ID   PDIA1_MACFU             Reviewed;         510 AA.
AC   Q2HWU2;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   13-SEP-2023, entry version 87.
DE   RecName: Full=Protein disulfide-isomerase;
DE            Short=PDI;
DE            EC=5.3.4.1 {ECO:0000250|UniProtKB:P07237};
DE   AltName: Full=Prolyl 4-hydroxylase subunit beta;
DE   Flags: Precursor;
GN   Name=P4HB; Synonyms=PDI, PDIA1;
OS   Macaca fuscata fuscata (Japanese macaque).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9543;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=17214666; DOI=10.1111/j.1600-0684.2006.00186.x;
RA   Higashino A., Fukuhara R., Tezuka T., Kageyama T.;
RT   "Molecular cloning and gene expression of endoplasmic reticulum stress
RT   proteins in Japanese monkey, Macaca fuscata.";
RL   J. Med. Primatol. 35:376-383(2006).
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. Homodimer. Monomers and
CC       homotetramers may also occur. Interacts with P4HA2, forming a
CC       heterotetramer consisting of 2 alpha subunits (P4HA2) and 2 beta
CC       (P4HB), where P4HB plays the role of a structural subunit; this
CC       tetramer catalyzes the formation of 4-hydroxyproline in collagen (By
CC       similarity). Also constitutes the structural subunit of the microsomal
CC       triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes
CC       both enzymes and retain them in the ER without contributing to the
CC       catalytic activity. Binds UBQLN1. Interacts with ERO1B. Interacts with
CC       ILDR2 (By similarity). Interacts with ERN1/IRE1A (via N-terminus); the
CC       interaction is enhanced by phosphorylation of P4HB by FAM20C in
CC       response to endoplasmic reticulum stress and results in attenuation of
CC       ERN1 activity (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P07237, 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   ---------------------------------------------------------------------------
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; AB232156; BAE79726.1; -; mRNA.
DR   AlphaFoldDB; Q2HWU2; -.
DR   BMRB; Q2HWU2; -.
DR   SMR; Q2HWU2; -.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0003756; F:protein disulfide isomerase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   CDD; cd02961; PDI_a_family; 1.
DR   CDD; cd02995; PDI_a_PDI_a'_C; 1.
DR   CDD; cd02982; PDI_b'_family; 1.
DR   CDD; cd02981; PDI_b_family; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 4.
DR   InterPro; IPR005788; PDI_thioredoxin-like_dom.
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:SF101; PROTEIN DISULFIDE-ISOMERASE; 1.
DR   Pfam; PF00085; Thioredoxin; 2.
DR   Pfam; PF13848; Thioredoxin_6; 1.
DR   PRINTS; PR00421; THIOREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 4.
DR   PROSITE; PS00014; ER_TARGET; 1.
DR   PROSITE; PS00194; THIOREDOXIN_1; 2.
DR   PROSITE; PS51352; THIOREDOXIN_2; 2.
PE   2: Evidence at transcript level;
KW   Acetylation; Cell membrane; Chaperone; Disulfide bond;
KW   Endoplasmic reticulum; Isomerase; Membrane; Phosphoprotein;
KW   Redox-active center; Repeat; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250"
FT   CHAIN           20..510
FT                   /note="Protein disulfide-isomerase"
FT                   /id="PRO_0000246155"
FT   DOMAIN          20..136
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          351..477
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          473..510
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           507..510
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   COMPBIAS        478..510
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ   SEQUENCE   510 AA;  57304 MW;  5F917B017F418BE2 CRC64;
     MLRRALLCLA VAAAPGLYAD APEEEDHVLV LRKSNFAEAL AAHKYLLVEF YAPWCGHCKA
     LAPEYAKAAG KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFRNG DTASPKEYTA
     GREADDIVNW LKKRTGPAAT TLPDGAAAES LVESSEVAVI GFFKDVESDS AKQFLQAAEA
     IDDIPFGITS NSDVFSKYQL DKDGVVLFKK FDEGRNNFEG EVTKENLLDF IKYNQLPLVI
     EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSNFKTA AESFKGKILF IFIDSDHTDN
     QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAER ITEFCHRFLE GKIKPHLMSQ
     ELPEDWDKQP VKVLVGKNFE EVAFDENKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE
     NIVIAKMDST ANEVEAIKVH SFPTLKFFPA SVDRTVIDYN GERTLDGFKK FLESGGQDGA
     GDDDDLEDLE EAEEPDMEED DDQKAVKDEL
//