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PADI4 peptidyl arginine deiminase 4 [ Homo sapiens (human) ]

Gene ID: 23569, updated on 7-Jun-2020

Summary

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Official Symbol
PADI4provided by HGNC
Official Full Name
peptidyl arginine deiminase 4provided by HGNC
Primary source
HGNC:HGNC:18368
See related
Ensembl:ENSG00000159339 MIM:605347
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PAD; PAD4; PDI4; PDI5; PADI5
Summary
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]
Expression
Restricted expression toward bone marrow (RPKM 64.4) See more
Orthologs
mouse all

Genomic context

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See PADI4 in Genome Data Viewer
Location:
1p36.13
Exon count:
18
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (17308195..17364004)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (17634690..17690495)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene peptidyl arginine deiminase 1 Neighboring gene peptidyl arginine deiminase 3 Neighboring gene microRNA 3972 Neighboring gene peptidyl arginine deiminase 6 Neighboring gene regulator of chromosome condensation 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PADI4‑mediated epithelial‑mesenchymal transition in lung cancer cells. Liu M, et al. Mol Med Rep, 2019 Apr. PMID 30816464, Free PMC Article
  2. Peptidylarginine deiminase-4 gene polymorphisms are associated with systemic lupus erythematosus and lupus nephritis. Massarenti L, et al. Scand J Rheumatol, 2019 Mar. PMID 30269634
  3. Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation. Muraro SP, et al. Sci Rep, 2018 Sep 21. PMID 30242250, Free PMC Article
  4. Peptidylarginine deiminase 4 concentration, but not PADI4 polymorphisms, is associated with ICU mortality in septic shock patients. Costa NA, et al. J Cell Mol Med, 2018 Oct. PMID 30044533, Free PMC Article
  5. Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, PADI4 Polymorphisms, and Clinical Characteristics in Rheumatoid Arthritis. Guderud K, et al. J Rheumatol, 2018 Aug. PMID 29858238

See all (165) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. This study shows that ubiquitous or nervous system expression of human PAD2 or PAD4 in Drosophila melanogaster have minimal impact on Drosophila melanogaster lifespan, fecundity, and the response to acute heat stress.
    Title: In vivo expression of peptidylarginine deiminase in Drosophila melanogaster.
  2. PAD4 exacerbates ischemic acute kidney injury and inflammation by promoting renal tubular NF-kappaB activity and inflammation via NEMO citrullination.
    Title: Peptidyl arginine deiminase-4 exacerbates ischemic AKI by finding NEMO.
  3. This study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of Rheumatoid Arthritis.
    Title: Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes.
  4. PADI4 expression levels, but not PADI4 polymorphisms, are associated with ICU mortality in septic shock patients.
    Title: Peptidylarginine deiminase 4 concentration, but not PADI4 polymorphisms, is associated with ICU mortality in septic shock patients.
  5. Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also anticitrullinated protein antibodies-positive. No association was observed between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status
    Title: Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, <i>PADI4</i> Polymorphisms, and Clinical Characteristics in Rheumatoid Arthritis.
  6. Activation of PAD4 by membranolytic insults that result in high levels of intracellular calcium (higher than physiological neutrophil activation) leads to rapid citrullination of p47(phox)/NCF1 and p67(phox)/NCF2, as well as their dissociation from PAD4
    Title: Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils.
  7. Required histone citrullination by PAD-4.
    Title: Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through PAD-4 and necroptosis pathways activation.
  8. these findings lead us to conclude that although PAD4 together with CR3-mediated ROS production is required for NET formation in response to A. fumigatus, PAD4-dependent NETosis is not required for A. fumigatus killing either in vitro or during infection.
    Title: Protein Deiminase 4 and CR3 Regulate <i>Aspergillus fumigatus</i> and β-Glucan-Induced Neutrophil Extracellular Trap Formation, but Hyphal Killing Is Dependent Only on CR3.
  9. PADI4mediated EMT transition is proposed to represent a novel mechanism underlying the epigenetic and phenotypic alterations in lung cancer cells, and the PADI4 associated signaling pathway may be a therapeutic target for treating lung cancer in a clinical setting.
    Title: PADI4‑mediated epithelial‑mesenchymal transition in lung cancer cells.
  10. High PADI4 expression is associated with esophageal squamous cell carcinoma tumor growth.
    Title: PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up-regulates CA9 expression.
Submit: New GeneRIF Correction See all GeneRIFs (135)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Rheumatoid arthritis
MedGen: C0003873 OMIM: 180300 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits.
NHGRI GWA Catalog
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
NHGRI GWA Catalog
Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci.
NHGRI GWA Catalog
The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population.
NHGRI GWA Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
arginine binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
calcium ion binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein-arginine deiminase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
protein-arginine deiminase activity IDA
Inferred from Direct Assay
more info
 PubMed 
protein-arginine deiminase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
cellular protein modification process TAS
Traceable Author Statement
more info
 PubMed 
chromatin organization ISS
Inferred from Sequence or Structural Similarity
more info
  
