BPIFA3

Superfamily

BPIFA3 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. This superfamily is also known as the BPI/LBP/PLUNC family or the BPI/LPB/CETP family. 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. [[File:BPIFfamily-BPIF-A3.png|thumb|left|BPIFA3 is a member of the BPI-fold gene family and the BPI/LBP/PLUNC protein superfamily]]

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. 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.

In humans, the BPIFA3 gene was first identified as a human PLUNC-related gene and later in mouse as 1700058C13Rik. Both were recognized as BPIF gene family members and were renamed BPIFA3 and Bpifa3, respectively.

Function

Little is known about BPIFA3's function. Due to its high degree of similarity to other members of the BPI/LBP/PLUNC superfamily, it is predicted to have binding activity to lipids such as phospholipids and lipopolysaccharides but this has never been confirmed.

A putative function of BPIFA3 in bacterial host defense has been suggested. Despite a near-exclusive expression of BPIFA3 in testis, only a single report implicates it in any normal or pathological states and that involves Otitis media (OM) in the ear. OM is a common disease of early childhood characterized by inflammation of the middle ear cavity and an effort was made to identify genetic risk factors. A genome-wide association study was done in the "Raine Study," a longitudinal birth cohort of 2,868 children in which 1532 blood samples drawn at 1,2, and 3 years of age were analyzed for gene expression correlated to a susceptibility to OM. Unexpectedly, BPIFA3 and BPIFA1 were the top hits, along with CAPN14 and GALNT14 genes, none of which has previously been implicated in OM. The investigators noted that BPIF gene family members encode proteins involved in the early recognition of bacterial pathogens as part of the host defense at the nasopharyngeal, oral and lung entrances, and that expression of BPIFA3 and BPIFA1 may be a logical consequence of chronic bacterial presence in the pus filled, OM infected ear.

References

References

1. "BPIFA3 BPI fold containing family A member 3 [Homo sapiens (human)] - Gene - NCBI".
2. "Bpifa3 BPI fold containing family A, member 3 [Mus musculus (house mouse)] - Gene - NCBI".
3. "Q9BQP9 - BPIA3_HUMAN".
4. (February 2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & Cellular Proteomics.
5. (November 2014). "A comparative encyclopedia of DNA elements in the mouse genome". Nature.
6. (January 2021). "The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals". Nucleic Acids Research.
7. "Gene: BPIFA3 - ENSG00000131059". The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.
8. (April 1998). "The BPI/LBP family of proteins: a structural analysis of conserved regions". Protein Science.
9. "CDD Conserved Protein Domain Family: BPI".
10. (July 1998). "Detecting distant relatives of mammalian LPS-binding and lipid transport proteins". Protein Science.
11. (August 2011). "Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily". Biochemical Society Transactions.
12. (15 April 2002). "PLUNC: A novel family of candidate host defense proteins expressed in the upper airways and nasopharynx". Human Molecular Genetics.
13. (October 2008). "Host biomarkers and biological pathways that are associated with the expression of experimental cerebral malaria in mice". Infection and Immunity.
14. "BPIFA3 Gene - GeneCards".
15. (2012). "Genome-wide association study to identify the genetic determinants of otitis media susceptibility in childhood". PLOS ONE.