PADI4_RAT
ID PADI4_RAT Reviewed; 666 AA.
AC O88807; O35117;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Protein-arginine deiminase type-4;
DE EC=3.5.3.15 {ECO:0000250|UniProtKB:Q9UM07};
DE AltName: Full=PAD-R4;
DE AltName: Full=Peptidylarginine deiminase IV;
DE AltName: Full=Peptidylarginine deiminase type alpha;
DE AltName: Full=Protein-arginine deiminase type IV;
GN Name=Padi4; Synonyms=Pad4, Pdi4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9738944; DOI=10.1016/s0014-5793(98)00893-x;
RA Ishigami A., Kuramoto M., Yamada M., Watanabe K., Senshu T.;
RT "Molecular cloning of two novel types of peptidylarginine deiminase cDNAs
RT from retinoic acid-treated culture of a newborn rat keratinocyte cell
RT line.";
RL FEBS Lett. 433:113-118(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Epidermis;
RX PubMed=9675292; DOI=10.1016/s0167-4838(98)00084-3;
RA Yamakoshi A., Ono H., Nishijyo T., Shiraiwa M., Takahara H.;
RT "Cloning of cDNA encoding a novel isoform (type IV) of peptidylarginine
RT deiminase from rat epidermis.";
RL Biochim. Biophys. Acta 1386:227-232(1998).
CC -!- FUNCTION: Catalyzes the citrullination/deimination of arginine residues
CC of proteins such as histones, thereby playing a key role in histone
CC code and regulation of stem cell maintenance. Citrullinates histone H1
CC at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17'
CC and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci,
CC respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key
CC regulator of stem cell maintenance by mediating citrullination of
CC histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results
CC in H1 displacement from chromatin and global chromatin decondensation,
CC thereby promoting pluripotency and stem cell maintenance. Promotes
CC profound chromatin decondensation during the innate immune response to
CC infection in neutrophils by mediating formation of H1R54ci (By
CC similarity). Required for the formation of neutrophil extracellular
CC traps (NETs); NETs are mainly composed of DNA fibers and are released
CC by neutrophils to bind pathogens during inflammation (By similarity).
CC Citrullination of histone H3 prevents their methylation by CARM1 and
CC HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at
CC 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9UM07,
CC ECO:0000250|UniProtKB:Q9Z183}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-arginyl-[protein] = L-citrullyl-[protein] + NH4(+);
CC Xref=Rhea:RHEA:18089, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:10588,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29965,
CC ChEBI:CHEBI:83397; EC=3.5.3.15;
CC Evidence={ECO:0000250|UniProtKB:Q9UM07};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q9UM07};
CC Note=Binds 5 Ca(2+) ions per subunit. {ECO:0000250|UniProtKB:Q9UM07};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UM07}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UM07}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q9UM07}. Note=Cytoplasmic granules of
CC eosinophils and neutrophils. {ECO:0000250|UniProtKB:Q9UM07}.
CC -!- TISSUE SPECIFICITY: Epidermis. {ECO:0000269|PubMed:9675292}.
CC -!- PTM: Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.
CC {ECO:0000250|UniProtKB:Q9UM07}.
CC -!- SIMILARITY: Belongs to the protein arginine deiminase family.
CC {ECO:0000305}.
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DR EMBL; AB010999; BAA32100.1; -; mRNA.
DR EMBL; AB008803; BAA23523.1; -; mRNA.
DR RefSeq; NP_058923.1; NM_017227.1.
DR AlphaFoldDB; O88807; -.
DR SMR; O88807; -.
DR STRING; 10116.ENSRNOP00000009081; -.
DR PhosphoSitePlus; O88807; -.
DR PaxDb; O88807; -.
DR PRIDE; O88807; -.
DR Ensembl; ENSRNOT00000009081; ENSRNOP00000009081; ENSRNOG00000006855.
DR GeneID; 29512; -.
DR KEGG; rno:29512; -.
DR UCSC; RGD:3290; rat.
DR CTD; 23569; -.
DR RGD; 3290; Padi4.
DR eggNOG; ENOG502QVJA; Eukaryota.
DR GeneTree; ENSGT00940000153217; -.
DR HOGENOM; CLU_021911_0_0_1; -.
DR InParanoid; O88807; -.
DR OMA; RVFQATR; -.
