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Protein / target

Protein-arginine deiminase type-4

Encoded byPADI4Q9UM07Homo sapiensSwiss-Prot
UniProt: Q9UM07Ensembl: ENSG00000159339HGNC: HGNC:18368NCBI Gene: 23569
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Histone H3R17 arginine deiminase

Strongest disease association

Arthritis, Rheumatoid

Via encoding gene PADI4 · Genetic evidence · score 0.85

Research activity

Emerging research

1 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance.

View complete UniProt function annotation

Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:19153223, PubMed:21245532, PubMed:25622091). Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci) (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci (PubMed:18209087). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription (PubMed:15345777). Involved for the formation of neutrophil extracellular traps (NETs) by mediating citrullination of histone H3 and initiating decondensation of chromatin and nuclear membrane rupture (PubMed:19153223, PubMed:25622091, PubMed:28574339, PubMed:32170015). NETs are mainly composed of DNA fibers and are released by neutrophils to trap pathogens during inflammation (PubMed:19153223). Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (PubMed:15731352)

Subcellular location

CytoplasmNucleusCytoplasmic granule
Domains and Gene Ontology detail (24)

Gene Ontology

  • Ccytoplasm
  • Ccytosol
  • Cnucleoplasm
  • Cnucleus
  • Cprotein-containing complex
  • Fcalcium ion binding
  • Fhistone arginine deiminase activity
  • Fhistone H3R17 arginine deiminase activity
  • Fhistone H3R2 arginine deiminase activity
  • Fhistone H3R26 arginine deiminase activity
  • Fhistone H3R8 arginine deiminase activity
  • Fidentical protein binding

663 aa · 74 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GOTranscriptional regulationUniProt · GO
View supporting evidence

Immune signalling

  • ·Catalyzes the citrullination/deimination of arginine residues of proteins such as histon…
  • ·innate immune response

Transcriptional regulation

  • ·Catalyzes the citrullination/deimination of arginine residues of proteins such as histon…
  • ·DNA-templated transcription

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PADI4

Gene-level evidence surfaced through the gene PADI4that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Arthritis, Rheumatoid
0.87Well supported

Genetic evidence dominant · Open Targets 0.67

Colitis, Ulcerative
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.31

Stroke
0.50Limited support

Genetic evidence dominant · Open Targets 0.29

Alcohol drinking
0.46Limited support

Genetic evidence dominant · Open Targets 0.28

Skin Neoplasms
0.42Limited support

Genetic evidence dominant · Open Targets 0.25

View evidence synthesis (5)
Arthritis, RheumatoidWell supported
0.87
agreement 0.73–1.00
Genetic85%Literature15%Genetic literaturedup

Open Targets aggregate 0.67 · 2 independent evidence families · 1 not counted as duplicate

Colitis, UlcerativeModerately supported
0.52
agreement 0.39–0.65
Genetic91%RNA expression6%Literature3%

Open Targets aggregate 0.31 · 3 independent evidence families

StrokeLimited support
0.50
agreement 0.36–0.64
Genetic89%Literature11%

Open Targets aggregate 0.29 · 2 independent evidence families

Alcohol drinkingLimited support
0.46
agreement 0.34–0.58
Genetic100%

Open Targets aggregate 0.28 · 1 independent evidence family

Skin NeoplasmsLimited support
0.42
agreement 0.28–0.56
Genetic98%Literature2%

Open Targets aggregate 0.25 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Arthritis, Rheumatoid0.67
Neurodegenerative Diseases0.32
Colitis, Ulcerative0.31
Stroke0.29
Alcohol drinking0.28
Skin Neoplasms0.25
Neoplasms0.17
Basal cell carcinoma0.15
Hair color0.13

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Neutrophil peptidylarginine deiminase 4 is essential for detrimental age-related cardiac remodelling and dysfunction in mice.19 cites

Van Bruggen S · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023

Recent

Neutrophil peptidylarginine deiminase 4 is essential for detrimental age-related cardiac remodelling and dysfunction in mice.

Van Bruggen S · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023

Europe PMC papers linked directly to this protein.