HGNC Approved Gene Symbol: BPI
Cytogenetic location: 20q11.23 Genomic coordinates (GRCh38) : 20:38,304,156-38,337,505 (from NCBI)
The bactericidal permeability-increasing protein (BPI) is associated with human neutrophil granules and has bactericidal activity on gram-negative organisms. Both BPI and lipopolysaccharide-binding protein (LBP; 151990) are involved in the defense against gram-negative bacterial infections and bind LPS with high affinity. Furthermore, they show 44% amino acid identity (Schumann et al., 1990).
Using oligonucleotides derived from the human BPI protein sequence to screen a human genomic library, Gray et al. (1989) isolated BPI genomic sequence. They screened a dimethyl sulfoxide-induced HL-60 cell cDNA library with oligonucleotides based on the genomic sequence and isolated a full-length human BPI cDNA. The cDNA predicts a 31-amino acid signal peptide followed by a 456-amino acid mature protein. The N-terminal half of the protein, which exhibits the antimicrobial activity, is basic and hydrophilic, whereas the C-terminal half is slightly acidic and contains several potential transmembrane regions. The difference between the calculated molecular mass of 50.6 kD and the experimental mass of approximately 58 kD may reflect the usage of 2 potential N-linked glycosylation sites. Northern blot analysis detected a 2-kb BPI transcript in mRNA prepared from the spleen of a patient with chronic myelogenous leukemia (CML; 608232); a lower level of BPI expression was found in normal spleen, but no BPI expression was detected in normal liver, placenta, or brain.
Hubacek et al. (1997) found that the BPI gene spans approximately 31.5 kb of DNA and contains 15 exons. Comparison of the genomic structures of BPI, LBP, PLTP (172425), and CETP (118470), which constitute a family of functionally related proteins, revealed a remarkable conservation of exon/intron junctions and exon size.
Using both Southern blot analysis of human/mouse somatic cell hybrids and in situ hybridization, Gray et al. (1993) mapped the BPI and LBP genes to 20q11.23-q12.
Gray, P. W., Corcorran, A. E., Eddy, R. L., Jr., Byers, M. G., Shows, T. B. The genes for the lipopolysaccharide binding protein (LBP) and the bactericidal permeability increasing protein (BPI) are encoded in the same region of human chromosome 20. Genomics 15: 188-190, 1993. [PubMed: 8432532] [Full Text: https://doi.org/10.1006/geno.1993.1030]
Gray, P. W., Flaggs, G., Leong, S. R., Gumina, R. J., Weiss, J., Ooi, C. E., Elsbach, P. Cloning of the cDNA of a human neutrophil bactericidal protein: structural and functional correlations. J. Biol. Chem. 264: 9505-9509, 1989. [PubMed: 2722846]
Hubacek, J. A., Buchler, C., Aslanidis, C., Schmitz, G. The genomic organization of the genes for human lipopolysaccharide binding protein (LBP) and bactericidal permeability increasing protein (BPI) is highly conserved. Biochem. Biophys. Res. Commun. 236: 427-430, 1997. [PubMed: 9240454] [Full Text: https://doi.org/10.1006/bbrc.1997.6970]
Schumann, R. R., Leong, S. R., Flaggs, G. W., Gray, P. W., Wright, S. D., Mathison, J. C., Tobias, P. S., Ulevitch, R. J. Structure and function of lipopolysaccharide binding protein. Science 249: 1429-1431, 1990. [PubMed: 2402637] [Full Text: https://doi.org/10.1126/science.2402637]