chromatin organization TAS
Traceable Author Statement
more info
  
chromatin remodeling ISS
Inferred from Sequence or Structural Similarity
more info
  
histone H3-R26 citrullination IDA
Inferred from Direct Assay
more info
 PubMed 
histone citrullination IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
histone citrullination IDA
Inferred from Direct Assay
more info
 PubMed 
innate immune response IEA
Inferred from Electronic Annotation
more info
  
nucleosome assembly ISS
Inferred from Sequence or Structural Similarity
more info
  
protein citrullination IDA
Inferred from Direct Assay
more info
 PubMed 
protein citrullination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
stem cell population maintenance ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cytosol TAS
Traceable Author Statement
more info
  
nucleoplasm TAS
Traceable Author Statement
more info
  
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
protein-containing complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 

General protein information

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Preferred Names
protein-arginine deiminase type-4
Names
HL-60 PAD
PADI-H protein
peptidyl arginine deiminase, type IV
peptidyl arginine deiminase, type V
protein-arginine deiminase type IV
NP_036519.2
XP_011539452.1
XP_011539453.1
XP_011539454.1
XP_011539455.1
XP_011539456.1
XP_011539457.1
XP_011539458.1
XP_011539459.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023261.2 RefSeqGene

    Range
    5009..60815
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_012387.3 → NP_036519.2  protein-arginine deiminase type-4

    See identical proteins and their annotated locations for NP_036519.2

    Status: REVIEWED

    Source sequence(s)
    AB017919, AC004824, AK314839
    Consensus CDS
    CCDS180.1
    UniProtKB/Swiss-Prot
    Q9UM07
    Related
    ENSP00000364597.4, ENST00000375448.4
    Conserved Domains (3) summary
    pfam03068
    Location:286 → 660
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    17308195..17364004
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011541151.1 → XP_011539453.1  protein-arginine deiminase type-4 isoform X2

    See identical proteins and their annotated locations for XP_011539453.1

    Conserved Domains (3) summary
    pfam03068
    Location:286 → 560
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  2. XM_011541156.1 → XP_011539458.1  protein-arginine deiminase type-4 isoform X6

    See identical proteins and their annotated locations for XP_011539458.1

    Conserved Domains (3) summary
    pfam03068
    Location:286 → 383
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  3. XM_011541154.2 → XP_011539456.1  protein-arginine deiminase type-4 isoform X4

    See identical proteins and their annotated locations for XP_011539456.1

    Conserved Domains (3) summary
    pfam03068
    Location:286 → 395
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  4. XM_011541153.1 → XP_011539455.1  protein-arginine deiminase type-4 isoform X4

    See identical proteins and their annotated locations for XP_011539455.1

    Conserved Domains (3) summary
    pfam03068
    Location:286 → 395
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  5. XM_011541155.1 → XP_011539457.1  protein-arginine deiminase type-4 isoform X5

    See identical proteins and their annotated locations for XP_011539457.1

    Conserved Domains (3) summary
    pfam03068
    Location:286 → 383
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:113 → 272
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  6. XM_011541150.1 → XP_011539452.1  protein-arginine deiminase type-4 isoform X1

    See identical proteins and their annotated locations for XP_011539452.1

    Conserved Domains (3) summary
    pfam03068
    Location:224 → 598
    PAD; Protein-arginine deiminase (PAD)
    pfam08526
    Location:1 → 111
    PAD_N; Protein-arginine deiminase (PAD) N-terminal domain
    pfam08527
    Location:114 → 210
    PAD_M; Protein-arginine deiminase (PAD) middle domain

  7. XM_011541157.1 → XP_011539459.1  protein-arginine deiminase type-4 isoform X7

    See identical proteins and their annotated locations for XP_011539459.1

    Conserved Domains (1) summary
    pfam03068
    Location:1 → 363
    PAD; Protein-arginine deiminase (PAD)

  8. XM_011541152.1 → XP_011539454.1  protein-arginine deiminase type-4 isoform X3

    See identical proteins and their annotated locations for XP_011539454.1

    Conserved Domains (2) summary
    pfam03068
    Location:107 → 481
    PAD; Protein-arginine deiminase (PAD)
    pfam08527
    Location:1 → 93
    PAD_M; Protein-arginine deiminase (PAD) middle domain

Reference GRCh38.p13 PATCHES

Genomic

  1. NW_011332688.1 Reference GRCh38.p13 PATCHES

    Range
    153421..209227
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UM07.2 GenPept UniProtKB/Swiss-Prot:Q9UM07

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