PADI4

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1WD8, 1WD9, 1WDA, 2DEW, 2DEX, 2DEY, 2DW5, 3APM, 3APN, 3B1T, 3B1U, 4DKT, 4X8C, 4X8G

Identifiers

Aliases

PADI4, PAD, PAD4, PADI5, PDI4, PDI5, peptidyl arginine deiminase 4

External IDs

MGI: 1338898 HomoloGene: 7883 GeneCards: PADI4

Gene location (Human)

Chr.	Chromosome 1 (human)^[1]

Band	No data available	Start	17,308,195 bp^[1]
Band	No data available	End	17,364,004 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 4 (mouse)^[2]

Band	No data available	Start	140,745,865 bp^[2]
Band	No data available	End	140,774,236 bp^[2]

RNA expression pattern

More reference expression data

Gene ontology
Molecular function	• metal ion binding • arginine deiminase activity • protein binding • hydrolase activity • protein-arginine deiminase activity • calcium ion binding • arginine binding • protein homodimerization activity
Cellular component	• nucleoplasm • nucleus • cytosol • cytoplasm • protein complex
Biological process	• chromatin remodeling • nucleosome assembly • regulation of transcription, DNA-templated • immune system process • histone H3-R26 citrullination • transcription, DNA-templated • stem cell population maintenance • histone citrullination • cellular protein modification process • innate immune response • covalent chromatin modification • chromatin organization • protein citrullination • arginine deiminase pathway
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


23569


18602

Ensembl


ENSG00000280908 ENSG00000159339


ENSMUSG00000025330

UniProt


Q9UM07


Q9Z183

RefSeq (mRNA)


NM_012387


NM_011061

RefSeq (protein)


NP_036519


NP_035191

Location (UCSC)

Chr 1: 17.31 – 17.36 Mb

Chr 1: 140.75 – 140.77 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Peptidyl arginine deiminase, type IV, also known as PADI4, is a human protein which in humans is encoded by the PADI4 gene.^[5]^[6]

Molecular biology

The human gene is found on the short arm of Chromosome 1 near the telomere (1p36.13). It is located on the Watson (plus) strand and is 55,806 bases long. The protein is 663 amino acids long with a molecular weight of 74,095 Da.^[5]

Function

This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response.^[6] PADI4 plays a role in the epigenetics, the deimination of arginines on histones 3 and 4 can act antagonistically to arginine methylation (Chromatin modifications and their function, Kouzarides 2007, Cell, review)

The protein may be found in oligomers and binds 5 calcium ions per subunit. It catalyses the reaction:

Protein L-arginine + H₂O = protein L-citrulline + NH₃

Subcellular and tissue distribution

It is normally found in the cytoplasm, nucleus and in cytoplasmic granules of eosinophils and neutrophils. It is not expressed in peripheral monocytes or lymphocytes. It is also expressed in rheumatoid arthritis synovial tissues.

References

1 2 3 ENSG00000159339 GRCh38: Ensembl release 89: ENSG00000280908, ENSG00000159339 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025330 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 Nakashima K, Hagiwara T, Ishigami A, Nagata S, Asaga H, Kuramoto M, Senshu T, Yamada M (September 1999). "Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3)". J. Biol. Chem. 274 (39): 27786–92. PMID 10488123. doi:10.1074/jbc.274.39.27786.
1 2 "Entrez Gene: PADI4 peptidyl arginine deiminase, type IV".

