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Q9Z183 (PADI4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein-arginine deiminase type-4

EC=3.5.3.15
Alternative name(s):
Peptidylarginine deiminase IV
Protein-arginine deiminase type IV
Gene names
Name:Padi4
Synonyms:Pdi4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length666 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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. Ref.4 Ref.5 Ref.6 Ref.7

Catalytic activity

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

Cofactor

Binds 5 calcium ions per subunit By similarity.

Enzyme regulation

Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family. Ref.7

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Expressed in pluripotent embryonic stem and induced pluripotent stem cells but not multipotent neural stem cells. Ref.7

Post-translational modification

Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme By similarity.

Disruption phenotype

Mice survive to adulthood and do not display detectable physical abnormality. However, mice were born at a rate lower than predicted by the Mendelian ratio and display defects in innate immune response. Mice are more susceptible to bacterial infection: neutrophils cannot form neutrophil extracellular traps (NETs) after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. Less than 10% of deficient mice produce a thrombus 48 hours after inferior vena cava stenosis whereas 90% of wild-type mice do. Ref.5 Ref.6

Sequence similarities

Belongs to the protein arginine deiminase family.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandCalcium
Metal-binding
   Molecular functionChromatin regulator
Hydrolase
   PTMCitrullination
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin modification

Inferred from mutant phenotype Ref.7. Source: UniProtKB

chromatin remodeling

Inferred from mutant phenotype Ref.7. Source: UniProtKB

histone H3-R26 citrullination

Inferred from sequence or structural similarity. Source: UniProtKB

histone citrullination

Inferred from direct assay Ref.7. Source: UniProtKB

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

nucleosome assembly

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

stem cell maintenance

Inferred from mutant phenotype Ref.7. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionarginine deiminase activity

Inferred from electronic annotation. Source: Ensembl

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein-arginine deiminase activity

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 666666Protein-arginine deiminase type-4
PRO_0000220034

Sites

Active site3501 By similarity
Active site4711 By similarity
Active site4731 By similarity
Active site6481 By similarity
Metal binding1531Calcium 1 By similarity
Metal binding1551Calcium 1 By similarity
Metal binding1551Calcium 2 By similarity
Metal binding1651Calcium 1 By similarity
Metal binding1651Calcium 3; via carbonyl oxygen By similarity
Metal binding1681Calcium 3 By similarity
Metal binding1761Calcium 1 By similarity
Metal binding1791Calcium 1 By similarity
Metal binding1791Calcium 2 By similarity
Metal binding3491Calcium 4 By similarity
Metal binding3511Calcium 5 By similarity
Metal binding3531Calcium 4 By similarity
Metal binding3691Calcium 5 By similarity
Metal binding3701Calcium 5; via carbonyl oxygen By similarity
Metal binding4071Calcium 4; via carbonyl oxygen By similarity
Metal binding4101Calcium 4; via carbonyl oxygen By similarity
Metal binding4111Calcium 4 By similarity
Binding site3741Substrate By similarity

Amino acid modifications

Modified residue2121Citrulline By similarity
Modified residue2181Citrulline By similarity
Modified residue3721Citrulline By similarity
Modified residue3741Citrulline By similarity
Modified residue3831Citrulline By similarity

Experimental info

Sequence conflict411G → S in BAA34246. Ref.1
Sequence conflict901E → Q in BAA34246. Ref.1
Sequence conflict991P → L in BAD16627. Ref.2
Sequence conflict1311Q → P in BAA34246. Ref.1
Sequence conflict2101R → K in BAA34246. Ref.1
Sequence conflict2221P → L in BAA34246. Ref.1
Sequence conflict4811A → V in BAA34246. Ref.1
Sequence conflict5731A → V in BAA34246. Ref.1
Sequence conflict6121H → R in BAA34246. Ref.1
Sequence conflict655 – 6562KP → T in BAD16627. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Z183 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: F25B7A7B69285C32

FASTA66674,415
        10         20         30         40         50         60 
MAQGAVIHVA PEQPTHAVCV VGTATPLDVR GSAPKGYTTF GITASPGVIV DVIHGPPVKK 

        70         80         90        100        110        120 
STMGASKWPL DPELEVTLQV KAASSRTDDE KVRVSYYGPK TSPVQALIYI TGVELSLSAD 

       130        140        150        160        170        180 
VTRTGRVKPA QAGKDQSTWT WGPGGRGAIL LVNCDKEDPQ ASGMDFEDDK ILDNKDLQDM 

       190        200        210        220        230        240 
SPMTLSTKTP KDFFEKYQLV LEVPKAKMNR VRVFRATRGK LPSRYKVALG PQQFSYCLEL 

       250        260        270        280        290        300 
PGGQHSTDFY VEGLAFPDAD FKGLIPLTIS LLDKSNPELP EALVFQDSVT FRVAPWIMTP 

