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Protein

Protein disulfide-isomerase A6

Gene

PDIA6

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

Functioni

May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:12204115). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (PubMed:24508390). May also regulate the UPR via the EIF2AK3 UPR sensor (PubMed:24508390). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (PubMed:15466936).3 Publications

Catalytic activityi

Catalyzes the rearrangement of -S-S- bonds in proteins.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei55NucleophileBy similarity1
Sitei56Contributes to redox potential valueBy similarity1
Sitei57Contributes to redox potential valueBy similarity1
Active sitei58NucleophileBy similarity1
Sitei118Lowers pKa of C-terminal Cys of first active siteBy similarity1
Active sitei190NucleophileBy similarity1
Sitei191Contributes to redox potential valueBy similarity1
Sitei192Contributes to redox potential valueBy similarity1
Active sitei193NucleophileBy similarity1
Sitei256Lowers pKa of C-terminal Cys of second active siteBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone, Isomerase

Enzyme and pathway databases

ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation

Names & Taxonomyi

Protein namesi
Recommended name:
Protein disulfide-isomerase A6 (EC:5.3.4.12 Publications)
Alternative name(s):
Endoplasmic reticulum protein 5
Short name:
ER protein 5
Short name:
ERp5
Protein disulfide isomerase P5
Thioredoxin domain-containing protein 7
Gene namesi
Name:PDIA6
Synonyms:ERP5, P5, TXNDC7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000143870.12
HGNCiHGNC:30168 PDIA6
MIMi611099 gene
neXtProtiNX_Q15084

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi55C → S: 50% decrease in enzyme activity; when associated with S-58. Abolishes enzyme activity; when associated with S-58; S-190 and S-193. 1 Publication1
Mutagenesisi58C → A: Accelerates dephosphorylation of ERN1; when associated with A-193. 1 Publication1
Mutagenesisi58C → S: 50% decrease in enzyme activity; when associated with S-55. 90% decrease in enzyme activity; when associated with S-193. Abolishes enzyme activity; when associated with S-55; S-190 and S-193. 1 Publication1
Mutagenesisi190C → S: 25% decrease in enzyme activity; when associated with S-193. Abolishes enzyme activity; when associated with S-55; S-58 and S-193. 1 Publication1
Mutagenesisi193C → A: Accelerates dephosphorylation of ERN1; when associated with A-58. 1 Publication1
Mutagenesisi193C → S: 90% decrease in enzyme activity; when associated with S-58. 25% decrease in enzyme activity; when associated with S-190. Abolishes enzyme activity; when associated with S-55; S-58 and S-190. 1 Publication1

Organism-specific databases

DisGeNETi10130
OpenTargetsiENSG00000143870
PharmGKBiPA134977905

Chemistry databases

ChEMBLiCHEMBL2146308

Polymorphism and mutation databases

DMDMi2501205

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Combined sources2 PublicationsAdd BLAST19
ChainiPRO_000003423620 – 440Protein disulfide-isomerase A6Add BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi55 ↔ 58Redox-activePROSITE-ProRule annotation
Modified residuei129PhosphoserineCombined sources1
Modified residuei156Phosphoserine; by FAM20C1 Publication1
Modified residuei158PhosphoserineCombined sources1
Disulfide bondi190 ↔ 193Redox-activePROSITE-ProRule annotation
Modified residuei428PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiQ15084
PaxDbiQ15084
PeptideAtlasiQ15084
PRIDEiQ15084
ProteomicsDBi60433
60434 [Q15084-2]

2D gel databases

OGPiQ15084
REPRODUCTION-2DPAGEiIPI00644989
Q15084

PTM databases

iPTMnetiQ15084
PhosphoSitePlusiQ15084
SwissPalmiQ15084

Expressioni

Tissue specificityi

Expressed in platelets (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000143870 Expressed in 237 organ(s), highest expression level in corpus epididymis
CleanExiHS_PDIA6
ExpressionAtlasiQ15084 baseline and differential
GenevisibleiQ15084 HS

