PADI4
Protein-arginine deiminase type-4
Also known as: PAD, PADI4_HUMAN, PADI5, PDI4, PDI5
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UM07
- Gene
- PADI4
- Ensembl
- ENSG00000159339
- Chromosome
- 1
- Canonical length
- 663 aa
- Protein class
- Disease related genes, Enzymes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
OverviewNCBI Gene
This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
663 residues, UniProt reviewed canonical sequence.
>Q9UM07|PADI4
1 MAQGTLIRVT PEQPTHAVCV LGTLTQLDIC SSAPEDCTSF SINASPGVVV DIAHGPPAKK
61 KSTGSSTWPL DPGVEVTLTM KVASGSTGDQ KVQISYYGPK TPPVKALLYL TGVEISLCAD
121 ITRTGKVKPT RAVKDQRTWT WGPCGQGAIL LVNCDRDNLE SSAMDCEDDE VLDSEDLQDM
181 SLMTLSTKTP KDFFTNHTLV LHVARSEMDK VRVFQATRGK LSSKCSVVLG PKWPSHYLMV
241 PGGKHNMDFY VEALAFPDTD FPGLITLTIS LLDTSNLELP EAVVFQDSVV FRVAPWIMTP
301 NTQPPQEVYA CSIFENEDFL KSVTTLAMKA KCKLTICPEE ENMDDQWMQD EMEIGYIQAP
361 HKTLPVVFDS PRNRGLKEFP IKRVMGPDFG YVTRGPQTGG ISGLDSFGNL EVSPPVTVRG
421 KEYPLGRILF GDSCYPSNDS RQMHQALQDF LSAQQVQAPV KLYSDWLSVG HVDEFLSFVP
481 APDRKGFRLL LASPRSCYKL FQEQQNEGHG EALLFEGIKK KKQQKIKNIL SNKTLREHNS
541 FVERCIDWNR ELLKRELGLA ESDIIDIPQL FKLKEFSKAE AFFPNMVNML VLGKHLGIPK
601 PFGPVINGRC CLEEKVCSLL EPLGLQCTFI NDFFTYHIRH GEVHCGTNVR RKPFSFKWWN
661 MVPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PADI4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.23
- Highest tissue expression
- 99 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 99 nTPM
- spleen: 29 nTPM
- lung: 7.8 nTPM
- adipose tissue: 1.7 nTPM
- liver: 1.6 nTPM
- thymus: 1.5 nTPM
Single-cell type
- neutrophil progenitors: 215 nCPM
- neutrophils: 162 nCPM
- platelets: 25 nCPM
- megakaryocytes: 19 nCPM
- monocyte progenitors: 17 nCPM
- monocytes: 12 nCPM
Immune cell
- neutrophil: 184 nTPM
- eosinophil: 98 nTPM
- basophil: 80 nTPM
- classical monocyte: 71 nTPM
- total PBMC: 36 nTPM
- myeloid DC: 14 nTPM
Brain region
- cerebral cortex: 2.4 nTPM
- basal ganglia: 1.4 nTPM
- white matter: 1.4 nTPM
- hippocampal formation: 1.2 nTPM
- pons: 1.2 nTPM
- amygdala: 1.1 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about PADI4.
Disease | AllUniProt
Conditions PADI4 is implicated in, by any mechanism.
- Rheumatoid arthritis (RA) MIM:180300
Disease | ImmuneIEDB
Conditions an epitope on PADI4 was assayed in.
- rheumatoid arthritis B cell
ReferencesPubMed · IEDB
Publications for PADI4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis.
2008 · Arthritis Rheum · RCR 2.9 · 120 citations - Peptidylarginine deiminase 4 (PADI4) identified as a conformation-dependent autoantigen in rheumatoid arthritis.
2005 · Scand J Rheumatol · RCR 1 · 43 citations
Reference: B cellIEDB
2 publications
- Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations - Citrullinated peptides of peptidyl arginine deiminase 4 as major B-cell epitopes in patients with rheumatoid arthritis.
2025 · Front Immunol
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.14
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.08
- DepMap mean gene effect
- 0.03
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- chromatin organization
- chromatin remodeling
- innate immune response
- nucleosome assembly
- post-translational protein modification
- protein modification process
- stem cell population maintenance
Molecular functions
- calcium ion binding
- histone arginine deiminase activity
- histone H3R26 arginine deiminase activity
- identical protein binding
- protein-arginine deiminase activity
- histone H3R17 arginine deiminase activity
- histone H3R2 arginine deiminase activity
- histone H3R8 arginine deiminase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein-arginine deiminase
- Cupredoxin
- Protein-arginine deiminase, C-terminal
- Protein-arginine deiminase (PAD), N-terminal
- Protein-arginine deiminase (PAD), central domain
- Protein-arginine deiminase, central domain superfamily
- PAD, N-terminal domain superfamily
- Protein-arginine deiminase (PAD)
- Protein-arginine deiminase (PAD) N-terminal domain
- Protein-arginine deiminase (PAD) middle domain
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PADI4 as an antibody target. Whether an autoantibody or antibody against PADI4 could matter depends on whether native PADI4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PADI4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label PADI4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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