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Aliases for PADI4 Gene

Aliases for PADI4 Gene

  • Peptidyl Arginine Deiminase, Type IV 2 3
  • Peptidyl Arginine Deiminase, Type V 2 3
  • Protein-Arginine Deiminase Type IV 3 4
  • EC 3.5.3.15 4 63
  • HL-60 PAD 3 4
  • PADI5 3 4
  • PAD4 3 4
  • PDI5 3 4
  • Peptidylarginine Deiminase IV 4
  • PADI-H Protein 3
  • PDI4 3
  • PAD 3

External Ids for PADI4 Gene

Previous HGNC Symbols for PADI4 Gene

  • PADI5

Previous GeneCards Identifiers for PADI4 Gene

  • GC00U991184
  • GC01P016675
  • GC01P017015
  • GC01P017379
  • GC01P017507
  • GC01P017634
  • GC01P015882

Summaries for PADI4 Gene

Entrez Gene Summary for PADI4 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]

GeneCards Summary for PADI4 Gene

PADI4 (Peptidyl Arginine Deiminase, Type IV) is a Protein Coding gene. Diseases associated with PADI4 include rheumatoid arthritis and palindromic rheumatism. Among its related pathways are Chromatin organization and protein citrullination. GO annotations related to this gene include calcium ion binding and arginine deiminase activity. An important paralog of this gene is PADI3.

UniProtKB/Swiss-Prot for PADI4 Gene

  • 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. 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). 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. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at Arg-2142, which favors its interaction with NCOA2/GRIP1.

Gene Wiki entry for PADI4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PADI4 Gene

Genomics for PADI4 Gene

Regulatory Elements for PADI4 Gene

Transcription factor binding sites by QIAGEN in the PADI4 gene promoter:

Genomic Location for PADI4 Gene

Chromosome:
1
Start:
17,308,195 bp from pter
End:
17,364,004 bp from pter
Size:
55,810 bases
Orientation:
Plus strand

Genomic View for PADI4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PADI4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PADI4 Gene

Proteins for PADI4 Gene

  • Protein details for PADI4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UM07-PADI4_HUMAN
    Recommended name:
    Protein-arginine deiminase type-4
    Protein Accession:
    Q9UM07
    Secondary Accessions:
    • A8K392
    • B2RBW0
    • Q5VTZ8
    • Q70SX4

    Protein attributes for PADI4 Gene

    Size:
    663 amino acids
    Molecular mass:
    74079 Da
    Cofactor:
    Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 5 Ca(2+) ions per subunit.;
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for PADI4 Gene

neXtProt entry for PADI4 Gene

Proteomics data for PADI4 Gene at MOPED

Selected DME Specific Peptides for PADI4 Gene

Post-translational modifications for PADI4 Gene

  • Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PADI4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for PADI4 Gene

Gene Families for PADI4 Gene

Protein Domains for PADI4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9UM07

UniProtKB/Swiss-Prot:

PADI4_HUMAN :
  • Belongs to the protein arginine deiminase family.
Family:
  • Belongs to the protein arginine deiminase family.
genes like me logo Genes that share domains with PADI4: view

Function for PADI4 Gene

Molecular function for PADI4 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.055 mM for fibrinogen {ECO:0000269 PubMed:15629448}; KM=0.064 mM for filaggrin {ECO:0000269 PubMed:15629448}; Vmax=33.2 umol/h/mg enzyme toward fibrinogen {ECO:0000269 PubMed:15629448}; Vmax=8.0 umol/h/mg enzyme toward filaggrin {ECO:0000269 PubMed:15629448}; pH dependence: Optimum pH is 6.5-9.0. {ECO:0000269 PubMed:15629448};
UniProtKB/Swiss-Prot CatalyticActivity:
Protein L-arginine + H(2)O = protein L-citrulline + NH(3).
UniProtKB/Swiss-Prot EnzymeRegulation:
Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family (PubMed:17002273). Incorporation of a carboxylate ortho to the backbone amide of Cl-amidine results in inhibitors with increased specificity for PADI4: N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) (PubMed:21882827). Strongly and specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of the family are not inhibited (PubMed:22004374).
UniProtKB/Swiss-Prot Function:
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. 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). 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. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at Arg-2142, which favors its interaction with NCOA2/GRIP1.

