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Protein

Protein disulfide-isomerase A2

Gene

PDIA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as an intracellular estrogen-binding protein. May be involved in modulating cellular levels and biological functions of estrogens in the pancreas. May act as a chaperone that inhibits aggregation of misfolded proteins.2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei71NucleophileBy similarity1
Sitei72Contributes to redox potential valueBy similarity1
Sitei73Contributes to redox potential valueBy similarity1
Active sitei74NucleophileBy similarity1
Sitei138Lowers pKa of C-terminal Cys of first active siteBy similarity1
Active sitei418NucleophileBy similarity1
Sitei419Contributes to redox potential valueBy similarity1
Sitei420Contributes to redox potential valueBy similarity1
Active sitei421NucleophileBy similarity1
Sitei482Lowers pKa of C-terminal Cys of second active siteBy similarity1

GO - Molecular functioni

  • disulfide oxidoreductase activity Source: ParkinsonsUK-UCL
  • protein disulfide isomerase activity Source: ProtInc
  • steroid binding Source: UniProtKB-KW

GO - Biological processi

  • cell redox homeostasis Source: InterPro
  • peptidyl-proline hydroxylation Source: GOC
  • protein folding Source: ProtInc
  • protein folding in endoplasmic reticulum Source: ParkinsonsUK-UCL
  • protein retention in ER lumen Source: ProtInc
  • regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: GO_Central
  • response to endoplasmic reticulum stress Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase

Keywords - Ligandi

Lipid-binding, Steroid-binding

Enzyme and pathway databases

BioCyciZFISH:HS02458-MONOMER.
BRENDAi5.3.4.1. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein disulfide-isomerase A2 (EC:5.3.4.1)
Alternative name(s):
Pancreas-specific protein disulfide isomerase
Short name:
PDIp
Gene namesi
Name:PDIA2
Synonyms:PDIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:14180. PDIA2.

Subcellular locationi

  • Endoplasmic reticulum lumen PROSITE-ProRule annotation

GO - Cellular componenti

  • endoplasmic reticulum Source: ProtInc
  • endoplasmic reticulum lumen Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18C → A: Impairs interchain disulfide bridge formation. 1 Publication1
Mutagenesisi284N → Q: Increases formation of a highly stable disulfide-bonded PDIA2 dimer. 1 Publication1
Mutagenesisi364C → A: No effect on interchain disulfide bridge formation. 1 Publication1

Organism-specific databases

DisGeNETi64714.
OpenTargetsiENSG00000185615.
PharmGKBiPA33153.

Polymorphism and mutation databases

BioMutaiPDIA2.
DMDMi21264492.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000003422222 – 525Protein disulfide-isomerase A2Add BLAST504

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi18Interchain1 Publication
Disulfide bondi71 ↔ 74Redox-activePROSITE-ProRule annotation
Glycosylationi127N-linked (GlcNAc...)1 Publication1
Glycosylationi284N-linked (GlcNAc...)1 Publication1
Disulfide bondi418 ↔ 421Redox-activePROSITE-ProRule annotation
Glycosylationi516N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

The disulfide-linked homodimer exhibits an enhanced chaperone activity.
Glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ13087.
PaxDbiQ13087.
PeptideAtlasiQ13087.
PRIDEiQ13087.

PTM databases

iPTMnetiQ13087.
PhosphoSitePlusiQ13087.

Expressioni

Tissue specificityi

Highly expressed in pancreas (at protein level).3 Publications

Gene expression databases

BgeeiENSG00000185615.
CleanExiHS_PDIA2.
ExpressionAtlasiQ13087. baseline and differential.
GenevisibleiQ13087. HS.

Organism-specific databases

HPAiHPA051692.
HPA053492.

