PDIA1_RABIT
ID PDIA1_RABIT Reviewed; 509 AA.
AC P21195;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 134.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1697592; DOI=10.1016/s0021-9258(18)55423-5;
RA Fliegel L., Newton E., Burns K., Michalak M.;
RT "Molecular cloning of cDNA encoding a 55-kDa multifunctional thyroid
RT hormone binding protein of skeletal muscle sarcoplasmic reticulum.";
RL J. Biol. Chem. 265:15496-15502(1990).
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-358 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; J05602; AAA31476.1; -; mRNA.
DR PIR; A38362; A38362.
DR RefSeq; NP_001164518.1; NM_001171047.1.
DR AlphaFoldDB; P21195; -.
DR SMR; P21195; -.
DR BioGRID; 1173214; 2.
DR PRIDE; P21195; -.
DR GeneID; 100328595; -.
DR KEGG; ocu:100328595; -.
DR CTD; 5034; -.
DR InParanoid; P21195; -.
DR Proteomes; UP000001811; 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 Cell membrane; Chaperone; Disulfide bond; Endoplasmic reticulum; Isomerase;
KW Membrane; Phosphoprotein; Redox-active center; Reference proteome; Repeat;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..509
FT /note="Protein disulfide-isomerase"
FT /id="PRO_0000034198"
FT DOMAIN 19..135
FT /note="Thioredoxin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 347..476
FT /note="Thioredoxin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 471..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 506..509
FT /note="Prevents secretion from ER"
FT COMPBIAS 479..509
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 54
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 57
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 398
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 401
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 55
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 56
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 121
FT /note="Lowers pKa of C-terminal Cys of first active site"
FT /evidence="ECO:0000250"
FT SITE 399
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 400
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000250"
FT SITE 462
FT /note="Lowers pKa of C-terminal Cys of second active site"
FT /evidence="ECO:0000250"
FT MOD_RES 223
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09103"
FT MOD_RES 272
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09103"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07237"
FT DISULFID 54..57
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DISULFID 398..401
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
SQ SEQUENCE 509 AA; 56808 MW; 093C8C18E209BAB5 CRC64;
MLRRAVLCLA LAVTAGWAWA AEEEDNVLVL KSSNFAEELA AHKHLLVEFY APWCGHCKAL
APEYAKAAGK LKAEGSDIRL AKVDATEESD LAQQYGVRGY PTIKFFKNGD TASPKEYTAG
READDIVNWL KKRTGPAATT LADSAAAESL VESSEVAVIG FFKDVESDAA KQFLLAAEAT
DDIPFGLTAS SDVFSRYQVH QDGVVLFKKF DEGRNNFEGE VTKEKLLDFI KHNQLPLVIE
FTEQTAPKIF GGEIKTHILL FLPRSAADHD GKLSGFKQAA EGFKGKILFI FIDSDHADNQ
RILEFFGLKK EECPAVRLIT LEEEMTKYKP ESDELTAEGI TEFCQRFLEG KIKPHLMSQE
LPEDWDRQPV KVLVGKNFEE VAFDEKKNVF VEFYAPWCGH CKQLAPIWDK LGETYKEHQD
IVIAKMDSTA NEVEAVKVHS FPTLKFFPAG PGRTVIDYNG ERTLDGFKKF LESGGQDGAG
DEDGLEDLEE AEEPDLEEDD DQKAVRDEL
