UniProtKB - P30101 (PDIA3_HUMAN)
Protein
Protein disulfide-isomerase A3
Gene
PDIA3
Organism
Homo sapiens (Human)
Status
Functioni
Caution
Was originally thought to be a phosphatidylinositol 4,5-bisphosphate phosphodiesterase type I (phospholipase C-alpha).Curated
Catalytic activityi
- Catalyzes the rearrangement of -S-S- bonds in proteins.1 Publication EC:5.3.4.1
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 57 | NucleophileBy similarity | 1 | |
Sitei | 58 | Contributes to redox potential valueBy similarity | 1 | |
Sitei | 59 | Contributes to redox potential valueBy similarity | 1 | |
Active sitei | 60 | NucleophileBy similarity | 1 | |
Sitei | 119 | Lowers pKa of C-terminal Cys of first active siteBy similarity | 1 | |
Active sitei | 406 | NucleophileBy similarity | 1 | |
Sitei | 407 | Contributes to redox potential valueBy similarity | 1 | |
Sitei | 408 | Contributes to redox potential valueBy similarity | 1 | |
Active sitei | 409 | NucleophileBy similarity | 1 | |
Sitei | 471 | Lowers pKa of C-terminal Cys of second active siteBy similarity | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: ProtInc
- disulfide oxidoreductase activity Source: ParkinsonsUK-UCL
- identical protein binding Source: IntAct
- peptide disulfide oxidoreductase activity Source: UniProtKB
- phospholipase C activity Source: ProtInc
- protein disulfide isomerase activity Source: GO_Central
- RNA binding Source: UniProtKB
GO - Biological processi
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
- antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
- cellular response to interleukin-7 Source: Ensembl
- positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
- protein folding Source: GO_Central
- protein folding in endoplasmic reticulum Source: ParkinsonsUK-UCL
- response to endoplasmic reticulum stress Source: GO_Central
Keywordsi
Molecular function | Isomerase |
Enzyme and pathway databases
BRENDAi | 5.3.4.1, 2681 |
PathwayCommonsi | P30101 |
Reactomei | R-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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000167004.12 |
HGNCi | HGNC:4606, PDIA3 |
MIMi | 602046, gene |
neXtProti | NX_P30101 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
- Endoplasmic reticulum lumen By similarity
Other locations
- Melanosome 2 Publications
Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:12643545).1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum lumen Source: Reactome
- MHC class I peptide loading complex Source: UniProtKB
Endosome
- recycling endosome membrane Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- cell surface Source: MGI
- focal adhesion Source: UniProtKB
- melanosome Source: UniProtKB-SubCell
- phagocytic vesicle Source: Reactome
Keywords - Cellular componenti
Endoplasmic reticulumPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 57 | C → A: No loss of activity. No loss of activity; when associated with A-406. 1 Publication | 1 | |
Mutagenesisi | 57 | C → S: Activity changed to serine protease. 1 Publication | 1 | |
Mutagenesisi | 60 | C → S: Activity changed to serine protease; when associated with S-409. 1 Publication | 1 | |
Mutagenesisi | 406 | C → A: No loss of activity. No loss of activity; when associated with A-57. 1 Publication | 1 | |
Mutagenesisi | 406 | C → S: Activity changed to serine protease. 1 Publication | 1 | |
Mutagenesisi | 409 | C → S: Activity changed to serine protease; when associated with S-60. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2923 |
OpenTargetsi | ENSG00000167004 |
PharmGKBi | PA29000 |
Miscellaneous databases
Pharosi | P30101, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4296001 |
DrugBanki | DB09130, Copper DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
Polymorphism and mutation databases
BioMutai | PDIA3 |
DMDMi | 2507461 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Combined sources5 PublicationsAdd BLAST | 24 | |
ChainiPRO_0000034225 | 25 – 505 | Protein disulfide-isomerase A3Add BLAST | 481 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 57 ↔ 60 | Redox-activePROSITE-ProRule annotation | ||
Disulfide bondi | 57 | Interchain (with C-115 in TAPBP); in linked form1 Publication | ||
Modified residuei | 61 | N6-methyllysineCombined sources | 1 | |
