PADI6_MOUSE
ID PADI6_MOUSE Reviewed; 682 AA.
AC Q8K3V4; Q75WC6;
DT 04-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Protein-arginine deiminase type-6;
DE EC=3.5.3.15 {ECO:0000305|PubMed:17587491};
DE AltName: Full=Arginine deiminase-like protein;
DE AltName: Full=Egg and embryo abundant PAD {ECO:0000303|PubMed:16137333};
DE Short=ePAD {ECO:0000303|PubMed:16137333};
DE AltName: Full=P75 {ECO:0000303|PubMed:16137333};
DE AltName: Full=Peptidylarginine deiminase VI {ECO:0000303|PubMed:16137333};
DE AltName: Full=Protein-arginine deiminase type VI;
GN Name=Padi6; Synonyms=Pad6 {ECO:0000303|PubMed:17587491}, Padi5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE, PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RC STRAIN=ICR; TISSUE=Ovary;
RX PubMed=12654293; DOI=10.1016/s0012-1606(02)00126-4;
RA Wright P.W., Bolling L.C., Calvert M.E., Sarmento O.F., Berkeley E.V.,
RA Shea M.C., Hao Z., Jayes F.C., Bush L.A., Shetty J., Shore A.N.,
RA Reddi P.P., Tung K.S., Samy E., Allietta M.M., Sherman N.E., Herr J.C.,
RA Coonrod S.A.;
RT "ePAD, an oocyte and early embryo-abundant peptidylarginine deiminase-like
RT protein that localizes to egg cytoplasmic sheets.";
RL Dev. Biol. 256:73-88(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=15087120; DOI=10.1016/j.gene.2003.12.038;
RA Chavanas S., Mechin M.-C., Takahara H., Kawada A., Nachat R., Serre G.,
RA Simon M.;
RT "Comparative analysis of the mouse and human peptidylarginine deiminase
RT gene clusters reveals highly conserved non-coding segments and a new human
RT gene, PADI6.";
RL Gene 330:19-27(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 425-432, SUBCELLULAR LOCATION, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16137333; DOI=10.1186/1477-7827-3-42;
RA Liu M., Oh A., Calarco P., Yamada M., Coonrod S.A., Talbot P.;
RT "Peptidylarginine deiminase (PAD) is a mouse cortical granule protein that
RT plays a role in preimplantation embryonic development.";
RL Reprod. Biol. Endocrinol. 3:42-42(2005).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17587491; DOI=10.1016/j.mce.2007.05.005;
RA Esposito G., Vitale A.M., Leijten F.P., Strik A.M., Koonen-Reemst A.M.,
RA Yurttas P., Robben T.J., Coonrod S., Gossen J.A.;
RT "Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal
RT sheet formation and female fertility.";
RL Mol. Cell. Endocrinol. 273:25-31(2007).
CC -!- FUNCTION: Catalyzes the deimination of arginine residues of proteins
CC (By similarity). In oocytes, is released during cortical reaction and
CC plays a role in preimplantation cleavage and early embryonic
CC development (PubMed:16137333). May be involved in cytoskeletal
CC reorganization in the egg and early embryo (PubMed:17587491).
CC {ECO:0000250, ECO:0000269|PubMed:16137333,
CC ECO:0000269|PubMed:17587491}.
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:0000305|PubMed:17587491};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12654293}. Nucleus
CC {ECO:0000269|PubMed:12654293}. Cytoplasmic vesicle, secretory vesicle,
CC Cortical granule {ECO:0000269|PubMed:16137333}. Note=Predominantly
CC cytoplasmic (oocyte cytoplasmic sheets), also nuclear. Released
CC extracellularly during the cortical reaction, and remains associated
CC with the blastomeres surfaces as a peripheral membrane protein until
CC the blastocyst stage of development (PubMed:16137333).
CC {ECO:0000269|PubMed:16137333}.
CC -!- TISSUE SPECIFICITY: Expressed at very high levels in oocytes. Weakly
CC expressed in testis. Expressed in primordial, primary, secondary and
CC Graafian follicles, and in immature oocytes, mature eggs and blastocyst
CC (at protein level). {ECO:0000269|PubMed:12654293,
CC ECO:0000269|PubMed:16137333}.
CC -!- DEVELOPMENTAL STAGE: Detected in developing oocytes and early embryo.
CC Detected in immature-germinal vesicle-stage oocytes, mature metaphase
CC II arrested eggs and pronuclear zygotes, 2-cell, 4-cell and morula
CC stages. Expression decreases in blastocyst stage.
CC {ECO:0000269|PubMed:12654293, ECO:0000269|PubMed:16137333}.
CC -!- PTM: Phosphorylation at Ser-2, possibly by RSK-type kinases, and Ser-
CC 434 creates binding sites for 14-3-3 proteins.
CC {ECO:0000250|UniProtKB:Q6TGC4}.
CC -!- DISRUPTION PHENOTYPE: Knockout aninmals are viable and present at the
CC expected Mendelian ratio. They do not exhibit any overt abnormalities.
