PDIA1_CRIGR
ID PDIA1_CRIGR Reviewed; 509 AA.
AC Q8R4U2;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 112.
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 AltName: Full=p58;
DE Flags: Precursor;
GN Name=P4HB; Synonyms=PDIA1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Small intestine;
RX PubMed=12020637; DOI=10.1016/s1388-1981(02)00128-2;
RA Cai T.-Q., Guo Q., Wong B., Milot D., Zhang L., Wright S.D.;
RT "Protein-disulfide isomerase is a component of an NBD-cholesterol
RT monomerizing protein complex from hamster small intestine.";
RL Biochim. Biophys. Acta 1581:100-108(2002).
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}.
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DR EMBL; AF364317; AAM00284.1; -; mRNA.
DR RefSeq; NP_001233622.1; NM_001246693.1.
DR AlphaFoldDB; Q8R4U2; -.
DR SMR; Q8R4U2; -.
DR STRING; 10029.XP_007634117.1; -.
DR GeneID; 100689433; -.
DR KEGG; cge:100689433; -.
DR CTD; 5034; -.
DR eggNOG; KOG0190; Eukaryota.
DR OrthoDB; 462118at2759; -.
DR PRO; PR:Q8R4U2; -.
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; Repeat; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..509
FT /note="Protein disulfide-isomerase"
FT /id="PRO_0000034194"
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 REGION 473..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 506..509
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT COMPBIAS 478..509
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 509 AA; 57010 MW; 9B9B7513DE918194 CRC64;
MLSRSLLCLA LAWVARVGAD APEEEDNVLV LKKSNFAEAL AAHNYLLVEF YAPWCGHCKA
LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFKNG DTASPKEYTA
GREADDIVNW LKKRTGPAAT TLSDTAAAET LIDSSEVAVI GFFKDVESDS AKQFLLAAEA
VDDIPFGITS NSGVFSKYQL DKDGVVLFKK FDEGRNNFEG EVTKEKLLDF IKHNQLPLVI
EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLGNFKKA AEGFKGKILF IFIDSDHTDN
QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITEFCHRFLE GKIKPHLMSQ
ELPEDWDKQP VKVLVGKNFE EVAFDEKKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE
NIIIAKMDST ANEVEAVKVH SFPTLKFFPA TADRTVIDYN GERTLDGFKK FLESGGQDGA
GDDDDVDLEE ALEPDMEEDD DQKAVKDEL