       310        320        330        340        350        360 
NTQPPQEVYV CRVSDNEDFL KSLATLTKKA KCKLTVCPEE ENIDDQWMQD EMEIGYIQAP 

       370        380        390        400        410        420 
HKTLPVVFDS PRDRGLKDFP VKRVMGPNFG YVTRKLYMSE LTGLDAFGNL EVSPPVTVRG 

       430        440        450        460        470        480 
KEYPLGRILI GNSGYSSSES RDMHQALQDF LSAQQVQAPV RLFSDWLFVG HVDEFLSFVP 

       490        500        510        520        530        540 
ARDKQGFRLL LSSPRACYQL FQELQSQGHG EATLFEGLKR KRQTINEILS NKKLRDQNAY 

       550        560        570        580        590        600 
VESCIDWNRA VLKRELGLAE GDIIDIPQLF KLAGNSRGNS KAQAFFPNMV NMLVLGKYLG 

       610        620        630        640        650        660 
IPKPFGPIID GHCCLEEEVR SHLEPLGLHC TFINDFYTYH VYNGEVHCGT NVRRKPFTFK 


WWHMVP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNAs of mouse peptidylarginine deiminase type I, type III and type IV, and the expression pattern of type I in mouse."
Rusd A.A., Ikejiri Y., Ono H., Yonekawa T., Shiraiwa M., Kawada A., Takahara H.
Eur. J. Biochem. 259:660-669(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Epidermis.
[2]"Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6."
Chavanas S., Mechin M.-C., Takahara H., Kawada A., Nachat R., Serre G., Simon M.
Gene 330:19-27(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/SvJ.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"Histone deimination antagonizes arginine methylation."
Cuthbert G.L., Daujat S., Snowden A.W., Erdjument-Bromage H., Hagiwara T., Yamada M., Schneider R., Gregory P.D., Tempst P., Bannister A.J., Kouzarides T.
Cell 118:545-553(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps."
Li P., Li M., Lindberg M.R., Kennett M.J., Xiong N., Wang Y.
J. Exp. Med. 207:1853-1862(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice."
Martinod K., Demers M., Fuchs T.A., Wong S.L., Brill A., Gallant M., Hu J., Wang Y., Wagner D.D.
Proc. Natl. Acad. Sci. U.S.A. 110:8674-8679(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"Citrullination regulates pluripotency and histone H1 binding to chromatin."
Christophorou M.A., Castelo-Branco G., Halley-Stott R.P., Oliveira C.S., Loos R., Radzisheuskaya A., Mowen K.A., Bertone P., Silva J.C., Zernicka-Goetz M., Nielsen M.L., Gurdon J.B., Kouzarides T.
Nature 507:104-108(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB013850 mRNA. Translation: BAA34246.1.
AB121692 Genomic DNA. Translation: BAD16627.1.
AL807805 Genomic DNA. Translation: CAM25732.1.
CCDSCCDS18854.1.
RefSeqNP_035191.2. NM_011061.2.
UniGeneMm.250358.

3D structure databases

ProteinModelPortalQ9Z183.
SMRQ9Z183. Positions 2-666.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000026381.

PTM databases

PhosphoSiteQ9Z183.

Proteomic databases

MaxQBQ9Z183.
PRIDEQ9Z183.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026381; ENSMUSP00000026381; ENSMUSG00000025330.
GeneID18602.
KEGGmmu:18602.
UCSCuc008vne.2. mouse.

Organism-specific databases

CTD23569.
MGIMGI:1338898. Padi4.

Phylogenomic databases

eggNOGNOG42085.
GeneTreeENSGT00390000008680.
HOGENOMHOG000220908.
HOVERGENHBG053016.
InParanoidA2AMU3.
KOK01481.
OMAVLGPQQP.
OrthoDBEOG7P5T09.
TreeFamTF331952.

Gene expression databases

BgeeQ9Z183.
CleanExMM_PADI4.
GenevestigatorQ9Z183.

Family and domain databases

InterProIPR008972. Cupredoxin.
IPR004303. PAD.
IPR013530. PAD_C.
IPR013732. PAD_N.
IPR013733. Prot_Arg_deaminase_cen_dom.
IPR016296. Protein-arginine_deiminase_sub.
[Graphical view]
PANTHERPTHR10837. PTHR10837. 1 hit.
PfamPF03068. PAD. 1 hit.
PF08527. PAD_M. 1 hit.
PF08526. PAD_N. 1 hit.
[Graphical view]
PIRSFPIRSF001247. Protein-arginine_deiminase. 1 hit.
SUPFAMSSF110083. SSF110083. 1 hit.
SSF49503. SSF49503. 1 hit.
ProtoNetSearch...

Other

NextBio294510.
PROQ9Z183.
SOURCESearch...

Entry information

Entry namePADI4_MOUSE
AccessionPrimary (citable) accession number: Q9Z183
Secondary accession number(s): A2AMU3, Q75WC7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 105 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot