PDIA3_RAT
ID PDIA3_RAT Reviewed; 505 AA.
AC P11598;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Protein disulfide-isomerase A3;
DE EC=5.3.4.1 {ECO:0000250|UniProtKB:P30101};
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 AltName: Full=HIP-70;
DE AltName: Full=Q-2;
DE Flags: Precursor;
GN Name=Pdia3; Synonyms=Erp60, Grp58;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3398923; DOI=10.1038/334268a0;
RA Bennett C.F., Balcarek J.M., Varrichio A., Crooke S.T.;
RT "Molecular cloning and complete amino-acid sequence of form-I
RT phosphoinositide-specific phospholipase C.";
RL Nature 334:268-270(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kito M., Urade R.;
RT "Role of novel microsomal cysteine proteases.";
RL Proc. Jpn. Acad., B, Phys. Biol. Sci. 71:189-192(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=1650195; DOI=10.1016/0006-291x(91)90161-y;
RA Martin J.L., Pumford N.R., Larosa A.C., Martin B.M., Gonzaga H.M.S.,
RA Beaven M.A., Pohl L.R.;
RT "A metabolite of halothane covalently binds to an endoplasmic reticulum
RT protein that is highly homologous to phosphatidylinositol-specific
RT phospholipase C-alpha but has no activity.";
RL Biochem. Biophys. Res. Commun. 178:679-685(1991).
RN [5]
RP PROTEIN SEQUENCE OF 26-43.
RC TISSUE=Brain, and Pituitary;
RX PubMed=2181662; DOI=10.1126/science.247.4949.1477;
RA Mobbs C.V., Fink G., Pfaff D.W.;
RT "HIP-70: a protein induced by estrogen in the brain and LH-RH in the
RT pituitary.";
RL Science 247:1477-1479(1990).
RN [6]
RP PROTEIN SEQUENCE OF 25-54; 258-269; 285-310; 347-350; 412-419 AND 434-463.
RC TISSUE=Liver;
RX PubMed=1657921; DOI=10.1016/s0021-9258(18)54928-0;
RA Srivastava S.P., Chen N.Q., Liu Y.X., Holtzman J.L.;
RT "Purification and characterization of a new isozyme of thiol:protein-
RT disulfide oxidoreductase from rat hepatic microsomes. Relationship of this
RT isozyme to cytosolic phosphatidylinositol-specific phospholipase C form
RT 1A.";
RL J. Biol. Chem. 266:20337-20344(1991).
RN [7]
RP PROTEIN SEQUENCE OF 26-34; 174-193; 433-446 AND 448-458.
RX PubMed=1321829; DOI=10.1016/s0021-9258(18)42159-x;
RA Urade R., Nasu M., Moriyama T., Wada K., Kito M.;
RT "Protein degradation by the phosphoinositide-specific phospholipase C-alpha
RT family from rat liver endoplasmic reticulum.";
RL J. Biol. Chem. 267:15152-15159(1992).
RN [8]
RP PROTEIN SEQUENCE OF 105-119; 148-161; 184-214; 259-271; 306-329; 336-344;
RP 352-363; 449-460 AND 472-482, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (DEC-2006) to UniProtKB.
RN [9]
RP MUTAGENESIS OF 502-GLN--LEU-505.
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 [10]
RP INHIBITION BY PHOSPHOLIPIDS.
RX PubMed=1330685; DOI=10.1016/0014-5793(92)81415-i;
RA Urade R., Kito M.;
RT "Inhibition by acidic phospholipids of protein degradation by ER-60
RT protease, a novel cysteine protease, of endoplasmic reticulum.";
RL FEBS Lett. 312:83-86(1992).
RN [11]
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).
CC -!- FUNCTION: Disulfide isomerase which catalyzes the formation,
CC isomerization, and reduction or oxidation of disulfide bonds (By
CC similarity). Associates with calcitriol, the active form of vitamin D3
CC which mediates the action of this vitamin on cells (By similarity).
CC Association with calcitriol does not affect its enzymatic activity (By
CC similarity). {ECO:0000250|UniProtKB:P30101}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000250|UniProtKB:P30101};
CC -!- ACTIVITY REGULATION: Seems to be inhibited by acidic phospholipids.
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 (By similarity). Interacts with MZB1 in a
CC calcium-dependent manner (By similarity). Interacts with SERPINA2 and
CC with the S and Z variants of SERPINA1. Interacts with ATP2A2 (By
CC similarity). {ECO:0000250|UniProtKB:P27773,
CC ECO:0000250|UniProtKB:P30101}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P30101}. Endoplasmic reticulum lumen
CC {ECO:0000250}. Melanosome {ECO:0000250|UniProtKB:P30101}.
CC -!- TISSUE SPECIFICITY: In caput epididymal spermatozoa, detected in the
CC head, mid and principal pieces. In cauda epididymal spermatozoa
CC detected only in the acrosome (at protein level).
CC {ECO:0000269|PubMed:20400973}.
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a phosphatidyl-inositol 4,5-
CC bisphosphate phosphodiesterase type I (phospholipase C-alpha) then was
CC thought (PubMed:1321829 and PubMed:1330685) to be a thiol protease.
