PDIA3_HUMAN
ID PDIA3_HUMAN Reviewed; 505 AA.
AC P30101; Q13453; Q14255; Q8IYF8; Q9UMU7;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 4.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Protein disulfide-isomerase A3;
DE EC=5.3.4.1 {ECO:0000269|PubMed:27897272, ECO:0000269|PubMed:7487104};
DE AltName: Full=58 kDa glucose-regulated protein;
DE AltName: Full=58 kDa microsomal protein;
DE Short=p58;
DE AltName: Full=Disulfide isomerase ER-60;
DE AltName: Full=Endoplasmic reticulum resident protein 57;
DE Short=ER protein 57;
DE Short=ERp57;
DE AltName: Full=Endoplasmic reticulum resident protein 60;
DE Short=ER protein 60;
DE Short=ERp60;
DE Flags: Precursor;
GN Name=PDIA3; Synonyms=ERP57, ERP60, GRP58;
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].
RX PubMed=7945384; DOI=10.1006/bbrc.1994.2469;
RA Hirano N., Shibasaki F., Katoh H., Sakai R., Tanaka T., Nishida J.,
RA Yazaki Y., Takenawa T., Hirai H.;
RT "Molecular cloning and characterization of a cDNA for bovine phospholipase
RT C-alpha: proposal of redesignation of phospholipase C-alpha.";
RL Biochem. Biophys. Res. Commun. 204:375-382(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-36 AND 130-144, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=7487104; DOI=10.1006/abbi.1995.0060;
RA Bourdi M., Demady D., Martin J.L., Jabbour S.K., Martin B.M., George J.W.,
RA Pohl L.R.;
RT "cDNA cloning and baculovirus expression of the human liver endoplasmic
RT reticulum P58: characterization as a protein disulfide isomerase isoform,
RT but not as a protease or a carnitine acyltransferase.";
RL Arch. Biochem. Biophys. 323:397-403(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8687406; DOI=10.1042/bj3160599;
RA Koivunen P., Helaakoski T., Annunen P., Veijola J., Raeisaenen S.,
RA Pihlajaniemi T., Kivirikko K.I.;
RT "ERp60 does not substitute for protein disulphide isomerase as the beta-
RT subunit of prolyl 4-hydroxylase.";
RL Biochem. J. 316:599-605(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=8624847; DOI=10.1016/1357-2725(95)00120-4;
RA Charnock-Jones D.S., Day K., Smith S.K.;
RT "Cloning, expression and genomic organization of human placental protein
RT disulfide isomerase (previously identified as phospholipase C alpha).";
RL Int. J. Biochem. Cell Biol. 28:81-89(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9205111; DOI=10.1006/geno.1997.4750;
RA Koivunen P., Horelli-Kuitunen N., Helaakoski T., Karvonen P., Jaakkola M.,
RA Palotie A., Kivirikko K.I.;
RT "Structures of the human gene for the protein disulfide isomerase-related
RT polypeptide ERp60 and a processed gene and assignment of these genes to
RT 15q15 and 1q21.";
RL Genomics 42:397-404(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-34 AND 504-505, AND
RP MUTAGENESIS OF CYS-57; CYS-60; CYS-406 AND CYS-409.
RC TISSUE=Liver epithelium;
RX PubMed=9399589; DOI=10.1093/oxfordjournals.jbchem.a021830;
RA Urade R., Oda T., Ito H., Moriyama T., Utsumi S., Kito M.;
RT "Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu
RT (QEDL) motifs of microsomal ER-60 protease.";
RL J. Biochem. 122:834-842(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, Lung, and Lymph;
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 [8]
RP PROTEIN SEQUENCE OF 25-54; 62-75 AND 95-104.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [9]
RP PROTEIN SEQUENCE OF 25-38.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP PROTEIN SEQUENCE OF 25-33.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [11]
RP PROTEIN SEQUENCE OF 26-42.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J.,
RA Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed lineage
RT kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [12]
RP PROTEIN SEQUENCE OF 63-73; 95-104; 108-129; 131-140; 259-271; 297-304;
RP 306-329; 336-344; 352-362; 367-397; 434-460 AND 472-482, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 95-104 AND 472-479.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [14]
RP MASS SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=11840567;
RX DOI=10.1002/1615-9861(200202)2:2<212::aid-prot212>3.0.co;2-h;
RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA Zvelebil M.J.;
RT "Cluster analysis of an extensive human breast cancer cell line protein
RT expression map database.";
RL Proteomics 2:212-223(2002).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [16]
RP INTERACTION WITH ERP27.
