Full text data of PDIA3
PDIA3
(ERP57, ERP60, GRP58)
[Confidence: high (present in two of the MS resources)]
Protein disulfide-isomerase A3; 5.3.4.1 (58 kDa glucose-regulated protein; 58 kDa microsomal protein; p58; Disulfide isomerase ER-60; Endoplasmic reticulum resident protein 57; ER protein 57; ERp57; Endoplasmic reticulum resident protein 60; ER protein 60; ERp60; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein disulfide-isomerase A3; 5.3.4.1 (58 kDa glucose-regulated protein; 58 kDa microsomal protein; p58; Disulfide isomerase ER-60; Endoplasmic reticulum resident protein 57; ER protein 57; ERp57; Endoplasmic reticulum resident protein 60; ER protein 60; ERp60; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00025252
IPI00025252 Protein disulfide-isomerase A3 precursor Protein disulfide-isomerase A3 precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 3 n/a 1 n/a n/a 1 n/a n/a n/a 1 4 3 ER lumen n/a found at its expected molecular weight found at molecular weight
IPI00025252 Protein disulfide-isomerase A3 precursor Protein disulfide-isomerase A3 precursor membrane n/a n/a n/a n/a n/a n/a n/a n/a 3 n/a 1 n/a n/a 1 n/a n/a n/a 1 4 3 ER lumen n/a found at its expected molecular weight found at molecular weight
UniProt
P30101
ID PDIA3_HUMAN Reviewed; 505 AA.
AC P30101; Q13453; Q14255; Q8IYF8; Q9UMU7;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 4.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Protein disulfide-isomerase A3;
DE EC=5.3.4.1;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT phospholipase C-alpha: proposal of redesignation of phospholipase C-
RT 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.,
RA George J.W., Pohl L.R.;
RT "cDNA cloning and baculovirus expression of the human liver
RT endoplasmic reticulum P58: characterization as a protein disulfide
RT isomerase isoform, but not as a protease or a carnitine
RT acyltransferase.";
RL Arch. Biochem. Biophys. 323:397-403(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8687406;
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
RT beta-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
RT protein disulfide isomerase (previously identified as phospholipase C
RT 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.,
RA Jaakkola M., Palotie A., Kivirikko K.I.;
RT "Structures of the human gene for the protein disulfide isomerase-
RT related polypeptide ERp60 and a processed gene and assignment of these
RT genes to 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;
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-
RT Leu (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
RT project: 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric 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.,
RA Simpson R.J., 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
RT lineage 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 MASS
RP 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
RT protein 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
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., 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
RT protein disulfide isomerase family member, interacts with ERp57.";
RL J. Biol. Chem. 281:33727-33738(2006).
RN [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA 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.,
RA Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection
RT antigen (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.,
RA Buerckstuemmer T., 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 INTERACTION WITH SERPINA2P AND SERPINA1, 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 [22]
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.,
RA Permi P.;
RT "NMR assignment of the N-terminal domain a of the glycoprotein
RT chaperone ERp57.";
RL J. Biomol. NMR 33:136-136(2005).
RN [23]
RP STRUCTURE BY NMR OF 357-485.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the second thioredoxin domain of human
RT protein disulfide-isomerase A3.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [24]
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
RT isomerase ERp57.";
RL Structure 14:1331-1339(2006).
RN [25]
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 -!- CATALYTIC ACTIVITY: Catalyzes the rearrangement of -S-S- bonds in
CC proteins.
CC -!- SUBUNIT: Subunit of the TAP complex, also known as the peptide
CC loading complex (PLC). Can form disulfide-linked heterodimers with
CC TAPBP. Interacts with ERP27 and CANX. Interacts with
CC SERPINA2P/SERPINA2 and with the S and Z variants of SERPINA1.
CC -!- INTERACTION:
CC P05067:APP; NbExp=3; IntAct=EBI-979862, EBI-77613;
CC Q96HE7:ERO1L; NbExp=3; IntAct=EBI-979862, EBI-2564539;
CC Q86YB8:ERO1LB; NbExp=2; IntAct=EBI-979862, EBI-2806988;
CC Q13162:PRDX4; NbExp=2; IntAct=EBI-979862, EBI-2211957;
CC Q13586:STIM1; NbExp=3; IntAct=EBI-979862, EBI-448878;
CC Q03518:TAP1; NbExp=4; IntAct=EBI-979862, EBI-747259;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Endoplasmic reticulum
CC lumen (By similarity). Melanosome. Note=Identified by mass
CC spectrometry in melanosome fractions from stage I to stage IV.
CC -!- TISSUE SPECIFICITY: Detected in the flagellum and head region of
CC spermatozoa (at protein level).
