Human Gene PADI4 (ENST00000375448.4_4) from GENCODE V47lift37
  Description: peptidyl arginine deiminase 4 (from RefSeq NM_012387.3)
Gencode Transcript: ENST00000375448.4_4
Gencode Gene: ENSG00000159339.13_5
Transcript (Including UTRs)
   Position: hg19 chr1:17,634,692-17,690,499 Size: 55,808 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chr1:17,634,718-17,690,250 Size: 55,533 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:17,634,692-17,690,499)mRNA (may differ from genome)Protein (663 aa)
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-  Comments and Description Text from UniProtKB
  ID: PADI4_HUMAN
DESCRIPTION: RecName: Full=Protein-arginine deiminase type-4; EC=3.5.3.15; AltName: Full=HL-60 PAD; AltName: Full=Peptidylarginine deiminase IV; AltName: Full=Protein-arginine deiminase type IV;
FUNCTION: Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.
CATALYTIC ACTIVITY: Protein L-arginine + H(2)O = protein L- citrulline + NH(3).
COFACTOR: Binds 5 calcium ions per subunit.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.055 mM for fibrinogen; KM=0.064 mM for filaggrin; Vmax=33.2 umol/h/mg enzyme toward fibrinogen; Vmax=8.0 umol/h/mg enzyme toward filaggrin; pH dependence: Optimum pH is 6.5-9.0;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasmic granule. Note=Cytoplasmic granules of eosinophils and neutrophils.
TISSUE SPECIFICITY: Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes.
DISEASE: Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:180300]. It is a systemic 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. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.
SIMILARITY: Belongs to the protein arginine deiminase family.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PADI4
Diseases sorted by gene-association score: rheumatoid arthritis* (267), palindromic rheumatism (13), hypersensitivity reaction type ii disease (6), ovarian benign neoplasm (5), multiple sclerosis, disease progression, modifier of (2), bone inflammation disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 95.73 RPKM in Whole Blood
Total median expression: 122.34 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -4.5026-0.173 Picture PostScript Text
3' UTR -67.60249-0.271 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008972 - Cupredoxin
IPR004303 - PAD
IPR013530 - PAD_C
IPR013732 - PAD_N
IPR013733 - Prot_Arg_deaminase_cen_dom
IPR016296 - Protein-arginine_deiminase_sub

Pfam Domains:
PF03068 - Protein-arginine deiminase (PAD)
PF08526 - Protein-arginine deiminase (PAD) N-terminal domain
PF08527 - Protein-arginine deiminase (PAD) middle domain

SCOP Domains:
110083 - Peptidylarginine deiminase Pad4, middle domain
49503 - Cupredoxins
55909 - Pentein

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1WD8 - X-ray MuPIT 1WD9 - X-ray MuPIT 1WDA - X-ray MuPIT 2DEW - X-ray MuPIT 2DEX - X-ray MuPIT 2DEY - X-ray MuPIT 2DW5 - X-ray MuPIT 3APM - X-ray MuPIT 3APN - X-ray MuPIT 3B1T - X-ray MuPIT 3B1U - X-ray MuPIT 4DKT - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UM07
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004668 protein-arginine deiminase activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0016990 arginine deiminase activity
GO:0034618 arginine binding
GO:0042803 protein homodimerization activity
GO:0046872 metal ion binding

Biological Process:
GO:0002376 immune system process
GO:0006325 chromatin organization
GO:0006334 nucleosome assembly
GO:0006338 chromatin remodeling
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006464 cellular protein modification process
GO:0018101 protein citrullination
GO:0019546 arginine deiminase pathway
GO:0019827 stem cell population maintenance
GO:0036413 histone H3-R26 citrullination
GO:0036414 histone citrullination
GO:0045087 innate immune response

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  AF229067 - Homo sapiens PADI-H protein mRNA, complete cds.
AK314839 - Homo sapiens cDNA, FLJ95726, highly similar to Homo sapiens peptidyl arginine deiminase, type IV (PADI4), mRNA.
LP895145 - Sequence 9 from Patent EP3253886.
LP895699 - Sequence 563 from Patent EP3253886.
AK290507 - Homo sapiens cDNA FLJ78525 complete cds, highly similar to Homo sapiens peptidyl arginine deiminase, type IV (PADI4), mRNA.
AB017919 - Homo sapiens mRNA for peptidylarginine deiminase type V, complete cds.
AK309637 - Homo sapiens cDNA, FLJ99678.
JD138644 - Sequence 119668 from Patent EP1572962.
BC025718 - Homo sapiens peptidyl arginine deiminase, type IV, mRNA (cDNA clone MGC:34387 IMAGE:5228777), complete cds.
CU693030 - Synthetic construct Homo sapiens gateway clone IMAGE:100019990 5' read PADI4 mRNA.
AB527709 - Synthetic construct DNA, clone: pF1KB6203, Homo sapiens PADI4 gene for peptidyl arginine deiminase, type IV, without stop codon, in Flexi system.
JF432820 - Synthetic construct Homo sapiens clone IMAGE:100074138 peptidyl arginine deiminase, type IV (PADI4) gene, encodes complete protein.
KJ898514 - Synthetic construct Homo sapiens clone ccsbBroadEn_07908 PADI4 gene, encodes complete protein.
JD278987 - Sequence 260011 from Patent EP1572962.
JD401058 - Sequence 382082 from Patent EP1572962.
JD086874 - Sequence 67898 from Patent EP1572962.
JD519800 - Sequence 500824 from Patent EP1572962.
JD444340 - Sequence 425364 from Patent EP1572962.
JD192373 - Sequence 173397 from Patent EP1572962.
JD432023 - Sequence 413047 from Patent EP1572962.
JD419058 - Sequence 400082 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-4921 - protein citrullination

Reactome (by CSHL, EBI, and GO)

Protein Q9UM07 (Reactome details) participates in the following event(s):

R-HSA-3247569 PADI4 deiminates Histones
R-HSA-1183128 PADIs:Ca2+ deiminate L-Arg to L-Cit in proteins
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-4839726 Chromatin organization

-  Other Names for This Gene
  Alternate Gene Symbols: A8K392, B2RBW0, ENST00000375448.1, ENST00000375448.2, ENST00000375448.3, NM_012387, PAD4, PADI4_HUMAN, PADI5, PDI5, Q5VTZ8, Q70SX4, Q9UM07, uc318mgq.1, uc318mgq.2
UCSC ID: ENST00000375448.4_4
RefSeq Accession: NM_012387.3
Protein: Q9UM07 (aka PADI4_HUMAN or PDI4_HUMAN)

-  Gene Model Information
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.