RX PubMed=16940051; DOI=10.1074/jbc.m604314200;
RA Alanen H.I., Williamson R.A., Howard M.J., Hatahet F.S., Salo K.E.H.,
RA Kauppila A., Kellokumpu S., Ruddock L.W.;
RT "ERp27, a new non-catalytic endoplasmic reticulum-located human protein
RT disulfide isomerase family member, interacts with ERp57.";
RL J. Biol. Chem. 281:33727-33738(2006).
RN [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP TISSUE SPECIFICITY.
RX PubMed=20400973; DOI=10.1038/aja.2010.19;
RA Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection antigen
RT (GP96) are unique to hamster caput epididymal spermatozoa.";
RL Asian J. Androl. 12:344-355(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=24188822; DOI=10.1016/j.febslet.2013.10.030;
RA Fujii T., Awaka S.Y., Takahashi Y., Fujita K., Tsuji H., Shimizu T.,
RA Gomi T., Tsukada K., Sakai H.;
RT "Modulation of H(+),K(+)-ATPase activity by the molecular chaperone ERp57
RT highly expressed in gastric parietal cells.";
RL FEBS Lett. 587:3898-3905(2013).
RN [23]
RP INTERACTION WITH SERPINA1 AND SERPINA2, AND SUBCELLULAR LOCATION.
RX PubMed=23826168; DOI=10.1371/journal.pone.0066889;
RA Marques P.I., Ferreira Z., Martins M., Figueiredo J., Silva D.I.,
RA Castro P., Morales-Hojas R., Simoes-Correia J., Seixas S.;
RT "SERPINA2 is a novel gene with a divergent function from SERPINA1.";
RL PLoS ONE 8:E66889-E66889(2013).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-319, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-61, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [26]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-24, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [27]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27897272; DOI=10.1038/srep37957;
RA Gaucci E., Raimondo D., Grillo C., Cervoni L., Altieri F., Nittari G.,
RA Eufemi M., Chichiarelli S.;
RT "Analysis of the interaction of calcitriol with the disulfide isomerase
RT ERp57.";
RL Sci. Rep. 6:37957-37957(2016).
RN [28]
RP STRUCTURE BY NMR OF 25-137.
RX PubMed=16258833; DOI=10.1007/s10858-005-2720-1;
RA Silvennoinen L., Koivunen P., Myllyharju J., Kilpelaeinen I., Permi P.;
RT "NMR assignment of the N-terminal domain a of the glycoprotein chaperone
RT ERp57.";
RL J. Biomol. NMR 33:136-136(2005).
RN [29]
RP STRUCTURE BY NMR OF 357-485.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the second thioredoxin domain of human protein
RT disulfide-isomerase A3.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-376, AND INTERACTION WITH
RP CANX.
RX PubMed=16905107; DOI=10.1016/j.str.2006.06.019;
RA Kozlov G., Maattanen P., Schrag J.D., Pollock S., Cygler M., Nagar B.,
RA Thomas D.Y., Gehring K.;
RT "Crystal structure of the bb' domains of the protein disulfide isomerase
RT ERp57.";
RL Structure 14:1331-1339(2006).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-505 IN COMPLEX WITH TAPBP,
RP SUBUNIT, INTERACTION WITH TAPBP, AND DISULFIDE BONDS.
RX PubMed=19119025; DOI=10.1016/j.immuni.2008.10.018;
RA Dong G., Wearsch P.A., Peaper D.R., Cresswell P., Reinisch K.M.;
RT "Insights into MHC class I peptide loading from the structure of the
RT tapasin-ERp57 thiol oxidoreductase heterodimer.";
RL Immunity 30:21-32(2009).
CC -!- FUNCTION: Disulfide isomerase which catalyzes the formation,
CC isomerization, and reduction or oxidation of disulfide bonds
CC (PubMed:7487104, PubMed:27897272). Associates with calcitriol, the
CC active form of vitamin D3 which mediates the action of this vitamin on
CC cells (PubMed:27897272). Association with calcitriol does not affect
CC its enzymatic activity (PubMed:27897272). {ECO:0000269|PubMed:27897272,
CC ECO:0000269|PubMed:7487104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000269|PubMed:27897272,
CC ECO:0000269|PubMed:7487104};
CC -!- SUBUNIT: Subunit of the TAP complex, also known as the peptide loading
CC complex (PLC). Can form disulfide-linked heterodimers with TAPBP.