CC -!- MASS SPECTROMETRY: Mass=54265.22; Method=MALDI; Range=25-505;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC -!- SIMILARITY: Contains 2 thioredoxin domains.
CC -!- CAUTION: Was originally thought to be a phosphatidylinositol 4,5-
CC bisphosphate phosphodiesterase type I (phospholipase C-alpha).
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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 PIR; JC5704; JC5704.
DR PIR; S55507; S55507.
DR PIR; S63994; S63994.
DR PIR; S68363; S68363.
DR RefSeq; NP_005304.3; NM_005313.4.
DR UniGene; Hs.591095; -.
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 PDBsum; 2ALB; -.
DR PDBsum; 2DMM; -.
DR PDBsum; 2H8L; -.
DR PDBsum; 3F8U; -.
DR ProteinModelPortal; P30101; -.
DR SMR; P30101; 25-493.
DR DIP; DIP-29132N; -.
DR IntAct; P30101; 49.
DR MINT; MINT-5000005; -.
DR STRING; 9606.ENSP00000300289; -.
DR PhosphoSite; P30101; -.
DR DMDM; 2507461; -.
DR DOSAC-COBS-2DPAGE; P30101; -.
DR REPRODUCTION-2DPAGE; P30101; -.
DR SWISS-2DPAGE; P30101; -.
DR UCD-2DPAGE; P30101; -.
DR PaxDb; P30101; -.
DR PRIDE; P30101; -.
DR DNASU; 2923; -.
DR Ensembl; ENST00000300289; ENSP00000300289; ENSG00000167004.
DR GeneID; 2923; -.
DR KEGG; hsa:2923; -.
DR UCSC; uc001zsu.3; human.
DR CTD; 2923; -.
DR GeneCards; GC15P044038; -.
DR HGNC; HGNC:4606; PDIA3.
DR HPA; CAB011199; -.
DR HPA; CAB015181; -.
DR HPA; HPA002645; -.
DR HPA; HPA003230; -.
DR MIM; 602046; gene.
DR neXtProt; NX_P30101; -.
DR PharmGKB; PA29000; -.
DR eggNOG; COG0526; -.
DR HOGENOM; HOG000162459; -.
DR HOVERGEN; HBG005920; -.
DR InParanoid; P30101; -.
DR KO; K08056; -.
DR OMA; FEKFISD; -.
DR OrthoDB; EOG7VHSX1; -.
DR PhylomeDB; P30101; -.
DR BRENDA; 5.3.4.1; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; PDIA3; human.
DR EvolutionaryTrace; P30101; -.
DR GenomeRNAi; 2923; -.
DR NextBio; 11593; -.
DR PRO; PR:P30101; -.
DR ArrayExpress; P30101; -.
DR Bgee; P30101; -.
DR CleanEx; HS_PDIA3; -.
DR Genevestigator; P30101; -.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0004629; F:phospholipase C activity; TAS:ProtInc.
DR GO; GO:0003756; F:protein disulfide isomerase activity; TAS:ProtInc.
DR GO; GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0006662; P:glycerol ether metabolic process; IEA:InterPro.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006606; P:protein import into nucleus; TAS:ProtInc.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0006621; P:protein retention in ER lumen; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 3.40.30.10; -; 3.
DR InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR005792; Prot_disulphide_isomerase.
DR InterPro; IPR005746; Thioredoxin.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 2.
DR PRINTS; PR00421; THIOREDOXIN.
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; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Isomerase; Polymorphism;
KW Redox-active center; Reference proteome; Repeat; Signal.
FT SIGNAL 1 24
FT CHAIN 25 505 Protein disulfide-isomerase A3.
FT /FTId=PRO_0000034225.
FT DOMAIN 25 133 Thioredoxin 1.
FT DOMAIN 343 485 Thioredoxin 2.
FT MOTIF 502 505 Prevents secretion from ER (By
FT similarity).
FT ACT_SITE 57 57 Nucleophile (By similarity).
FT ACT_SITE 60 60 Nucleophile (By similarity).
FT ACT_SITE 406 406 Nucleophile (By similarity).
FT ACT_SITE 409 409 Nucleophile (By similarity).
FT SITE 58 58 Contributes to redox potential value (By
FT similarity).
FT SITE 59 59 Contributes to redox potential value (By
FT similarity).
FT SITE 119 119 Lowers pKa of C-terminal Cys of first
FT active site (By similarity).
FT SITE 407 407 Contributes to redox potential value (By
FT similarity).
FT SITE 408 408 Contributes to redox potential value (By
FT similarity).
FT SITE 471 471 Lowers pKa of C-terminal Cys of second
FT active site (By similarity).
FT DISULFID 57 60 Redox-active; alternate (By similarity).
FT DISULFID 57 57 Interchain (with C-115 in TAPBP);
FT alternate.
