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Protein

Protein disulfide-isomerase A3

Gene

PDIA3

Organism
Homo sapiens (Human)
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei57NucleophileBy similarity1
Sitei58Contributes to redox potential valueBy similarity1
Sitei59Contributes to redox potential valueBy similarity1
Active sitei60NucleophileBy similarity1
Sitei119Lowers pKa of C-terminal Cys of first active siteBy similarity1
Active sitei406NucleophileBy similarity1
Sitei407Contributes to redox potential valueBy similarity1
Sitei408Contributes to redox potential valueBy similarity1
Active sitei409NucleophileBy similarity1
Sitei471Lowers pKa of C-terminal Cys of second active siteBy similarity1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: ProtInc
  • disulfide oxidoreductase activity Source: ParkinsonsUK-UCL
  • phospholipase C activity Source: ProtInc
  • poly(A) RNA binding Source: UniProtKB
  • protein disulfide isomerase activity Source: ProtInc

GO - Biological processi

  • antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
  • cell redox homeostasis Source: InterPro
  • positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  • protein folding Source: Reactome
  • protein folding in endoplasmic reticulum Source: ParkinsonsUK-UCL
  • protein import into nucleus Source: ProtInc
  • protein retention in ER lumen Source: ProtInc
  • response to endoplasmic reticulum stress Source: GO_Central
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Enzyme and pathway databases

BioCyciZFISH:HS09499-MONOMER.
BRENDAi5.3.4.1. 2681.
ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-901042. Calnexin/calreticulin cycle.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

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
Gene namesi
Name:PDIA3
Synonyms:ERP57, ERP60, GRP58
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:4606. PDIA3.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: MGI
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • myelin sheath Source: Ensembl
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi57C → A: No loss of activity. No loss of activity; when associated with A-406. 1 Publication1
Mutagenesisi57C → S: Activity changed to serine protease. 1 Publication1
Mutagenesisi60C → S: Activity changed to serine protease; when associated with S-409. 1 Publication1
Mutagenesisi406C → A: No loss of activity. No loss of activity; when associated with A-57. 1 Publication1
Mutagenesisi406C → S: Activity changed to serine protease. 1 Publication1
Mutagenesisi409C → S: Activity changed to serine protease; when associated with S-60. 1 Publication1

Organism-specific databases

DisGeNETi2923.
OpenTargetsiENSG00000167004.
PharmGKBiPA29000.

Polymorphism and mutation databases

BioMutaiPDIA3.
DMDMi2507461.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Combined sources5 PublicationsAdd BLAST24
ChainiPRO_000003422525 – 505Protein disulfide-isomerase A3Add BLAST481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 60Redox-activePROSITE-ProRule annotation
Disulfide bondi57Interchain (with C-115 in TAPBP); in linked form1 Publication
Modified residuei61N6-methyllysineCombined sources1
Disulfide bondi85 ↔ 921 Publication
Modified residuei129N6-succinyllysineBy similarity1
Modified residuei152N6-acetyllysineBy similarity1
Modified residuei218N6-succinyllysineBy similarity1
Modified residuei252N6-acetyllysineBy similarity1
Modified residuei319PhosphothreonineCombined sources1
Modified residuei362N6-acetyllysineBy similarity1
Disulfide bondi406 ↔ 409Redox-activePROSITE-ProRule annotation
Modified residuei494N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Disulfide bond, Methylation, Phosphoprotein

Proteomic databases

EPDiP30101.
PaxDbiP30101.
PeptideAtlasiP30101.
PRIDEiP30101.
TopDownProteomicsiP30101.

2D gel databases

DOSAC-COBS-2DPAGEP30101.
REPRODUCTION-2DPAGEP30101.
SWISS-2DPAGEP30101.
UCD-2DPAGEP30101.

PTM databases

iPTMnetiP30101.
PhosphoSitePlusiP30101.
SwissPalmiP30101.

Expressioni

Tissue specificityi

Detected in the flagellum and head region of spermatozoa (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000167004.
CleanExiHS_PDIA3.
ExpressionAtlasiP30101. baseline and differential.
GenevisibleiP30101. HS.

Organism-specific databases

HPAiCAB011199.
CAB015181.
HPA002645.
HPA003230.

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. Interacts with SERPINA2 and with the S and Z variants of SERPINA1. Interacts with ATP2A2 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-979862,EBI-77613
CalrP184182EBI-979862,EBI-916742From a different organism.
CLUP109092EBI-979862,EBI-1104674
ERO1AQ96HE73EBI-979862,EBI-2564539
ERO1BQ86YB82EBI-979862,EBI-2806988
PRDX4Q131622EBI-979862,EBI-2211957
STIM1Q135863EBI-979862,EBI-448878
TAP1Q035184EBI-979862,EBI-747259

Protein-protein interaction databases

BioGridi109180. 124 interactors.
DIPiDIP-29132N.
IntActiP30101. 76 interactors.
MINTiMINT-5000005.
STRINGi9606.ENSP00000300289.

