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Identification
HMDB Protein ID HMDBP00673
Secondary Accession Numbers
  • 5946
Name Protein-arginine deiminase type-4
Synonyms
  1. HL-60 PAD
  2. Peptidylarginine deiminase IV
  3. Protein-arginine deiminase type IV
Gene Name PADI4
Protein Type Unknown
Biological Properties
General Function Involved in protein-arginine deiminase activity
Specific 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.
Pathways Not Available
Reactions
Protein L-arginine + Water → protein L-citrulline + Ammonia details
GO Classification
Biological Process
cellular protein modification process
chromatin modification
peptidyl-citrulline biosynthetic process from peptidyl-arginine
regulation of transcription, DNA-dependent
transcription, DNA-dependent
Cellular Component
cytoplasm
nucleus
Component
cell part
intracellular part
cytoplasm
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
protein-arginine deiminase activity
calcium ion binding
Molecular Function
protein-arginine deiminase activity
calcium ion binding
Process
metabolic process
macromolecule metabolic process
peptidyl-arginine modification
peptidyl-citrulline biosynthetic process from peptidyl-arginine
macromolecule modification
protein modification process
peptidyl-amino acid modification
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Cytoplasmic granule
Gene Properties
Chromosome Location 1
Locus 1p36.13
SNPs PADI4
Gene Sequence
>1992 bp
ATGGCCCAGGGGACATTGATCCGTGTGACCCCAGAGCAGCCCACCCATGCCGTGTGTGTG
CTGGGCACCTTGACTCAGCTTGACATCTGCAGCTCTGCCCCTGAGGACTGCACGTCCTTC
AGCATCAACGCCTCCCCAGGGGTGGTCGTGGATATTGCCCACAGCCCTCCAGCCAAGAAG
AAATCCACAGGTTCCTCCACATGGCCCCTGGACCCTGGGGTAGAGGTGACCCTGACGATG
AAAGCGGCCAGTGGTAGCACAGGCGACCAGAAGGTTCAGATTTCATACTACGGACCCAAG
ACTCCACCAGTCAAAGCTCTACTCTACCTCACCGCGGTGGAAATCTCCCTGTGCGCAGAC
ATCACCCGCACCGGCAAAGTGAAGCCAACCAGAGCTGTGAAAGATCAGAGGACCTGGACC
TGGGGCCCTTGTGGACAGGGTGCCATCCTGCTGGTGAACTGTGACAGAGACAATCTCGAA
TCTTCTGCCATGGACTGCGAGGATGATGAAGTGCTTGACAGCGAAGACCTGCAGGACATG
TCGCTGATGACCCTGAGCACGAAGACCCCCAAGGACTTCTTCACAAACCATACACTGGTG
CTCCACGTGGCCAGGTCTGAGATGGACAAAGTGAGGGTGTTTCAGGCCACACGGGGCAAA
CTGTCCTCCAAGTGCAGCGTAGTCTTGGGTCCCAAGTGGCCCTCTCACTACCTGATGGTC
CCCGGTGGAAAGCACAACATGGACTTCTACGTGGAGGCCCTCGCTTTCCCGGACACCGAC
TTCCCGGGGCTCATTACCCTCACCATCTCCCTGCTGGACACGTCCAACCTGGAGCTCCCC
GAGGCTGTGGTGTTCCAAGACAGCGTGGTCTTCCGCGTGGCGCCCTGGATCATGACCCCC
AACACCCAGCCCCCGCAGGAGGTGTACGCGTGCAGTATTTTTGAAAATGAGGACTTCCTG
AAGTCAGTGACTACTCTGGCCATGAAAGCCAAGTGCAAGCTGACCATCTGCCCTGAGGAG
GAGAACATGGATGACCAGTGGATGCAGGATGAAATGGAGATCGGCTACATCCAAGCCCCA
CACAAAACGCTGCCCGTGGTCTTCGACTCTCCAAGGAACAGAGGCCTGAAGGAGTTTCCC
ATCAAACGAGTGATGGGTCCAGATTTTGGCTATGTAACTCGAGGGCCCCAAACAGGGGGT
ATCAGTGGACTGGACTCCTTTGGGAACCTGGAAGTGAGCCCCCCAGTCACAGTCAGGGGC
AAGGAATACCCGCTGGGCAGGATTCTCTTCGGGGACAGCTGTTATCCCAGCAATGACAGC
CGGCAGATGCACCAGGCCCTGCAGGACTTCCTCAGTGCCCAGCAGGTGCAGGCCCCTGTG
AAGCTCTATTCTGACTGGCTGTCCGTGGGCCACGTGGACGAGTTCCTGAGCTTTGTGCCA
GCACCCGACAGGAAGGGCTTCCGGCTGCTCCTGGCCAGCCCCAGGTCCTGCTACAAACTG
TTCCAGGAGCAGCAGAATGAGGGCCACGGGGAGGCCCTGCTGTTCGAAGGGATCAAGAAA
AAAAAACAGCAGAAAATAAAGAACATTCTGTCAAACAAGACATTGAGAGAACATAATTCA
TTTGTGGAGAGATGCATCGACTGGAACCGCGAGCTGCTGAAGCGGGAGCTGGGCCTGGCC
