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 27-MAR-2024, entry version 251. 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 {ECO:0000312|HGNC:HGNC:4606}; 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 FUNCTION, DISULFIDE BOND, ACTIVE SITE, AND MUTAGENESIS OF CYS-60 AND RP CYS-409. RX PubMed=11825568; DOI=10.1016/s1074-7613(02)00263-7; RA Dick T.P., Bangia N., Peaper D.R., Cresswell P.; RT "Disulfide bond isomerization and the assembly of MHC class I-peptide RT complexes."; RL Immunity 16:87-98(2002). RN [15] 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 [16] 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 [17] RP FUNCTION, DISULFIDE BOND, AND ACTIVE SITE. RX PubMed=16193070; DOI=10.1038/sj.emboj.7600814; RA Peaper D.R., Wearsch P.A., Cresswell P.; RT "Tapasin and ERp57 form a stable disulfide-linked dimer within the MHC RT class I peptide-loading complex."; RL EMBO J. 24:3613-3623(2005). RN [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. 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 [30] 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 [31] 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 [32] 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 [33] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-505 IN COMPLEX WITH TAPBP, RP SUBUNIT, INTERACTION WITH TAPBP, DISULFIDE BONDS, AND ACTIVE SITE. 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). RN [34] {ECO:0007744|PDB:7QPD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.73 ANGSTROMS) OF 25-505 IN MHC CLASS I RP PEPTIDE LOADING COMPLEX, FUNCTION, SUBUNIT, DISULFIDE BOND, AND ACTIVE RP SITE. RX PubMed=35948544; DOI=10.1038/s41467-022-32384-z; RA Domnick A., Winter C., Susac L., Hennecke L., Hensen M., Zitzmann N., RA Trowitzsch S., Thomas C., Tampe R.; RT "Molecular basis of MHC I quality control in the peptide loading complex."; RL Nat. Commun. 13:4701-4701(2022). RN [35] {ECO:0007744|PDB:7QNG} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF MUTANT ALA-60 IN MHC CLASS I RP PEPTIDE LOADING COMPLEX, FUNCTION, SUBUNIT, AND DISULFIDE BOND. RX PubMed=36104323; DOI=10.1038/s41467-022-32841-9; RA Mueller I.K., Winter C., Thomas C., Spaapen R.M., Trowitzsch S., Tampe R.; RT "Structure of an MHC I-tapasin-ERp57 editing complex defines chaperone RT promiscuity."; RL Nat. Commun. 13:5383-5383(2022). CC -!- FUNCTION: Protein disulfide isomerase that catalyzes the formation, CC isomerization, and reduction or oxidation of disulfide bonds in client CC proteins and functions as a protein folding chaperone (PubMed:7487104, CC PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323). CC Core component of the major histocompatibility complex class I (MHC I) CC peptide loading complex where it functions as an essential folding CC chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the CC MHC I complex with high affinity antigens in the endoplasmic reticulum. CC Therefore, plays a crucial role in the presentation of antigens to CC cytotoxic T cells in adaptive immunity (PubMed:35948544, CC PubMed:36104323). {ECO:0000269|PubMed:11825568, CC ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:27897272, CC ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, 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 -!- ACTIVITY REGULATION: Association with calcitriol does not affect its CC enzymatic activity. {ECO:0000269|PubMed:27897272}. CC -!- SUBUNIT: Part of the major histocompatibility complex class I (MHC I) CC peptide loading complex composed of TAP1, TAP2, B2M, MHC heavy chain, CC TAPBP, PDIA3, and CALR (PubMed:19119025, PubMed:35948544, CC PubMed:36104323). Interacts with ERP27 and CANX (PubMed:16940051, CC PubMed:16905107). Interacts with SERPINA2 and with the S and Z variants CC of SERPINA1 (PubMed:23826168). Interacts with ATP2A2 (By similarity). CC {ECO:0000250|UniProtKB:P27773, ECO:0000269|PubMed:16905107, CC ECO:0000269|PubMed:16940051, ECO:0000269|PubMed:19119025, CC ECO:0000269|PubMed:23826168, ECO:0000269|PubMed:35948544, CC ECO:0000269|PubMed:36104323}. CC -!- INTERACTION: CC P30101; P05067: APP; NbExp=6; IntAct=EBI-979862, EBI-77613; CC P30101; P13569: CFTR; NbExp=12; IntAct=EBI-979862, EBI-349854; 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|UniProtKB:P11598}. Melanosome CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. CC Note=Identified by mass spectrometry in melanosome fractions from stage CC I to stage IV (PubMed:12643545). {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 -!