DR OrthoDB; 787070at2759; -.
DR PhylomeDB; O88807; -.
DR TreeFam; TF331952; -.
DR BRENDA; 3.5.3.15; 5301.
DR Reactome; R-RNO-3247509; Chromatin modifying enzymes.
DR PRO; PR:O88807; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000006855; Expressed in pancreas and 13 other tissues.
DR Genevisible; O88807; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0034618; F:arginine binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004668; F:protein-arginine deiminase activity; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0036414; P:histone citrullination; ISS:UniProtKB.
DR GO; GO:0036413; P:histone H3-R26 citrullination; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006334; P:nucleosome assembly; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IEA:Ensembl.
DR GO; GO:0018101; P:protein citrullination; ISO:RGD.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR Gene3D; 2.60.40.1700; -; 1.
DR Gene3D; 2.60.40.1860; -; 1.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR004303; PAD.
DR InterPro; IPR013530; PAD_C.
DR InterPro; IPR036556; PAD_central_sf.
DR InterPro; IPR013732; PAD_N.
DR InterPro; IPR038685; PAD_N_sf.
DR InterPro; IPR013733; Prot_Arg_deaminase_cen_dom.
DR PANTHER; PTHR10837; PTHR10837; 1.
DR Pfam; PF03068; PAD; 1.
DR Pfam; PF08527; PAD_M; 1.
DR Pfam; PF08526; PAD_N; 1.
DR PIRSF; PIRSF001247; Protein-arginine_deiminase; 1.
DR SUPFAM; SSF110083; SSF110083; 1.
DR SUPFAM; SSF49503; SSF49503; 1.
PE 2: Evidence at transcript level;
KW Calcium; Chromatin regulator; Citrullination; Cytoplasm; Hydrolase;
KW Immunity; Innate immunity; Metal-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..666
FT /note="Protein-arginine deiminase type-4"
FT /id="PRO_0000220035"
FT ACT_SITE 350
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT ACT_SITE 471
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT ACT_SITE 473
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT ACT_SITE 648
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 349
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 351
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 353
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 369
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 370
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 374
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 407
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT MOD_RES 212
FT /note="Citrulline"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT MOD_RES 218
FT /note="Citrulline"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT MOD_RES 372
FT /note="Citrulline"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT MOD_RES 374
FT /note="Citrulline"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT MOD_RES 383
FT /note="Citrulline"
FT /evidence="ECO:0000250|UniProtKB:Q9UM07"
FT CONFLICT 655
FT /note="K -> E (in Ref. 2; BAA23523)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 666 AA; 74467 MW; 70F23BB3B04C813B CRC64;
MAQGAVIHVA PEEPTHAVCV VGTATPLDIR GSAPRGSTSF SITASPEVVV DVIHGPPSKK
STTGASKWPL DPKLEVTLQM KAASSRIDDQ KVRISYYGPK TSSTQALLYL TGVELSLSAD
VTRTGKAKPA PAGKDQSTWT WGPDGHGAIL LVNCDKEDPK SSGMDFEDDK VLDNKDLQDM
SPMTLSTKTP KDFFDKYQLV LQVPKAKMNK VRVFRATRGK LPSRYKVVLG PQQFSHRLEL
LGGQHSTDFY VEGLAFPDAD FKGLIPLTIS LLDKSNPELP EALVFQDTVM FRVAPWIMTP
NTQPPQEVYV CRFSDNEDFL KSLATFTKKA KCKLTVCPEE ENQDDQWMQD EMEIGYIQAP
HKTLPVVFDS PRDRGLKDFP VKRVMGPNFG YVTRGLYRAE VTGLDAFGNL EVSPPVTVRG
KEYPLGRILI GSSGYSSSES RDMHQILQDF LGAQQVQAPV RLFSDWLFVG HVDEFLSFVP
ARGKQGFRLL LSSPRACYQM FQELQTEGHG EASLFEGLKR KRQTISDILS SQKLRDQNAY
VESCIDWNRE VLKRELGLTE GDIIDIPQLF RIVGNSRGNP KAEAFFPNMV NMLVLGKHLG
IPKPFGPIIN GRCCLEEKVC SLLEPLGLHC TFINDFYSYH MYHGEVHCGT NVRRKPFAFK
WWHMVP
