Sign in to NCBI
Format

Send to:

Choose Destination

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

Gene ID: 23569, updated on 6-Jan-2019

Summary

Go to the top of the page Help
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

Go to the top of the page Help
See PADI4 in Genome Data Viewer
Location:
1p36.13
Exon count:
18
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations. Hua J, et al. PLoS One, 2018. PMID 29518108, Free PMC Article
  2. Hypoxia‑induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast‑like synoviocytes in rheumatoid arthritis. Fan T, et al. Mol Med Rep, 2018 Apr. PMID 29393388, Free PMC Article
  3. The relationship of PADI4_94 polymorphisms with the morbidity of rheumatoid arthritis in Caucasian and Asian populations: a meta-analysis and system review. Lu C, et al. Clin Rheumatol, 2018 Feb. PMID 29302826
  4. Meta-analysis of the association between PADI4 -92C/G polymorphism and rheumatoid arthritis in the Chinese population. Guo ZY, et al. Braz J Med Biol Res, 2017 Aug 17. PMID 28832760, Free PMC Article
  5. PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population. Baños-Hernández CJ, et al. Hum Immunol, 2017 Sep. PMID 28551357

See all (148) citations in PubMed

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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. Molecular interplay between the dimer interface and the substrate-binding site of human PAD4 has been reported.
    Title: Molecular Interplay between the Dimer Interface and the Substrate-Binding Site of Human Peptidylarginine Deiminase 4.
  2. PADI4 may be closely associated with hypoxiainduced autophagy, and the inhibition of hypoxiainduced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RAFLS.
    Title: Hypoxia‑induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast‑like synoviocytes in rheumatoid arthritis.
  3. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to Rheumatoid Arthritis in Egyptian Population in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one.
    Title: Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population.
  4. our meta-analysis demonstrated that the PADI4_94 polymorphisms might contribute to RA susceptibility especially in Asian populations but not in Caucasian populations.
    Title: The relationship of PADI4_94 polymorphisms with the morbidity of rheumatoid arthritis in Caucasian and Asian populations: a meta-analysis and system review.
  5. Meta-analysis indicated a significantly increased association between PADI -104C/T polymorphism and rheumatoid arthritis (RA) in Chinese and Japanese populations (which were the majority of included populations in the analysis).
    Title: Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations.
  6. PADI4 interacted with SYVN1 directly and that overexpression of PADI4 suppressed the ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may abrogate the initiation of chronic RA by suppressing the proliferative signals of RA synoviocytes.
    Title: Inhibitory effects of ubiquitination of synoviolin by PADI4.
  7. mRNA expression of PADI2, PADI4 and Sp1 is upregulated in rheumatoid arthritis bone marrow CD34+ cells independently of the systemic inflammation or treatment regimen.
    Title: The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD34+ cells in rheumatoid arthritis.
  8. this study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for rheumatoid arthritis
    Title: PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population.
  9. The T allele of PADI4 rs2240340 is associated with Rheumatoid Arthritis in Asians.
    Title: NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singaporean Chinese.
  10. PADI4 contributes to gastric tumorigenesis by upregulating CXCR2, KRT14 and TNF-alpha expression.
    Title: PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels.
Submit: New GeneRIF Correction See all GeneRIFs (119)

Phenotypes

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from BioSystems

Go to the top of the page Help
  • Chromatin modifying enzymes, organism-specific biosystem (from REACTOME)
    Chromatin modifying enzymes, organism-specific biosystemEukaryotic DNA is associated with histone proteins and organized into a complex nucleoprotein structure called chromatin. This structure decreases the accessibility of DNA but also helps to protect i...
  • Chromatin organization, organism-specific biosystem (from REACTOME)
    Chromatin organization, organism-specific biosystemChromatin organization refers to the composition and conformation of complexes between DNA, protein and RNA. It is determined by processes that result in the specification, formation or maintenance o...
  • protein citrullination, organism-specific biosystem (from BIOCYC)
    protein citrullination, organism-specific biosystemGeneral Background : L-CITRULLINE is a non-standard amino acid that is not normally present in proteins. The term citrulline was coined in 1930 from Citrullus, the Latin name of the watermelon, fro...
  • protein citrullination, conserved biosystem (from BIOCYC)
    protein citrullination, conserved biosystemGeneral Background |FRAME: L-CITRULLINE| is a non-standard amino acid that is not normally present in proteins. The term citrulline was coined in 1930 from |FRAME:TAX-3653|, the Latin name of the w...

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
arginine binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
arginine deiminase activity IDA
Inferred from Direct Assay
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 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein homodimerization activity IMP
Inferred from Mutant Phenotype
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 
protein-arginine deiminase activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
arginine deiminase pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
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

Go to the top of the page Help
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)

Go to the top of the page Help

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
    5007..60811
    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 Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 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.p12 PATCHES

Genomic

  1. NW_011332688.1 Reference GRCh38.p12 PATCHES

    Range
    153419..209223
    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

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous
You are here: NCBI > Genes & Expression > Gene
Support Center