BPIFA1

Last updated
BPIFA1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases BPIFA1 , LUNX, NASG, PLUNC, SPLUNC1, SPURT, bA49G10.5, BPI fold containing family A member 1
External IDs OMIM: 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 Mb Chr 2: 153.98 – 153.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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 BPIFfamily-BPIF-A1.png
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]

Related Research Articles

<span class="mw-page-title-main">Respiratory tract</span> Organs involved in transmission of air to and from the point where gases diffuse into tissue

The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa.

<span class="mw-page-title-main">Epithelial sodium channel</span> Group of membrane proteins

The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.

<span class="mw-page-title-main">Lipopolysaccharide binding protein</span> Protein in humans

Lipopolysaccharide binding protein (LBP) is a protein that in humans is encoded by the LBP gene.

<span class="mw-page-title-main">PRSS8</span> Protein-coding gene in the species Homo sapiens

Prostasin is a protein that in humans is encoded by the PRSS8 gene.

<span class="mw-page-title-main">ELF5</span> Protein-coding gene

E74-like factor 5 , is a gene found in both mice and humans. In humans it is also called ESE2.

<span class="mw-page-title-main">BPIFB2</span> Protein-coding gene in the species Homo sapiens

BPI fold-containing family B, member 2, (BPIFB2) also known as bactericidal/permeability-increasing protein-like 1, is a protein that in humans is encoded by the BPIFB2 gene.

<span class="mw-page-title-main">TMEM8B</span> Protein-coding gene in humans

Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.

<span class="mw-page-title-main">Lipid-binding serum glycoprotein</span>

In molecular biology, the lipid-binding serum glycoproteins family, also known as the BPI/LBP/Plunc family or LBP/BPI/CETP family represents a family which includes mammalian lipid-binding serum glycoproteins and/or proteins containing a structural motif known as the BPI fold. Members of this family include:

<span class="mw-page-title-main">FOXJ1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein J1 is a protein that in humans is encoded by the FOXJ1 gene. It is a member of the Forkhead/winged helix (FOX) family of transcription factors that is involved in ciliogenesis. FOXJ1 is expressed in ciliated cells of the lung, choroid plexus, reproductive tract, embryonic kidney and pre-somite embryo stage.

The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

<span class="mw-page-title-main">BPIFA3</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family A, member 3 (BPIFA3) is a protein that in humans is encoded by the BPIFA3 gene. The gene is also known as SPLUNC3 and C20orf71 in humans and the orthologous 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 with little or no expression in other tissues. The Human Protein Atlas project and Mouse ENCODE Consortium report RNA-Seq expression at RPKM levels 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.

<span class="mw-page-title-main">BPIFB4</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 4 (BPIFB4) is a protein that in humans is encoded by the BPIFB4 gene. It was formerly known as "Long palate, lung and nasal epithelium carcinoma-associated protein 4" encoded by the LPLUNC4 gene. The BPIFB4 gene sequence predicts 4 transcripts ; 3 isoforms have been well characterized. In a variety of mammals, BPIFB4 is generally expressed in very high levels in the olfactory epithelium, high levels in the gonads and pituitary, moderate levels in white blood cells (monocytes) It can occur either localized in the cytoplasm of cells or secreted and circulated systemically in blood plasma.

<span class="mw-page-title-main">BPIFB1</span> Protein-coding gene in the species Homo sapiens

BPI fold-containing family B member 1 (BPIFB1) is a protein that in humans is encoded by the BPIFB1 gene. BPIFB1 is a secreted protein, expressed at very high levels in mucosa of the airways and salivary glands, and at moderate levels in the digestive tract and pancreas.

<span class="mw-page-title-main">BPIFB3</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 3 (BPIFB3) is a protein that in humans is encoded by the BPIFB3 gene. Two variants have been detected in humans.

<span class="mw-page-title-main">BPIFB5P</span> Pseudogene in the species Homo sapiens

BPI fold containing family B, member 5 is a non-human protein encoded by the Bpifb5 gene, also known as Lplunc5. The BPIFB5 protein and Bpifb5 gene have been characterized in mammals such as rodents and even-toed ungulates but are apparently lacking in primates and other vertebrates such as birds, reptiles, and amphibians. The protein in rodents is expressed at moderately high levels in mucosa of the airways and at moderate levels in salivary glands, esophagus, and gonads ; in even-toed ungulates expression is high in testis, moderate in brain and striated muscle, and low in kidney.

<span class="mw-page-title-main">BPIFB6</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family B, member 6 (BPIFB6), also known as bactericidal/permeability-increasing protein-like 3 (BPIL3), is a protein that in humans is encoded by the BPIFB6 gene, also known as BPIL3 and LPLUNC6. It is expressed at high levels in hypertrophic tonsils, at relatively moderate levels in oronasal epithelium including nasal mucosa, tongue, and salivary gland, as well as esophageal mucosa at lesser levels. Orthologs are present in many vertebrate species including mammals, birds, reptiles, and amphibians.

<span class="mw-page-title-main">BPIFB9P</span> Pseudogene in the species Homo sapiens

Vomeromodulin is a non-human protein also known as BPI fold containing family B, member 9 (BPIFB9) in the rat encoded by the Bpifb9/RYF3 gene, and as BPI fold containing family B, member 9A (BPIFB9A) encoded by the Bpifb9a gene in the mouse. This protein has been characterized in mammals such as rodents, carnivores, even-toed ungulates, insectivores, bats, lagomorphs, and shrews but is apparently absent in primates and other vertebrates such as birds, reptiles, and amphibians. Its function is associated with detection of chemical odorant pheromone molecules.

<span class="mw-page-title-main">BPIFA2</span> Protein-coding gene in the species Homo sapiens

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. The BPIFA2 gene sequence predicts multiple transcripts ; 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.

<span class="mw-page-title-main">BPIFA4P</span> Pseudogene in the species Homo sapiens

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/Bpifa4 gene but is somewhat divergent from the other species. Latherin/BPIFA4 is a secreted protein found in saliva and sweat.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000198183 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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".

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