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Protein

Protein disulfide-isomerase A3

Gene

Pdia3

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

Functioni

Catalytic activityi

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

Enzyme regulationi

Seems to be inhibited by acidic phospholipids.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei57 – 571NucleophileBy similarity
Sitei58 – 581Contributes to redox potential valueBy similarity
Sitei59 – 591Contributes to redox potential valueBy similarity
Active sitei60 – 601NucleophileBy similarity
Sitei119 – 1191Lowers pKa of C-terminal Cys of first active siteBy similarity
Active sitei406 – 4061NucleophileBy similarity
Sitei407 – 4071Contributes to redox potential valueBy similarity
Sitei408 – 4081Contributes to redox potential valueBy similarity
Active sitei409 – 4091NucleophileBy similarity
Sitei471 – 4711Lowers pKa of C-terminal Cys of second active siteBy similarity

GO - Molecular functioni

  • MHC class I protein binding Source: RGD
  • peptidase activity Source: RGD
  • protein disulfide isomerase activity Source: GO_Central
  • protein-disulfide reductase (glutathione) activity Source: RGD

GO - Biological processi

  • cell redox homeostasis Source: InterPro
  • cellular response to nonylphenol Source: RGD
  • cellular response to transforming growth factor beta stimulus Source: RGD
  • cellular response to vitamin D Source: RGD
  • circadian rhythm Source: RGD
  • positive regulation of protein folding Source: RGD
  • response to benzene Source: RGD
  • response to endoplasmic reticulum stress Source: GO_Central
  • response to ethanol Source: RGD
  • response to genistein Source: RGD
  • response to hyperoxia Source: RGD
  • response to hypoxia Source: RGD
  • response to ischemia Source: RGD
  • response to leptin Source: RGD
  • response to nutrient levels Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Names & Taxonomyi

Protein namesi
Recommended name:
Protein disulfide-isomerase A3 (EC:5.3.4.1)
Alternative name(s):
58 kDa glucose-regulated protein
58 kDa microsomal protein
Short name:
p58
Disulfide isomerase ER-60
Endoplasmic reticulum resident protein 57
Short name:
ER protein 57
Short name:
ERp57
Endoplasmic reticulum resident protein 60
Short name:
ER protein 60
Short name:
ERp60
HIP-70
Q-2
Gene namesi
Name:Pdia3
Synonyms:Erp60, Grp58
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68430. Pdia3.

Subcellular locationi

  • Endoplasmic reticulum By similarity
  • Endoplasmic reticulum lumen By similarity
  • Melanosome By similarity

GO - Cellular componenti

  • acrosomal vesicle Source: RGD
  • apical plasma membrane Source: RGD
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: UniProtKB-SubCell
  • extracellular region Source: RGD
  • extracellular space Source: RGD
  • melanosome Source: UniProtKB-SubCell
  • mitochondrial intermembrane space Source: RGD
  • mitochondrion Source: RGD
  • nucleus Source: RGD
  • plasma membrane Source: RGD
  • smooth endoplasmic reticulum Source: UniProtKB
  • TAP complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi502 – 5054QEDL → AAGL: Failure to prevent secretion from ER. 1 Publication
Mutagenesisi502 – 5054Missing : Failure to prevent secretion from ER. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 24241 PublicationAdd
BLAST
Chaini25 – 505481Protein disulfide-isomerase A3PRO_0000034227Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi57 ↔ 60Redox-activePROSITE-ProRule annotation
Disulfide bondi57 – 57Interchain (with C-115 in TAPBP); in linked formBy similarity
Disulfide bondi85 ↔ 92By similarity
Modified residuei129 – 1291N6-succinyllysineBy similarity
Modified residuei152 – 1521N6-acetyllysineBy similarity
Modified residuei218 – 2181N6-succinyllysineBy similarity
Modified residuei252 – 2521N6-acetyllysineBy similarity
Modified residuei319 – 3191PhosphothreonineBy similarity
Modified residuei362 – 3621N6-acetyllysineBy similarity
Disulfide bondi406 ↔ 409Redox-activePROSITE-ProRule annotation
Modified residuei494 – 4941N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiP11598.
PRIDEiP11598.

