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{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
{{Infobox_gene}}


'''Palate, lung, and nasal epithelium clone protein'''<ref>{{cite journal|last=Ghafouri|first=B.|title=PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid|journal=Biochem Soc Trans|pmid=12887311|volume=31|issue=4|pages=810–4|doi=10.1042/bst0310810|year=2003}}</ref> ('''PLUNC''') is a [[gene]] encoding a [[secretory protein]]. It is also called Secretory protein in upper respiratory tracts (SPURT). In humans, it is encoded by the ''BPIFA1'' gene, previously called ''PLUNC''.<ref name="pmid11018263">{{cite journal | vauthors = Bingle CD, Bingle L | title = Characterisation of the human plunc gene, a gene product with an upper airways and nasopharyngeal restricted expression pattern | journal = Biochimica et Biophysica Acta | volume = 1493 | issue = 3 | pages = 363–7 | date = Oct 2000 | pmid = 11018263 | doi = 10.1016/S0167-4781(00)00196-2 }}</ref><ref name="pmid11251963">{{cite journal | vauthors = Iwao K, Watanabe T, Fujiwara Y, Takami K, Kodama K, Higashiyama M, Yokouchi H, Ozaki K, Monden M, Tanigami A | title = Isolation of a novel human lung-specific gene, LUNX, a potential molecular marker for detection of micrometastasis in non-small-cell lung cancer | journal = International Journal of Cancer | volume = 91 | issue = 4 | pages = 433–7 | date = Feb 2001 | pmid = 11251963 | doi = 10.1002/1097-0215(200002)9999:9999<::AID-IJC1059>3.0.CO;2-B }}</ref>
'''BPI fold containing family A, member 1''' (BPIFA1), also known as '''Palate, lung, and nasal epithelium clone''' (PLUNC),<ref name=Ghafouri-2003>{{cite journal|last=Ghafouri|first=B.|title=PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid|journal=Biochem Soc Trans|pmid=12887311|volume=31|issue=4|pages=810–4|doi=10.1042/bst0310810|year=2003}}</ref> is a [[protein]] that in humans is encoded by the ''BPIFA1'' gene.<ref>{{cite web |title=BPIFA1 BPI fold containing family A member 1 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/51297 |website=www.ncbi.nlm.nih.gov}}</ref><ref name="Bingle-2001">{{cite journal | vauthors = Bingle CD, Bingle L | title = Characterisation of the human plunc gene, a gene product with an upper airways and nasopharyngeal restricted expression pattern | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1493 | issue = 3 | pages = 363–7 | date = Oct 2000 | pmid = 11018263 | doi = 10.1016/S0167-4781(00)00196-2 }}</ref> It was also formerly known as "Secretory protein in upper respiratory tracts" (SPURT). The ''BPIFA1'' gene sequence predicts 4 [[Transcription_(biology)|transcripts]] ([[Alternative splicing|splice variants]]); 3 mRNA variants have been well characterized. The resulting BPIFA1 is a secreted protein, expressed at very high levels in [[Mucous membrane|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.<ref>{{cite web |title=Gene : BPIFA1 - ENSG00000198183 |url=https://bgee.org/gene/ENSG00000198183/ |website=bgee.org |publisher=The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals}}</ref> The protein can be detected on the apical side of epithelial cells and in airway surface liquid, nasal mucus, and sputum.<ref>{{cite web |title=Q9NP55 - BPIA1_HUMAN |url=https://www.uniprot.org/uniprotkb/Q9NP55/entry |website=www.uniprot.org}}</ref>