CC {ECO:0000305|PubMed:3398923}.
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DR EMBL; X12355; CAA30916.1; -; mRNA.
DR EMBL; D63378; BAA09695.1; -; mRNA.
DR EMBL; BC062393; AAH62393.1; -; mRNA.
DR PIR; A28807; A28807.
DR PIR; A61354; A61354.
DR RefSeq; NP_059015.1; NM_017319.1.
DR AlphaFoldDB; P11598; -.
DR SMR; P11598; -.
DR BioGRID; 248111; 4.
DR IntAct; P11598; 8.
DR MINT; P11598; -.
DR STRING; 10116.ENSRNOP00000020478; -.
DR CarbonylDB; P11598; -.
DR iPTMnet; P11598; -.
DR PhosphoSitePlus; P11598; -.
DR SwissPalm; P11598; -.
DR World-2DPAGE; 0004:P11598; -.
DR jPOST; P11598; -.
DR PaxDb; P11598; -.
DR PRIDE; P11598; -.
DR GeneID; 29468; -.
DR KEGG; rno:29468; -.
DR UCSC; RGD:68430; rat.
DR CTD; 2923; -.
DR RGD; 68430; Pdia3.
DR eggNOG; KOG0190; Eukaryota.
DR HOGENOM; CLU_025879_6_0_1; -.
DR InParanoid; P11598; -.
DR OrthoDB; 462118at2759; -.
DR PhylomeDB; P11598; -.
DR TreeFam; TF106382; -.
DR Reactome; R-RNO-1236974; ER-Phagosome pathway.
DR Reactome; R-RNO-901042; Calnexin/calreticulin cycle.
DR Reactome; R-RNO-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:P11598; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P11598; RN.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:RGD.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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:0005758; C:mitochondrial intermembrane space; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0042825; C:TAP complex; IDA:RGD.
DR GO; GO:0061779; C:Tapasin-ERp57 complex; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:RGD.
DR GO; GO:0008233; F:peptidase activity; IDA:RGD.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IBA:GO_Central.
DR GO; GO:0019153; F:protein-disulfide reductase (glutathione) activity; IMP:RGD.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISO:RGD.
DR GO; GO:0098761; P:cellular response to interleukin-7; ISO:RGD.
DR GO; GO:1904148; P:cellular response to nonylphenol; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0071305; P:cellular response to vitamin D; IDA:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0002502; P:peptide antigen assembly with MHC class I protein complex; ISO:RGD.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:1903334; P:positive regulation of protein folding; IDA:RGD.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:1901423; P:response to benzene; IEP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IBA:GO_Central.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0033595; P:response to genistein; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:0044321; P:response to leptin; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
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 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:1657921"
FT CHAIN 25..505
FT /note="Protein disulfide-isomerase A3"
FT /id="PRO_0000034227"
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 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:0000250|UniProtKB:P30101"
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:0000250|UniProtKB:P30101"
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:0000250"
FT DISULFID 85..92
FT /evidence="ECO:0000250"
FT DISULFID 406..409
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT MUTAGEN 502..505
FT /note="QEDL->AAGL: Failure to prevent secretion from ER."
FT /evidence="ECO:0000269|PubMed:9399589"
FT MUTAGEN 502..505
FT /note="Missing: Failure to prevent secretion from ER."
FT /evidence="ECO:0000269|PubMed:9399589"
FT CONFLICT 1..13
FT /note="MRFSCLALLPGVA -> MPSAALRCSRAWR (in Ref. 1;
FT CAA30916)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="S -> T (in Ref. 1; CAA30916)"
FT /evidence="ECO:0000305"
FT CONFLICT 232..240
FT /note="IKKFIQESI -> SRSLFRKA (in Ref. 1; CAA30916)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="F -> L (in Ref. 2; BAA09695)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 56623 MW; EAC7F0C0BD4F1471 CRC64;
MRFSCLALLP GVALLLASAL LASASDVLEL TDENFESRVS DTGSAGLMLV EFFAPWCGHC
KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY PTLKIFRDGE EAGAYDGPRT
ADGIVSHLKK QAGPASVPLR TEDEFKKFIS DKDASVVGFF RDLFSDGHSE FLKAASNLRD
NYRFAHTNVE SLVKEYDDNG EGITIFRPLH LANKFEDKIV AYTEKKMTSG KIKKFIQESI
FGLCPHMTED NKDLIQGKDL LTAYYDVDYE KNTKGSNYWR NRVMMVAKTF LDAGHKLNFA
VASRKTFSHE LSDFGLESTT GEIPVVAIRT AKGEKFVMQE EFSRDGKALE RFLQEYFDGN
LKRYLKSEPI PETNEGPVKV VVAESFDDIV NAEDKDVLIE FYAPWCGHCK NLEPKYKELG
EKLSKDPNIV IAKMDATAND VPSPYEVKGF PTIYFSPANK KLTPKKYEGG RELNDFISYL
QREATNPPII QEEKPKKKKK AQEDL