Organism-specific databases

HPAiCAB034347
HPA034652
HPA034653

Interactioni

Subunit structurei

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 (PubMed:12475965). Interacts with MICA on the surface of tumor cells, leading to MICA disulfide bond reduction which is required for its release from tumor cells (PubMed:17495932). Interacts with ITGB3 following platelet stimulation (PubMed:15466936). Interacts with ERN1; the interaction is direct (PubMed:24508390). Interacts with EIF2AK3 (PubMed:24508390).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PRDX4Q131622EBI-1043087,EBI-2211957

Protein-protein interaction databases

BioGridi115434, 108 interactors
CORUMiQ15084
IntActiQ15084, 47 interactors
MINTiQ15084
STRINGi9606.ENSP00000272227

Structurei

Secondary structure

1440
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ15084
SMRiQ15084
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15084

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 133Thioredoxin 1PROSITE-ProRule annotationAdd BLAST114
Domaini154 – 287Thioredoxin 2PROSITE-ProRule annotationAdd BLAST134

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi437 – 440Prevents secretion from ERPROSITE-ProRule annotation4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi422 – 434Asp/Glu-rich (acidic)Add BLAST13

Sequence similaritiesi

Belongs to the protein disulfide isomerase family.Curated

Keywords - Domaini

Redox-active center, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0191 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00860000133723
HOGENOMiHOG000012631
HOVERGENiHBG053548
InParanoidiQ15084
KOiK09584
OMAiPHILDCD
OrthoDBiEOG091G07Z0
PhylomeDBiQ15084
TreeFamiTF315231

Family and domain databases

InterProiView protein in InterPro
IPR005788 Disulphide_isomerase
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PfamiView protein in Pfam
PF00085 Thioredoxin, 2 hits
SUPFAMiSSF52833 SSF52833, 3 hits
TIGRFAMsiTIGR01126 pdi_dom, 2 hits
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00194 THIOREDOXIN_1, 2 hits
PS51352 THIOREDOXIN_2, 2 hits

Sequences (5+)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q15084-1) [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
MALLVLGLVS CTFFLAVNGL YSSSDDVIEL TPSNFNREVI QSDSLWLVEF
60 70 80 90 100
YAPWCGHCQR LTPEWKKAAT ALKDVVKVGA VDADKHHSLG GQYGVQGFPT
110 120 130 140 150
IKIFGSNKNR PEDYQGGRTG EAIVDAALSA LRQLVKDRLG GRSGGYSSGK
160 170 180 190 200
QGRSDSSSKK DVIELTDDSF DKNVLDSEDV WMVEFYAPWC GHCKNLEPEW
210 220 230 240 250
AAAASEVKEQ TKGKVKLAAV DATVNQVLAS RYGIRGFPTI KIFQKGESPV
260 270 280 290 300
DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDIAKRT CEEHQLCVVA
310 320 330 340 350
VLPHILDTGA AGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQSELETALG
360 370 380 390 400
IGGFGYPAMA AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG
410 420 430 440
GAFPTIVERE PWDGRDGELP VEDDIDLSDV ELDDLGKDEL
Length:440
Mass (Da):48,121
Last modified:November 1, 1997 - v1
Checksum:i06895409F0265D7C
GO
Isoform 2 (identifier: Q15084-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MALLVL → MRRDLREKLVWVCRPLAPVEVPANISSDFQPCSPTSPAHSLSRKSPIMYPSTTMANAP

Show »
Length:492
Mass (Da):53,901
Checksum:i987BB19EC01F116C
GO
Isoform 3 (identifier: Q15084-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MALLV → MI

Note: No experimental confirmation available.
Show »
Length:437
Mass (Da):47,838
Checksum:i80571DED0FA33DB3
GO
Isoform 4 (identifier: Q15084-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MALLVL → MYPSTTMANAP