2D gel databases

World-2DPAGE0004:P11598.

PTM databases

iPTMnetiP11598.
PhosphoSiteiP11598.

Expressioni

Tissue specificityi

In caput epididymal spermatozoa, detected in the head, mid and principal pieces. In cauda epididymal spermatozoa detected only in the acrosome (at protein level).1 Publication

Gene expression databases

GenevisibleiP11598. RN.

Interactioni

Subunit structurei

Subunit of the TAP complex, also known as the peptide loading complex (PLC). Can form disulfide-linked heterodimers with TAPBP. Interacts with ERP27 and CANX (By similarity). Interacts with MZB1 in a calcium-dependent manner (By similarity). Interacts with SERPINA2 and with the S and Z variants of SERPINA1. Interacts with ATP2A2 (By similarity).By similarity

GO - Molecular functioni

  • MHC class I protein binding Source: RGD

Protein-protein interaction databases

BioGridi248111. 4 interactions.
IntActiP11598. 6 interactions.
MINTiMINT-4575564.
STRINGi10116.ENSRNOP00000020478.

Structurei

3D structure databases

ProteinModelPortaliP11598.
SMRiP11598. Positions 25-488.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 133109Thioredoxin 1PROSITE-ProRule annotationAdd
BLAST
Domaini343 – 485143Thioredoxin 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi502 – 5054Prevents 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

eggNOGiKOG0190. Eukaryota.
COG0526. LUCA.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP11598.
KOiK08056.
OMAiQINFAIA.
OrthoDBiEOG7VHSX1.
PhylomeDBiP11598.
TreeFamiTF106382.

Family and domain databases

Gene3Di3.40.30.10. 3 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.
PROSITEiPS00194. 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.

P11598-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFSCLALLP GVALLLASAL LASASDVLEL TDENFESRVS DTGSAGLMLV
60 70 80 90 100
EFFAPWCGHC KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY
110 120 130 140 150
PTLKIFRDGE EAGAYDGPRT ADGIVSHLKK QAGPASVPLR TEDEFKKFIS
160 170 180 190 200
DKDASVVGFF RDLFSDGHSE FLKAASNLRD NYRFAHTNVE SLVKEYDDNG
210 220 230 240 250
EGITIFRPLH LANKFEDKIV AYTEKKMTSG KIKKFIQESI FGLCPHMTED
260 270 280 290 300
NKDLIQGKDL LTAYYDVDYE KNTKGSNYWR NRVMMVAKTF LDAGHKLNFA
310 320 330 340 350
VASRKTFSHE LSDFGLESTT GEIPVVAIRT AKGEKFVMQE EFSRDGKALE
360 370 380 390 400
RFLQEYFDGN LKRYLKSEPI PETNEGPVKV VVAESFDDIV NAEDKDVLIE
410 420 430 440 450
FYAPWCGHCK NLEPKYKELG EKLSKDPNIV IAKMDATAND VPSPYEVKGF
460 470 480 490 500
PTIYFSPANK KLTPKKYEGG RELNDFISYL QREATNPPII QEEKPKKKKK

AQEDL
Length:505
Mass (Da):56,623
Last modified:February 1, 1996 - v2
Checksum:iEAC7F0C0BD4F1471
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 1313MRFSC…LPGVA → MPSAALRCSRAWR (PubMed:3398923).CuratedAdd
BLAST
Sequence conflicti98 – 981S → T in CAA30916 (PubMed:3398923).Curated
Sequence conflicti232 – 2409IKKFIQESI → SRSLFRKA in CAA30916 (PubMed:3398923).Curated
Sequence conflicti476 – 4761F → L in BAA09695 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12355 mRNA. Translation: CAA30916.1.
D63378 mRNA. Translation: BAA09695.1.
BC062393 mRNA. Translation: AAH62393.1.
PIRiA28807.
A61354.
RefSeqiNP_059015.1. NM_017319.1.
UniGeneiRn.11527.

Genome annotation databases

GeneIDi29468.
KEGGirno:29468.
UCSCiRGD:68430. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X12355 mRNA. Translation: CAA30916.1.
D63378 mRNA. Translation: BAA09695.1.
BC062393 mRNA. Translation: AAH62393.1.
PIRiA28807.
A61354.
RefSeqiNP_059015.1. NM_017319.1.
UniGeneiRn.11527.

