-60 PAD, PADI4, PADI5, PDI5)

Function

• catalyzes the citrullination/deimination of Arg residues of proteins
• citrullinates histone H3 at Arg-8 &/or Arg-17 & histone H4 at Arg-3, which prevents their methylation by CARM1 & HRMT1L2/PRMT1 & represses transcription
• citrullinates EP300/P300 at Arg-2142, which favors its interaction with NCOA2/GRIP1.
• binds 5 Ca+2 per subunit

protein L-arginine + H2O <--> protein L-citrulline + NH3

Kinetic parameters:

• KM=0.055 mM for fibrinogen
• KM=0.064 mM for filaggrin
• Vmax=33.2 umol/h/mg enzyme toward fibrinogen
• Vmax=8.0 umol/h/mg enzyme toward filaggrin
• pH dependence: Optimum pH is 6.5-9.0

Compartment

• cytoplasm, nucleus
• cytoplasmic granules of eosinophils & neutrophils

Expression

• expressed in eosinophils & neutrophils
• Not expressed in peripheral monocytes or lymphocytes

Pathology

• PADI4 gene is thought to be a rheumatoid arthritis susceptibility locus
• citrullination of proteins in synovial tissues may lead to a break in tolerance to citrullinated peptides in rheumatoid arthritis patients

More general terms

• protein-arginine deiminase

Database

• OMIM: https://mirror.omim.org/entry/180300
• OMIM: https://mirror.omim.org/entry/605347
• UniProt: http://www.uniprot.org/uniprot/Q9UM07.html