FT DISULFID 85 92
FT DISULFID 406 409 Redox-active (By similarity).
FT VARIANT 415 415 K -> R (in dbSNP:rs6413485).
FT /FTId=VAR_020027.
FT MUTAGEN 57 57 C->A: No loss of activity. No loss of
FT activity; when associated with A-406.
FT MUTAGEN 57 57 C->S: Activity changed to serine
FT protease.
FT MUTAGEN 60 60 C->S: Activity changed to serine
FT protease; when associated with S-409.
FT MUTAGEN 406 406 C->A: No loss of activity. No loss of
FT activity; when associated with A-57.
FT MUTAGEN 406 406 C->S: Activity changed to serine
FT protease.
FT MUTAGEN 409 409 C->S: Activity changed to serine
FT protease; when associated with S-60.
FT CONFLICT 19 19 A -> G (in Ref. 6; BAA11928).
FT CONFLICT 22 22 A -> V (in Ref. 6; BAA11928).
FT CONFLICT 217 217 D -> Y (in Ref. 1; BAA03759).
FT CONFLICT 225 225 Q -> P (in Ref. 4; CAA89996).
FT CONFLICT 238 238 E -> G (in Ref. 4; CAA89996).
FT CONFLICT 272 272 N -> D (in Ref. 1; BAA03759 and 5;
FT AAC51518).
FT CONFLICT 355 355 D -> G (in Ref. 1; BAA03759).
FT CONFLICT 358 358 D -> G (in Ref. 1; BAA03759).
FT CONFLICT 368 368 E -> D (in Ref. 1; BAA03759).
FT TURN 32 34
FT HELIX 35 38
FT STRAND 43 53
FT HELIX 58 73
FT TURN 74 77
FT STRAND 80 84
FT TURN 85 87
FT HELIX 89 94
FT STRAND 99 107
FT STRAND 110 114
FT HELIX 121 131
FT STRAND 136 138
FT HELIX 142 149
FT STRAND 151 153
FT STRAND 155 161
FT HELIX 166 177
FT TURN 178 181
FT STRAND 182 187
FT HELIX 190 196
FT STRAND 198 206
FT HELIX 209 211
FT STRAND 218 221
FT HELIX 229 239
FT TURN 240 243
FT TURN 249 251
FT HELIX 252 255
FT STRAND 256 265
FT TURN 269 271
FT HELIX 273 292
FT STRAND 298 303
FT TURN 304 307
FT HELIX 308 311
FT HELIX 312 314
FT STRAND 325 329
FT STRAND 331 333
FT STRAND 335 337
FT HELIX 347 358
FT STRAND 376 381
FT TURN 383 385
FT HELIX 386 390
FT STRAND 396 402
FT HELIX 407 422
FT TURN 423 425
FT STRAND 427 435
FT TURN 436 438
FT STRAND 449 456
FT HELIX 473 483
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
//
ID PDIA3_HUMAN Reviewed; 505 AA.
AC P30101; Q13453; Q14255; Q8IYF8; Q9UMU7;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 4.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Protein disulfide-isomerase A3;
DE EC=5.3.4.1;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT phospholipase C-alpha: proposal of redesignation of phospholipase C-
RT 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.,
RA George J.W., Pohl L.R.;
RT "cDNA cloning and baculovirus expression of the human liver
RT endoplasmic reticulum P58: characterization as a protein disulfide
RT isomerase isoform, but not as a protease or a carnitine
RT acyltransferase.";
RL Arch. Biochem. Biophys. 323:397-403(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8687406;
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
RT beta-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
RT protein disulfide isomerase (previously identified as phospholipase C
RT 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.,
RA Jaakkola M., Palotie A., Kivirikko K.I.;
RT "Structures of the human gene for the protein disulfide isomerase-
RT related polypeptide ERp60 and a processed gene and assignment of these
RT genes to 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;
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-
RT Leu (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
RT project: 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric 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.,
RA Simpson R.J., 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
RT lineage 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 MASS
RP 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
RT protein 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
RT protein expression map database.";
RL Proteomics 2:212-223(2002).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., 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
RT protein disulfide isomerase family member, interacts with ERp57.";
RL J. Biol. Chem. 281:33727-33738(2006).
RN [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA 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.,
RA Shivaji S.;
RT "Glucose-regulated protein precursor (GRP78) and tumor rejection
RT antigen (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.,
RA Buerckstuemmer T., 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 INTERACTION WITH SERPINA2P AND SERPINA1, 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 [22]
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.,
RA Permi P.;
RT "NMR assignment of the N-terminal domain a of the glycoprotein
RT chaperone ERp57.";
RL J. Biomol. NMR 33:136-136(2005).