CC Interacts with ERP27 and CANX. Interacts with SERPINA2 and with the S
CC and Z variants of SERPINA1. Interacts with ATP2A2.
CC {ECO:0000250|UniProtKB:P27773, ECO:0000269|PubMed:16905107,
CC ECO:0000269|PubMed:16940051, ECO:0000269|PubMed:19119025,
CC ECO:0000269|PubMed:23826168}.
CC -!- INTERACTION:
CC P30101; P05067: APP; NbExp=6; IntAct=EBI-979862, EBI-77613;
CC P30101; P10909: CLU; NbExp=2; IntAct=EBI-979862, EBI-1104674;
CC P30101; Q96HE7: ERO1A; NbExp=3; IntAct=EBI-979862, EBI-2564539;
CC P30101; Q86YB8: ERO1B; NbExp=2; IntAct=EBI-979862, EBI-2806988;
CC P30101; P30101: PDIA3; NbExp=2; IntAct=EBI-979862, EBI-979862;
CC P30101; Q13162: PRDX4; NbExp=2; IntAct=EBI-979862, EBI-2211957;
CC P30101; Q13586: STIM1; NbExp=3; IntAct=EBI-979862, EBI-448878;
CC P30101; Q03518: TAP1; NbExp=5; IntAct=EBI-979862, EBI-747259;
CC P30101; P18418: Calr; Xeno; NbExp=2; IntAct=EBI-979862, EBI-916742;
CC P30101; P24643: CANX; Xeno; NbExp=3; IntAct=EBI-979862, EBI-15596385;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:23826168}. Endoplasmic reticulum lumen
CC {ECO:0000250}. Melanosome {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV (PubMed:12643545).
CC {ECO:0000269|PubMed:12643545}.
CC -!- TISSUE SPECIFICITY: Detected in the flagellum and head region of
CC spermatozoa (at protein level) (PubMed:20400973). Expressed in liver,
CC stomach and colon (at protein level). Expressed in gastric parietal
CC cells and chief cells (at protein level) (PubMed:24188822).
CC {ECO:0000269|PubMed:20400973, ECO:0000269|PubMed:24188822}.
CC -!- MASS SPECTROMETRY: Mass=54265.22; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11840567};
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a phosphatidylinositol 4,5-
CC bisphosphate phosphodiesterase type I (phospholipase C-alpha).
CC {ECO:0000305}.
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DR EMBL; D16234; BAA03759.1; -; mRNA.
DR EMBL; U42068; AAC50331.1; -; mRNA.
DR EMBL; Z49835; CAA89996.1; -; mRNA.
DR EMBL; U75885; AAC51518.1; -; Genomic_DNA.
DR EMBL; U75875; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75876; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75877; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75878; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75879; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75880; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75881; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75882; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75883; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; U75884; AAC51518.1; JOINED; Genomic_DNA.
DR EMBL; D83485; BAA11928.1; -; mRNA.
DR EMBL; BC014433; AAH14433.1; -; mRNA.
DR EMBL; BC036000; AAH36000.4; -; mRNA.
DR EMBL; BC071878; AAH71878.1; -; mRNA.
DR CCDS; CCDS10101.1; -.
DR PIR; JC5704; JC5704.
DR PIR; S55507; S55507.
DR PIR; S63994; S63994.
DR PIR; S68363; S68363.
DR RefSeq; NP_005304.3; NM_005313.4.
DR PDB; 2ALB; NMR; -; A=25-137.
DR PDB; 2DMM; NMR; -; A=357-485.
DR PDB; 2H8L; X-ray; 2.00 A; A/B/C=134-376.
DR PDB; 3F8U; X-ray; 2.60 A; A/C=25-505.
DR PDB; 6ENY; EM; 5.80 A; D=25-505.
DR PDBsum; 2ALB; -.
DR PDBsum; 2DMM; -.
DR PDBsum; 2H8L; -.
DR PDBsum; 3F8U; -.
DR PDBsum; 6ENY; -.
DR AlphaFoldDB; P30101; -.
DR BMRB; P30101; -.
DR SMR; P30101; -.
DR BioGRID; 109180; 367.
DR ComplexPortal; CPX-2375; Tapasin-ERp57 complex.
DR CORUM; P30101; -.
DR DIP; DIP-29132N; -.
DR IntAct; P30101; 160.
DR MINT; P30101; -.
DR STRING; 9606.ENSP00000300289; -.
DR BindingDB; P30101; -.
DR ChEMBL; CHEMBL4296001; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 8.A.88.2.7; the calciquestrin (casq) family.
