InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PADI4

Summary

InnateDB Protein

IDBP-91813.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PADI4

Protein Name

peptidyl arginine deiminase, type IV

Synonyms

PAD; PAD4; PADI5; PDI4; PDI5;

Species

Homo sapiens

Ensembl Protein

ENSP00000364597

InnateDB Gene

IDBG-91809 (PADI4)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15339660, ECO:0000269PubMed:15345777, ECO:0000269PubMed:15731352, ECO:0000269PubMed:16567635, ECO:0000269PubMed:18209087, ECO:0000269PubMed:21245532}.

Subcellular Localization

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

Disease Associations

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:0000269PubMed: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:0000269PubMed:12833157, ECO:0000269PubMed:21245532}.

Tissue Specificity

Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes. {ECO:0000269PubMed:11435484}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 22 experimentally validated interaction(s) in this database.

Experimentally validated
Total	22 [view]
Protein-Protein	21 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004668	protein-arginine deiminase activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0016990	arginine deiminase activity

Biological Process

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:0016568	chromatin modification
GO:0018101	protein citrullination
GO:0019827	stem cell maintenance
GO:0036413	histone H3-R26 citrullination
GO:0036414	histone citrullination
GO:0045087	innate immune response

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR008972 Cupredoxin
IPR013530 Protein-arginine deiminase, C-terminal
IPR013732 Protein-arginine deiminase (PAD) N-terminal
IPR013733 Protein-arginine deiminase (PAD), central domain
IPR016296 Protein-arginine deiminase, subgroup

PFAM

PF03068
PF08526
PF08527

PRINTS

PIRSF

PIRSF001247

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9UM07