Disease relevance of C19orf2

• We previously identified a novel cellular protein, RPB5-mediating protein (RMP), that retains corepressor activity and functionally antagonizes transcriptional modulation via hepatitis B virus X protein [1].
• The cloning and comprehensive molecular analysis of NNX3 as presented will form the basis for elucidating its function and, conversely, will constitute a marker for Reed-Sternberg cells in Hodgkin disease [2].
• The expression of human NNX3 was most notable in human skeletal muscle and in ganglion cells and was also evident in human tumors and derived cell lines [2].
• Surprisingly, NNX3 was immunochemically detected in Reed-Sternberg cells of Hodgkin disease, in parallel with restin, a cytoplasmic protein we previously characterized (J. Delabie et al., 1993, Leuk. Lymphoma 12, 21-26) [2].
• After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015) [3].

High impact information on C19orf2

• Using a yeast two-hybrid method, we isolated a putative corepressor, DNA methyltransferase 1-associating protein (DMAP1), which was found to bind to the CC domain of RMP [1].
• Furthermore, RMP has an inhibitory effect on transcriptional activation by VP16 in the absence of HBx [4].
• By far-Western blot screening, we cloned a novel gene encoding a 508-amino-acid-residue RPB5-binding protein from a HepG2 cDNA library and designated it RPB5-mediating protein (RMP) [4].
• Unconventional prefoldin RPB5 interactor (URI), an evolutionary conserved member of the prefoldin family of molecular chaperones, forms a large prefoldin like complex and plays a central role in the regulation of nutrient-sensitive, TOR (target-of-rapamycin)-dependent gene expression programs in yeast [5].
• Human metapneumovirus (hMPV) is a recently described paramyxovirus associated with upper and lower respiratory-tract infection (URI and LRI, respectively) [6].

Chemical compound and disease context of C19orf2

• SETTING: Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP) [7].
• CONCLUSIONS: Flu-like symptoms (abdominal cramps, malaise and URI) were reported in 4% of patients participating in clinical trials of travoprost but seldom reported postmarketing [8].

Biological context of C19orf2

• Human and mouse NNX3 genes are composed of nine exons coding for proteins that are unrelated to any known protein [2].
• A novel protein, named NNX3, was molecularly characterized by cloning its cDNA, and its gene was mapped to chromosome 19q12 [2].
• Thus, URI is a component of a signaling pathway that coordinates nutrient availability with gene expression [5].
• At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/NA1 genotype (P = 0.038) [9].
• METHODS: We performed a retrospective review of 734 patients with a diagnosis of acute sinusitis (n = 367) or URI (n = 367) at a family practice residency training site over a 3-year period [10].

Anatomical context of C19orf2

• Putative nuclear targeting signals were predicted, but NNX3 protein and two truncated versions remained localized in the cytoplasm of transfected Cos cells [2].
• A prospective tympanometric and microbiologic study of 28 pre-schoolchildren was undertaken to better define the effect of acute URI on induction of eustachian tube dysfunction [11].
• Although colonization of the nasopharynx of well children with Pn or HF was associated with a higher incidence of abnormal middle ear pressure, colonization with Pn or HF during URI did not influence the frequency of tympanogram abnormality [11].
• The role of SSO was particularly significant in case of pneumonia, URI, urinary tract infections, seizures, gastroenteritis, abdominal pain, infant fever, injuries [12].
• However, Staph. aureus was found as the sole organism in children with exudate more often than in the children with only URI [13].

Associations of C19orf2 with chemical compounds

• RESULTS: Twenty-four patients receiving daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h [14].
• A pepstatin A molecule fits into the large substrate-binding cleft between the two domains of RMP in an extended conformation up to the alanine residue at the P2' position [15].
• Simultaneous administration of PAS granules produced a significant decrease in the absorption of RMP, whereas Na-PAS tablets had no effect [16].
• The use of ribavirin 5'-phosphate (RMP, 1,2,4-triazole-3-carboxamide riboside 5-monophosphate) as the phosphate donor obviates this difficulty since this triazole heterocycle does not significantly absorb at the wavelengths used to detect most nucleoside analogs [17].
• Replacement of Trp39 of Rhizomucor pusillus pepsin (RMPP) by Asn or Cys resulted in a marked decrease in the milk-clotting and proteolytic activities [18].

Analytical, diagnostic and therapeutic context of C19orf2

• In Western blotting and immunoprecipitation, human NNX3 appeared as a doublet of Mr 64K-66K, while mouse NNX3 was a 70-kDa protein, both apparently much larger than the predicted 50 kDa, due in part to a stretch of 16-18 acidic residues hinging two nearly equally sized domains [2].
• OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period [3].
• We obtained pre- and post-season viral serologic studies, biweekly nose and throat viral cultures, daily urinalysis, biweekly telephone follow-up for URI and renal complaints, and clinical assessments as indicated [19].
• RMP analysis produced hit rates of up to 21%, dependent on the biological activity class, and led to an average approximately 3600-fold improvement over random selection for the activity classes that were used as test cases [20].
• 45 of these patients were chemotherapy naive (CN-RMP) and 42 had received one prior course of chemotherapy (CP-RMP) [21].

References