DR GlyGen; P30101; 3 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P30101; -.
DR MetOSite; P30101; -.
DR PhosphoSitePlus; P30101; -.
DR SwissPalm; P30101; -.
DR BioMuta; PDIA3; -.
DR DMDM; 2507461; -.
DR DOSAC-COBS-2DPAGE; P30101; -.
DR REPRODUCTION-2DPAGE; P30101; -.
DR SWISS-2DPAGE; P30101; -.
DR UCD-2DPAGE; P30101; -.
DR CPTAC; CPTAC-421; -.
DR CPTAC; CPTAC-422; -.
DR EPD; P30101; -.
DR jPOST; P30101; -.
DR MassIVE; P30101; -.
DR PaxDb; P30101; -.
DR PeptideAtlas; P30101; -.
DR PRIDE; P30101; -.
DR ProteomicsDB; 54635; -.
DR TopDownProteomics; P30101; -.
DR Antibodypedia; 1223; 955 antibodies from 46 providers.
DR DNASU; 2923; -.
DR Ensembl; ENST00000300289.10; ENSP00000300289.5; ENSG00000167004.14.
DR GeneID; 2923; -.
DR KEGG; hsa:2923; -.
DR MANE-Select; ENST00000300289.10; ENSP00000300289.5; NM_005313.5; NP_005304.3.
DR CTD; 2923; -.
DR DisGeNET; 2923; -.
DR GeneCards; PDIA3; -.
DR HGNC; HGNC:4606; PDIA3.
DR HPA; ENSG00000167004; Low tissue specificity.
DR MIM; 602046; gene.
DR neXtProt; NX_P30101; -.
DR OpenTargets; ENSG00000167004; -.
DR PharmGKB; PA29000; -.
DR VEuPathDB; HostDB:ENSG00000167004; -.
DR eggNOG; KOG0190; Eukaryota.
DR GeneTree; ENSGT00940000155425; -.
DR HOGENOM; CLU_025879_6_0_1; -.
DR InParanoid; P30101; -.
DR OMA; YIAKHAT; -.
DR OrthoDB; 462118at2759; -.
DR PhylomeDB; P30101; -.
DR TreeFam; TF106382; -.
DR BRENDA; 5.3.4.1; 2681.
DR PathwayCommons; P30101; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-901042; Calnexin/calreticulin cycle.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; P30101; -.
DR SIGNOR; P30101; -.
DR BioGRID-ORCS; 2923; 27 hits in 1069 CRISPR screens.
DR ChiTaRS; PDIA3; human.
DR EvolutionaryTrace; P30101; -.
DR GenomeRNAi; 2923; -.
DR Pharos; P30101; Tbio.
DR PRO; PR:P30101; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P30101; protein.
DR Bgee; ENSG00000167004; Expressed in corpus epididymis and 203 other tissues.
DR ExpressionAtlas; P30101; baseline and differential.
DR Genevisible; P30101; HS.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042824; C:MHC class I peptide loading complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; TAS:Reactome.
DR GO; GO:0055038; C:recycling endosome membrane; TAS:Reactome.
DR GO; GO:0061779; C:Tapasin-ERp57 complex; IPI:ComplexPortal.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004629; F:phospholipase C activity; TAS:ProtInc.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IBA:GO_Central.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0002502; P:peptide antigen assembly with MHC class I protein complex; IDA:ComplexPortal.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; TAS:ParkinsonsUK-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR CDD; cd03069; PDI_b_ERp57; 1.
DR InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR041868; PDIA3_PDI_b.
DR InterPro; IPR005792; Prot_disulphide_isomerase.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 2.
DR SUPFAM; SSF52833; SSF52833; 4.
DR TIGRFAMs; TIGR01130; ER_PDI_fam; 1.
DR TIGRFAMs; TIGR01126; pdi_dom; 2.
DR PROSITE; PS00194; THIOREDOXIN_1; 2.