GAGAGTGACATCATTGACATCCCGCAGCTCTTCAAGCTCAAAGAGTTCTCTAAGGCGGAA
GCTTTTTTCCCCAACATGGTGAACATGCTGGTGCTAGGGAAGCACCTGGGCATCCCCAAG
CCCTTCGGGCCCGTCATCAACGGCCGCTGCTGCCTGGAGGAGAAGGTGTGTTCCCTGCTG
GAGCCACTGGGCCTCCAGTGCACCTTCATCAACGACTTCTTCACCTACCACATCAGGCAT
GGGGAGGTGCACTGCGGCACCAACGTGCGCAGAAAGCCCTTCTCCTTCAAGTGGTGGAAC
ATGGTGCCCTGA
Protein Properties
Number of Residues 663
Molecular Weight 74078.65
Theoretical pI 6.584
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Protein-arginine deiminase type-4
MAQGTLIRVTPEQPTHAVCVLGTLTQLDICSSAPEDCTSFSINASPGVVVDIAHGPPAKK
KSTGSSTWPLDPGVEVTLTMKVASGSTGDQKVQISYYGPKTPPVKALLYLTGVEISLCAD
ITRTGKVKPTRAVKDQRTWTWGPCGQGAILLVNCDRDNLESSAMDCEDDEVLDSEDLQDM
SLMTLSTKTPKDFFTNHTLVLHVARSEMDKVRVFQATRGKLSSKCSVVLGPKWPSHYLMV
PGGKHNMDFYVEALAFPDTDFPGLITLTISLLDTSNLELPEAVVFQDSVVFRVAPWIMTP
NTQPPQEVYACSIFENEDFLKSVTTLAMKAKCKLTICPEEENMDDQWMQDEMEIGYIQAP
HKTLPVVFDSPRNRGLKEFPIKRVMGPDFGYVTRGPQTGGISGLDSFGNLEVSPPVTVRG
KEYPLGRILFGDSCYPSNDSRQMHQALQDFLSAQQVQAPVKLYSDWLSVGHVDEFLSFVP
APDRKGFRLLLASPRSCYKLFQEQQNEGHGEALLFEGIKKKKQQKIKNILSNKTLREHNS
FVERCIDWNRELLKRELGLAESDIIDIPQLFKLKEFSKAEAFFPNMVNMLVLGKHLGIPK
PFGPVINGRCCLEEKVCSLLEPLGLQCTFINDFFTYHIRHGEVHCGTNVRRKPFSFKWWN
MVP
GenBank ID Protein 5913971
UniProtKB/Swiss-Prot ID Q9UM07
UniProtKB/Swiss-Prot Entry Name PADI4_HUMAN
PDB IDs
GenBank Gene ID AB017919
GeneCard ID PADI4
GenAtlas ID PADI4
HGNC ID HGNC:18368
References
General References
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  3. Lee YH, Coonrod SA, Kraus WL, Jelinek MA, Stallcup MR: Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3611-6. Epub 2005 Feb 24. [PubMed:15731352 ]
  4. Chavanas S, Mechin MC, Takahara H, Kawada A, Nachat R, Serre G, Simon M: Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene. 2004 Apr 14;330:19-27. [PubMed:15087120 ]
  5. Nakashima K, Hagiwara T, Ishigami A, Nagata S, Asaga H, Kuramoto M, Senshu T, Yamada M: Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3). J Biol Chem. 1999 Sep 24;274(39):27786-92. [PubMed:10488123 ]
  6. Asaga H, Nakashima K, Senshu T, Ishigami A, Yamada M: Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils. J Leukoc Biol. 2001 Jul;70(1):46-51. [PubMed:11435484 ]
  7. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003 Aug;34(4):395-402. [PubMed:12833157 ]
  8. Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T: Histone deimination antagonizes arginine methylation. Cell. 2004 Sep 3;118(5):545-53. [PubMed:15339660 ]
  9. Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA: Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2. [PubMed:15345777 ]
  10. Nakayama-Hamada M, Suzuki A, Kubota K, Takazawa T, Ohsaka M, Kawaida R, Ono M, Kasuya A, Furukawa H, Yamada R, Yamamoto K: Comparison of enzymatic properties between hPADI2 and hPADI4. Biochem Biophys Res Commun. 2005 Feb 4;327(1):192-200. [PubMed:15629448 ]
  11. Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M: Structural basis for Ca(2+)-induced activation of human PAD4. Nat Struct Mol Biol. 2004 Aug;11(8):777-83. Epub 2004 Jul 11. [PubMed:15247907 ]
  12. Hoppe B, Heymann GA, Tolou F, Kiesewetter H, Doerner T, Salama A: 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 (Berl). 2004 Nov;82(11):762-7. Epub 2004 Aug 25. [PubMed:15338034 ]