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Q9Z183

- PADI4_MOUSE

UniProt

Q9Z183 - PADI4_MOUSE

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Protein

Protein-arginine deiminase type-4

Gene

Padi4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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/GRIP1.4 Publications

Catalytic activityi

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

Cofactori

Binds 5 calcium ions per subunit.By similarity

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi153 – 1531Calcium 1By similarity
Metal bindingi155 – 1551Calcium 1By similarity
Metal bindingi155 – 1551Calcium 2By similarity
Metal bindingi165 – 1651Calcium 1By similarity
Metal bindingi165 – 1651Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi168 – 1681Calcium 3By similarity
Metal bindingi176 – 1761Calcium 1By similarity
Metal bindingi179 – 1791Calcium 1By similarity
Metal bindingi179 – 1791Calcium 2By similarity
Metal bindingi349 – 3491Calcium 4By similarity
Active sitei350 – 3501By similarity
Metal bindingi351 – 3511Calcium 5By similarity
Metal bindingi353 – 3531Calcium 4By similarity
Metal bindingi369 – 3691Calcium 5By similarity
Metal bindingi370 – 3701Calcium 5; via carbonyl oxygenBy similarity
Binding sitei374 – 3741SubstrateBy similarity
Metal bindingi407 – 4071Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi410 – 4101Calcium 4; via carbonyl oxygenBy similarity
Metal bindingi411 – 4111Calcium 4By similarity
Active sitei471 – 4711By similarity
Active sitei473 – 4731By similarity
Active sitei648 – 6481By similarity

GO - Molecular functioni

  1. arginine deiminase activity Source: Ensembl
  2. calcium ion binding Source: UniProtKB
  3. protein-arginine deiminase activity Source: UniProtKB

GO - Biological processi

  1. chromatin modification Source: UniProtKB
  2. chromatin remodeling Source: UniProtKB
  3. histone citrullination Source: UniProtKB
  4. histone H3-R26 citrullination Source: UniProtKB
  5. innate immune response Source: UniProtKB-KW
  6. nucleosome assembly Source: UniProtKB
  7. regulation of transcription, DNA-templated Source: UniProtKB-KW
  8. stem cell maintenance Source: UniProtKB
  9. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase

Keywords - Biological processi

Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein-arginine deiminase type-4 (EC:3.5.3.15)
Alternative name(s):
Peptidylarginine deiminase IV
Protein-arginine deiminase type IV
Gene namesi
Name:Padi4
Synonyms:Pdi4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:1338898. Padi4.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 666666Protein-arginine deiminase type-4PRO_0000220034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei212 – 2121CitrullineBy similarity
Modified residuei218 – 2181CitrullineBy similarity
Modified residuei372 – 3721CitrullineBy similarity
Modified residuei374 – 3741CitrullineBy similarity
Modified residuei383 – 3831CitrullineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Citrullination

Proteomic databases

MaxQBiQ9Z183.
PRIDEiQ9Z183.

PTM databases

PhosphoSiteiQ9Z183.

Expressioni

Tissue specificityi

Expressed in pluripotent embryonic stem and induced pluripotent stem cells but not multipotent neural stem cells.1 Publication

Gene expression databases

BgeeiQ9Z183.
CleanExiMM_PADI4.
GenevestigatoriQ9Z183.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026381.

Structurei

3D structure databases

ProteinModelPortaliQ9Z183.
SMRiQ9Z183. Positions 2-666.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the protein arginine deiminase family.Curated

Phylogenomic databases

eggNOGiNOG42085.
GeneTreeiENSGT00390000008680.
HOGENOMiHOG000220908.
HOVERGENiHBG053016.
InParanoidiQ9Z183.
KOiK01481.
OMAiVLGPQQP.
OrthoDBiEOG7P5T09.
TreeFamiTF331952.

