PDIA1_RAT
ID PDIA1_RAT Reviewed; 509 AA.
AC P04785; P13700;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Protein disulfide-isomerase;
DE Short=PDI;
DE EC=5.3.4.1 {ECO:0000250|UniProtKB:P07237};
DE AltName: Full=Cellular thyroid hormone-binding protein;
DE AltName: Full=Prolyl 4-hydroxylase subunit beta;
DE Flags: Precursor;
GN Name=P4hb; Synonyms=Pdia1;
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].
RC TISSUE=Liver;
RX PubMed=3840230; DOI=10.1038/317267a0;
RA Edman J.C., Ellis L., Blacher R.W., Roth R.A., Rutter W.J.;
RT "Sequence of protein disulphide isomerase and implications of its
RT relationship to thioredoxin.";
RL Nature 317:267-270(1985).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 20-34.
RC STRAIN=LEC; TISSUE=Liver;
RX PubMed=8251535; DOI=10.1016/0304-4165(93)90033-5;
RA Yokoi T., Nagayama S., Kajiwara R., Kawaguchi Y., Horiuchi R., Kamataki T.;
RT "Identification of protein disulfide isomerase and calreticulin as
RT autoimmune antigens in LEC strain of rats.";
RL Biochim. Biophys. Acta 1158:339-344(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-509.
RC TISSUE=Liver;
RX PubMed=3178809; DOI=10.1016/s0006-291x(88)81282-8;
RA Boado R.J., Campbell D.A., Chopra I.J.;
RT "Nucleotide sequence of rat liver iodothyronine 5'-monodeiodinase (5' MD):
RT its identity with the protein disulfide isomerase.";
RL Biochem. Biophys. Res. Commun. 155:1297-1304(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 129-394.
RC TISSUE=Liver;
RX PubMed=2841089; DOI=10.1210/endo-123-3-1264;
RA Boado R.J., Chopra I.J., Flink I.L., Campbell D.A.;
RT "Enzyme binding-inhibiting assay for iodothyronine 5'-monodeiodinase (5'-
RT MD) and its application to isolation of complementary deoxyribonucleic acid
RT clones for the 5'-MD in rat liver.";
RL Endocrinology 123:1264-1273(1988).
RN [6]
RP PROTEIN SEQUENCE OF 233-249; 288-302 AND 341-352, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [7]
RP PROTEIN SEQUENCE OF 471-494.
RX PubMed=8366073; DOI=10.1016/s0021-9258(19)36501-9;
RA Noiva R., Freedman R.B., Lennarz W.J.;
RT "Peptide binding to protein disulfide isomerase occurs at a site distinct
RT from the active sites.";
RL J. Biol. Chem. 268:19210-19217(1993).
RN [8]
RP SHOWS THAT PROTEIN IS NOT IDENTICAL TO THYROXINE DEIODINASE.
RX PubMed=2757644; DOI=10.1016/0006-291x(89)92389-9;
RA Schoenmakers C.H.H., Pigmans I.G.A.J., Hawkins H.C., Freedman R.B.,
RA Visser T.J.;
RT "Rat liver type I iodothyronine deiodinase is not identical to protein
RT disulfide isomerase.";
RL Biochem. Biophys. Res. Commun. 162:857-868(1989).
CC -!- FUNCTION: This multifunctional protein catalyzes the formation,
CC breakage and rearrangement of disulfide bonds. At the cell surface,
CC seems to act as a reductase that cleaves disulfide bonds of proteins
CC attached to the cell. May therefore cause structural modifications of
CC exofacial proteins. Inside the cell, seems to form/rearrange disulfide
CC bonds of nascent proteins. At high concentrations and following
CC phosphorylation by FAM20C, functions as a chaperone that inhibits
CC aggregation of misfolded proteins. At low concentrations, facilitates
CC aggregation (anti-chaperone activity). May be involved with other
CC chaperones in the structural modification of the TG precursor in
CC hormone biogenesis. Also acts as a structural subunit of various
CC enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol
CC transfer protein MTTP. Receptor for LGALS9; the interaction retains
CC P4HB at the cell surface of Th2 T helper cells, increasing disulfide
CC reductase activity at the plasma membrane, altering the plasma membrane
CC redox state and enhancing cell migration.
CC {ECO:0000250|UniProtKB:P07237}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000250|UniProtKB:P07237};
CC -!- SUBUNIT: Heterodimer; heterodimerizes with the protein microsomal
CC triglyceride transfer MTTP. Homodimer. Monomers and homotetramers may
CC also occur. Interacts with P4HA2, forming a heterotetramer consisting
CC of 2 alpha subunits (P4HA2) and 2 beta (P4HB), where P4HB plays the
CC role of a structural subunit; this tetramer catalyzes the formation of
CC 4-hydroxyproline in collagen (By similarity). Also constitutes the
CC structural subunit of the microsomal triacylglycerol transfer protein
CC MTTP in mammalian cells. Stabilizes both enzymes and retain them in the
CC ER without contributing to the catalytic activity. Binds UBQLN1.
CC Interacts with ERO1B. Interacts with ILDR2 (By similarity). Interacts
CC with ERN1/IRE1A (via N-terminus); the interaction is enhanced by
CC phosphorylation of P4HB by FAM20C in response to endoplasmic reticulum
CC stress and results in attenuation of ERN1 activity (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P07237,
CC ECO:0000250|UniProtKB:P09103}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P07237}. Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P07237}. Melanosome
CC {ECO:0000250|UniProtKB:P07237}. Cell membrane
CC {ECO:0000250|UniProtKB:P09103}; Peripheral membrane protein
CC {ECO:0000305}. Note=Highly abundant. In some cell types, seems to be
CC also secreted or associated with the plasma membrane, where it
CC undergoes constant shedding and replacement from intracellular sources.