Structurei

Secondary structure

1505
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 29Combined sources3
Turni32 – 34Combined sources3
Helixi35 – 38Combined sources4
Helixi39 – 41Combined sources3
Beta strandi43 – 53Combined sources11
Helixi58 – 73Combined sources16
Turni74 – 77Combined sources4
Beta strandi80 – 84Combined sources5
Turni85 – 87Combined sources3
Helixi89 – 94Combined sources6
Beta strandi99 – 107Combined sources9
Beta strandi110 – 114Combined sources5
Helixi121 – 131Combined sources11
Beta strandi136 – 138Combined sources3
Helixi142 – 149Combined sources8
Beta strandi151 – 153Combined sources3
Beta strandi155 – 161Combined sources7
Helixi166 – 177Combined sources12
Turni178 – 181Combined sources4
Beta strandi182 – 187Combined sources6
Helixi190 – 196Combined sources7
Beta strandi198 – 206Combined sources9
Helixi209 – 211Combined sources3
Beta strandi218 – 221Combined sources4
Helixi229 – 239Combined sources11
Turni240 – 243Combined sources4
Turni249 – 251Combined sources3
Helixi252 – 255Combined sources4
Beta strandi256 – 265Combined sources10
Turni269 – 271Combined sources3
Helixi273 – 292Combined sources20
Beta strandi298 – 303Combined sources6
Turni304 – 307Combined sources4
Helixi308 – 311Combined sources4
Helixi312 – 314Combined sources3
Beta strandi325 – 329Combined sources5
Beta strandi331 – 333Combined sources3
Beta strandi335 – 337Combined sources3
Helixi347 – 358Combined sources12
Beta strandi376 – 381Combined sources6
Turni383 – 385Combined sources3
Helixi386 – 390Combined sources5
Beta strandi396 – 402Combined sources7
Helixi407 – 422Combined sources16
Turni423 – 425Combined sources3
Beta strandi427 – 435Combined sources9
Turni436 – 438Combined sources3
Beta strandi449 – 456Combined sources8
Helixi473 – 483Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ALBNMR-A25-137[»]
2DMMNMR-A357-485[»]
2H8LX-ray2.00A/B/C134-376[»]
3F8UX-ray2.60A/C25-505[»]
ProteinModelPortaliP30101.
SMRiP30101.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30101.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 133Thioredoxin 1PROSITE-ProRule annotationAdd BLAST109
Domaini343 – 485Thioredoxin 2PROSITE-ProRule annotationAdd BLAST143

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi502 – 505Prevents secretion from ERBy similarity4

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.
GeneTreeiENSGT00860000133691.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP30101.
KOiK08056.
OMAiQINFAIA.
OrthoDBiEOG091G05J9.
PhylomeDBiP30101.
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.

P30101-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLRRLALFP GVALLLAAAR LAAASDVLEL TDDNFESRIS DTGSAGLMLV
60 70 80 90 100
EFFAPWCGHC KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY
110 120 130 140 150
PTLKIFRDGE EAGAYDGPRT ADGIVSHLKK QAGPASVPLR TEEEFKKFIS
160 170 180 190 200
DKDASIVGFF DDSFSEAHSE FLKAASNLRD NYRFAHTNVE SLVNEYDDNG
210 220 230 240 250
EGIILFRPSH LTNKFEDKTV AYTEQKMTSG KIKKFIQENI FGICPHMTED
260 270 280 290 300
NKDLIQGKDL LIAYYDVDYE KNAKGSNYWR NRVMMVAKKF LDAGHKLNFA
310 320 330 340 350
VASRKTFSHE LSDFGLESTA GEIPVVAIRT AKGEKFVMQE EFSRDGKALE
360 370 380 390 400
RFLQDYFDGN LKRYLKSEPI PESNDGPVKV VVAENFDEIV NNENKDVLIE
410 420 430 440 450
FYAPWCGHCK NLEPKYKELG EKLSKDPNIV IAKMDATAND VPSPYEVRGF
460 470 480 490 500
PTIYFSPANK KLNPKKYEGG RELSDFISYL QREATNPPVI QEEKPKKKKK

AQEDL
Length:505
Mass (Da):56,782
Last modified:November 1, 1997 - v4
Checksum:i529E5B6692D0D7E9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19A → G in BAA11928 (PubMed:9399589).Curated1
Sequence conflicti22A → V in BAA11928 (PubMed:9399589).Curated1
Sequence conflicti217D → Y in BAA03759 (PubMed:7945384).Curated1
Sequence conflicti225Q → P in CAA89996 (PubMed:8624847).Curated1
Sequence conflicti238E → G in CAA89996 (PubMed:8624847).Curated1
Sequence conflicti272N → D in BAA03759 (PubMed:7945384).Curated1
Sequence conflicti272N → D in AAC51518 (PubMed:9205111).Curated1
Sequence conflicti355D → G in BAA03759 (PubMed:7945384).Curated1
Sequence conflicti358D → G in BAA03759 (PubMed:7945384).Curated1
Sequence conflicti368E → D in BAA03759 (PubMed:7945384).Curated1

