BPIFB1 explained

BPI fold-containing family B member 1 (BPIFB1) is a protein that in humans is encoded by the BPIFB1 gene.^[1] BPIFB1 is a secreted protein, expressed at very high levels in mucosa of the airways (respiratory and olfactory epithelium) and salivary glands, and at moderate levels in the digestive tract (tongue, stomach, intestinal epithelium) and pancreas.^[2]

Superfamily

BPIFB1 is a member of a BPI fold protein superfamily defined by the presence of the bactericidal/permeability-increasing protein fold (BPI fold) which is formed by two similar domains in a "boomerang" shape.^[3] This superfamily is also known as the BPI/LBP/PLUNC family or the BPI/LPB/CETP family.^[4] The BPI fold creates apolar binding pockets that can interact with hydrophobic and amphipathic molecules, such as the acyl carbon chains of lipopolysaccharide found on Gram-negative bacteria, but members of this family may have many other functions.

Genes for the BPI/LBP/PLUNC superfamily are found in all vertebrate species, including distant homologs in non-vertebrate species such as insects, mollusks, and roundworms.^{[5] [6]} Within that broad grouping is the BPIF gene family whose members encode the BPI fold structural motif and are found clustered on a single chromosome, e.g., Chromosome 20 in humans, Chromosome 2 in mouse, Chromosome 3 in rat, Chromosome 17 in pig, Chromosome 13 in cow. The BPIF gene family is split into two groupings, BPIFA and BPIFB. In humans, BIPFA consists of 3 protein encoding genes BPIFA1, BPIFA2, BPIFA3, and 1 pseudogene BPIFA4P; while BPIFB consists of 5 protein encoding genes BPIFB1, BPIFB2, BPIFB3, BPIFB4, BPIFB6 and 2 pseudogenes BPIFB5P, BPIFB9P. What appears as pseudogenes in humans may appear as fully functional genes in other species.

BPIFB1 was also identified as the LPLUNC1 gene (long-palate lung and nasal epithelium clone 1) in mouse,^[7] but subsequently PLUNC proteins were classified as a subfamily of the BPI fold superfamily.^[8] In a systematic analysis of the chicken genome, the Lplunc1(Bpifb1) / Lplunc5(Bpifb5) branch of the gene family was determined to be absent, therefore BPIFB1 and BPIFB5 proteins likely arose only after the speciation of mammals.^[9]

Function

In mammals, the BPIFB1 protein is involved in the innate immune response to bacterial exposure in the mucosa of the mouth, nasal cavities, lungs, and digestive tract.^[10] It has a role in sensing and responding to Gram-negative bacteria and contributes to anti-bacterial activity.

In humans it is abnormally expressed in a respiratory diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma. It is also differentially in tumors such as nasopharyngeal carcinoma (NPC), gastric cancer, salivary gland tumors, and lung cancer therefore BPIFB1 has been considered to be a therapeutic target for these conditions. For example, BPIFB1 expression is suppressed in NPC but when the gene is over-expressed in cell cultures and in mice, tumor cell migration and invasion (metastases) is reduced.^[11]

