BPIFA1

BPI fold containing family A, member 1 (BPIFA1), also known as Palate, lung, and nasal epithelium clone (PLUNC),[5] is a protein that in humans is encoded by the BPIFA1 gene.[6][7] It was also formerly known as "Secretory protein in upper respiratory tracts" (SPURT). The BPIFA1 gene sequence predicts 4 transcripts (splice variants); 3 mRNA variants have been well characterized. The resulting BPIFA1 is a secreted protein, expressed at very high levels in mucosa of the airways (olfactory and respiratory and epithelium) and salivary glands; at high levels in oropharyneal epithelium, including tongue and tonsils; and at moderate levels many other tissue types and glands including pituitary, testis, lung, bladder, blood, prostate, pancreas, levels in the digestive tract (tongue, stomach, intestinal epithelium) and pancreas.[8] The protein can be detected on the apical side of epithelial cells and in airway surface liquid, nasal mucus, and sputum.[9]

BPIFA1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBPIFA1, LUNX, NASG, PLUNC, SPLUNC1, SPURT, bA49G10.5, BPI fold containing family A member 1
External IDsOMIM: 607412 MGI: 1338036 HomoloGene: 7895 GeneCards: BPIFA1
Orthologs
SpeciesHumanMouse
Entrez

51297

18843

Ensembl

ENSG00000198183

ENSMUSG00000027483

UniProt

Q9NP55

P97361

RefSeq (mRNA)

NM_001243193
NM_016583
NM_130852

NM_011126

RefSeq (protein)

NP_001230122
NP_057667
NP_570913

NP_035256

Location (UCSC)Chr 20: 33.24 – 33.24 MbChr 2: 153.98 – 153.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Superfamily

BPIFA1 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.[10] This superfamily is also known as the BPI/LBP/PLUNC family or the BPI/LPB/CETP family.[11] 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.

BPIFA1 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.[12][13] 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 BPIFA1 gene was first identified as an ortholog of the mouse Plunc gene[7] which had earlier been identified from a differential display screen of the embryonic mouse palate.[14] Subsequently, using microarray analysis techniques of human epithelial tissues, the SPURT gene and, separately, the SPLUNC1 gene were identified.[15][16] These were all recognized to be, in fact, the same gene within the BPI/LBP/PLUNC family.

Function

BPIFA1 has multiple functions but perhaps its most prominent ones are related to BPIFA1's localization in nasal, olfactory, oral, and respiratory epithelium and the mucous/fluids that coat them. BPIFA1/SPLUNC1 binds with high affinity and specificity to dipalmitoylphosphatidylcholine, one of the major and most important surfactant phospholipids in the airway and lungs.[17] By lowering the surface tension in mucosal fluids, BPIFA1/SPLUNC1 inhibits bacteria like Klebsiella from proliferating as a biofilm on epithelium.[18] The protein physically interacts with pathogens, causing "bacterial cell coating" that inhibits the epithelial sodium channel of bacteria, makes bacteria like Pseudomonas more permeable, and attracts macrophages and neutrophils for a bactericidal effect. [19][20] As such, BPIFA1 plays a role in innate immune defense in the airways.

BPIFA1/PLUNC's ability to regulate ENaC is pH-sensitive and fails in acidic cystic fibrosis airways.[21] Thus, defective BPIFA1/PLUNC1 gene function is thought to contribute to the development of lung pathology in cystic fibrosis patients.

It may also serve as a potential molecular marker for detection of micrometastasis in non-small-cell lung cancer.[22]

References
  1. GRCh38: Ensembl release 89: ENSG00000198183 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027483 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Ghafouri, B. (2003). "PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid". Biochem Soc Trans. 31 (4): 810–4. doi:10.1042/bst0310810. PMID 12887311.
  6. "BPIFA1 BPI fold containing family A member 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  7. Bingle CD, Bingle L (Oct 2000). "Characterisation of the human plunc gene, a gene product with an upper airways and nasopharyngeal restricted expression pattern". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1493 (3): 363–7. doi:10.1016/S0167-4781(00)00196-2. PMID 11018263.
  8. "Gene : BPIFA1 - ENSG00000198183". bgee.org. The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.
  9. "Q9NP55 - BPIA1_HUMAN". www.uniprot.org.
  10. Beamer LJ, Carroll SF, Eisenberg D (April 1998). "The BPI/LBP family of proteins: a structural analysis of conserved regions". Protein Science. 7 (4): 906–914. doi:10.1002/pro.5560070408. PMC 2143972. PMID 9568897.
  11. "CDD Conserved Protein Domain Family: BPI". www.ncbi.nlm.nih.gov.
  12. Beamer LJ, Fischer D, Eisenberg D (July 1998). "Detecting distant relatives of mammalian LPS-binding and lipid transport proteins". Protein Science. 7 (7): 1643–1646. doi:10.1002/pro.5560070721. PMC 2144061. PMID 9684900.
  13. Bingle CD, Seal RL, Craven CJ (August 2011). "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. doi:10.1042/BST0390977. PMC 3196848. PMID 21787333.
  14. Weston WM, LeClair EE, Trzyna W, McHugh LM, Nugent P, Lafferty CM, Ma LL, Tuan RS, Greene RM (May 1999). "Differential Display Identification of plunc, a Novel Gene Expressed in Embryonic Palate, Nasal Epithelium, and Adult Lung". Journal of Biological Chemistry. 274 (19): 13698–13703. doi:10.1074/jbc.274.19.13698. PMID 10224143.
  15. Di YP, Harper R, Zhao Y, Pahlavan N, Finkbeiner W, Wu R (January 2003). "Molecular Cloning and Characterization of spurt, a Human Novel Gene That Is Retinoic Acid-inducible and Encodes a Secretory Protein Specific in Upper Respiratory Tracts". Journal of Biological Chemistry. 278 (2): 1165–1173. doi:10.1074/jbc.M210523200. PMID 12409287.
  16. Zhang B, Nie X, Xiao B, Xiang J, Shen S, Gong J, et al. (September 2003). "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 and Cancer. 38 (1): 80–90. doi:10.1002/gcc.10247. PMID 12874788. S2CID 24805514.
  17. Ning F, Wang C, Berry KZ, Kandasamy P, Liu H, Murphy RC, et al. (December 2014). "Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands". The FASEB Journal. 28 (12): 5349–5360. doi:10.1096/fj.14-259291. PMC 4232288. PMID 25223608.
  18. Liu Y, Bartlett JA, Di ME, BombergerJM, Chan YR, GakharL, et al. (May 2013). "SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection". The American Journal of Pathology. 182 (5): 1519–1531. doi:10.1016/j.ajpath.2013.01.050. PMC 3644735. PMID 23499554.
  19. Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R (Jul 2009). "SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage". Proceedings of the National Academy of Sciences of the United States of America. 106 (27): 11412–7. Bibcode:2009PNAS..10611412G. doi:10.1073/pnas.0903609106. PMC 2708735. PMID 19541605.
  20. Sayeed S, Nistico L, St Croix C, Di YP, et al. (January 2013). "Multifunctional Role of Human SPLUNC1 in Pseudomonas aeruginosa Infection". Infection and Immunity. 81 (1): 285–291. doi:10.1128/IAI.00500-12. PMC 3536124. PMID 23132494.
  21. Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R (Oct 2013). "Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways". Proceedings of the National Academy of Sciences of the United States of America. 110 (40): 15973–8. Bibcode:2013PNAS..11015973G. doi:10.1073/pnas.1311999110. PMC 3791714. PMID 24043776.
  22. "Entrez Gene: PLUNC".

Further reading
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