Human Gene PDIA6 (uc002rau.3)
  Description: Homo sapiens protein disulfide isomerase family A, member 6 (PDIA6), mRNA.
RefSeq Summary (NM_005742): This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, two catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. This protein inhibits the aggregation of misfolded proteins and exhibits both isomerase and chaperone activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016].
Transcript (Including UTRs)
   Position: hg19 chr2:10,923,517-10,952,960 Size: 29,444 Total Exon Count: 13 Strand: -
Coding Region
   Position: hg19 chr2:10,924,384-10,952,822 Size: 28,439 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:10,923,517-10,952,960)mRNA (may differ from genome)Protein (440 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeTreefamUniProtKB
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PDIA6_HUMAN
DESCRIPTION: RecName: Full=Protein disulfide-isomerase A6; EC=5.3.4.1; AltName: Full=Endoplasmic reticulum protein 5; Short=ER protein 5; Short=ERp5; AltName: Full=Protein disulfide isomerase P5; AltName: Full=Thioredoxin domain-containing protein 7; Flags: Precursor;
FUNCTION: 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.
CATALYTIC ACTIVITY: Catalyzes the rearrangement of -S-S- bonds in proteins.
SUBUNIT: 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.
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen (By similarity). Cell membrane. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
TISSUE SPECIFICITY: Expressed in platelets (at protein level).
SIMILARITY: Belongs to the protein disulfide isomerase family.
SIMILARITY: Contains 2 thioredoxin domains.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PDIA6
CDC HuGE Published Literature: PDIA6
Positive Disease Associations: Osteoporosis , Respiratory Function Tests
Related Studies:
  1. Osteoporosis
    Kathryn L Lunetta et al. BMC medical genetics 2007, Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study., BMC medical genetics. [PubMed 17903295]
    Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.
  2. Respiratory Function Tests
    Jemma B Wilk et al. BMC medical genetics 2007, Framingham Heart Study genome-wide association: results for pulmonary function measures., BMC medical genetics. [PubMed 17903307]
    GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • D002994 Clofibrate
  • D010634 Phenobarbital
  • C006253 pirinixic acid
  • C016104 sodium bichromate
  • C576882 1-(2-trifluoromethoxyphenyl)-2-nitroethanone
  • D015632 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C016403 2,4-dinitrotoluene
  • C477187 5-(4-methylpiperazin-1-yl)-2-(2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl)benzimidazole
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 79.67 RPKM in Cells - Cultured fibroblasts
Total median expression: 1282.29 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -84.60138-0.613 Picture PostScript Text
3' UTR -211.07867-0.243 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR005788 - Disulphide_isomerase
IPR005746 - Thioredoxin
IPR012336 - Thioredoxin-like_fold
IPR017937 - Thioredoxin_CS
IPR013766 - Thioredoxin_domain

Pfam Domains:
PF00085 - Thioredoxin

SCOP Domains:
52833 - Thioredoxin-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1X5D - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q15084
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003756 protein disulfide isomerase activity
GO:0005515 protein binding
GO:0015037 peptide disulfide oxidoreductase activity
GO:0016853 isomerase activity

Biological Process:
GO:0006457 protein folding
GO:0034976 response to endoplasmic reticulum stress
GO:0036498 IRE1-mediated unfolded protein response
GO:0043277 apoptotic cell clearance
GO:0043687 post-translational protein modification
GO:0044267 cellular protein metabolic process
GO:0045454 cell redox homeostasis
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005615 extracellular space
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005789 endoplasmic reticulum membrane
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0034663 endoplasmic reticulum chaperone complex
GO:0042470 melanosome
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK127433 - Homo sapiens cDNA FLJ45525 fis, clone BRTHA2026311, highly similar to Protein disulfide isomerase A6 precursor (EC 5.3.4.1).
AK125449 - Homo sapiens cDNA FLJ43460 fis, clone OCBBF2035823.
BC001312 - Homo sapiens protein disulfide isomerase family A, member 6, mRNA (cDNA clone MGC:5517 IMAGE:3454007), complete cds.
GQ891476 - Homo sapiens clone HEL-S-197 epididymis secretory sperm binding protein mRNA, complete cds.
AK131234 - Homo sapiens cDNA FLJ16143 fis, clone BRAMY2038516, highly similar to Protein disulfide-isomerase A6 precursor (EC 5.3.4.1).
AK225496 - Homo sapiens mRNA for protein disulfide isomerase-associated 6 variant, clone: KAT00394.
U79278 - Human protein disulfide isomerase-related protein P5 mRNA, partial cds.
D49489 - Homo sapiens mRNA for protein disulfide isomerase-related protein P5, complete cds.
AK289428 - Homo sapiens cDNA FLJ76201 complete cds, highly similar to Homo sapiens protein disulfide isomerase family A, member 6 (PDIA6), mRNA.
JD273613 - Sequence 254637 from Patent EP1572962.
AK026926 - Homo sapiens cDNA: FLJ23273 fis, clone HEP02611, highly similar to HSU79278 Human protein disulfide isomerase-related protein P5 mRNA.
AK294347 - Homo sapiens cDNA FLJ58502 complete cds, highly similar to Protein disulfide-isomerase A6 precursor (EC 5.3.4.1).
AK297547 - Homo sapiens cDNA FLJ58023 complete cds, highly similar to Protein disulfide-isomerase A6 precursor (EC 5.3.4.1).
JD263255 - Sequence 244279 from Patent EP1572962.
JD348737 - Sequence 329761 from Patent EP1572962.
KJ892929 - Synthetic construct Homo sapiens clone ccsbBroadEn_02323 PDIA6 gene, encodes complete protein.
DQ891186 - Synthetic construct clone IMAGE:100003816; FLH169976.01X; RZPDo839A0598D protein disulfide isomerase family A, member 6 (PDIA6) gene, encodes complete protein.
DQ894369 - Synthetic construct Homo sapiens clone IMAGE:100008829; FLH169972.01L; RZPDo839A0597D protein disulfide isomerase family A, member 6 (PDIA6) gene, encodes complete protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q15084 (Reactome details) participates in the following event(s):

R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-381070 IRE1alpha activates chaperones
R-HSA-381119 Unfolded Protein Response (UPR)
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
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification

-  Other Names for This Gene
  Alternate Gene Symbols: ERP5, NM_005742, NP_005733, P5, PDIA6_HUMAN, Q15084, Q53RC7, Q6ZSH5, Q99778, TXNDC7
UCSC ID: uc002rau.3
RefSeq Accession: NM_005742
Protein: Q15084 (aka PDIA6_HUMAN)
CCDS: CCDS1675.1, CCDS62852.1, CCDS62853.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005742.2
exon count: 13CDS single in 3' UTR: no RNA size: 2344
ORF size: 1323CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2846.00frame shift in genome: no % Coverage: 99.32
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.