3D structure databases

ProteinModelPortaliP11598.
SMRiP11598. Positions 25-488.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248111. 4 interactions.
IntActiP11598. 6 interactions.
MINTiMINT-4575564.
STRINGi10116.ENSRNOP00000020478.

PTM databases

iPTMnetiP11598.
PhosphoSiteiP11598.

2D gel databases

World-2DPAGE0004:P11598.

Proteomic databases

PaxDbiP11598.
PRIDEiP11598.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29468.
KEGGirno:29468.
UCSCiRGD:68430. rat.

Organism-specific databases

CTDi2923.
RGDi68430. Pdia3.

Phylogenomic databases

eggNOGiKOG0190. Eukaryota.
COG0526. LUCA.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP11598.
KOiK08056.
OMAiQINFAIA.
OrthoDBiEOG7VHSX1.
PhylomeDBiP11598.
TreeFamiTF106382.

Miscellaneous databases

PROiP11598.

Gene expression databases

GenevisibleiP11598. RN.

Family and domain databases

Gene3Di3.40.30.10. 3 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.
PROSITEiPS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and complete amino-acid sequence of form-I phosphoinositide-specific phospholipase C."
    Bennett C.F., Balcarek J.M., Varrichio A., Crooke S.T.
    Nature 334:268-270(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Role of novel microsomal cysteine proteases."
    Kito M., Urade R.
    Proc. Jpn. Acad., B, Phys. Biol. Sci. 71:189-192(1995)
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  4. "A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity."
    Martin J.L., Pumford N.R., Larosa A.C., Martin B.M., Gonzaga H.M.S., Beaven M.A., Pohl L.R.
    Biochem. Biophys. Res. Commun. 178:679-685(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE.
    Tissue: Liver.
  5. "HIP-70: a protein induced by estrogen in the brain and LH-RH in the pituitary."
    Mobbs C.V., Fink G., Pfaff D.W.
    Science 247:1477-1479(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-43.
    Tissue: Brain and Pituitary.
  6. "Purification and characterization of a new isozyme of thiol:protein-disulfide oxidoreductase from rat hepatic microsomes. Relationship of this isozyme to cytosolic phosphatidylinositol-specific phospholipase C form 1A."
    Srivastava S.P., Chen N.Q., Liu Y.X., Holtzman J.L.
    J. Biol. Chem. 266:20337-20344(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 25-54; 258-269; 285-310; 347-350; 412-419 AND 434-463.
    Tissue: Liver.
  7. "Protein degradation by the phosphoinositide-specific phospholipase C-alpha family from rat liver endoplasmic reticulum."
    Urade R., Nasu M., Moriyama T., Wada K., Kito M.
    J. Biol. Chem. 267:15152-15159(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-34; 174-193; 433-446 AND 448-458.
  8. Lubec G., Afjehi-Sadat L.
    Submitted (DEC-2006) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 105-119; 148-161; 184-214; 259-271; 306-329; 336-344; 352-363; 449-460 AND 472-482, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Spinal cord.
  9. "Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu (QEDL) motifs of microsomal ER-60 protease."
    Urade R., Oda T., Ito H., Moriyama T., Utsumi S., Kito M.
    J. Biochem. 122:834-842(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF 502-GLN--LEU-505.
  10. "Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum."
    Urade R., Kito M.
    FEBS Lett. 312:83-86(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INHIBITION BY PHOSPHOLIPIDS.
  11. "Glucose-regulated protein precursor (GRP78) and tumor rejection antigen (GP96) are unique to hamster caput epididymal spermatozoa."
    Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S.
    Asian J. Androl. 12:344-355(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiPDIA3_RAT
AccessioniPrimary (citable) accession number: P11598
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: February 1, 1996
Last modified: July 6, 2016
This is version 166 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 thought to be a phosphatidyl-inositol 4,5-bisphosphate phosphodiesterase type I (phospholipase C-alpha) then was thought (PubMed:1321829 and PubMed:1330685) to be a thiol protease.1 Publication

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.