RN [23]
RP STRUCTURE BY NMR OF 357-485.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of the second thioredoxin domain of human
RT protein disulfide-isomerase A3.";
RL Submitted (OCT-2006) to the PDB data bank.
RN [24]
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
RT isomerase ERp57.";
RL Structure 14:1331-1339(2006).
RN [25]
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 -!- CATALYTIC ACTIVITY: Catalyzes the rearrangement of -S-S- bonds in
CC proteins.
CC -!- SUBUNIT: Subunit of the TAP complex, also known as the peptide
CC loading complex (PLC). Can form disulfide-linked heterodimers with
CC TAPBP. Interacts with ERP27 and CANX. Interacts with
CC SERPINA2P/SERPINA2 and with the S and Z variants of SERPINA1.
CC -!- INTERACTION:
CC P05067:APP; NbExp=3; IntAct=EBI-979862, EBI-77613;
CC Q96HE7:ERO1L; NbExp=3; IntAct=EBI-979862, EBI-2564539;
CC Q86YB8:ERO1LB; NbExp=2; IntAct=EBI-979862, EBI-2806988;
CC Q13162:PRDX4; NbExp=2; IntAct=EBI-979862, EBI-2211957;
CC Q13586:STIM1; NbExp=3; IntAct=EBI-979862, EBI-448878;
CC Q03518:TAP1; NbExp=4; IntAct=EBI-979862, EBI-747259;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Endoplasmic reticulum
CC lumen (By similarity). Melanosome. Note=Identified by mass
CC spectrometry in melanosome fractions from stage I to stage IV.
CC -!- TISSUE SPECIFICITY: Detected in the flagellum and head region of
CC spermatozoa (at protein level).
CC -!- MASS SPECTROMETRY: Mass=54265.22; Method=MALDI; Range=25-505;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC -!- SIMILARITY: Contains 2 thioredoxin domains.
CC -!- CAUTION: Was originally thought to be a phosphatidylinositol 4,5-
CC bisphosphate phosphodiesterase type I (phospholipase C-alpha).
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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 PIR; JC5704; JC5704.
DR PIR; S55507; S55507.
DR PIR; S63994; S63994.
DR PIR; S68363; S68363.
DR RefSeq; NP_005304.3; NM_005313.4.
DR UniGene; Hs.591095; -.
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 PDBsum; 2ALB; -.
DR PDBsum; 2DMM; -.
DR PDBsum; 2H8L; -.
DR PDBsum; 3F8U; -.
DR ProteinModelPortal; P30101; -.
DR SMR; P30101; 25-493.
DR DIP; DIP-29132N; -.
DR IntAct; P30101; 49.
DR MINT; MINT-5000005; -.
DR STRING; 9606.ENSP00000300289; -.
DR PhosphoSite; P30101; -.
DR DMDM; 2507461; -.
DR DOSAC-COBS-2DPAGE; P30101; -.
DR REPRODUCTION-2DPAGE; P30101; -.
DR SWISS-2DPAGE; P30101; -.
DR UCD-2DPAGE; P30101; -.
DR PaxDb; P30101; -.
DR PRIDE; P30101; -.
DR DNASU; 2923; -.
DR Ensembl; ENST00000300289; ENSP00000300289; ENSG00000167004.
DR GeneID; 2923; -.
DR KEGG; hsa:2923; -.
DR UCSC; uc001zsu.3; human.
DR CTD; 2923; -.
DR GeneCards; GC15P044038; -.
DR HGNC; HGNC:4606; PDIA3.
DR HPA; CAB011199; -.
DR HPA; CAB015181; -.
DR HPA; HPA002645; -.
DR HPA; HPA003230; -.
DR MIM; 602046; gene.
DR neXtProt; NX_P30101; -.
DR PharmGKB; PA29000; -.
DR eggNOG; COG0526; -.
DR HOGENOM; HOG000162459; -.
DR HOVERGEN; HBG005920; -.
DR InParanoid; P30101; -.
DR KO; K08056; -.
DR OMA; FEKFISD; -.
DR OrthoDB; EOG7VHSX1; -.
DR PhylomeDB; P30101; -.
DR BRENDA; 5.3.4.1; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; PDIA3; human.
DR EvolutionaryTrace; P30101; -.
DR GenomeRNAi; 2923; -.
DR NextBio; 11593; -.
DR PRO; PR:P30101; -.
DR ArrayExpress; P30101; -.
DR Bgee; P30101; -.
DR CleanEx; HS_PDIA3; -.
DR Genevestigator; P30101; -.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0004629; F:phospholipase C activity; TAS:ProtInc.
DR GO; GO:0003756; F:protein disulfide isomerase activity; TAS:ProtInc.
