Disease relevance of RENBP

• In the present study, we have expressed human RnBP in Escherichia coli JM 109 cells under the transcriptional control of taq promoter and purified it by conventional column chromatographies [1].
• The data do not exclude a role of RnBP in essential hypertension [2].
• A fragment of the human RnBP gene (nucleotides -739 to +244) linked to the chloramphenicol acetyltransferase gene was transfected into human Wilms' tumor G401 and mouse L929 cells [3].
• Its closest homologue, CUG-binding protein (CUG-bp), is a human RBP that has been implicated in the disease myotonic dystrophy and binds CUG repeats in the 3' untranslated region (UTR) of the mRNA for myotonic dystrophy protein kinase (DMPK) [7] [8] [4].
• None of the patients with tumour demonstrated any indication of hepatic metastases pre-operatively or at the time of laparotomy but, as a group, had lower pre-operative concentrations of RBP (p < 0.001) and pre-albumin (p < 0.01) than patients with no tumour load [5].

High impact information on RENBP

• A technique to detect RNA-binding proteins (RBP) involving hybridization of RNA probe to proteins transferred to a membrane was used to study RBP in different mammalian cells and in cells after genotoxic stress [6].
• The expression of these RBP varied substantially in nine different human and hamster cell lines, with no detectable RBP in two human myeloid lines [6].
• We have examined the affinity of two recently synthesized flavin analogs for the isoalloxazine binding site of riboflavin-binding protein (RBP) [7].
• Herein, a molecular genetic approach was employed to investigate if RnBP might affect renin, prorenin and/or blood pressure levels [2].
• The complete genomic structure of the RnBP gene, including the identified repetitive sequence elements, provides an essential tool for further studies of the RnBP gene in hypertensive patients with a different genetic background [2].

Chemical compound and disease context of RENBP

• To identify the active site residue(s), we have constructed ten cysteine residue mutants (C41S, C66S, C104S, C125S, C210S, C239S, C302S, C380S, C386S, and C390S) for human GlcNAc 2-epimerase and expressed them in Escherichia coli cells [8].
• To further investigate the relationship between structure and function of recombinant human (rh) RnBP as a GlcNAc 2-epimerase, we have constructed several C-terminal deletion and multi-cysteine/serine mutants of rhGlcNAc 2-epimerase and expressed them in Escherichia coli cells [9].
• The serum and cutaneous concentrations of beta-carotene and vitamin A and the serum concentrations of retinal-binding protein (RBP) and prealbumin were investigated in ten patients with chronic renal failure [10].
• Recently, the N-acylglucosamine 2-epimerase (AGE) gene from porcine kidney was cloned in E. coli, and a strain with a high AGE expression level was constructed for practical applications, which enabled the complete enzymatic synthesis of NeuAc with a high conversion rate from the substrates, namely, N-acetylglucosamine and pyruvate [11].
• By using the affinity purified antibody against RBP obtained from the urine of the patients with cadmium poisoning (Itai-Itai disease), the immunoreactive substances were located by light microscopy in the proximal tubules of the human kidney [12].

Biological context of RENBP

• RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system [2].
• This renders the RnBP gene a promising candidate gene in human hypertension [2].
• On the other hand, the downregulation of renin-binding protein transcript was detected in mature DCs using a cDNA microarray [13].
• The expression of this chimeric gene in G401 cells was 4-fold higher than that in L929 cells, the tissue-specific regulation of RnBP gene expression thus being suggested [3].
• The RnBP gene was found to be located in human chromosome X by means of polymerase chain reaction of hybrid DNAs from human and hamster somatic cells [3].

Anatomical context of RENBP

• Most renin-binding protein was recovered in the cytosol fraction and was not associated with sedimentable subcellular organelles [14].
• Secreting organs (liver, salivary glands, and intestinal mucosa) showed high specific activities of UDP-GlcNAc 2-epimerase/ManNAc kinase, whereas significant levels of these activities were absent from other organs (lung, kidney, spleen, brain, heart, skeletal muscle, and testis) [15].
• To evaluate the role of this motif in the formation of an RnBP-renin heterodimer and an RnBP homodimer, a porcine mutant cDNA involving Leu185----Asp and Leu192----Asp substitutions was constructed and expressed in vitro and in Xenopus oocytes [16].
• The kidney mRNA directed the synthesis of a high level of RnBP, whereas the liver, adrenal and pituitary gland mRNAs gave as low but significant level of it [17].
• MEASUREMENTS: Gene expression of angiotensinogen, renin, renin binding protein, angiotensin converting enzyme (ACE) and angiotensin II (ang II) receptor type 1 in human preadipocytes; ACE protein and ang II production of human adipose tissue stromal cells differentiated or not in primary culture [18].

Associations of RENBP with chemical compounds

• Our recent studies demonstrated that the human RnBP is the enzyme N-acetyl-D-glucosamine (GlcNAc) 2-epimerase [Takahashi, S. et al. (1999) J. Biochem. 125, 348-353] [19].
• Identification of functionally important cysteine residues of the human renin-binding protein as the enzyme N-acetyl-D-glucosamine 2-epimerase [9].
• On the other hand, N-ethylmaleimide (NEM), a SH-alkylating reagent inhibited the GlcNAc 2-epimerase activity concomitant with the decaying of the dimer to the monomer of the enzyme [20].
• The GlcNAc 2-epimerase activity of recombinant human RnBP was specifically inhibited by SH-reagents such as N-ethylmaleimide, 5, 5'-dithiobis-2-nitrobenzoate, and iodoacetic acid, indicating that the most probable reactive site is a cysteine residue [8].
• Northern blot analysis revealed no UDP-GlcNAc 2-epimerase/ManNAc kinase mRNA in the non-secreting tissues [15].

Regulatory relationships of RENBP

• Renin inhibits N-acetyl-D-glucosamine 2-epimerase (renin-binding protein) [19].

Other interactions of RENBP

• We have developed a new assay method for GlcNAc 2-epimerase activity using a system of N-acyl-D-hexosamine oxidase coupled with peroxidase and employed this method to study the effects of renin on GlcNAc 2-epimerase activity [19].
• The hydrophobic domain followed by a leucine-zipper motif in RnBP is encoded by the sixth exon [3].

Analytical, diagnostic and therapeutic context of RENBP

• The expression of the C380S mutant in E. coli cells was detected on Western blotting, whereas GlcNAc 2-epimerase activity was not detected in the extract [8].
• Evidence for induction of these RBP was found in six of seven lines after treatment with DNA-damaging agents; UV radiation was the most effective agent [6].
• Analysis of hybrid lines indicated that the Alu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting [21].
• Whereas the site is absent in the structure of ABP, it is strongly predicted to be present in RBP which shares the same trg transducer with GGBP [22].
• Thermal unfolding parameters of hens' egg-white riboflavin-binding-protein (RBP) were measured by differential scanning calorimetry [23].

References