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UniProtKB - Q15084 (PDIA6_HUMAN)

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Protein

Protein disulfide-isomerase A6

Gene

PDIA6

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

Functioni

May function as a chaperone that inhibits aggregation of misfolded proteins. Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin.2 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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:30168. PDIA6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 → 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 → 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.

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.
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. Interacts with MICA on the surface of tumor cells, leading to MICA disulfide bond reduction which is required for its release from tumor cells. Interacts with ITGB3 following platelet stimulation.2 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi115434. 93 interactors.
IntActiQ15084. 39 interactors.
MINTiMINT-3030897.
STRINGi9606.ENSP00000272227.

Structurei

Secondary structure

1440
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 30Combined sources3
Turni32 – 34Combined sources3
Helixi35 – 38Combined sources4
Turni39 – 41Combined sources3
Beta strandi46 – 51Combined sources6
Helixi56 – 71Combined sources16
Turni72 – 75Combined sources4
Beta strandi76 – 82Combined sources7
Turni83 – 85Combined sources3
Helixi87 – 92Combined sources6
Beta strandi100 – 104Combined sources5
Beta strandi112 – 114Combined sources3
Helixi120 – 139Combined sources20
Beta strandi162 – 164Combined sources3
Turni167 – 169Combined sources3
Helixi170 – 173Combined sources4
Turni174 – 176Combined sources3
Beta strandi178 – 186Combined sources9
Helixi191 – 211Combined sources21
Beta strandi214 – 221Combined sources8
Helixi222 – 224Combined sources3
Helixi226 – 231Combined sources6
Beta strandi236 – 243Combined sources8
Beta strandi247 – 252Combined sources6
Helixi258 – 271Combined sources14

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...

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.
IPR012336. Thioredoxin-like_fold.
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

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

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

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.

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: July 5, 2017
This is version 191 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. 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