DR GO; GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0006662; P:glycerol ether metabolic process; IEA:InterPro.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006606; P:protein import into nucleus; TAS:ProtInc.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR GO; GO:0006621; P:protein retention in ER lumen; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 3.40.30.10; -; 3.
DR InterPro; IPR005788; Disulphide_isomerase.
DR InterPro; IPR005792; Prot_disulphide_isomerase.
DR InterPro; IPR005746; Thioredoxin.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 2.
DR PRINTS; PR00421; THIOREDOXIN.
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; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Isomerase; Polymorphism;
KW Redox-active center; Reference proteome; Repeat; Signal.
FT SIGNAL 1 24
FT CHAIN 25 505 Protein disulfide-isomerase A3.
FT /FTId=PRO_0000034225.
FT DOMAIN 25 133 Thioredoxin 1.
FT DOMAIN 343 485 Thioredoxin 2.
FT MOTIF 502 505 Prevents secretion from ER (By
FT similarity).
FT ACT_SITE 57 57 Nucleophile (By similarity).
FT ACT_SITE 60 60 Nucleophile (By similarity).
FT ACT_SITE 406 406 Nucleophile (By similarity).
FT ACT_SITE 409 409 Nucleophile (By similarity).
FT SITE 58 58 Contributes to redox potential value (By
FT similarity).
FT SITE 59 59 Contributes to redox potential value (By
FT similarity).
FT SITE 119 119 Lowers pKa of C-terminal Cys of first
FT active site (By similarity).
FT SITE 407 407 Contributes to redox potential value (By
FT similarity).
FT SITE 408 408 Contributes to redox potential value (By
FT similarity).
FT SITE 471 471 Lowers pKa of C-terminal Cys of second
FT active site (By similarity).
FT DISULFID 57 60 Redox-active; alternate (By similarity).
FT DISULFID 57 57 Interchain (with C-115 in TAPBP);
FT alternate.
FT DISULFID 85 92
FT DISULFID 406 409 Redox-active (By similarity).
FT VARIANT 415 415 K -> R (in dbSNP:rs6413485).
FT /FTId=VAR_020027.
FT MUTAGEN 57 57 C->A: No loss of activity. No loss of
FT activity; when associated with A-406.
FT MUTAGEN 57 57 C->S: Activity changed to serine
FT protease.
FT MUTAGEN 60 60 C->S: Activity changed to serine
FT protease; when associated with S-409.
FT MUTAGEN 406 406 C->A: No loss of activity. No loss of
FT activity; when associated with A-57.
FT MUTAGEN 406 406 C->S: Activity changed to serine
FT protease.
FT MUTAGEN 409 409 C->S: Activity changed to serine
FT protease; when associated with S-60.
FT CONFLICT 19 19 A -> G (in Ref. 6; BAA11928).
FT CONFLICT 22 22 A -> V (in Ref. 6; BAA11928).
FT CONFLICT 217 217 D -> Y (in Ref. 1; BAA03759).
FT CONFLICT 225 225 Q -> P (in Ref. 4; CAA89996).
FT CONFLICT 238 238 E -> G (in Ref. 4; CAA89996).
FT CONFLICT 272 272 N -> D (in Ref. 1; BAA03759 and 5;
FT AAC51518).
FT CONFLICT 355 355 D -> G (in Ref. 1; BAA03759).
FT CONFLICT 358 358 D -> G (in Ref. 1; BAA03759).
FT CONFLICT 368 368 E -> D (in Ref. 1; BAA03759).
FT TURN 32 34
FT HELIX 35 38
FT STRAND 43 53
FT HELIX 58 73
FT TURN 74 77
FT STRAND 80 84
FT TURN 85 87
FT HELIX 89 94
FT STRAND 99 107
FT STRAND 110 114
FT HELIX 121 131
FT STRAND 136 138
FT HELIX 142 149
FT STRAND 151 153
FT STRAND 155 161
FT HELIX 166 177
FT TURN 178 181
FT STRAND 182 187
FT HELIX 190 196
FT STRAND 198 206
FT HELIX 209 211
FT STRAND 218 221
FT HELIX 229 239
FT TURN 240 243
FT TURN 249 251
FT HELIX 252 255
FT STRAND 256 265
FT TURN 269 271
FT HELIX 273 292
FT STRAND 298 303
FT TURN 304 307
FT HELIX 308 311
FT HELIX 312 314
FT STRAND 325 329
FT STRAND 331 333
FT STRAND 335 337
FT HELIX 347 358
FT STRAND 376 381
FT TURN 383 385
FT HELIX 386 390
FT STRAND 396 402
FT HELIX 407 422
FT TURN 423 425
FT STRAND 427 435
FT TURN 436 438
FT STRAND 449 456
FT HELIX 473 483
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
//
MIM
602046
*RECORD*
*FIELD* NO
602046
*FIELD* TI
*602046 PROTEIN DISULFIDE ISOMERASE, FAMILY A, MEMBER 3; PDIA3
;;GLUCOSE-REGULATED PROTEIN, 58-KD; GRP58;;
read moreERp57;;
ER60
*FIELD* TX
CLONING
The cDNA encoding human GRP58 was cloned independently by Bourdi et al.
