PADI6_HUMAN
ID PADI6_HUMAN Reviewed; 694 AA.
AC Q6TGC4; Q330K5; Q70SX3;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Protein-arginine deiminase type-6;
DE EC=3.5.3.15;
DE AltName: Full=Peptidyl arginine deiminase-like protein;
DE AltName: Full=Peptidylarginine deiminase VI;
DE Short=hPADVI;
DE AltName: Full=Protein-arginine deiminase type VI;
GN Name=PADI6; Synonyms=PAD6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=15625577;
RA Zhang J., Dai J., Zhao E., Lin Y., Zeng L., Chen J., Zheng H., Wang Y.,
RA Li X., Ying K., Xie Y., Mao Y.;
RT "cDNA cloning, gene organization and expression analysis of human
RT peptidylarginine deiminase type VI.";
RL Acta Biochim. Pol. 51:1051-1058(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Ovary;
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 X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-13 IN COMPLEX WITH SFN, X-RAY
RP CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 441-449 IN COMPLEX WITH SFN, AND
RP PHOSPHORYLATION AT SER-10 AND SER-446.
RX PubMed=22634725; DOI=10.1016/j.jsb.2012.05.010;
RA Rose R., Rose M., Ottmann C.;
RT "Identification and structural characterization of two 14-3-3 binding sites
RT in the human peptidylarginine deiminase type VI.";
RL J. Struct. Biol. 180:65-72(2012).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN PREMBL2,
RP AND VARIANTS PREMBL2 GLN-211 AND ARG-540.
RX PubMed=27545678; DOI=10.1016/j.ajhg.2016.06.024;
RA Xu Y., Shi Y., Fu J., Yu M., Feng R., Sang Q., Liang B., Chen B., Qu R.,
RA Li B., Yan Z., Mao X., Kuang Y., Jin L., He L., Sun X., Wang L.;
RT "Mutations in PADI6 cause female infertility characterized by early
RT embryonic arrest.";
RL Am. J. Hum. Genet. 99:744-752(2016).
CC -!- FUNCTION: Catalyzes the deimination of arginine residues of proteins
CC (By similarity). May be involved in cytoskeletal reorganization in the
CC egg and early embryo (PubMed:27545678). {ECO:0000250,
CC ECO:0000269|PubMed:27545678}.
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 (By similarity). May be involved in cytoskeletal
CC reorganization in the egg and early embryo (PubMed:27545678).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q8K3V4,
CC ECO:0000269|PubMed:27545678}.
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 -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q6TGC4; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10892722, EBI-742054;
CC Q6TGC4; O95198: KLHL2; NbExp=3; IntAct=EBI-10892722, EBI-746999;
CC Q6TGC4; O43463: SUV39H1; NbExp=3; IntAct=EBI-10892722, EBI-349968;
CC Q6TGC4; Q8TF50: ZNF526; NbExp=3; IntAct=EBI-10892722, EBI-11035148;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27545678}. Nucleus
CC {ECO:0000250|UniProtKB:Q8K3V4}. Cytoplasmic vesicle, secretory vesicle,
CC Cortical granule {ECO:0000250|UniProtKB:Q8K3V4}. 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. {ECO:0000250|UniProtKB:Q8K3V4}.
CC -!- TISSUE SPECIFICITY: Highly expressed in oocytes and weakly expressed in
CC other somatic tissues. {ECO:0000269|PubMed:15625577,
CC ECO:0000269|PubMed:27545678}.
CC -!- PTM: Phosphorylation at Ser-10, possibly by RSK-type kinases, and Ser-
CC 446 creates binding sites for 14-3-3 proteins.
CC {ECO:0000269|PubMed:22634725}.
CC -!- DISEASE: Preimplantation embryonic lethality 2 (PREMBL2) [MIM:617234]:
CC A rare cause of female primary infertility. In affected women,
CC ovulation and fertilization proceed normally but embryos are arrested
CC at early stages of development. Inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:27545678}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein arginine deiminase family.
CC {ECO:0000305}.
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DR EMBL; AY443100; AAS07634.1; -; mRNA.
DR EMBL; AY422079; AAR38850.1; -; mRNA.
DR EMBL; AJ549502; CAD70706.1; -; Genomic_DNA.
DR CCDS; CCDS72715.1; -.
DR RefSeq; NP_997304.3; NM_207421.4.
DR PDB; 4DAT; X-ray; 1.40 A; B=441-449.
DR PDB; 4DAU; X-ray; 2.00 A; B=1-13.
DR PDBsum; 4DAT; -.
DR PDBsum; 4DAU; -.
DR AlphaFoldDB; Q6TGC4; -.
DR SMR; Q6TGC4; -.
DR BioGRID; 131667; 15.
DR ELM; Q6TGC4; -.
DR IntAct; Q6TGC4; 5.
DR STRING; 9606.ENSP00000483125; -.
DR BindingDB; Q6TGC4; -.
DR ChEMBL; CHEMBL3638347; -.
DR DrugBank; DB00155; Citrulline.
DR iPTMnet; Q6TGC4; -.
DR PhosphoSitePlus; Q6TGC4; -.
DR BioMuta; PADI6; -.
DR DMDM; 408360253; -.
DR MassIVE; Q6TGC4; -.
DR PeptideAtlas; Q6TGC4; -.
