Disease relevance of PDIA6

• Human P5 (hP5) was expressed in the Escherichia coli pET system and purified by sequential Ni(2+)-chelating resin column chromatography [1].
• The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1 [2].
• Strikingly, all nucleotide substitutions in the MOMP P5 loop regions of variants were nonsynonymous, suggesting that variants with alterated amino acid compositions of the surface-exposed parts of MOMP P5 obtained a selective advantage during persistence of the infection by nonencapsulated H. influenzae in chronic bronchitis patients [3].
• One mucoid P. aeruginosa clinical isolate and its derived nonmucoid variant, as well as two other nonmucoid variant P. aeruginosa strains (all from cystic fibrosis patients), showed similar production of five differently migrating proteases (P1 to P5, numbered according to increasing net negative charge) in pH 9 PAGE and one protease in pH 4 PAGE [4].
• The P5 multicopy gene family in the MHC is related in sequence to human endogenous retroviruses HERV-L and HERV-16 [5].

High impact information on PDIA6

• Antibody reaction was used to show the selective synthesis of immune proteins P4 and P5 with mRNA from pupae subjected to injury or infection [6].
• Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57 [7].
• Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists [7].
• It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin beta(3) subunit during platelet stimulation [7].
• Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure [7].

Biological context of PDIA6

• In addition, in three variants derived sequentially from one H. influenzae strain, a frameshift mutation resulted in the formation of a stop codon in the region encoding the signal sequence of the MOMP P5 gene [3].
• Duplicate copies of this sequence also occur in the active site of rat and human protein disulphide isomerase (also known as the beta-subunit of human prolyl 4-hydroxylase, tri-iodothyronine-binding protein) and in Form I phosphoinositide-specific phospholipase C, indicating that P5 falls into this newly defined superfamily of proteins [8].
• The MOMP P5 variants with alterations in MOMP P5 were shown to result from DNA point mutations and codon deletions [3].
• The nature of this variability was determined by DNA sequence analysis of the P5 gene from five different H. influenzae strains and their seven MOMP P5 variants which were isolated from patients with chronic infections of the lower respiratory tract [3].
• These two fusion events between members of HLA class I and P5 families reflect the existence of a duplication unit including two class I genes and a P5 sequence [9].

Anatomical context of PDIA6

• As in follicular fluid, cleavage of IGFBP-2 by rhPAPP-A was dose-dependently enhanced by IGFs and inhibited by a peptide derived from the heparin-binding domain of IGFBP-5 (P5) [10].
• Although the function of P5 genes is not known, one of the family members, P5-1, was found previously to be specifically transcribed in lymphoid cells and tissue [5].
• The distances between the upper margin of the hemisphere and the cingulate sulcus, especially important for avoiding damage to the cingulate gyrus and other mesiolimbic structures, were 13.54-30.00 (21.28 +/- 3.89) mm and 12.22-29.52 (21.12 +/- 3.90) mm at the level of P5 and P7 [11].

Associations of PDIA6 with chemical compounds

• RNA blots probed with P5 cDNA show two poly(A)+ RNA species which are elevated in hydroxyurea-resistant cells [8].
• Others (sphingosine 1-phosphate kinase and PtdIns4 P 5-kinase) are implicated in pathways that also involve PLD activation [12].
• Three of the synthesized peptides, namely CAALCLAR (P1), YRRGRCGGLCLAR (P5) and YRRGRAhxCGGLCLAR (P8), point in the direction of C3a antagonists [13].

Other interactions of PDIA6

• The predicted 440-amino-acid (aa) sequence of human P5 contains two thioredoxin-like domains, which are also found in members of the protein disulfide isomerase superfamily [14].

Analytical, diagnostic and therapeutic context of PDIA6

• These clones were used to estimate the sizes of the mRNAs by Northern blotting and to estimate, by RNA/DNA hybridization, the levels of P4 and P5 mRNA [6].
• Surface plasmon resonance experiments demonstrated that alpha1-antitrypsin interacts with hPDIR, but not with hPDI or human P5 (hP5) [15].

References