Note: No experimental confirmation available.
Show »
Length:445
Mass (Da):48,646
Checksum:i1C9AE81DD2216FFD
GO
Isoform 5 (identifier: Q15084-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MALLVL → MRIITAPASKVSRGSNELMILARRSDRGSPTSPAHSLSRKSPIMYPSTTMANAP

Note: No experimental confirmation available.
Show »
Length:488
Mass (Da):53,261
Checksum:i79DDA7AC1EF6C39D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JNG5C9JNG5_HUMAN
Protein disulfide-isomerase A6
PDIA6
11Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti64E → K in BAH12614 (PubMed:14702039).Curated1
Sequence conflicti187A → V in BAH12614 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022152214K → R2 PublicationsCorresponds to variant dbSNP:rs4807Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0218031 – 6MALLVL → MRRDLREKLVWVCRPLAPVE VPANISSDFQPCSPTSPAHS LSRKSPIMYPSTTMANAP in isoform 2. 1 Publication6
Alternative sequenceiVSP_0551731 – 6MALLVL → MYPSTTMANAP in isoform 4. 1 Publication6
Alternative sequenceiVSP_0551741 – 6MALLVL → MRIITAPASKVSRGSNELMI LARRSDRGSPTSPAHSLSRK SPIMYPSTTMANAP in isoform 5. 1 Publication6
Alternative sequenceiVSP_0543701 – 5MALLV → MI in isoform 3. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49489 mRNA Translation: BAA08450.1
AK127433 mRNA Translation: BAC86977.1
AK131234 mRNA Translation: BAG54757.1
AK289428 mRNA Translation: BAF82117.1
AK294347 mRNA Translation: BAH11740.1
AK297547 mRNA Translation: BAH12614.1
AC092687 Genomic DNA Translation: AAY24070.1
CH471053 Genomic DNA Translation: EAX00950.1
BC001312 mRNA Translation: AAH01312.1
U79278 mRNA Translation: AAB50217.1
CCDSiCCDS1675.1 [Q15084-1]
CCDS62852.1 [Q15084-3]
CCDS62853.1 [Q15084-4]
CCDS62854.1 [Q15084-2]
CCDS62855.1 [Q15084-5]
PIRiJC4369
RefSeqiNP_001269633.1, NM_001282704.1 [Q15084-2]
NP_001269634.1, NM_001282705.1 [Q15084-5]
NP_001269635.1, NM_001282706.1 [Q15084-4]
NP_001269636.1, NM_001282707.1 [Q15084-3]
NP_005733.1, NM_005742.3 [Q15084-1]
UniGeneiHs.212102
Hs.580464

Genome annotation databases

EnsembliENST00000272227; ENSP00000272227; ENSG00000143870 [Q15084-1]
ENST00000381611; ENSP00000371024; ENSG00000143870 [Q15084-4]
ENST00000404371; ENSP00000385385; ENSG00000143870 [Q15084-2]
ENST00000404824; ENSP00000384459; ENSG00000143870 [Q15084-5]
ENST00000540494; ENSP00000438778; ENSG00000143870 [Q15084-3]
ENST00000617249; ENSP00000481892; ENSG00000143870 [Q15084-2]
GeneIDi10130
KEGGihsa:10130
UCSCiuc002rau.5 human [Q15084-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49489 mRNA Translation: BAA08450.1
AK127433 mRNA Translation: BAC86977.1
AK131234 mRNA Translation: BAG54757.1
AK289428 mRNA Translation: BAF82117.1
AK294347 mRNA Translation: BAH11740.1
AK297547 mRNA Translation: BAH12614.1
AC092687 Genomic DNA Translation: AAY24070.1
CH471053 Genomic DNA Translation: EAX00950.1
BC001312 mRNA Translation: AAH01312.1
U79278 mRNA Translation: AAB50217.1
CCDSiCCDS1675.1 [Q15084-1]
CCDS62852.1 [Q15084-3]
CCDS62853.1 [Q15084-4]
CCDS62854.1 [Q15084-2]
CCDS62855.1 [Q15084-5]
PIRiJC4369
RefSeqiNP_001269633.1, NM_001282704.1 [Q15084-2]
NP_001269634.1, NM_001282705.1 [Q15084-5]
NP_001269635.1, NM_001282706.1 [Q15084-4]
NP_001269636.1, NM_001282707.1 [Q15084-3]
NP_005733.1, NM_005742.3 [Q15084-1]
UniGeneiHs.212102
Hs.580464