- PTM: Within the major histocompatibility complex class I (MHC I) CC peptide loading complex forms reversible disulfide-linked heterodimers CC with TAPBP as part of its protein folding chaperone activity. This is CC essential to assist the dynamic assembly of the MHC I complex with high CC affinity antigens in the endoplasmic reticulum. CC {ECO:0000269|PubMed:11825568}. CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P27773}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7QNG; X-ray; 2.70 A; B=1-505. DR PDB; 7QPD; EM; 3.73 A; E=25-505. DR PDBsum; 2ALB; -. DR PDBsum; 2DMM; -. DR PDBsum; 2H8L; -. DR PDBsum; 3F8U; -. DR PDBsum; 6ENY; -. DR PDBsum; 7QNG; -. DR PDBsum; 7QPD; -. DR AlphaFoldDB; P30101; -. DR BMRB; P30101; -. DR EMDB; EMD-14119; -. DR EMDB; EMD-3906; -. DR SMR; P30101; -. DR BioGRID; 109180; 446. DR ComplexPortal; CPX-2375; Tapasin-ERp57 complex. DR CORUM; P30101; -. DR DIP; DIP-29132N; -. DR IntAct; P30101; 168. 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 GlyCosmos; P30101; 2 sites, 1 glycan. DR GlyGen; P30101; 9 sites, 2 O-linked glycans (8 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 CPTAC; CPTAC-421; -. DR CPTAC; CPTAC-422; -. DR EPD; P30101; -. DR jPOST; P30101; -. DR MassIVE; P30101; -. DR PaxDb; 9606-ENSP00000300289; -. DR PeptideAtlas; P30101; -. DR PRIDE; P30101; -. DR ProteomicsDB; 54635; -. DR Pumba; P30101; -. DR TopDownProteomics; P30101; -. DR Antibodypedia; 1223; 1026 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 AGR; HGNC:4606; -. DR CTD; 2923; -. DR DisGeNET; 2923; -. DR GeneCards; PDIA3; -. DR HGNC; HGNC:4606; PDIA3. DR HPA; ENSG00000167004; Tissue enhanced (thyroid). 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; HRTQDSV; -. DR OrthoDB; 5399045at2759; -. 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; 32 hits in 1145 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 205 other cell types or tissues. DR ExpressionAtlas; P30101; baseline and differential. 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:0002250; P:adaptive immune response; IEA:UniProtKB-KW. 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:0070527; P:platelet aggregation; IEA:Ensembl. 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; cd02995; PDI_a_PDI_a'_C; 1. DR CDD; cd03073; PDI_b'_ERp72_ERp57; 1. DR CDD; cd03069; PDI_b_ERp57; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 4. DR InterPro; IPR005788; PDI_thioredoxin-like_dom. 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 NCBIfam; TIGR01130; ER_PDI_fam; 1. DR NCBIfam; TIGR01126; pdi_dom; 2. DR PANTHER; PTHR18929; PROTEIN DISULFIDE ISOMERASE; 1. DR PANTHER; PTHR18929:SF132; PROTEIN DISULFIDE-ISOMERASE A3; 1. DR Pfam; PF00085; Thioredoxin; 2. DR Pfam; PF13848; Thioredoxin_6; 1. DR PRINTS; PR00421; THIOREDOXIN. DR SUPFAM; SSF52833; Thioredoxin-like; 4. DR PROSITE; PS00194; THIOREDOXIN_1; 2. DR PROSITE; PS51352; THIOREDOXIN_2; 2. DR SWISS-2DPAGE; P30101; -. DR UCD-2DPAGE; P30101; -. DR Genevisible; P30101; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Adaptive immunity; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Immunity; Isomerase; Methylation; KW Phosphoprotein; 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|UniProtKB:P11598" 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:0000269|PubMed:11825568, FT ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:19119025" FT ACT_SITE 60 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:11825568, FT ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:19119025" FT ACT_SITE 406 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:19119025, FT ECO:0000269|PubMed:35948544, ECO:0007744|PDB:3F8U, FT ECO:0007744|PDB:7QPD" FT ACT_SITE 409 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:19119025, FT ECO:0000269|PubMed:35948544, ECO:0007744|PDB:3F8U, FT ECO:0007744|PDB:7QPD" 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; reversible" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691, FT ECO:0000269|PubMed:16193070" FT DISULFID 57 FT /note="Interchain (with C-115 in TAPBP); in linked form; FT reversible" FT /evidence="ECO:0000269|PubMed:11825568, FT ECO:0000269|PubMed:16193070, ECO:0000269|PubMed:19119025" FT DISULFID 85..92 FT /evidence="ECO:0000269|PubMed:19119025, FT ECO:0000269|PubMed:35948544, ECO:0000269|PubMed:36104323, FT ECO:0007744|PDB:3F8U, ECO:0007744|PDB:7QNG, FT ECO:0007744|PDB:7QPD" FT DISULFID 406..409 FT /note="Redox-active" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691, FT ECO:0000269|PubMed:19119025, ECO:0000269|PubMed:35948544, FT ECO:0000269|PubMed:36104323, ECO:0007744|PDB:3F8U, FT ECO:0007744|PDB:7QNG, ECO:0007744|PDB:7QPD" 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->A: Trapped via disulfide bond with TAPBP." FT /evidence="ECO:0000269|PubMed:11825568" 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->A: No effect on disulfide bond with TAPBP." FT /evidence="ECO:0000269|PubMed:11825568" 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 //