Nakashima K, Hagiwara T, Ishigami A, et al. (1999). "Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3).". J. Biol. Chem. 274 (39): 27786–92. PMID 10488123. doi:10.1074/jbc.274.39.27786.
Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.". Genome Res. 10 (10): 1546–60. PMC 310934 . PMID 11042152. doi:10.1101/gr.140200.
Asaga H, Nakashima K, Senshu T, et al. (2001). "Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils.". J. Leukoc. Biol. 70 (1): 46–51. PMID 11435484.
Nakashima K, Hagiwara T, Yamada M (2003). "Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes.". J. Biol. Chem. 277 (51): 49562–8. PMID 12393868. doi:10.1074/jbc.M208795200.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
Suzuki A, Yamada R, Chang X, et al. (2003). "Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.". Nat. Genet. 34 (4): 395–402. PMID 12833157. doi:10.1038/ng1206.
Barton A, Bowes J, Eyre S, et al. (2004). "A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population.". Arthritis Rheum. 50 (4): 1117–21. PMID 15077293. doi:10.1002/art.20169.
Chavanas S, Méchin MC, Takahara H, et al. (2004). "Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6.". Gene. 330: 19–27. PMID 15087120. doi:10.1016/j.gene.2003.12.038.
Arita K, Hashimoto H, Shimizu T, et al. (2004). "Structural basis for Ca(2+)-induced activation of human PAD4.". Nat. Struct. Mol. Biol. 11 (8): 777–83. PMID 15247907. doi:10.1038/nsmb799.
Hoppe B, Heymann GA, Tolou F, et al. (2005). "High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach.". J. Mol. Med. 82 (11): 762–7. PMID 15338034. doi:10.1007/s00109-004-0584-6.
Cuthbert GL, Daujat S, Snowden AW, et al. (2004). "Histone deimination antagonizes arginine methylation.". Cell. 118 (5): 545–53. PMID 15339660. doi:10.1016/j.cell.2004.08.020.
Wang Y, Wysocka J, Sayegh J, et al. (2004). "Human PAD4 regulates histone arginine methylation levels via demethylimination.". Science. 306 (5694): 279–83. PMID 15345777. doi:10.1126/science.1101400.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
Nakayama-Hamada M, Suzuki A, Kubota K, et al. (2005). "Comparison of enzymatic properties between hPADI2 and hPADI4.". Biochem. Biophys. Res. Commun. 327 (1): 192–200. PMID 15629448. doi:10.1016/j.bbrc.2004.11.152.
Lee YH, Coonrod SA, Kraus WL, et al. (2005). "Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination.". Proc. Natl. Acad. Sci. U.S.A. 102 (10): 3611–6. PMC 553305 . PMID 15731352. doi:10.1073/pnas.0407159102.
Kearney PL, Bhatia M, Jones NG, et al. (2005). "Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis.". Biochemistry. 44 (31): 10570–82. PMID 16060666. doi:10.1021/bi050292m.
Ikari K, Kuwahara M, Nakamura T, et al. (2005). "Association between PADI4 and rheumatoid arthritis: a replication study.". Arthritis Rheum. 52 (10): 3054–7. PMID 16200584. doi:10.1002/art.21309.
Chang X, Han J (2006). "Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors.". Mol. Carcinog. 45 (3): 183–96. PMID 16355400. doi:10.1002/mc.20169.
Plenge RM, Padyukov L, Remmers EF, et al. (2006). "Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.". Am. J. Hum. Genet. 77 (6): 1044–60. PMC 1285162 . PMID 16380915. doi:10.1086/498651.
Hoppe B, Häupl T, Gruber R, et al. (2006). "Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study.". Arthritis Research & Therapy. 8 (2): R34. PMC 1526594 . PMID 16469113. doi:10.1186/ar1889.

PDB gallery

1wd8: Calcium free form of human peptidylarginine deiminase type4 (PAD4)

1wd9: Calcium bound form of human peptidylarginine deiminase type4 (PAD4)

1wda: Crystal structure of human peptidylarginine deiminase type4 (PAD4) in complex with benzoyl-L-arginine amide

2dew: Crystal structure of human peptidylarginine deiminase 4 in complex with histone H3 N-terminal tail including Arg8

2dex: Crystal structure of human peptidylarginine deiminase 4 in complex with histone H3 N-terminal peptide including Arg17

2dey: Crystal structure of human peptidylarginine deiminase 4 in complex with histone H4 N-terminal tail including Arg3

2dw5: Crystal structure of human peptidylarginine deiminase 4 in complex with N-alpha-benzoyl-N5-(2-fluoro-1-iminoethyl)-L-ornithine amide

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PADI4

Molecular biology

Function

Subcellular and tissue distribution

References

Further reading