CC Female mice exhibit dispersal of the cytoskeletal sheets in oocytes
CC that lead to a failure of zygotes to progress beyond the 2-cell stage
CC and infertility (PubMed:17587491). Male fertility is not affected
CC (PubMed:17587491). {ECO:0000269|PubMed:17587491}.
CC -!- SIMILARITY: Belongs to the protein arginine deiminase family.
CC {ECO:0000305}.
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DR EMBL; AF529423; AAM94858.1; -; mRNA.
DR EMBL; AB121692; BAD16628.1; -; Genomic_DNA.
DR EMBL; BC053724; AAH53724.1; -; mRNA.
DR CCDS; CCDS38936.1; -.
DR RefSeq; NP_694746.2; NM_153106.2.
DR AlphaFoldDB; Q8K3V4; -.
DR SMR; Q8K3V4; -.
DR STRING; 10090.ENSMUSP00000044044; -.
DR PhosphoSitePlus; Q8K3V4; -.
DR REPRODUCTION-2DPAGE; Q8K3V4; -.
DR MaxQB; Q8K3V4; -.
DR PaxDb; Q8K3V4; -.
DR PRIDE; Q8K3V4; -.
DR ProteomicsDB; 287765; -.
DR Antibodypedia; 73123; 85 antibodies from 13 providers.
DR DNASU; 242726; -.
DR Ensembl; ENSMUST00000038749; ENSMUSP00000044044; ENSMUSG00000040935.
DR GeneID; 242726; -.
DR KEGG; mmu:242726; -.
DR UCSC; uc008vnc.1; mouse.
DR CTD; 353238; -.
DR MGI; MGI:2655198; Padi6.
DR VEuPathDB; HostDB:ENSMUSG00000040935; -.
DR eggNOG; ENOG502QVJA; Eukaryota.
DR GeneTree; ENSGT00940000153217; -.
DR HOGENOM; CLU_021911_0_0_1; -.
DR InParanoid; Q8K3V4; -.
DR OMA; VAPCIFT; -.
DR OrthoDB; 787070at2759; -.
DR PhylomeDB; Q8K3V4; -.
DR TreeFam; TF331952; -.
DR BRENDA; 3.5.3.15; 3474.
DR Reactome; R-MMU-3247509; Chromatin modifying enzymes.
DR BioGRID-ORCS; 242726; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Padi6; mouse.
DR PRO; PR:Q8K3V4; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8K3V4; protein.
DR Bgee; ENSMUSG00000040935; Expressed in primary oocyte and 21 other tissues.
DR ExpressionAtlas; Q8K3V4; baseline and differential.
DR Genevisible; Q8K3V4; MM.
DR GO; GO:0060473; C:cortical granule; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004668; F:protein-arginine deiminase activity; IMP:MGI.
DR GO; GO:0007028; P:cytoplasm organization; IMP:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:MGI.
DR GO; GO:0040016; P:embryonic cleavage; IDA:UniProtKB.
DR GO; GO:0036414; P:histone citrullination; IBA:GO_Central.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0043143; P:regulation of translation by machinery localization; IMP:MGI.
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 1: Evidence at protein level;
KW Calcium; Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing;
KW Hydrolase; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..682
FT /note="Protein-arginine deiminase type-6"
FT /id="PRO_0000220037"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6TGC4"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6TGC4"
FT CONFLICT 63
FT /note="T -> A (in Ref. 3; AAH53724)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="I -> T (in Ref. 3; AAH53724)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="N -> NN (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="T -> I (in Ref. 1; AAM94858)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 76778 MW; 8B9A0371C40BA216 CRC64;
MSFQNSLSLS LVNPTHALCM VGMEITLDIS KCAPDKCKSF TIRGSPRILI HISSSVIAGK
EDTVVWRSMN HPTVALVRMV APSPTVDEDK VLVSYFCPDQ EVPTATAVLF LTGIEISLEA
DIYRDGQLDM PSDKQAKKKW MWGMNGWGAI LLVNCSPNAV GQPDEQSFQE GPREIQNLSQ
MNVTVEGPTS ILQNYQLILH TSEEEAKKTR VYWSQRGSSA YELVVGPNKP VYLLPTFENR
RKEAFYVEAT EFPSPSFSGL ISLSLSLVEK AHDECIPEIP LYKDTVMFRV APYIFMPSTQ
MPLEVYLCRE LQLQGFVDSV TKLSEKSKVQ VVKVYEDPNR QSKWLQDEMA FCYTQAPHKT
VSLILDTPRV SKLEDFPMKY TLTPGSGYLI RQTEDHRVAS LDSIGNLMVS PPVKAQGKDY
PLGRVLIGGS FYPSSEGRDM NKGLREFVYA QQVQAPVELF SDWLMTGHMD QFMCFVPTND
KNNDQKDFRL LLASPSACFE LFEQKQKEGY GNVTLFEDIG AEQLLSNGRE SKTISQILAD
KSFREQNTYV EKCISLNRTL LKTELGLEDK DIILIPQLFC LEQLTNVPSN QQSTKLFARP
YFPDMLQIIV LGKNLGIPKP FGPKINGTCC LEEKVCGLLE PLGLKCTFID DFDCYLANIG
DVCASAIINR VPFAFKWWKM TP