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X5DNMR-A161-280[»]
3VWWX-ray1.93A/B25-140[»]
3W8JX-ray2.10A/B20-140[»]
4EF0X-ray1.50A/B27-140[»]
4GWRX-ray1.81A/B160-274[»]
ProteinModelPortaliQ15084
SMRiQ15084
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115434, 108 interactors
CORUMiQ15084
IntActiQ15084, 47 interactors
MINTiQ15084
STRINGi9606.ENSP00000272227

Chemistry databases

ChEMBLiCHEMBL2146308

PTM databases

iPTMnetiQ15084
PhosphoSitePlusiQ15084
SwissPalmiQ15084

Polymorphism and mutation databases

DMDMi2501205

2D gel databases

OGPiQ15084
REPRODUCTION-2DPAGEiIPI00644989
Q15084

Proteomic databases

EPDiQ15084
PaxDbiQ15084
PeptideAtlasiQ15084
PRIDEiQ15084
ProteomicsDBi60433
60434 [Q15084-2]

Protocols and materials databases

DNASUi10130
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000272227; ENSP00000272227; ENSG00000143870 [Q15084-1]
ENST00000381611; ENSP00000371024; ENSG00000143870 [Q15084-4]
ENST00000404371; ENSP00000385385; ENSG00000143870 [Q15084-2]
ENST00000404824; ENSP00000384459; ENSG00000143870 [Q15084-5]
ENST00000540494; ENSP00000438778; ENSG00000143870 [Q15084-3]
ENST00000617249; ENSP00000481892; ENSG00000143870 [Q15084-2]
GeneIDi10130
KEGGihsa:10130
UCSCiuc002rau.5 human [Q15084-1]

Organism-specific databases

CTDi10130
DisGeNETi10130
EuPathDBiHostDB:ENSG00000143870.12
GeneCardsiPDIA6
HGNCiHGNC:30168 PDIA6
HPAiCAB034347
HPA034652
HPA034653
MIMi611099 gene
neXtProtiNX_Q15084
OpenTargetsiENSG00000143870
PharmGKBiPA134977905
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0191 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00860000133723
HOGENOMiHOG000012631
HOVERGENiHBG053548
InParanoidiQ15084
KOiK09584
OMAiPHILDCD
OrthoDBiEOG091G07Z0
PhylomeDBiQ15084
TreeFamiTF315231

Enzyme and pathway databases

ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation

Miscellaneous databases

ChiTaRSiPDIA6 human
EvolutionaryTraceiQ15084
GenomeRNAii10130
PROiPR:Q15084
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143870 Expressed in 237 organ(s), highest expression level in corpus epididymis
CleanExiHS_PDIA6
ExpressionAtlasiQ15084 baseline and differential
GenevisibleiQ15084 HS

Family and domain databases

InterProiView protein in InterPro
IPR005788 Disulphide_isomerase
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PfamiView protein in Pfam
PF00085 Thioredoxin, 2 hits
SUPFAMiSSF52833 SSF52833, 3 hits
TIGRFAMsiTIGR01126 pdi_dom, 2 hits
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00194 THIOREDOXIN_1, 2 hits
PS51352 THIOREDOXIN_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiPDIA6_HUMAN
AccessioniPrimary (citable) accession number: Q15084
Secondary accession number(s): B3KY95
, B5MCQ5, B7Z254, B7Z4M8, F8WA83, Q53RC7, Q6ZSH5, Q99778
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 10, 2018
This is version 203 of the entry and version 1 of the sequence. See 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

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

Documents

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