(1995), Koivunen et al. (1996), and Hirano et al. (1995). All reported
that the gene encodes a 505-amino acid polypeptide with significant
homology to human protein disulfide isomerase (PDI; 176790). Bourdi et
al. (1995) noted that the sequence includes a putative nuclear
localization motif and an endoplasmic reticulum (ER)-retention/retrieval
motif. Koivunen et al. (1997) noted that the GRP58 sequence has 2
thioredoxin-like domains. Koivunen et al. (1997) showed by Northern
blotting that GRP58 is expressed as a 2-kb message most abundantly in
liver, placenta, and lung, and at lower levels in all other tissues
tested.
GENE FUNCTION
Several laboratories have examined the functional properties of GRP58.
Bourdi et al. (1995) found that the GRP58 protein had protein disulfide
isomerase activity. Koivunen et al. (1996) showed that GRP58 could not
substitute for the beta subunit of PDI. When coexpressed with alpha
prolyl 4-hydroxylase, GRP58 did not form prolyl 4-hydroxylase tetramers,
nor did it have prolyl 4-hydroxylase activity. Hirano et al. (1995)
expressed human GRP58 and found that the protein had a thiol-dependent
reductase activity. They showed that the expression level of GRP58 is
increased after oncogenic transformation of normal rat kidney cells and
NIH 3T3 cells.
Oliver et al. (1997) used a crosslinking approach to screen antisera to
several ER luminal proteins in order to find proteins that interact
specifically with glycoproteins in the ER. They identified GRP58 as one
such protein. The authors suggested that GRP58 functions in combination
with calnexin (114217) and calreticulin (109091) as a molecular
chaperone of glycoprotein biosynthesis.
Using specific antibodies and inhibitors of PDI activity, Ellerman et
al. (2006) determined that Erp57 on the surface of the mouse sperm head
was involved in sperm-egg fusion. They hypothesized that thiol-disulfide
exchange in gamete fusion may produce conformational changes in
fusion-active proteins.
GENE STRUCTURE
Koivunen et al. (1997) examined the genomic organization of the GRP58
gene and reported that it is encoded on 13 exons spanning 18 kb; no
similarity was found between the genomic structures of the GRP58, PDI,
and thioredoxin (187700) genes.
MAPPING
Koivunen et al. (1997) used fluorescence in situ hybridization to map
the GRP58 gene to human chromosome 15q15. They also observed that humans
have a processed pseudogene, GRP58P, which is nearly identical to GRP58
and maps to chromosome 1q21.
By Southern blot analysis of an interspecific backcross, Briquet-Laugier
et al. (1998) mapped the Grp58 gene to mouse chromosome 2.
ANIMAL MODEL
PDIA3 is part of the major histocompatibility complex (MHC) class I
peptide-loading complex (see TAP1; 170260), which is essential for final
antigen conformation and export from the ER to the cell surface. To
avoid embryonic lethality, Garbi et al. (2006) generated mice with a
conditional deletion of Pdia3 in the B-cell compartment. These mice
retained functional B cells with decreased MHC class I expression, as
shown by flow cytometry and immunoblot analysis. Immunoprecipitation
analysis showed that Pdia3 mediated recruitment of MHC class I molecules
and Calr (109091) into the peptide-loading complex. Lack of Pdia3
resulted in suboptimal peptide loading and decreased T-cell activation.
Garbi et al. (2006) concluded that PDIA3 is central to assembly of the
peptide-loading complex and contributes quantitatively and qualitatively
to MHC class I antigen presentation.
*FIELD* RF
1. Bourdi, M.; Demady, D.; Martin, J. L.; Jabbour, S. K.; Martin,
B. M.; George, J. W.; Pohl, L. R.: cDNA cloning and baculovirus expression
of the human liver endoplasmic reticulum P58: characterization as
a protein disulfide isomerase isoform, but not as a protease or a
carnitine acyltransferase. Arch. Biochem. Biophys. 323: 397-403,
1995.
2. Briquet-Laugier, V.; Xia, Y.-R.; Rooke, K.; Mehrabian, M.; Lusis,
A. J.; Doolittle, M. H.: Mapping of three members of the mouse protein
disulfide isomerase family. Mammalian Genome 9: 176-177, 1998.