DR PRIDE; Q6TGC4; -.
DR ProteomicsDB; 67394; -.
DR Antibodypedia; 73123; 85 antibodies from 13 providers.
DR DNASU; 353238; -.
DR Ensembl; ENST00000619609.1; ENSP00000483125.1; ENSG00000276747.1.
DR Ensembl; ENST00000625380.1; ENSP00000485805.1; ENSG00000280949.1.
DR GeneID; 353238; -.
DR KEGG; hsa:353238; -.
DR MANE-Select; ENST00000619609.1; ENSP00000483125.1; NM_207421.4; NP_997304.3.
DR UCSC; uc031trf.2; human.
DR CTD; 353238; -.
DR DisGeNET; 353238; -.
DR GeneCards; PADI6; -.
DR HGNC; HGNC:20449; PADI6.
DR HPA; ENSG00000276747; Not detected.
DR MalaCards; PADI6; -.
DR MIM; 610363; gene.
DR MIM; 617234; phenotype.
DR neXtProt; NX_Q6TGC4; -.
DR OpenTargets; ENSG00000276747; -.
DR PharmGKB; PA134975206; -.
DR VEuPathDB; HostDB:ENSG00000276747; -.
DR eggNOG; ENOG502QVJA; Eukaryota.
DR GeneTree; ENSGT00940000153217; -.
DR HOGENOM; CLU_021911_0_0_1; -.
DR InParanoid; Q6TGC4; -.
DR OMA; VAPCIFT; -.
DR OrthoDB; 787070at2759; -.
DR PhylomeDB; Q6TGC4; -.
DR BioCyc; MetaCyc:G66-31585-MON; -.
DR BRENDA; 3.5.3.15; 2681.
DR PathwayCommons; Q6TGC4; -.
DR Reactome; R-HSA-3247509; Chromatin modifying enzymes.
DR SignaLink; Q6TGC4; -.
DR BioGRID-ORCS; 353238; 7 hits in 207 CRISPR screens.
DR ChiTaRS; PADI6; human.
DR GenomeRNAi; 353238; -.
DR Pharos; Q6TGC4; Tbio.
DR PRO; PR:Q6TGC4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6TGC4; protein.
DR Bgee; ENSG00000276747; Expressed in granulocyte and 4 other tissues.
DR GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0007028; P:cytoplasm organization; IEA:Ensembl.
DR GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0040016; P:embryonic cleavage; ISS:UniProtKB.
DR GO; GO:0036414; P:histone citrullination; IBA:GO_Central.
DR GO; GO:0043143; P:regulation of translation by machinery localization; IEA:Ensembl.
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 3D-structure; Calcium; Cytoplasm; Cytoplasmic vesicle; Disease variant;
KW Hydrolase; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..694
FT /note="Protein-arginine deiminase type-6"
FT /id="PRO_0000220036"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22634725"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22634725"
FT VARIANT 211
FT /note="H -> Q (in PREMBL2; dbSNP:rs775156958)"
FT /evidence="ECO:0000269|PubMed:27545678"
FT /id="VAR_078106"
FT VARIANT 540
FT /note="G -> R (in PREMBL2; dbSNP:rs1057517684)"
FT /evidence="ECO:0000269|PubMed:27545678"
FT /id="VAR_078107"
FT CONFLICT 487
FT /note="F -> S (in Ref. 1; AAS07634)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="K -> N (in Ref. 1; AAS07634)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="M -> I (in Ref. 2; AAR38850)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="A -> T (in Ref. 2; AAR38850)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 694 AA; 77727 MW; 5D56D6AFF5CE36AD CRC64;
MVSVEGRAMS FQSIIHLSLD SPVHAVCVLG TEICLDLSGC APQKCQCFTI HGSGRVLIDV
ANTVISEKED ATIWWPLSDP TYATVKMTSP SPSVDADKVS VTYYGPNEDA PVGTAVLYLT
GIEVSLEVDI YRNGQVEMSS DKQAKKKWIW GPSGWGAILL VNCNPADVGQ QLEDKKTKKV
IFSEEITNLS QMTLNVQGPS CILKKYRLVL HTSKEESKKA RVYWPQKDNS STFELVLGPD
QHAYTLALLG NHLKETFYVE AIAFPSAEFS GLISYSVSLV EESQDPSIPE TVLYKDTVVF
RVAPCVFIPC TQVPLEVYLC RELQLQGFVD TVTKLSEKSN SQVASVYEDP NRLGRWLQDE
MAFCYTQAPH KTTSLILDTP QAADLDEFPM KYSLSPGIGY MIQDTEDHKV ASMDSIGNLM
VSPPVKVQGK EYPLGRVLIG SSFYPSAEGR AMSKTLRDFL YAQQVQAPVE LYSDWLMTGH
VDEFMCFIPT DDKNEGKKGF LLLLASPSAC YKLFREKQKE GYGDALLFDE LRADQLLSNG
REAKTIDQLL ADESLKKQNE YVEKCIHLNR DILKTELGLV EQDIIEIPQL FCLEKLTNIP
SDQQPKRSFA RPYFPDLLRM IVMGKNLGIP KPFGPQIKGT CCLEEKICCL LEPLGFKCTF
INDFDCYLTE VGDICACANI RRVPFAFKWW KMVP
