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Protein

Protein disulfide-isomerase

Gene

P4hb

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP (By similarity).By similarity

Catalytic activityi

Catalyzes the rearrangement of -S-S- bonds in proteins.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei55 – 551NucleophileBy similarity
Sitei56 – 561Contributes to redox potential valueBy similarity
Sitei57 – 571Contributes to redox potential valueBy similarity
Active sitei58 – 581NucleophileBy similarity
Sitei122 – 1221Lowers pKa of C-terminal Cys of first active siteBy similarity
Active sitei399 – 3991NucleophileBy similarity
Sitei400 – 4001Contributes to redox potential valueBy similarity
Sitei401 – 4011Contributes to redox potential valueBy similarity
Active sitei402 – 4021NucleophileBy similarity
Sitei463 – 4631Lowers pKa of C-terminal Cys of second active siteBy similarity

GO - Molecular functioni

  1. enzyme binding Source: RGD
  2. poly(A) RNA binding Source: Ensembl
  3. procollagen-proline 4-dioxygenase activity Source: Ensembl
  4. protein disulfide isomerase activity Source: RGD
  5. protein heterodimerization activity Source: RGD

GO - Biological processi

  1. cell redox homeostasis Source: InterPro
  2. cellular response to hypoxia Source: Ensembl
  3. peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: Ensembl
  4. protein folding Source: GOC
  5. regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: GO_Central
  6. response to endoplasmic reticulum stress Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase

Enzyme and pathway databases

BRENDAi5.3.4.1. 5301.
ReactomeiREACT_317923. Detoxification of Reactive Oxygen Species.
REACT_336611. Hedgehog ligand biogenesis.
REACT_345465. Chylomicron-mediated lipid transport.
REACT_352858. Collagen biosynthesis and modifying enzymes.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein disulfide-isomerase (EC:5.3.4.1)
Short name:
PDI
Alternative name(s):
Cellular thyroid hormone-binding protein
Prolyl 4-hydroxylase subunit beta
Gene namesi
Name:P4hb
Synonyms:Pdia1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3244. P4hb.

Subcellular locationi

Endoplasmic reticulum lumen PROSITE-ProRule annotation. Melanosome By similarity. Cell membrane Curated; Peripheral membrane protein Curated
Note: Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources. Localizes near CD4-enriched regions on lymphoid cell surfaces (By similarity).By similarity

GO - Cellular componenti

  1. endoplasmic reticulum Source: GO_Central
  2. endoplasmic reticulum-Golgi intermediate compartment Source: Ensembl
  3. endoplasmic reticulum lumen Source: UniProtKB-SubCell
  4. extracellular vesicular exosome Source: Ensembl
  5. focal adhesion Source: Ensembl
  6. melanosome Source: UniProtKB-SubCell
  7. plasma membrane Source: UniProtKB-SubCell
  8. procollagen-proline 4-dioxygenase complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19191 PublicationAdd
BLAST
Chaini20 – 509490Protein disulfide-isomerasePRO_0000034199Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi55 ↔ 58Redox-activePROSITE-ProRule annotation
Modified residuei202 – 2021N6-acetyllysineBy similarity
Modified residuei224 – 2241N6-succinyllysineBy similarity
Modified residuei273 – 2731N6-succinyllysineBy similarity
Disulfide bondi399 ↔ 402Redox-activePROSITE-ProRule annotation

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

PaxDbiP04785.
PRIDEiP04785.

PTM databases

PhosphoSiteiP04785.

Expressioni

Gene expression databases

GenevestigatoriP04785.

Interactioni

Subunit structurei

Homodimer. Monomers and homotetramers may also occur. Also constitutes the structural subunit of prolyl 4-hydroxylase and of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity. Binds UBQLN1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi247538. 1 interaction.
IntActiP04785. 3 interactions.
MINTiMINT-4996344.
STRINGi10116.ENSRNOP00000051841.

Structurei

3D structure databases

ProteinModelPortaliP04785.
SMRiP04785. Positions 20-359, 370-473.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 136117Thioredoxin 1PROSITE-ProRule annotationAdd
BLAST
Domaini335 – 477143Thioredoxin 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi506 – 5094Prevents secretion from ER

Sequence similaritiesi

Belongs to the protein disulfide isomerase family.Curated
Contains 2 thioredoxin domains.PROSITE-ProRule annotation

Keywords - Domaini

Redox-active center, Repeat, Signal

Phylogenomic databases

eggNOGiCOG0526.
GeneTreeiENSGT00760000119201.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP04785.
KOiK09580.
OMAiYRDHENI.
OrthoDBiEOG7VHSX1.
PhylomeDBiP04785.
TreeFamiTF106381.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005788. Disulphide_isomerase.
IPR005792. Prot_disulphide_isomerase.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF00085. Thioredoxin. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 4 hits.
TIGRFAMsiTIGR01130. ER_PDI_fam. 1 hit.
TIGR01126. pdi_dom. 2 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04785-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSRALLCLA LAWAARVGAD ALEEEDNVLV LKKSNFAEAL AAHNYLLVEF
60 70 80 90 100
YAPWCGHCKA LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG
110 120 130 140 150
YPTIKFFKNG DTASPKEYTA GREADDIVNW LKKRTGPAAT TLSDTAAAES
160 170 180 190 200
LVDSSEVTVI GFFKDAGSDS AKQFLLAAEA VDDIPFGITS NSDVFSKYQL
210 220 230 240 250
DKDGVVLFKK FDEGRNNFEG EITKEKLLDF IKHNQLPLVI EFTEQTAPKI
260 270 280 290 300
FGGEIKTHIL LFLPKSVSDY DGKLSNFKKA AEGFKGKILF IFIDSDHTDN
310 320 330 340 350
QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITQFCHHFLE
360 370 380 390 400
GKIKPHLMSQ ELPEDWDKQP VKVLVGKNFE EVAFDEKKNV FVEFYAPWCG
410 420 430 440 450
HCKQLAPIWD KLGETYKDHE NIVIAKMDST ANEVEAVKVH SFPTLKFFPA
460 470 480 490 500
SADRTVIDYN GERTLDGFKK FLESGGQDGA GDNDDLDLEE ALEPDMEEDD

