PDIA1_PONAB
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 03-AUG-2022, entry version 100.
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 PRIDE; Q5R5B6; -.
DR GeneID; 100173809; -.
DR KEGG; pon:100173809; -.
DR CTD; 5034; -.
DR eggNOG; KOG0190; Eukaryota.
DR InParanoid; Q5R5B6; -.
DR OrthoDB; 462118at2759; -.
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 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 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