Family and domain databases

InterProiIPR008972. Cupredoxin.
IPR004303. PAD.
IPR013530. PAD_C.
IPR013732. PAD_N.
IPR013733. Prot_Arg_deaminase_cen_dom.
IPR016296. Protein-arginine_deiminase_sub.
[Graphical view]
PANTHERiPTHR10837. PTHR10837. 1 hit.
PfamiPF03068. PAD. 1 hit.
PF08527. PAD_M. 1 hit.
PF08526. PAD_N. 1 hit.
[Graphical view]
PIRSFiPIRSF001247. Protein-arginine_deiminase. 1 hit.
SUPFAMiSSF110083. SSF110083. 1 hit.
SSF49503. SSF49503. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9Z183-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAQGAVIHVA PEQPTHAVCV VGTATPLDVR GSAPKGYTTF GITASPGVIV
60 70 80 90 100
DVIHGPPVKK STMGASKWPL DPELEVTLQV KAASSRTDDE KVRVSYYGPK
110 120 130 140 150
TSPVQALIYI TGVELSLSAD VTRTGRVKPA QAGKDQSTWT WGPGGRGAIL
160 170 180 190 200
LVNCDKEDPQ ASGMDFEDDK ILDNKDLQDM SPMTLSTKTP KDFFEKYQLV
210 220 230 240 250
LEVPKAKMNR VRVFRATRGK LPSRYKVALG PQQFSYCLEL PGGQHSTDFY
260 270 280 290 300
VEGLAFPDAD FKGLIPLTIS LLDKSNPELP EALVFQDSVT FRVAPWIMTP
310 320 330 340 350
NTQPPQEVYV CRVSDNEDFL KSLATLTKKA KCKLTVCPEE ENIDDQWMQD
360 370 380 390 400
EMEIGYIQAP HKTLPVVFDS PRDRGLKDFP VKRVMGPNFG YVTRKLYMSE
410 420 430 440 450
LTGLDAFGNL EVSPPVTVRG KEYPLGRILI GNSGYSSSES RDMHQALQDF
460 470 480 490 500
LSAQQVQAPV RLFSDWLFVG HVDEFLSFVP ARDKQGFRLL LSSPRACYQL
510 520 530 540 550
FQELQSQGHG EATLFEGLKR KRQTINEILS NKKLRDQNAY VESCIDWNRA
560 570 580 590 600
VLKRELGLAE GDIIDIPQLF KLAGNSRGNS KAQAFFPNMV NMLVLGKYLG
610 620 630 640 650
IPKPFGPIID GHCCLEEEVR SHLEPLGLHC TFINDFYTYH VYNGEVHCGT
660
NVRRKPFTFK WWHMVP
Length:666
Mass (Da):74,415
Last modified:July 27, 2011 - v3
Checksum:iF25B7A7B69285C32
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti41 – 411G → S in BAA34246. (PubMed:10092850)Curated
Sequence conflicti90 – 901E → Q in BAA34246. (PubMed:10092850)Curated
Sequence conflicti99 – 991P → L in BAD16627. (PubMed:15087120)Curated
Sequence conflicti131 – 1311Q → P in BAA34246. (PubMed:10092850)Curated
Sequence conflicti210 – 2101R → K in BAA34246. (PubMed:10092850)Curated
Sequence conflicti222 – 2221P → L in BAA34246. (PubMed:10092850)Curated
Sequence conflicti481 – 4811A → V in BAA34246. (PubMed:10092850)Curated
Sequence conflicti573 – 5731A → V in BAA34246. (PubMed:10092850)Curated
Sequence conflicti612 – 6121H → R in BAA34246. (PubMed:10092850)Curated
Sequence conflicti655 – 6562KP → T in BAD16627. (PubMed:15087120)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB013850 mRNA. Translation: BAA34246.1.
AB121692 Genomic DNA. Translation: BAD16627.1.
AL807805 Genomic DNA. Translation: CAM25732.1.
CCDSiCCDS18854.1.
RefSeqiNP_035191.2. NM_011061.2.
UniGeneiMm.250358.

Genome annotation databases

EnsembliENSMUST00000026381; ENSMUSP00000026381; ENSMUSG00000025330.
GeneIDi18602.
KEGGimmu:18602.
UCSCiuc008vne.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB013850 mRNA. Translation: BAA34246.1 .
AB121692 Genomic DNA. Translation: BAD16627.1 .
AL807805 Genomic DNA. Translation: CAM25732.1 .
CCDSi CCDS18854.1.
RefSeqi NP_035191.2. NM_011061.2.
UniGenei Mm.250358.

3D structure databases

ProteinModelPortali Q9Z183.
SMRi Q9Z183. Positions 2-666.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000026381.

PTM databases

PhosphoSitei Q9Z183.

Proteomic databases

MaxQBi Q9Z183.
PRIDEi Q9Z183.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000026381 ; ENSMUSP00000026381 ; ENSMUSG00000025330 .
GeneIDi 18602.
KEGGi mmu:18602.
UCSCi uc008vne.2. mouse.

Organism-specific databases

CTDi 23569.
MGIi MGI:1338898. Padi4.

Phylogenomic databases

eggNOGi NOG42085.
GeneTreei ENSGT00390000008680.
HOGENOMi HOG000220908.
HOVERGENi HBG053016.
InParanoidi Q9Z183.
KOi K01481.
OMAi VLGPQQP.
OrthoDBi EOG7P5T09.
TreeFami TF331952.

Miscellaneous databases

NextBioi 294510.
PROi Q9Z183.
SOURCEi Search...

Gene expression databases

Bgeei Q9Z183.
CleanExi MM_PADI4.
Genevestigatori Q9Z183.

Family and domain databases

InterProi IPR008972. Cupredoxin.
IPR004303. PAD.
IPR013530. PAD_C.
IPR013732. PAD_N.
IPR013733. Prot_Arg_deaminase_cen_dom.
IPR016296. Protein-arginine_deiminase_sub.
[Graphical view ]
PANTHERi PTHR10837. PTHR10837. 1 hit.
Pfami PF03068. PAD. 1 hit.
PF08527. PAD_M. 1 hit.
PF08526. PAD_N. 1 hit.
[Graphical view ]
PIRSFi PIRSF001247. Protein-arginine_deiminase. 1 hit.
SUPFAMi SSF110083. SSF110083. 1 hit.
SSF49503. SSF49503. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. 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. Cited for: FUNCTION, TISSUE SPECIFICITY, ENZYME REGULATION.

Entry informationi

Entry nameiPADI4_MOUSE
AccessioniPrimary (citable) accession number: Q9Z183
Secondary accession number(s): A2AMU3, Q75WC7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3