DQKAVKDEL
Length:509
Mass (Da):56,951
Last modified:October 1, 1989 - v2
Checksum:i3056107F5E8B1B54
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 402AL → P in CAA26675 (PubMed:3840230).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21018 mRNA. Translation: AAA40620.1.
BC061857 mRNA. Translation: AAH61857.1.
X02918 mRNA. Translation: CAA26675.1.
M21476 mRNA. Translation: AAA40619.1.
PIRiA24595. ISRTSS.
S68028.
RefSeqiNP_037130.1. NM_012998.1.
UniGeneiRn.4234.

Genome annotation databases

EnsembliENSRNOT00000054958; ENSRNOP00000051841; ENSRNOG00000036689.
GeneIDi25506.
KEGGirno:25506.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21018 mRNA. Translation: AAA40620.1.
BC061857 mRNA. Translation: AAH61857.1.
X02918 mRNA. Translation: CAA26675.1.
M21476 mRNA. Translation: AAA40619.1.
PIRiA24595. ISRTSS.
S68028.
RefSeqiNP_037130.1. NM_012998.1.
UniGeneiRn.4234.

3D structure databases

ProteinModelPortaliP04785.
SMRiP04785. Positions 20-359, 370-473.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247538. 1 interaction.
IntActiP04785. 3 interactions.
MINTiMINT-4996344.
STRINGi10116.ENSRNOP00000051841.

PTM databases

PhosphoSiteiP04785.

Proteomic databases

PaxDbiP04785.
PRIDEiP04785.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000054958; ENSRNOP00000051841; ENSRNOG00000036689.
GeneIDi25506.
KEGGirno:25506.

Organism-specific databases

CTDi5034.
RGDi3244. P4hb.

Phylogenomic databases

eggNOGiCOG0526.
GeneTreeiENSGT00760000119201.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP04785.
KOiK09580.
OMAiYRDHENI.
OrthoDBiEOG7VHSX1.
PhylomeDBiP04785.
TreeFamiTF106381.

Enzyme and pathway databases

BRENDAi5.3.4.1. 5301.
ReactomeiREACT_317923. Detoxification of Reactive Oxygen Species.
REACT_336611. Hedgehog ligand biogenesis.
REACT_345465. Chylomicron-mediated lipid transport.
REACT_352858. Collagen biosynthesis and modifying enzymes.

Miscellaneous databases

NextBioi606925.
PROiP04785.

Gene expression databases

GenevestigatoriP04785.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005788. Disulphide_isomerase.
IPR005792. Prot_disulphide_isomerase.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF00085. Thioredoxin. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 4 hits.
TIGRFAMsiTIGR01130. ER_PDI_fam. 1 hit.
TIGR01126. pdi_dom. 2 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin."
    Edman J.C., Ellis L., Blacher R.W., Roth R.A., Rutter W.J.
    Nature 317:267-270(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  3. "Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats."
    Yokoi T., Nagayama S., Kajiwara R., Kawaguchi Y., Horiuchi R., Kamataki T.
    Biochim. Biophys. Acta 1158:339-344(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-34.
    Strain: LEC.
    Tissue: Liver.
  4. "Nucleotide sequence of rat liver iodothyronine 5'-monodeiodinase (5' MD): its identity with the protein disulfide isomerase."
    Boado R.J., Campbell D.A., Chopra I.J.
    Biochem. Biophys. Res. Commun. 155:1297-1304(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-509.
    Tissue: Liver.
  5. "Enzyme binding-inhibiting assay for iodothyronine 5'-monodeiodinase (5'-MD) and its application to isolation of complementary deoxyribonucleic acid clones for the 5'-MD in rat liver."
    Boado R.J., Chopra I.J., Flink I.L., Campbell D.A.
    Endocrinology 123:1264-1273(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 129-394.
    Tissue: Liver.
  6. Lubec G., Afjehi-Sadat L., Chen W.-Q.
    Submitted (MAR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 233-249; 288-302 AND 341-352, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Hippocampus and Spinal cord.
  7. "Peptide binding to protein disulfide isomerase occurs at a site distinct from the active sites."
    Noiva R., Freedman R.B., Lennarz W.J.
    J. Biol. Chem. 268:19210-19217(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 471-494.
  8. "Rat liver type I iodothyronine deiodinase is not identical to protein disulfide isomerase."
    Schoenmakers C.H.H., Pigmans I.G.A.J., Hawkins H.C., Freedman R.B., Visser T.J.
    Biochem. Biophys. Res. Commun. 162:857-868(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: SHOWS THAT PROTEIN IS NOT IDENTICAL TO THYROXINE DEIODINASE.

Entry informationi

Entry nameiPDIA1_RAT
AccessioniPrimary (citable) accession number: P04785
Secondary accession number(s): P13700
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: October 1, 1989
Last modified: April 1, 2015
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally (PubMed:8251535 and PubMed:3178809) thought to be identical to thyroxine deiodinase but this was later shown to be incorrect.1 Publication

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.