Disulfide bondi | 85 ↔ 92 | 1 Publication | ||
Modified residuei | 129 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 152 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 218 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 252 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 319 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 362 | N6-acetyllysineBy similarity | 1 | |
Disulfide bondi | 406 ↔ 409 | Redox-activePROSITE-ProRule annotation | ||
Modified residuei | 494 | N6-acetyllysineBy similarity | 1 |
Keywords - PTMi
Acetylation, Disulfide bond, Methylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-421 CPTAC-422 |
EPDi | P30101 |
jPOSTi | P30101 |
MassIVEi | P30101 |
PaxDbi | P30101 |
PeptideAtlasi | P30101 |
PRIDEi | P30101 |
ProteomicsDBi | 54635 |
TopDownProteomicsi | P30101 |
2D gel databases
DOSAC-COBS-2DPAGEi | P30101 |
REPRODUCTION-2DPAGEi | P30101 |
SWISS-2DPAGEi | P30101 |
UCD-2DPAGEi | P30101 |
PTM databases
GlyGeni | P30101, 1 site |
iPTMneti | P30101 |
MetOSitei | P30101 |
PhosphoSitePlusi | P30101 |
SwissPalmi | P30101 |
Expressioni
Tissue specificityi
Detected in the flagellum and head region of spermatozoa (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000167004, Expressed in corpus epididymis and 240 other tissues |
ExpressionAtlasi | P30101, baseline and differential |
Genevisiblei | P30101, HS |
Organism-specific databases
HPAi | ENSG00000167004, Low tissue specificity |
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 PublicationsBinary interactionsi
Hide detailsP30101
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 109180, 196 interactors |
ComplexPortali | CPX-2375, Tapasin-ERp57 complex |
CORUMi | P30101 |
DIPi | DIP-29132N |
IntActi | P30101, 142 interactors |
MINTi | P30101 |
STRINGi | 9606.ENSP00000300289 |
Miscellaneous databases
RNActi | P30101, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P30101 |
SMRi | P30101 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P30101 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 25 – 133 | Thioredoxin 1PROSITE-ProRule annotationAdd BLAST | 109 | |
Domaini | 343 – 485 | Thioredoxin 2PROSITE-ProRule annotationAdd BLAST | 143 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 502 – 505 | Prevents secretion from ERBy similarity | 4 |
Sequence similaritiesi
Belongs to the protein disulfide isomerase family.Curated
Keywords - Domaini
Redox-active center, Repeat, SignalPhylogenomic databases
eggNOGi | KOG0190, Eukaryota |
GeneTreei | ENSGT00940000155425 |
HOGENOMi | CLU_025879_6_0_1 |
InParanoidi | P30101 |
OMAi | VAIVKMD |
OrthoDBi | 462118at2759 |
PhylomeDBi | P30101 |
TreeFami | TF106382 |
Family and domain databases
CDDi | cd03069, PDI_b_ERp57, 1 hit |
Gene3Di | 3.40.30.10, 4 hits |
InterProi | View protein in InterPro IPR005788, Disulphide_isomerase IPR041868, PDIA3_PDI_b IPR005792, Prot_disulphide_isomerase IPR036249, Thioredoxin-like_sf IPR017937, Thioredoxin_CS IPR013766, Thioredoxin_domain |
Pfami | View protein in Pfam PF00085, Thioredoxin, 2 hits |
SUPFAMi | SSF52833, SSF52833, 4 hits |
TIGRFAMsi | TIGR01130, ER_PDI_fam, 1 hit TIGR01126, pdi_dom, 2 hits |
PROSITEi | View protein in PROSITE PS00194, THIOREDOXIN_1, 2 hits PS51352, THIOREDOXIN_2, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
P30101-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7BZJ3 | H7BZJ3_HUMAN | Protein disulfide-isomerase A3 | PDIA3 | 123 | Annotation score: | ||
F8WBW5 | F8WBW5_HUMAN | Protein disulfide-isomerase A3 | PDIA3 | 75 | Annotation score: | ||
F8WBS6 | F8WBS6_HUMAN | Protein disulfide-isomerase A3 | PDIA3 | 71 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 19 | A → G in BAA11928 (PubMed:9399589).Curated | 1 | |
Sequence conflicti | 22 | A → V in BAA11928 (PubMed:9399589).Curated | 1 | |
Sequence conflicti | 217 | D → Y in BAA03759 (PubMed:7945384).Curated | 1 | |
Sequence conflicti | 225 | Q → P in CAA89996 (PubMed:8624847).Curated | 1 | |
Sequence conflicti | 238 | E → G in CAA89996 (PubMed:8624847).Curated | 1 | |
Sequence conflicti | 272 | N → D in BAA03759 (PubMed:7945384).Curated | 1 | |
Sequence conflicti | 272 | N → D in AAC51518 (PubMed:9205111).Curated | 1 | |
Sequence conflicti | 355 | D → G in BAA03759 (PubMed:7945384).Curated | 1 | |
