Biology:BPIFA2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


BPI fold containing family A, member 2 (BPIFA2), also known as Parotid Secretory Protein (PSP), is a protein that in humans is encoded by the BPIFA2 gene.[1] The BPIFA2 gene sequence predicts multiple transcripts (splice variants); 2 mRNA variants have been well characterized. The resulting BPIFA2 is a secreted protein, expressed at very high levels in the parotid (salivary) gland; at high levels in oropharyngeal mucosa, including tongue; and at moderate levels many other tissue types and glands including mammary gland, testis, lung, bladder, blood, prostate, adrenal gland, kidney, and pancreas.[2]

Superfamily

BPIFA2 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.

BPIFA2 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.[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.

In humans, the BPIFA2 gene was first identified as a human PLUNC-related gene.[7] It had been identified shortly before as human PSP[8] and nearly a decade and half earlier as the mouse PSP gene.[9]

Function

The function of PSP had remained unknown for many years until it was finally recognized to be within the BPI/LBP/PLUNC family, and then the bactericidal properties of that family was recognized for BPIFA2/PSP/SPLUNC2.[10] It is primarily secreted into saliva and is therefore among the first line of defense against pathogens entering the mouth. BPIFA1 can bind to lipopolysaccharide (LPS) on bacteria and induce clumping agglutination of bacteria, a major antibacterial function for salivary proteins.[11] For example, BPIFA2 protein was shown to inhibit the growth of Pseudomonas aeruginosa, although it did not cause agglutination of these bacteria.[12]

Like BPIFA1/PLUNC which acts as a surfactant to lower the surface tension in mucosal fluids, BPIFA2/PIP also is a crucial surfactant in saliva. When the gene is silenced in a knockout mouse, the saliva exhibits the surface tension of water.[13] Further, without BPIFA2/PIP, levels of LPS in saliva were lower than in normal mice and the knockout mice exhibited signs of endotoxemia, suggesting bacteria were bypassing the first line of defense and passing into the digestive tract to cause mild inflammation.

References

  1. ↑ "BPIFA2 BPI fold containing family A member 2 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/140683. 
  2. ↑ "Gene : BPIFA2 - ENSG00000131050". The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals. https://bgee.org/gene/ENSG00000131050/. 
  3. ↑ "The BPI/LBP family of proteins: a structural analysis of conserved regions". Protein Science 7 (4): 906–914. April 1998. doi:10.1002/pro.5560070408. PMID 9568897. 
  4. ↑ "CDD Conserved Protein Domain Family: BPI". https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00188. 
  5. ↑ "Detecting distant relatives of mammalian LPS-binding and lipid transport proteins". Protein Science 7 (7): 1643–1646. July 1998. doi:10.1002/pro.5560070721. PMID 9684900. 
  6. ↑ "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. doi:10.1042/BST0390977. PMID 21787333. 
  7. ↑ Bingle, CD; Craven, CJ (15 April 2002). "PLUNC: A novel family of candidate host defense proteins expressed in the upper airways and nasopharynx". Human Molecular Genetics 11 (8): 937–943. doi:10.1093/hmg/11.8.937. PMID 11971875. 
  8. ↑ "Homo sapiens parotid secretory protein mRNA, complete cds". NLM NCBI. 7 November 2001. https://www.ncbi.nlm.nih.gov/nuccore/AF432917.1. 
  9. ↑ Madsen, Hans O.; Hjorth, J.Peter (1985). "Molecular cloning of mouse PSP mRNA". Nucleic Acids Research 13 (1): 1–13. doi:10.1093/nar/13.1.1. PMID 2582349. 
  10. ↑ "Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein". Histochemistry and Cell Biology 132 (3): 339–349. September 2009. doi:10.1007/s00418-009-0610-4. PMID 19499239. https://core.ac.uk/reader/50540?utm_source=linkout. Retrieved 17 February 2023. 
  11. ↑ Gorr, Sven-Ulrik; Abdolhosseini, Mahsa; Shelar, Anuradha; Sotsky, Julie (1 August 2011). "Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein". Biochemical Society Transactions 39 (4): 1028–1032. doi:10.1042/BST0391028. PMID 21787342. 
  12. ↑ Prokopovic, V; Popovic, M; Andjelkovic, U; Marsavelski, A; Raskovic, B; Gavrovic-Jankulovic, M; Polovic, N (March 2014). "Isolation, biochemical characterization and anti-bacterial activity of BPIFA2 protein.". Archives of Oral Biology 59 (3): 302–9. doi:10.1016/j.archoralbio.2013.12.005. PMID 24581853. 
  13. ↑ Nandula, Seshagiri Rao; Huxford, Ian; Wheeler, Thomas T.; Aparicio, Conrado; Gorr, Sven‐Ulrik (August 2020). "The parotid secretory protein BPIFA2 is a salivary surfactant that affects lipopolysaccharide action". Experimental Physiology 105 (8): 1280–1292. doi:10.1113/EP088567. PMID 32390232. 

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