Enzyme Numbers (IUBMB) for PADI4 Gene

Gene Ontology (GO) - Molecular Function for PADI4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004668 protein-arginine deiminase activity IDA 15339660
GO:0005509 calcium ion binding IDA 16567635
GO:0005515 protein binding IPI 21584310
GO:0016990 arginine deiminase activity IDA 21584310
genes like me logo Genes that share ontologies with PADI4: view
genes like me logo Genes that share phenotypes with PADI4: view

Animal Models for PADI4 Gene

MGI Knock Outs for PADI4:

Animal Model Products

miRNA for PADI4 Gene

miRTarBase miRNAs that target PADI4

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PADI4

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for PADI4 Gene

Localization for PADI4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PADI4 Gene

Cytoplasm. Nucleus. Cytoplasmic granule. Note=Cytoplasmic granules of eosinophils and neutrophils.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PADI4 Gene COMPARTMENTS Subcellular localization image for PADI4 gene
Compartment Confidence
nucleus 5
extracellular 2
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for PADI4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 15339660
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with PADI4: view

Pathways & Interactions for PADI4 Gene

genes like me logo Genes that share pathways with PADI4: view

Pathways by source for PADI4 Gene

1 BioSystems pathway for PADI4 Gene
2 Reactome pathways for PADI4 Gene

Gene Ontology (GO) - Biological Process for PADI4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006325 chromatin organization TAS --
GO:0006334 nucleosome assembly ISS --
GO:0006338 chromatin remodeling ISS --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with PADI4: view

No data available for SIGNOR curated interactions for PADI4 Gene

Drugs & Compounds for PADI4 Gene

(10) Drugs for PADI4 Gene - From: DrugBank, DGIdb, NovoSeek, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Citrulline Approved Nutra Full agonist, Agonist, Target 0
Azithromycin Approved Pharma Target 309
Doxycycline Approved, Investigational Pharma Target 204
Streptomycin Approved Pharma Target 18
Tetracycline Approved Pharma Target 81

(5) Additional Compounds for PADI4 Gene - From: NovoSeek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Ammonia
  • Ammonia anhydrous
  • Ammonia inhalant
  • Ammonia solution strong [usan]
  • Ammonia water
  • Ammoniak
7664-41-7
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
ACPA
229021-64-1
baee
FIBRINOGEN
genes like me logo Genes that share compounds with PADI4: view

Transcripts for PADI4 Gene

Unigene Clusters for PADI4 Gene

Peptidyl arginine deiminase, type IV:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PADI4

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PADI4 Gene

No ASD Table

Relevant External Links for PADI4 Gene

GeneLoc Exon Structure for
PADI4
ECgene alternative splicing isoforms for
PADI4

Expression for PADI4 Gene

mRNA expression in normal human tissues for PADI4 Gene

mRNA differential expression in normal tissues according to GTEx for PADI4 Gene

This gene is overexpressed in Whole Blood (x47.5).

Protein differential expression in normal tissues from HIPED for PADI4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (19.4), Neutrophil (18.2), Lavage (7.7), and Saliva (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for PADI4 Gene



SOURCE GeneReport for Unigene cluster for PADI4 Gene Hs.522969

mRNA Expression by UniProt/SwissProt for PADI4 Gene

Q9UM07-PADI4_HUMAN
Tissue specificity: Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes.
genes like me logo Genes that share expression patterns with PADI4: view

