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protein-arginine deiminase-4 (peptidylarginine deiminase 4, HL-60 PAD, PADI4, PADI5, PDI5)
Function:
1) catalyzes the citrullination/deimination of Arg residues of proteins
2) citrullinates histone H3 at Arg-8 &/or Arg-17 & histone H4 at Arg-3, which prevents their methylation by CARM1 & HRMT1L2/PRMT1 & represses transcription
3) citrullinates EP300/P300 at Arg-2142, which favors its interaction with NCOA2/GRIP1.
4) 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:
1) PADI4 gene is thought to be a rheumatoid arthritis susceptibility locus
2) citrullination of proteins in synovial tissues may lead to a break in tolerance to citrullinated peptides in rheumatoid arthritis patients
General
protein-arginine deiminase type-1 (peptidylarginine deiminase 1, PADI, PDI)
Properties
SIZE: MW = 74 kD
entity length = 663 aa
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Ca+2-binding site
SITE: 153-153
Ca+2-binding site
SITE: 155-155
Ca+2-binding site
SITE: 157-157
Ca+2-binding site
SITE: 165-165
Ca+2-binding site
SITE: 168-168
Ca+2-binding site
SITE: 170-170
Ca+2-binding site
SITE: 176-176
Ca+2-binding site
SITE: 179-179
Ca+2-binding site
SITE: 349-349
aspartate residue {D350}
Ca+2-binding site
SITE: 351-351
Ca+2-binding site
SITE: 353-353
Ca+2-binding site
SITE: 369-369
Ca+2-binding site
SITE: 370-370
Ca+2-binding site
SITE: 373-373
binding site
SITE: 374-374
FOR-BINDING-OF: Substrate.
Ca+2-binding site
SITE: 388-388
Ca+2-binding site
SITE: 407-407
Ca+2-binding site
SITE: 410-410
Ca+2-binding site
SITE: 411-411
histidine residue {H471}
aspartate residue {D473}
binding site
SITE: 639-639
FOR-BINDING-OF: Substrate; via carbonyl oxygen.
cysteine residue {C645}
Database Correlations
OMIM correlations
UniProt Q9UM07
PFAM correlations
ENZYME 3.5.3.15
References
UniProt :accession Q9UM07