Mass spectrometryi

Molecular mass is 54265.22 Da from positions 25 - 505. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020027415K → R.Corresponds to variant rs6413485dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16234 mRNA. Translation: BAA03759.1.
U42068 mRNA. Translation: AAC50331.1.
Z49835 mRNA. Translation: CAA89996.1.
U75885
, U75875, U75876, U75877, U75878, U75879, U75880, U75881, U75882, U75883, U75884 Genomic DNA. Translation: AAC51518.1.
D83485 mRNA. Translation: BAA11928.1.
BC014433 mRNA. Translation: AAH14433.1.
BC036000 mRNA. Translation: AAH36000.4.
BC071878 mRNA. Translation: AAH71878.1.
CCDSiCCDS10101.1.
PIRiJC5704.
S55507.
S63994.
S68363.
RefSeqiNP_005304.3. NM_005313.4.
UniGeneiHs.591095.

Genome annotation databases

EnsembliENST00000300289; ENSP00000300289; ENSG00000167004.
GeneIDi2923.
KEGGihsa:2923.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D16234 mRNA. Translation: BAA03759.1.
U42068 mRNA. Translation: AAC50331.1.
Z49835 mRNA. Translation: CAA89996.1.
U75885
, U75875, U75876, U75877, U75878, U75879, U75880, U75881, U75882, U75883, U75884 Genomic DNA. Translation: AAC51518.1.
D83485 mRNA. Translation: BAA11928.1.
BC014433 mRNA. Translation: AAH14433.1.
BC036000 mRNA. Translation: AAH36000.4.
BC071878 mRNA. Translation: AAH71878.1.
CCDSiCCDS10101.1.
PIRiJC5704.
S55507.
S63994.
S68363.
RefSeqiNP_005304.3. NM_005313.4.
UniGeneiHs.591095.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ALBNMR-A25-137[»]
2DMMNMR-A357-485[»]
2H8LX-ray2.00A/B/C134-376[»]
3F8UX-ray2.60A/C25-505[»]
ProteinModelPortaliP30101.
SMRiP30101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109180. 124 interactors.
DIPiDIP-29132N.
IntActiP30101. 76 interactors.
MINTiMINT-5000005.
STRINGi9606.ENSP00000300289.

PTM databases

iPTMnetiP30101.
PhosphoSitePlusiP30101.
SwissPalmiP30101.

Polymorphism and mutation databases

BioMutaiPDIA3.
DMDMi2507461.

2D gel databases

DOSAC-COBS-2DPAGEP30101.
REPRODUCTION-2DPAGEP30101.
SWISS-2DPAGEP30101.
UCD-2DPAGEP30101.

Proteomic databases

EPDiP30101.
PaxDbiP30101.
PeptideAtlasiP30101.
PRIDEiP30101.
TopDownProteomicsiP30101.

Protocols and materials databases

DNASUi2923.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300289; ENSP00000300289; ENSG00000167004.
GeneIDi2923.
KEGGihsa:2923.

Organism-specific databases

CTDi2923.
DisGeNETi2923.
GeneCardsiPDIA3.
HGNCiHGNC:4606. PDIA3.
HPAiCAB011199.
CAB015181.
HPA002645.
HPA003230.
MIMi602046. gene.
neXtProtiNX_P30101.
OpenTargetsiENSG00000167004.
PharmGKBiPA29000.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0190. Eukaryota.
COG0526. LUCA.
GeneTreeiENSGT00860000133691.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP30101.
KOiK08056.
OMAiQINFAIA.
OrthoDBiEOG091G05J9.
PhylomeDBiP30101.
TreeFamiTF106382.

Enzyme and pathway databases

BioCyciZFISH:HS09499-MONOMER.
BRENDAi5.3.4.1. 2681.
ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-901042. Calnexin/calreticulin cycle.
R-HSA-983170. Antigen Presentation: Folding, assembly and peptide loading of class I MHC.

Miscellaneous databases

ChiTaRSiPDIA3. human.
EvolutionaryTraceiP30101.
GenomeRNAii2923.
PROiP30101.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167004.
CleanExiHS_PDIA3.
ExpressionAtlasiP30101. baseline and differential.
GenevisibleiP30101. HS.

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...

Entry informationi

Entry nameiPDIA3_HUMAN
AccessioniPrimary (citable) accession number: P30101
Secondary accession number(s): Q13453
, Q14255, Q8IYF8, Q9UMU7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 200 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was originally thought to be a phosphatidylinositol 4,5-bisphosphate phosphodiesterase type I (phospholipase C-alpha).Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.