Sequence conflicti | 358 | D → G in BAA03759 (PubMed:7945384).Curated | 1 | |
Sequence conflicti | 368 | E → D in BAA03759 (PubMed:7945384).Curated | 1 |
Mass spectrometryi
Molecular mass is 54265.22 Da. Determined by MALDI. 1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_020027 | 415 | K → R. Corresponds to variant dbSNP:rs6413485Ensembl. | 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 |
CCDSi | CCDS10101.1 |
PIRi | JC5704 S55507 S63994 S68363 |
RefSeqi | NP_005304.3, NM_005313.4 |
Genome annotation databases
Ensembli | ENST00000300289; ENSP00000300289; ENSG00000167004 |
GeneIDi | 2923 |
KEGGi | hsa:2923 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS10101.1 |
PIRi | JC5704 S55507 S63994 S68363 |
RefSeqi | NP_005304.3, NM_005313.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ALB | NMR | - | A | 25-137 | [»] | |
2DMM | NMR | - | A | 357-485 | [»] | |
2H8L | X-ray | 2.00 | A/B/C | 134-376 | [»] | |
3F8U | X-ray | 2.60 | A/C | 25-505 | [»] | |
6ENY | electron microscopy | 5.80 | D | 25-505 | [»] | |
BMRBi | P30101 | |||||
SMRi | P30101 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109180, 196 interactors |
ComplexPortali | CPX-2375, Tapasin-ERp57 complex |
CORUMi | P30101 |
DIPi | DIP-29132N |
IntActi | P30101, 142 interactors |
MINTi | P30101 |
STRINGi | 9606.ENSP00000300289 |
Chemistry databases
ChEMBLi | CHEMBL4296001 |
DrugBanki | DB09130, Copper DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
PTM databases
GlyGeni | P30101, 1 site |
iPTMneti | P30101 |
MetOSitei | P30101 |
PhosphoSitePlusi | P30101 |
SwissPalmi | P30101 |
Polymorphism and mutation databases
BioMutai | PDIA3 |
DMDMi | 2507461 |
2D gel databases
DOSAC-COBS-2DPAGEi | P30101 |
REPRODUCTION-2DPAGEi | P30101 |
SWISS-2DPAGEi | P30101 |
UCD-2DPAGEi | P30101 |
Proteomic databases
CPTACi | CPTAC-421 CPTAC-422 |
EPDi | P30101 |
jPOSTi | P30101 |
MassIVEi | P30101 |
PaxDbi | P30101 |
PeptideAtlasi | P30101 |
PRIDEi | P30101 |
ProteomicsDBi | 54635 |
TopDownProteomicsi | P30101 |
Protocols and materials databases
Antibodypediai | 1223, 893 antibodies |
DNASUi | 2923 |
Genome annotation databases
Ensembli | ENST00000300289; ENSP00000300289; ENSG00000167004 |
GeneIDi | 2923 |
KEGGi | hsa:2923 |
Organism-specific databases
CTDi | 2923 |
DisGeNETi | 2923 |
EuPathDBi | HostDB:ENSG00000167004.12 |
GeneCardsi | PDIA3 |
HGNCi | HGNC:4606, PDIA3 |
HPAi | ENSG00000167004, Low tissue specificity |
MIMi | 602046, gene |
neXtProti | NX_P30101 |
OpenTargetsi | ENSG00000167004 |
PharmGKBi | PA29000 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0190, Eukaryota |
GeneTreei | ENSGT00940000155425 |
HOGENOMi | CLU_025879_6_0_1 |
InParanoidi | P30101 |
OMAi | VAIVKMD |
OrthoDBi | 462118at2759 |
PhylomeDBi | P30101 |
TreeFami | TF106382 |
Enzyme and pathway databases
BRENDAi | 5.3.4.1, 2681 |
PathwayCommonsi | P30101 |
Reactomei | R-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
BioGRID-ORCSi | 2923, 16 hits in 840 CRISPR screens |
ChiTaRSi | PDIA3, human |
EvolutionaryTracei | P30101 |
GenomeRNAii | 2923 |
Pharosi | P30101, Tbio |
PROi | PR:P30101 |
RNActi | P30101, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167004, Expressed in corpus epididymis and 240 other tissues |
ExpressionAtlasi | P30101, baseline and differential |
Genevisiblei | P30101, HS |
Family and domain databases
CDDi | cd03069, PDI_b_ERp57, 1 hit |
Gene3Di | 3.40.30.10, 4 hits |
InterProi | View protein in InterPro IPR005788, Disulphide_isomerase IPR041868, PDIA3_PDI_b IPR005792, Prot_disulphide_isomerase IPR036249, Thioredoxin-like_sf IPR017937, Thioredoxin_CS IPR013766, Thioredoxin_domain |
Pfami | View protein in Pfam PF00085, Thioredoxin, 2 hits |
SUPFAMi | SSF52833, SSF52833, 4 hits |
TIGRFAMsi | TIGR01130, ER_PDI_fam, 1 hit TIGR01126, pdi_dom, 2 hits |
PROSITEi | View protein in PROSITE PS00194, THIOREDOXIN_1, 2 hits PS51352, THIOREDOXIN_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PDIA3_HUMAN | |
Accessioni | P30101Primary (citable) accession number: P30101 Secondary accession number(s): Q13453 Q9UMU7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | November 1, 1997 | |
Last modified: | December 2, 2020 | |
This is version 235 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations