Disease relevance of PIR

• The sets of sequences examined were taken from the 1989 PIR database and consisted of 1,792 "super-family" proteins selected to have little sequence identity, 623 E. coli sequences, and 398 human sequences [1].
• The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms [2].
• Sixteen of 24 residents in the village of Arso PIR II taking supervised weekly chloroquine prophylaxis (5 mg base/kg) had asexual parasitemia with P. vivax at least once during eight weeks of surveillance [3].
• Similarly, in Wor, a village near Arso PIR, the gametocyte rate for P. falciparum diminished from 83% to 25% in transmigrants from Java between their eleventh and twenty-fifth month of residence in Irian Jaya, a period during which the falciparum malaria rate remained stable between 30% and 50% [4].
• RESULTS: The survival of osteosarcoma patients treated with PIR was significantly better than that with DOX (p = 0.023) based on 2-year follow-up [5].

High impact information on PIR

• Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages [6].
• A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain [6].
• Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not [6].
• In contrast, the PIR-B protein has an uncharged transmembrane region and a long cytoplasmic tail containing four potential immunoreceptor tyrosine-based inhibitory motifs [7].
• Mapping studies indicated that ZIP interacted through its ZZ zinc finger domain with the phosphorylated insulin receptor interacting region (PIR) of Grb14 [8].

Chemical compound and disease context of PIR

• OBJECTIVE: To conduct a retrospective evaluation of tetrahydropyranyladriamycin (PIR)-based combination chemotherapy for osteosarcomas in comparison with doxorubicin (DOX)-based regimens to determine differences in response and toxicities between DOX- and PIR-containing regimens [5].
• This study compares the loop diuretic piretanide 6 mg in a slow-release formulation (PIR) with hydrochlorothiazide 25 mg (HCT) and the fixed combination altizide 15 mg-spironolactone 25 mg (ALT-SP) in hypertension [9].

Biological context of PIR

• Pirin is a recently identified eukaryotic protein implicated in transcriptional activation and apoptosis [10].
• These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-kappaB transcription pathway and the interaction with NFI in DNA replication [11].
• The PIR of Grb14, which also interacts with the catalytic domain of the insulin receptor (IR) and inhibits its activity, was preferentially phosphorylated by PKCzeta [8].
• In the two-hybrid system, two domains of rGrb14 can mediate the interaction with insulin receptors: the Src homology 2 (SH2) domain and a region between the PH and SH2 domains that we named PIR (for phosphorylated insulin receptor-interacting region) [12].
• The RESID Database can be used to predict atomic masses for peptides, and is being enhanced to provide molecular structures for graphical presentation on the PIR Web site using widely available molecular viewing programs [13].

Associations of PIR with chemical compounds

• Molecular surface comparisons of YhhW and Pirin with structurally similar proteins suggested quercetin as a potential ligand [10].
• The five highly conserved motifs can be used to discriminate the known 5-methylcytosine forming methyltransferases from all other methyltransferases of known sequence, and from all other identified proteins in the PIR, GenBank and EMBL databases [14].
• The N-terminal amino acid sequence of the first 20 amino acids, which was registered at the PIR Data Submission as the N-terminal partial sequence of Gly m 2, was determined according the Edman degradation method [15].
• A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995 [16].
• To this end, I evaluated the conservation of the 5-residue motif in all the apolipoprotein sequences known (PIR data bank no. 42) and tested the thyroid hormone binding properties of two animal apolipoproteins that were available (bovine apo A-I and rabbit apo E) [17].

Other interactions of PIR

• In the same subjects, the effects of PD and PIR on the GH response to GHRH (1.0 microg/kg i.v. at 0 minutes) have also been studied [18].
• The PIR-Inter-national databases and search tools are accessible on the PIR web site at http://pir.georgetown.edu/ and at the MIPS web site at http://www.mips.biochem.mpg.de [19].
• Between the PH (pleckstrin homology) and SH2 (Src homology 2) domains is a new binding domain implicated in the interaction with receptor tyrosine kinases called PIR (phosphorylated insulin receptor interaction region) [20].
• In rigorous jackknife tests, unknown sequences from Pfam-A and PIR-PSD were compared with the probes for each family [21].
• We show here that pirA (sll1773) encoding an ortholog of Pirin together with an adjacent gene, pirB (ssl3389), was upregulated under high salinity and some other stress conditions in a cyanobacterium Synechocystis sp. PCC 6803 [22].

Analytical, diagnostic and therapeutic context of PIR

• Purification, crystallization and preliminary X-ray analysis of human pirin [23].
• The PIR Protein Sequence Database entries are classified into superfamilies, families and homology domains, for which sequence alignments are available [24].
• These observations, together with an ensemble of sequence analyses and previous NMR results, all support the view of PIR as essentially unstructured but with a potentially structured short stretch encompassing residues 399-407 [20].
• Treatment was initiated 3 h after infection and consisted of a single subcutaneous injection of AMX at doses ranging from 2.5 to 10 mg/kg (PS strains), 5 to 100 (PIR strains), and 25 to 3,000 (PR strains) [25].
• An epidemiologic study of hyperendemic malaria in Arso PIR, a village in northeastern Irian Jaya (Indonesian New Guinea), revealed evidence suggesting suppression of gametocytemia independent of immune control of the asexual parasitemia [4].

References