3. Ellerman, D. A.; Myles, D. G.; Primakoff, P.: A role for sperm
surface protein disulfide isomerase activity in gamete fusion: evidence
for the participation of ERp57. Dev. Cell 10: 831-837, 2006.
4. Garbi, N.; Tanaka, S.; Momburg, F.; Hammerling, G. J.: Impaired
assembly of the major histocompatibility complex class I peptide-loading
complex in mice deficient in the oxidoreductase ERp57. Nature Immun. 7:
93-102, 2006.
5. Hirano, N.; Shibasaki, F.; Sakai, R.; Tanaka, T.; Nishida, J.;
Yazaki, Y.; Takenawa, T.; Hirai, H.: Molecular cloning of the human
glucose-regulated protein ERp57/GRP58, a thiol-dependent reductase:
identification of its secretory form and inducible expression by the
oncogenic transformation. Europ. J. Biochem. 234: 336-342, 1995.
6. Koivunen, P.; Helaakoski, T.; Annunen, P.; Veijola, J.; Raisanen,
S.; Pihlajaniemi, T.; Kivirikko, K. I.: ERp60 does not substitute
for protein disulphide isomerase as the beta-subunit of prolyl 4-hydroxylase. Biochem.
J. 316: 599-605, 1996.
7. Koivunen, P.; Horelli-Kuitunen, N.; Helaakoski, T.; Karvonen, P.;
Jaakkola, M.; Palotie, A.; Kivirikko, K. I.: Structures of the human
gene for the protein disulfide isomerase-related polypeptide ERp60
and a processed gene and assignment of these genes to 15q15 and 1q21. Genomics 42:
397-404, 1997.
8. Oliver, J. D.; van der Wal, F. J.; Bulleid, N. J.; High, S.: Interaction
of the thiol-dependent reductase ERp57 with nascent glycoproteins. Science 275:
86-88, 1997.
*FIELD* CN
Paul J. Converse - updated: 8/4/2006
Patricia A. Hartz - updated: 7/11/2006
Victor A. McKusick - updated: 3/27/1998
*FIELD* CD
Jennifer P. Macke: 10/13/1997
*FIELD* ED
mgross: 08/29/2006
terry: 8/4/2006
terry: 7/26/2006
mgross: 7/11/2006
terry: 7/11/2006
dkim: 11/13/1998
carol: 4/10/1998
dholmes: 3/27/1998
alopez: 10/22/1997
alopez: 10/13/1997
*RECORD*
*FIELD* NO
602046
*FIELD* TI
*602046 PROTEIN DISULFIDE ISOMERASE, FAMILY A, MEMBER 3; PDIA3
;;GLUCOSE-REGULATED PROTEIN, 58-KD; GRP58;;
read moreERp57;;
ER60
*FIELD* TX
CLONING
The cDNA encoding human GRP58 was cloned independently by Bourdi et al.
(1995), Koivunen et al. (1996), and Hirano et al. (1995). All reported
that the gene encodes a 505-amino acid polypeptide with significant
homology to human protein disulfide isomerase (PDI; 176790). Bourdi et
al. (1995) noted that the sequence includes a putative nuclear
localization motif and an endoplasmic reticulum (ER)-retention/retrieval
motif. Koivunen et al. (1997) noted that the GRP58 sequence has 2
thioredoxin-like domains. Koivunen et al. (1997) showed by Northern
blotting that GRP58 is expressed as a 2-kb message most abundantly in
liver, placenta, and lung, and at lower levels in all other tissues
tested.
GENE FUNCTION
Several laboratories have examined the functional properties of GRP58.
Bourdi et al. (1995) found that the GRP58 protein had protein disulfide
isomerase activity. Koivunen et al. (1996) showed that GRP58 could not
substitute for the beta subunit of PDI. When coexpressed with alpha
prolyl 4-hydroxylase, GRP58 did not form prolyl 4-hydroxylase tetramers,
nor did it have prolyl 4-hydroxylase activity. Hirano et al. (1995)
expressed human GRP58 and found that the protein had a thiol-dependent
reductase activity. They showed that the expression level of GRP58 is
increased after oncogenic transformation of normal rat kidney cells and
NIH 3T3 cells.
Oliver et al. (1997) used a crosslinking approach to screen antisera to
several ER luminal proteins in order to find proteins that interact
specifically with glycoproteins in the ER. They identified GRP58 as one
such protein. The authors suggested that GRP58 functions in combination
with calnexin (114217) and calreticulin (109091) as a molecular
chaperone of glycoprotein biosynthesis.
Using specific antibodies and inhibitors of PDI activity, Ellerman et
al. (2006) determined that Erp57 on the surface of the mouse sperm head
was involved in sperm-egg fusion. They hypothesized that thiol-disulfide
exchange in gamete fusion may produce conformational changes in
fusion-active proteins.