Protein tissue co-expression partners for PADI4 Gene

- Elite partner

Primer Products

In Situ Assay Products

Orthologs for PADI4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PADI4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia PADI4 35
  • 82.98 (n)
  • 74.32 (a)
PADI4 36
  • 74 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PADI4 35
  • 83.56 (n)
  • 76.7 (a)
PADI4 36
  • 58 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Padi4 35
  • 79.81 (n)
  • 73.56 (a)
Padi4 16
Padi4 36
  • 73 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia PADI4 35
  • 96.75 (n)
  • 95.87 (a)
PADI4 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Padi4 35
  • 79.81 (n)
  • 74.77 (a)
oppossum
(Monodelphis domestica)
Mammalia PADI4 36
  • 67 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 63 (a)
OneToMany
-- 36
  • 66 (a)
OneToMany
zebrafish
(Danio rerio)
Actinopterygii padi2 36
  • 45 (a)
OneToMany
Species with no ortholog for PADI4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PADI4 Gene

ENSEMBL:
Gene Tree for PADI4 (if available)
TreeFam:
Gene Tree for PADI4 (if available)

Paralogs for PADI4 Gene

Paralogs for PADI4 Gene

Pseudogenes.org Pseudogenes for PADI4 Gene

genes like me logo Genes that share paralogs with PADI4: view

Variants for PADI4 Gene

Sequence variations from dbSNP and Humsavar for PADI4 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs1612843 -- 17,360,666(-) TGCTA(C/G)GTGGG intron-variant
rs1613229 -- 17,334,931(-) ctcct(A/G)ggctc intron-variant
VAR_053562 -
VAR_053561 -
VAR_053560 -

Structural Variations from Database of Genomic Variants (DGV) for PADI4 Gene

Variant ID Type Subtype PubMed ID
nsv834291 CNV Gain 17160897
esv2674909 CNV Deletion 23128226
nsv511142 CNV Loss 21212237
esv33950 CNV Gain+Loss 17666407
esv21592 CNV Loss 19812545
esv4441 CNV Deletion 18987735
esv2744563 CNV Deletion 23290073
nsv511681 CNV Loss 21212237
dgv23e199 CNV Deletion 23128226
dgv26n67 CNV Loss 20364138
esv2668971 CNV Deletion 23128226
esv2744574 CNV Deletion 23290073
esv2744586 CNV Deletion 23290073

Variation tolerance for PADI4 Gene

Residual Variation Intolerance Score: 92.85% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.99; 68.32% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PADI4 Gene

HapMap Linkage Disequilibrium report
PADI4
Human Gene Mutation Database (HGMD)
PADI4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PADI4 Gene

Disorders for PADI4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for PADI4 Gene - From: OMIM, DISEASES, NovoSeek, and GeneCards

Disorder Aliases PubMed IDs
rheumatoid arthritis
  • rheumatoid arthritis, progression of
palindromic rheumatism
  • hench-rosenberg syndrome
bone inflammation disease
  • bone inflammatory disease
arthritis
  • inflammatory disorder of joint
multiple sclerosis, disease progression, modifier of
  • multiple sclerosis 1
- elite association
Search PADI4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PADI4_HUMAN
  • Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269 PubMed:12833157}. Note=The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (PubMed:12833157). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (PubMed:21245532). {ECO:0000269 PubMed:12833157, ECO:0000269 PubMed:21245532}.

Relevant External Links for PADI4

Genetic Association Database (GAD)
PADI4
Human Genome Epidemiology (HuGE) Navigator
PADI4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PADI4
genes like me logo Genes that share disorders with PADI4: view

No data available for Genatlas for PADI4 Gene

Publications for PADI4 Gene

  1. Histone arginine methylation and its dynamic regulation. (PMID: 16146736) Wysocka J. … Coonrod S. (Front. Biosci. 2006) 23 25 26 67
  2. Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. (PMID: 16355400) Chang X. … Han J. (Mol. Carcinog. 2006) 25 26 67
  3. Human PAD4 regulates histone arginine methylation levels via demethylimination. (PMID: 15345777) Wang Y. … Coonrod S.A. (Science 2004) 25 26 67
  4. Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3). (PMID: 10488123) Nakashima K. … Yamada M. (J. Biol. Chem. 1999) 2 23 67
  5. Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper. (PMID: 19895906) Ebringer A. … Wilson C. (Autoimmun Rev 2010) 23 67

Products for PADI4 Gene

Sources for PADI4 Gene

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