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
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.
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.
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.
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.
ModBase Predicted Comparative 3D Structure on Q15084
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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.
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