ID   PDIA1_PONAB             Reviewed;         508 AA.
AC   Q5R5B6;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   13-SEP-2023, entry version 105.
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   AltName: Full=p55;
DE   Flags: Precursor;
GN   Name=P4HB; Synonyms=PDIA1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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-357 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}.
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DR   EMBL; CR860947; CAH93050.1; -; mRNA.
DR   RefSeq; NP_001126805.1; NM_001133333.1.
DR   AlphaFoldDB; Q5R5B6; -.
DR   BMRB; Q5R5B6; -.
DR   SMR; Q5R5B6; -.
DR   STRING; 9601.ENSPPYP00000009818; -.
DR   GeneID; 100173809; -.
DR   KEGG; pon:100173809; -.
DR   CTD; 5034; -.
DR   eggNOG; KOG0190; Eukaryota.
DR   InParanoid; Q5R5B6; -.
DR   OrthoDB; 5399045at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
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; Reference proteome; Repeat; Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000250"
FT   CHAIN           18..508
FT                   /note="Protein disulfide-isomerase"
FT                   /id="PRO_0000034197"
FT   DOMAIN          18..134
FT                   /note="Thioredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          349..475
FT                   /note="Thioredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   REGION          471..508
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           505..508
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   COMPBIAS        476..508
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        53
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        56
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        397
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        400
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   SITE            54
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            55
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            120
FT                   /note="Lowers pKa of C-terminal Cys of first active site"
FT                   /evidence="ECO:0000250"
FT   SITE            398
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            399
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            461
FT                   /note="Lowers pKa of C-terminal Cys of second active site"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         200
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09103"
FT   MOD_RES         222
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09103"
FT   MOD_RES         271
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P09103"
FT   MOD_RES         331
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07237"
FT   MOD_RES         357
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07237"
FT   MOD_RES         427
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P07237"
FT   DISULFID        53..56
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        397..400
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
SQ   SEQUENCE   508 AA;  57033 MW;  114D79D9BC740400 CRC64;
     MLRRALLCLA VAGLVCADAP EEEDHVLVLR KSNFAEALAA HKYLLVEFYA PWCGHCKALA
     PEYAKAAGKL KAEGSEIRLA KVDATEESDL AQQYGVRGYP TIKFFRNGDT ASPKEYTAGR
     EADDIVNWLK KRTGPAATIL PDGAAAESLV ESSEVAVVGF FKDVESDSAK QFLQAAEAID
     DIPFGITSNS DVFSKYQLDK DGVVLFKKFD EGRNNFEGEV TKENLLDFIK HNQLPLVIEF
     TEQTAPKIFG GEIKTHILLF LPKSVSDYDG KLSNFKTAAE SFKGKILFIF IDSDHTDNQR
     ILEFFGLKKE ECPAVRLITL EEEMTKYKPE SEELTAERIT EFCHRFLEGK IKPHLMSQEL
     PDDWDKQPVK VLVGKNFEDV AFDEKKNVFV EFYAPWCGHC KQLAPIWDKL GETYKDHENI
     VIAKMDSTAN EVEAVKVHSF PTLKFFPASA DRTVIDYNGE RTLDGFKKFL ESGGQDGAGD
     DDDLEDLEEA EEPDMEEDDD QKAVKDEL
//