DR PROSITE; PS51352; THIOREDOXIN_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Isomerase; Methylation; Phosphoprotein;
KW Redox-active center; Reference proteome; Repeat; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:1286669, ECO:0000269|PubMed:7487104,
FT ECO:0000269|PubMed:9150948, ECO:0000269|PubMed:9399589,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 25..505
FT /note="Protein disulfide-isomerase A3"
FT /id="PRO_0000034225"
FT DOMAIN 25..133
FT /note="Thioredoxin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 343..485
FT /note="Thioredoxin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 484..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 502..505
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000250"
FT COMPBIAS 489..505
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 57
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 60
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 406
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 409
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 58
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 59
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 119
FT /note="Lowers pKa of C-terminal Cys of first active site"
FT /evidence="ECO:0000250"
FT SITE 407
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 408
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 471
FT /note="Lowers pKa of C-terminal Cys of second active site"
FT /evidence="ECO:0000250"
FT MOD_RES 61
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 129
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT MOD_RES 218
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT MOD_RES 319
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 362
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT MOD_RES 494
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27773"
FT DISULFID 57..60
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DISULFID 57
FT /note="Interchain (with C-115 in TAPBP); in linked form"
FT /evidence="ECO:0000269|PubMed:19119025"
FT DISULFID 85..92
FT /evidence="ECO:0000269|PubMed:19119025"
FT DISULFID 406..409
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT VARIANT 415
FT /note="K -> R (in dbSNP:rs6413485)"
FT /id="VAR_020027"
FT MUTAGEN 57
FT /note="C->A: No loss of activity. No loss of activity; when
FT associated with A-406."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 57
FT /note="C->S: Activity changed to serine protease."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 60
FT /note="C->S: Activity changed to serine protease; when
FT associated with S-409."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 406
FT /note="C->A: No loss of activity. No loss of activity; when
FT associated with A-57."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 406
FT /note="C->S: Activity changed to serine protease."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 409
FT /note="C->S: Activity changed to serine protease; when
FT associated with S-60."
FT /evidence="ECO:0000269|PubMed:9399589"
FT CONFLICT 19
FT /note="A -> G (in Ref. 6; BAA11928)"
FT /evidence="ECO:0000305"
FT CONFLICT 22
FT /note="A -> V (in Ref. 6; BAA11928)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="D -> Y (in Ref. 1; BAA03759)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="Q -> P (in Ref. 4; CAA89996)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="E -> G (in Ref. 4; CAA89996)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="N -> D (in Ref. 1; BAA03759 and 5; AAC51518)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="D -> G (in Ref. 1; BAA03759)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="D -> G (in Ref. 1; BAA03759)"
FT /evidence="ECO:0000305"
FT CONFLICT 368
FT /note="E -> D (in Ref. 1; BAA03759)"
FT /evidence="ECO:0000305"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:2ALB"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:2ALB"
FT STRAND 43..53
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 58..73
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 85..87
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 121..131
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 166..177
FT /evidence="ECO:0007829|PDB:2H8L"
FT TURN 178..181
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 190..196
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 229..239
FT /evidence="ECO:0007829|PDB:2H8L"
FT TURN 240..243
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 252..255
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 256..265
FT /evidence="ECO:0007829|PDB:2H8L"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 273..292
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 298..303
FT /evidence="ECO:0007829|PDB:2H8L"
FT TURN 304..307
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 308..311
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:2H8L"
FT HELIX 347..358
FT /evidence="ECO:0007829|PDB:2H8L"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 383..385
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 386..390
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 396..402
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 407..422
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 423..425
FT /evidence="ECO:0007829|PDB:3F8U"
FT STRAND 427..435
FT /evidence="ECO:0007829|PDB:3F8U"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:2DMM"
FT STRAND 449..456
FT /evidence="ECO:0007829|PDB:3F8U"
FT HELIX 473..483
FT /evidence="ECO:0007829|PDB:3F8U"
SQ SEQUENCE 505 AA; 56782 MW; 529E5B6692D0D7E9 CRC64;
MRLRRLALFP GVALLLAAAR LAAASDVLEL TDDNFESRIS DTGSAGLMLV EFFAPWCGHC
KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY PTLKIFRDGE EAGAYDGPRT
ADGIVSHLKK QAGPASVPLR TEEEFKKFIS DKDASIVGFF DDSFSEAHSE FLKAASNLRD
NYRFAHTNVE SLVNEYDDNG EGIILFRPSH LTNKFEDKTV AYTEQKMTSG KIKKFIQENI
FGICPHMTED NKDLIQGKDL LIAYYDVDYE KNAKGSNYWR NRVMMVAKKF LDAGHKLNFA
VASRKTFSHE LSDFGLESTA GEIPVVAIRT AKGEKFVMQE EFSRDGKALE RFLQDYFDGN
LKRYLKSEPI PESNDGPVKV VVAENFDEIV NNENKDVLIE FYAPWCGHCK NLEPKYKELG
EKLSKDPNIV IAKMDATAND VPSPYEVRGF PTIYFSPANK KLNPKKYEGG RELSDFISYL
QREATNPPVI QEEKPKKKKK AQEDL