GENE STRUCTURE
Koivunen et al. (1997) examined the genomic organization of the GRP58
gene and reported that it is encoded on 13 exons spanning 18 kb; no
similarity was found between the genomic structures of the GRP58, PDI,
and thioredoxin (187700) genes.
MAPPING
Koivunen et al. (1997) used fluorescence in situ hybridization to map
the GRP58 gene to human chromosome 15q15. They also observed that humans
have a processed pseudogene, GRP58P, which is nearly identical to GRP58
and maps to chromosome 1q21.
By Southern blot analysis of an interspecific backcross, Briquet-Laugier
et al. (1998) mapped the Grp58 gene to mouse chromosome 2.
ANIMAL MODEL
PDIA3 is part of the major histocompatibility complex (MHC) class I
peptide-loading complex (see TAP1; 170260), which is essential for final
antigen conformation and export from the ER to the cell surface. To
avoid embryonic lethality, Garbi et al. (2006) generated mice with a
conditional deletion of Pdia3 in the B-cell compartment. These mice
retained functional B cells with decreased MHC class I expression, as
shown by flow cytometry and immunoblot analysis. Immunoprecipitation
analysis showed that Pdia3 mediated recruitment of MHC class I molecules
and Calr (109091) into the peptide-loading complex. Lack of Pdia3
resulted in suboptimal peptide loading and decreased T-cell activation.
Garbi et al. (2006) concluded that PDIA3 is central to assembly of the
peptide-loading complex and contributes quantitatively and qualitatively
to MHC class I antigen presentation.
*FIELD* RF
1. Bourdi, M.; Demady, D.; Martin, J. L.; Jabbour, S. K.; Martin,
B. M.; George, J. W.; Pohl, L. R.: cDNA cloning and baculovirus expression
of the human liver endoplasmic reticulum P58: characterization as
a protein disulfide isomerase isoform, but not as a protease or a
carnitine acyltransferase. Arch. Biochem. Biophys. 323: 397-403,
1995.
2. Briquet-Laugier, V.; Xia, Y.-R.; Rooke, K.; Mehrabian, M.; Lusis,
A. J.; Doolittle, M. H.: Mapping of three members of the mouse protein
disulfide isomerase family. Mammalian Genome 9: 176-177, 1998.
3. Ellerman, D. A.; Myles, D. G.; Primakoff, P.: A role for sperm
surface protein disulfide isomerase activity in gamete fusion: evidence
for the participation of ERp57. Dev. Cell 10: 831-837, 2006.
4. Garbi, N.; Tanaka, S.; Momburg, F.; Hammerling, G. J.: Impaired
assembly of the major histocompatibility complex class I peptide-loading
complex in mice deficient in the oxidoreductase ERp57. Nature Immun. 7:
93-102, 2006.
5. Hirano, N.; Shibasaki, F.; Sakai, R.; Tanaka, T.; Nishida, J.;
Yazaki, Y.; Takenawa, T.; Hirai, H.: Molecular cloning of the human
glucose-regulated protein ERp57/GRP58, a thiol-dependent reductase:
identification of its secretory form and inducible expression by the
oncogenic transformation. Europ. J. Biochem. 234: 336-342, 1995.
6. Koivunen, P.; Helaakoski, T.; Annunen, P.; Veijola, J.; Raisanen,
S.; Pihlajaniemi, T.; Kivirikko, K. I.: ERp60 does not substitute
for protein disulphide isomerase as the beta-subunit of prolyl 4-hydroxylase. Biochem.
J. 316: 599-605, 1996.
7. Koivunen, P.; Horelli-Kuitunen, N.; Helaakoski, T.; Karvonen, P.;
Jaakkola, M.; Palotie, A.; Kivirikko, K. I.: Structures of the human
gene for the protein disulfide isomerase-related polypeptide ERp60
and a processed gene and assignment of these genes to 15q15 and 1q21. Genomics 42:
397-404, 1997.
8. Oliver, J. D.; van der Wal, F. J.; Bulleid, N. J.; High, S.: Interaction
of the thiol-dependent reductase ERp57 with nascent glycoproteins. Science 275:
86-88, 1997.
*FIELD* CN
Paul J. Converse - updated: 8/4/2006
Patricia A. Hartz - updated: 7/11/2006
Victor A. McKusick - updated: 3/27/1998
*FIELD* CD
Jennifer P. Macke: 10/13/1997
*FIELD* ED
mgross: 08/29/2006
terry: 8/4/2006
terry: 7/26/2006
mgross: 7/11/2006
terry: 7/11/2006
dkim: 11/13/1998
carol: 4/10/1998
dholmes: 3/27/1998
alopez: 10/22/1997
alopez: 10/13/1997