Interactioni

Subunit structurei

Monomer; predominantly as monomer under reducing conditions. Homodimer; disulfide-linked. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK1P163333EBI-1752525,EBI-389883

Protein-protein interaction databases

BioGridi122240. 19 interactors.
IntActiQ13087. 10 interactors.
MINTiMINT-1513985.
STRINGi9606.ENSP00000219406.

Structurei

3D structure databases

ProteinModelPortaliQ13087.
SMRiQ13087.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 152Thioredoxin 1PROSITE-ProRule annotationAdd BLAST126
Domaini367 – 496Thioredoxin 2PROSITE-ProRule annotationAdd BLAST130

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi522 – 525Prevents secretion from ERPROSITE-ProRule annotation4

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.
HOVERGENiHBG005920.
InParanoidiQ13087.
KOiK09581.
OMAiQEVPPDW.
OrthoDBiEOG091G08WM.
PhylomeDBiQ13087.
TreeFamiTF106381.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005792. 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.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13087-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRQLLPVLL LLLLRASCPW GQEQGARSPS EEPPEEEIPK EDGILVLSRH
60 70 80 90 100
TLGLALREHP ALLVEFYAPW CGHCQALAPE YSKAAAVLAA ESMVVTLAKV
110 120 130 140 150
DGPAQRELAE EFGVTEYPTL KFFRNGNRTH PEEYTGPRDA EGIAEWLRRR
160 170 180 190 200
VGPSAMRLED EAAAQALIGG RDLVVIGFFQ DLQDEDVATF LALAQDALDM
210 220 230 240 250
TFGLTDRPRL FQQFGLTKDT VVLFKKFDEG RADFPVDEEL GLDLGDLSRF
260 270 280 290 300
LVTHSMRLVT EFNSQTSAKI FAARILNHLL LFVNQTLAAH RELLAGFGEA
310 320 330 340 350
APRFRGQVLF VVVDVAADNE HVLQYFGLKA EAAPTLRLVN LETTKKYAPV
360 370 380 390 400
DGGPVTAASI TAFCHAVLNG QVKPYLLSQE IPPDWDQRPV KTLVGKNFEQ
410 420 430 440 450
VAFDETKNVF VKFYAPWCTH CKEMAPAWEA LAEKYQDHED IIIAELDATA
460 470 480 490 500
NELDAFAVHG FPTLKYFPAG PGRKVIEYKS TRDLETFSKF LDNGGVLPTE
510 520
EPPEEPAAPF PEPPANSTMG SKEEL
Length:525
Mass (Da):58,206
Last modified:May 27, 2002 - v2
Checksum:iB741851AA2C40540
GO
Isoform 2 (identifier: Q13087-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-183: Missing.

Show »
Length:522
Mass (Da):57,850
Checksum:i815CD5F3060B5747
GO

Sequence cautioni

The sequence AAC50401 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence AAH75029 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence BAG58339 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96T → M in BAG58339 (PubMed:14702039).Curated1
Sequence conflicti484L → Q in BAG58339 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04808739P → S.Corresponds to variant rs45455191dbSNPEnsembl.1
Natural variantiVAR_048088119T → R.Corresponds to variant rs45614840dbSNPEnsembl.1
Natural variantiVAR_048089185E → K.Corresponds to variant rs419949dbSNPEnsembl.1
Natural variantiVAR_048090286T → M.Corresponds to variant rs2685127dbSNPEnsembl.1
Natural variantiVAR_048091382P → A.Corresponds to variant rs45529833dbSNPEnsembl.1
Natural variantiVAR_048092388R → Q.Corresponds to variant rs400037dbSNPEnsembl.1
Natural variantiVAR_048093502P → S.3 PublicationsCorresponds to variant rs1048786dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039292181 – 183Missing in isoform 2. Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB127078 mRNA. Translation: BAE48734.1.
AE006463 Genomic DNA. Translation: AAK61223.1.
Z69667 Genomic DNA. Translation: CAI95586.1.
Z69667 Genomic DNA. Translation: CAO78188.1.
CH471112 Genomic DNA. Translation: EAW85838.1.
BC000537 mRNA. Translation: AAH00537.2.
BC075029 mRNA. Translation: AAH75029.1. Sequence problems.
U19948 mRNA. Translation: AAC50401.1. Sequence problems.
AK295383 mRNA. Translation: BAG58339.1. Different initiation.
CCDSiCCDS42089.1. [Q13087-1]
RefSeqiNP_006840.2. NM_006849.2. [Q13087-1]
UniGeneiHs.66581.