Further reading

• Larocque RC, Sabeti P, Duggal P, Chowdhury F, Khan AI, Lebrun LM, Harris JB, Ryan ET, Qadri F, Calderwood SB . 6 . A variant in long palate, lung and nasal epithelium clone 1 is associated with cholera in a Bangladeshi population . Genes and Immunity . 10 . 3 . 267–272 . April 2009 . 19212328 . 2672110 . 10.1038/gene.2009.2 .
• Zhang B, Nie X, Xiao B, Xiang J, Shen S, Gong J, Zhou M, Zhu S, Zhou J, Qian J, Lu H, He X, Li X, Hu G, Li G . 6 . Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray . Genes, Chromosomes & Cancer . 38 . 1 . 80–90 . September 2003 . 12874788 . 10.1002/gcc.10247 . 24805514 .
• Bingle CD, Seal RL, Craven CJ . Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily . Biochemical Society Transactions . 39 . 4 . 977–983 . August 2011 . 21787333 . 3196848 . 10.1042/BST0390977 .
• Bingle CD, Craven CJ . PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx . Human Molecular Genetics . 11 . 8 . 937–943 . April 2002 . 11971875 . 10.1093/hmg/11.8.937 .
• Bingle CD, Wilson K, Lunn H, Barnes FA, High AS, Wallace WA, Rassl D, Campos MA, Ribeiro M, Bingle L . 6 . Human LPLUNC1 is a secreted product of goblet cells and minor glands of the respiratory and upper aerodigestive tracts . Histochemistry and Cell Biology . 133 . 5 . 505–515 . May 2010 . 20237794 . 2852594 . 10.1007/s00418-010-0683-0 .
• Bingle L, Wilson K, Musa M, Araujo B, Rassl D, Wallace WA, LeClair EE, Mauad T, Zhou Z, Mall MA, Bingle CD . 6 . BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease . Histochemistry and Cell Biology . 138 . 5 . 749–758 . November 2012 . 22767025 . 3470695 . 10.1007/s00418-012-0990-8 .
• Shin OS, Uddin T, Citorik R, Wang JP, Della Pelle P, Kradin RL, Bingle CD, Bingle L, Camilli A, Bhuiyan TR, Shirin T, Ryan ET, Calderwood SB, Finberg RW, Qadri F, Larocque RC, Harris JB . 6 . LPLUNC1 modulates innate immune responses to Vibrio cholerae . The Journal of Infectious Diseases . 204 . 9 . 1349–1357 . November 2011 . 21900486 . 3182310 . 10.1093/infdis/jir544 .

Notes and References

1. Web site: Entrez Gene: BPI fold containing family B, member 1 .
2. Web site: Gene : BPIFB1 - ENSG00000125999 . bgee.org . The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals . 15 February 2023.
3. Beamer LJ, Carroll SF, Eisenberg D . The BPI/LBP family of proteins: a structural analysis of conserved regions . Protein Science . 7 . 4 . 906–914 . April 1998 . 9568897 . 2143972 . 10.1002/pro.5560070408 .
4. Web site: CDD Conserved Protein Domain Family: BPI . www.ncbi.nlm.nih.gov.
5. Beamer LJ, Fischer D, Eisenberg D . Detecting distant relatives of mammalian LPS-binding and lipid transport proteins . Protein Science . 7 . 7 . 1643–1646 . July 1998 . 9684900 . 2144061 . 10.1002/pro.5560070721 .
6. Bingle CD, Seal RL, Craven CJ . Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily . Biochemical Society Transactions . 39 . 4 . 977–983 . August 2011 . 21787333 . 3196848 . 10.1042/BST0390977 .
7. Hou J, Yashiro K, Okazaki Y, Saijoh Y, Hayashizaki Y, Hamada H . Identification of a novel left-right asymmetrically expressed gene in the mouse belonging to the BPI/PLUNC superfamily . Developmental Dynamics . 229 . 2 . 373–379 . February 2004 . 14745963 . 10.1002/dvdy.10450 . 21625082 . free .
8. Bingle CD, Seal RL, Craven CJ . Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily . Biochemical Society Transactions . 39 . 4 . 977–983 . August 2011 . 21787333 . 3196848 . 10.1042/BST0390977 .
9. Chiang SC, Veldhuizen EJ, Barnes FA, Craven CJ, Haagsman HP, Bingle CD . Identification and characterisation of the BPI/LBP/PLUNC-like gene repertoire in chickens reveals the absence of a LBP gene . Developmental and Comparative Immunology . 35 . 3 . 285–295 . March 2011 . 20959152 . 3253384 . 10.1016/j.dci.2010.09.013 .
10. Li J, Xu P, Wang L, Feng M, Chen D, Yu X, Lu Y . Molecular biology of BPIFB1 and its advances in disease . Annals of Translational Medicine . 8 . 10 . 651 . May 2020 . 32566588 . 7290611 . 10.21037/atm-20-3462 . free .
11. Wei F, Wu Y, Tang L, He Y, Shi L, Xiong F, Gong Z, Guo C, Li X, Liao Q, Zhang W, Zhou M, Xiang B, Li X, Li Y, Li G, Xiong W, Zeng Z . 6 . BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM . British Journal of Cancer . 118 . 2 . 233–247 . January 2018 . 29123267 . 5785741 . 10.1038/bjc.2017.385 .