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FLASH GENE
Symbol PADI4 contributors: mct/pgu - updated : 30-05-2023
HGNC name peptidyl arginine deiminase, type IV
HGNC id 18368
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunespleen    
Nervousbrain    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
 bone marrow  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticeosinophil
Blood/Hematopoieticgranulocyte Homo sapiens
Blood/Hematopoieticmonocyte Homo sapiens
Blood/Hematopoieticneutrophil
Lymphoid/Immunemacrophage Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text cord blood
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal IgG-like domains bind to the regulatory domain of TP53
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to rattus padi4
    ortholog to murine Padi4
    Homologene
    FAMILY protein arginine deiminase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • may be playing a role in granulocyte and macrophage development leading to inflammation and immune response
  • may be mediating gene expression by regulating arginine methylation and citrullination in histones
  • catalyzing the post-translational citrullination of proteins
  • playing a role in the regulation of TP53 target gene expression
  • citrullinated the histone chaperone protein, nucleophosmin (NPM1), at the arginine 197, and citrullination of NPM1 by PADI4 resulted in its translocation from the nucleoli to the nucleoplasm
  • promotes the deimination of arginine residues in histones and may regulate transcription in the context of the chromatin
  • converts peptidyl arginine to citrulline in histone H3 and can repress gene expression
  • catalyze the hydrolysis of peptidyl-arginine to form peptidyl-citrulline, and play important roles in a variety of cell signaling pathways, including apoptosis, differentiation, and transcriptional regulation
  • autodeimination of PADI4 alters protein-protein interactions but not activity
  • homodimeric enzyme that catalyzes CaČ&
  • 8314;-dependent protein citrullination, which results in the conversion of arginine to citrulline
  • protein citrullination by PADI4 thus emerges as a novel mechanism for controlling a de novo DNA methyltransferase
  • PADI4 is an enzyme implicated in citrullination in the Rheumatoid arthritis (RA) synovium
  • catalyzes the deimination of histone arginine residues to citrulline
  • HIF-dependent recruitment of PADI4 to target genes and local histone citrullination are required for transcriptional responses to hypoxia
  • accelerate metastasis by promoting IL-8 expression in gastric cancer cells
  • PADI4 is dispensable for cell-autonomous HSC maintenance, differentiation and haematopoietic regeneration
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component dimeric, but monomeric PADI4 is still active but does not display cooperative calcium binding
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    Ca2+
    protein
  • PADI4 and HDAC1 collaborate to generate a repressive chromatin environment on the pS2 promoter
  • interaction with TP53 (TP53 transactivated peptidylarginine deiminase type 4 (PADI4) through an intronic TP53-binding site)
  • histone deacetylase (HDAC2) and PADI4 interact with TP53 through CDKN1A promoter to regulate gene expression
  • preferentially citrullinates ING4 in the same NLS region and thereby disrupts the interaction between ING4 and TP53
  • binding of PADI4 to ING4 stabilizes ING4 and protects it from rapid degradation
  • TAL1 interacts with the peptidylarginine deiminase IV (PADI4), and PADI4 acts as a coactivator of TAL1 by counteracting repressive histone arginine methylation
  • DNMT3A and PADI4 interact, and PADI4 citrullinate DNMT3A
  • PADI4 interacted with SYVN1 directly and overexpression of PADI4 suppressed the ubiquitination of proteins
  • GIMAP5 promoted the transport of M6PR from the cytoplasm to the cell membrane, thereby inhibiting the enhancement of EMT-related PADI4
  • PADI4 interacting with NUPR1, and NUPR1/PADI4 complex could have crucial functions in modulating DNA-repair, favoring metastasis, or facilitating citrullination of other proteins
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in gastric cancer
    tumoral     --over  
    in lung cancer cells
    Susceptibility
  • to rheumatoid arthritis (RA)
  • to oesophageal cancer
  • Variant & Polymorphism SNP
  • may contribute to an inherited predisposition to RA in a Chinese population
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    PADI4 associated signaling pathway may be a therapeutic target for treating lung cancer in a clinical setting
    ANIMAL & CELL MODELS