Genome annotation databases

EnsembliENST00000219406; ENSP00000219406; ENSG00000185615. [Q13087-1]
ENST00000404312; ENSP00000384410; ENSG00000185615. [Q13087-2]
GeneIDi64714.
KEGGihsa:64714.
UCSCiuc002cgo.2. human. [Q13087-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB127078 mRNA. Translation: BAE48734.1.
AE006463 Genomic DNA. Translation: AAK61223.1.
Z69667 Genomic DNA. Translation: CAI95586.1.
Z69667 Genomic DNA. Translation: CAO78188.1.
CH471112 Genomic DNA. Translation: EAW85838.1.
BC000537 mRNA. Translation: AAH00537.2.
BC075029 mRNA. Translation: AAH75029.1. Sequence problems.
U19948 mRNA. Translation: AAC50401.1. Sequence problems.
AK295383 mRNA. Translation: BAG58339.1. Different initiation.
CCDSiCCDS42089.1. [Q13087-1]
RefSeqiNP_006840.2. NM_006849.2. [Q13087-1]
UniGeneiHs.66581.

3D structure databases

ProteinModelPortaliQ13087.
SMRiQ13087.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122240. 19 interactors.
IntActiQ13087. 10 interactors.
MINTiMINT-1513985.
STRINGi9606.ENSP00000219406.

PTM databases

iPTMnetiQ13087.
PhosphoSitePlusiQ13087.

Polymorphism and mutation databases

BioMutaiPDIA2.
DMDMi21264492.

Proteomic databases

MaxQBiQ13087.
PaxDbiQ13087.
PeptideAtlasiQ13087.
PRIDEiQ13087.

Protocols and materials databases

DNASUi64714.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219406; ENSP00000219406; ENSG00000185615. [Q13087-1]
ENST00000404312; ENSP00000384410; ENSG00000185615. [Q13087-2]
GeneIDi64714.
KEGGihsa:64714.
UCSCiuc002cgo.2. human. [Q13087-1]

Organism-specific databases

CTDi64714.
DisGeNETi64714.
GeneCardsiPDIA2.
H-InvDBHIX0202311.
HGNCiHGNC:14180. PDIA2.
HPAiHPA051692.
HPA053492.
MIMi608012. gene.
neXtProtiNX_Q13087.
OpenTargetsiENSG00000185615.
PharmGKBiPA33153.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0190. Eukaryota.
COG0526. LUCA.
GeneTreeiENSGT00860000133691.
HOVERGENiHBG005920.
InParanoidiQ13087.
KOiK09581.
OMAiQEVPPDW.
OrthoDBiEOG091G08WM.
PhylomeDBiQ13087.
TreeFamiTF106381.

Enzyme and pathway databases

BioCyciZFISH:HS02458-MONOMER.
BRENDAi5.3.4.1. 2681.

Miscellaneous databases

GenomeRNAii64714.
PROiQ13087.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185615.
CleanExiHS_PDIA2.
ExpressionAtlasiQ13087. baseline and differential.
GenevisibleiQ13087. HS.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005792. 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.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDIA2_HUMAN
AccessioniPrimary (citable) accession number: Q13087
Secondary accession number(s): A6ZJ64
, B4DI27, Q2WGM4, Q4TT67, Q6B010, Q96KJ6, Q9BW95
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 27, 2002
Last modified: November 30, 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
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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. 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.