CC Localizes near CD4-enriched regions on lymphoid cell surfaces.
CC Colocalizes with MTTP in the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:P07237}.
CC -!- PTM: Phosphorylation of Ser-359 by FAM20C is induced by endoplasmic
CC reticulum stress and results in a functional switch from oxidoreductase
CC to molecular chaperone. It also promotes interaction with ERN1.
CC {ECO:0000250|UniProtKB:P07237}.
CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:8251535 and PubMed:3178809) thought to
CC be identical to thyroxine deiodinase but this was later shown to be
CC incorrect. {ECO:0000305|PubMed:2757644}.
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DR EMBL; M21018; AAA40620.1; -; mRNA.
DR EMBL; BC061857; AAH61857.1; -; mRNA.
DR EMBL; X02918; CAA26675.1; -; mRNA.
DR EMBL; M21476; AAA40619.1; -; mRNA.
DR PIR; A24595; ISRTSS.
DR PIR; S68028; S68028.
DR RefSeq; NP_037130.2; NM_012998.2.
DR AlphaFoldDB; P04785; -.
DR SMR; P04785; -.
DR BioGRID; 247538; 2.
DR IntAct; P04785; 8.
DR MINT; P04785; -.
DR STRING; 10116.ENSRNOP00000051841; -.
DR iPTMnet; P04785; -.
DR PhosphoSitePlus; P04785; -.
DR jPOST; P04785; -.
DR PaxDb; P04785; -.
DR PRIDE; P04785; -.
DR Ensembl; ENSRNOT00000054958; ENSRNOP00000051841; ENSRNOG00000036689.
DR GeneID; 25506; -.
DR KEGG; rno:25506; -.
DR CTD; 5034; -.
DR RGD; 3244; P4hb.
DR eggNOG; KOG0190; Eukaryota.
DR GeneTree; ENSGT00940000157351; -.
DR HOGENOM; CLU_025879_1_0_1; -.
DR InParanoid; P04785; -.
DR OMA; FCDRFLE; -.
DR OrthoDB; 462118at2759; -.
DR PhylomeDB; P04785; -.
DR TreeFam; TF106381; -.
DR BRENDA; 5.3.4.1; 5301.
DR Reactome; R-RNO-1650814; Collagen biosynthesis and modifying enzymes.
DR Reactome; R-RNO-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-RNO-8866423; VLDL assembly.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR Reactome; R-RNO-8963888; Chylomicron assembly.
DR Reactome; R-RNO-8964041; LDL remodeling.
DR Reactome; R-RNO-9020591; Interleukin-12 signaling.
DR Reactome; R-RNO-9020933; Interleukin-23 signaling.
DR PRO; PR:P04785; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000036689; Expressed in jejunum and 20 other tissues.
DR Genevisible; P04785; RN.
DR GO; GO:0005856; C:cytoskeleton; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISO:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016222; C:procollagen-proline 4-dioxygenase complex; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0003779; F:actin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0004656; F:procollagen-proline 4-dioxygenase activity; IEA:Ensembl.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IMP:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISO:RGD.
DR GO; GO:0016972; F:thiol oxidase activity; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
DR GO; GO:0098761; P:cellular response to interleukin-7; ISO:RGD.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISO:RGD.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:RGD.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; ISO:RGD.
DR GO; GO:1902175; P:regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD.
DR InterPro; IPR005788; Disulphide_isomerase.
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; PS00014; ER_TARGET; 1.
DR PROSITE; PS00194; THIOREDOXIN_1; 2.
DR PROSITE; PS51352; THIOREDOXIN_2; 2.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Chaperone; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Isomerase; Membrane; Phosphoprotein;
KW Redox-active center; Reference proteome; Repeat; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:8251535"
FT CHAIN 20..509
FT /note="Protein disulfide-isomerase"
FT /id="PRO_0000034199"
FT DOMAIN 20..136
FT /note="Thioredoxin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 335..477
FT /note="Thioredoxin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT MOTIF 506..509
FT /note="Prevents secretion from ER"
FT ACT_SITE 55
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 58
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 399
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 402
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 56
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 57
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 122
FT /note="Lowers pKa of C-terminal Cys of first active site"
FT /evidence="ECO:0000250"
FT SITE 400
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 401
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 463
FT /note="Lowers pKa of C-terminal Cys of second active site"
FT /evidence="ECO:0000250"
FT MOD_RES 202
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09103"
FT MOD_RES 224
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09103"
FT MOD_RES 273
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09103"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT DISULFID 55..58
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DISULFID 399..402
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT CONFLICT 39..40
FT /note="AL -> P (in Ref. 1; CAA26675)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 56951 MW; 3056107F5E8B1B54 CRC64;
MLSRALLCLA LAWAARVGAD ALEEEDNVLV LKKSNFAEAL AAHNYLLVEF YAPWCGHCKA
LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFKNG DTASPKEYTA
GREADDIVNW LKKRTGPAAT TLSDTAAAES LVDSSEVTVI GFFKDAGSDS AKQFLLAAEA
VDDIPFGITS NSDVFSKYQL DKDGVVLFKK FDEGRNNFEG EITKEKLLDF IKHNQLPLVI
EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSNFKKA AEGFKGKILF IFIDSDHTDN
QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITQFCHHFLE GKIKPHLMSQ
ELPEDWDKQP VKVLVGKNFE EVAFDEKKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE
NIVIAKMDST ANEVEAVKVH SFPTLKFFPA SADRTVIDYN GERTLDGFKK FLESGGQDGA
GDNDDLDLEE ALEPDMEEDD DQKAVKDEL
