BPI fold containing family A, member 3 (BPIFA3) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''BPIFA3''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The gene is also known as ''SPLUNC3'' and ''C20orf71'' in humans and the

orthologous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

gene in mice is ''1700058C13Rik''. There are multiple variants of the BPIFA3 projected to be a secreted protein. It is very highly expressed in

testis A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...

with little or no expression in other tissues. The Human Protein Atlas project and Mouse ENCODE Consortium report

RNA-Seq RNA-Seq (named as an abbreviation of RNA sequencing) is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also k ...

expression at RPKM levels (reads per kilobases of transcript per 1 million mapped reads ) of 29.1 for human testis and 69.4 for mouse, but 0 for all other tissues. Similarly, the Bgee consortium, using multiple techniques in addition to RNA-Seq, reports a relative Expression Score of 95.8 out of 100 for testis and 99.0 for sperm in humans; however low levels of BPIFA3 between 20 and 30 were seen for a variety of tissues such as muscle, glands, prostate, nervous system, and skin.

Superfamily

BPIFA3 is a member of a BPI fold

protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...

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 Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low- ...

family. The BPI fold creates apolar binding pockets that can interact with hydrophobic and

amphipathic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

molecules, such as the acyl carbon chains of

lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

found on

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

, but members of this family may have many other functions. BPIFfamily-BPIF-A3

Genes for the BPI/LBP/PLUNC superfamily are found in all vertebrate species, including distant

homologs Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same loci, where they provide points along each chromosome th ...

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 In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have t ...

and are found clustered on a single chromosome, e.g.,

Chromosome 20 Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced i ...

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 BPI fold containing family A, member 4 (BPIFA4) is a non-human protein encoded by the ''Bpifa4'' gene in mammals such as monkey, cat, and cow but does not appear in rodents and humans. It is also known as Latherin in horse, encoded by the ''Lath/ ...

''; 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 Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...

and

lipopolysaccharides Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

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 Otitis media is a group of Inflammation, inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pullin ...

(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 In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different individuals to see if any variant is associated with a trait. GWA s ...

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 Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during infections, regardless of cause. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collect ...

filled, OM infected ear.

References

External links

* * {{MeshName, BPIFA3+protein,+human Human proteins Genes Genes on human chromosome 20