== 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.<ref name="Beamer-1998-A">{{cite journal | vauthors = Beamer LJ, Carroll SF, Eisenberg D | title = The BPI/LBP family of proteins: a structural analysis of conserved regions | journal = Protein Science | volume = 7 | issue = 4 | pages = 906–914 | date = April 1998 | pmid = 9568897 | pmc = 2143972 | doi = 10.1002/pro.5560070408 }}</ref> This superfamily is also known as the [[Lipid-binding serum glycoprotein|BPI/LBP/PLUNC]] family or the [[Bactericidal/permeability-increasing protein|BPI]]/[[Lipopolysaccharide binding protein|LPB]]/[[Cholesteryl ester transfer protein|CETP]] family.<ref>{{cite web |title=CDD Conserved Protein Domain Family: BPI |url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cl00188 |website=www.ncbi.nlm.nih.gov}}</ref> The BPI fold creates apolar binding pockets that can interact with hydrophobic and [[Amphiphile|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-A1.png|thumb|left|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 [[sequence homology|homologs]] in non-vertebrate species such as insects, mollusks, and roundworms.<ref name="Beamer-1998-B">{{cite journal | vauthors = Beamer LJ, Fischer D, Eisenberg D | title = Detecting distant relatives of mammalian LPS-binding and lipid transport proteins | journal = Protein Science | volume = 7 | issue = 7 | pages = 1643–1646 | date = July 1998 | pmid = 9684900 | pmc = 2144061 | doi = 10.1002/pro.5560070721 }}</ref><ref name="Bingle-2011">{{cite journal | vauthors = Bingle CD, Seal RL, Craven CJ | title = Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily | journal = Biochemical Society Transactions | volume = 39 | issue = 4 | pages = 977–983 | date = August 2011 | pmid = 21787333 | pmc = 3196848 | doi = 10.1042/BST0390977 }}</ref> 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<ref name="Bingle-2001"/> which had earlier been identified from a [[differential display]] screen of the embryonic mouse [[palate]].<ref name="Weston-1999">{{cite journal | vauthors = Weston WM, LeClair EE, Trzyna W, McHugh LM, Nugent P, Lafferty CM, Ma LL, Tuan RS, Greene RM | title=Differential Display Identification of plunc, a Novel Gene Expressed in Embryonic Palate, Nasal Epithelium, and Adult Lung | journal=Journal of Biological Chemistry | date=May 1999 | volume=274 | issue=19 | pages=13698–13703 | doi=10.1074/jbc.274.19.13698 | pmid=10224143 | url=https://www.jbc.org/article/S0021-9258(18)36932-1/fulltext | doi-access=free }}</ref> Subsequently, using [[microarray analysis techniques]] of human epithelial tissues, the ''SPURT'' gene and, separately, the ''SPLUNC1'' gene were identified.<ref name="Di-2003">{{cite journal | vauthors = Di YP, Harper R, Zhao Y, Pahlavan N, Finkbeiner W, Wu R |title=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=Journal of Biological Chemistry |date=January 2003 |volume=278 |issue=2 |pages=1165–1173 |doi=10.1074/jbc.M210523200 |pmid=12409287 |doi-access=free }}</ref><ref name="Zhang-2003">{{cite journal | vauthors = Zhang B, Nie X, Xiao B, Xiang J, Shen S, Gong J, et al. |title=Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray |journal=Genes, Chromosomes and Cancer |date=September 2003 |volume=38 |issue=1 |pages=80–90 |doi=10.1002/gcc.10247 |pmid=12874788|s2cid=24805514 }}</ref> These were all recognized to be, in fact, the same gene within the BPI/LBP/PLUNC family.


== Function ==
== 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.<ref name="Ning-2014">{{cite journal | vauthors = Ning F, Wang C, Berry KZ, Kandasamy P, Liu H, Murphy RC, et al. |title=Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands |journal=The FASEB Journal |date=December 2014 |volume=28 |issue=12 |pages=5349–5360 |doi=10.1096/fj.14-259291 |doi-access=free |pmid=25223608 |pmc=4232288}}</ref> By lowering the surface tension in mucosal fluids, BPIFA1/SPLUNC1 inhibits bacteria like ''[[Klebsiella]]'' from proliferating as a biofilm on epithelium.<ref name="Liu-2013">{{cite journal | vauthors= Liu Y, Bartlett JA, Di ME, BombergerJM, Chan YR, GakharL, et al. |title=SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection |journal=The American Journal of Pathology |date=May 2013 |volume=182 |issue=5 |pages=1519–1531 |doi=10.1016/j.ajpath.2013.01.050 |pmid=23499554 |pmc=3644735}}</ref> 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. <ref name=GarciaCaballero2009>{{cite journal | vauthors = Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R | title = SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 27 | pages = 11412–7 | date = Jul 2009 | pmid = 19541605 | pmc = 2708735 | doi = 10.1073/pnas.0903609106 | bibcode = 2009PNAS..10611412G | doi-access = free }}</ref><ref name="Sayeed-2013">{{cite journal | vauthors = Sayeed S, Nistico L, St Croix C, Di YP, et al. |title=Multifunctional Role of Human SPLUNC1 in Pseudomonas aeruginosa Infection |journal=Infection and Immunity |date=January 2013 |volume=81 |issue=1 |pages=285–291 |doi=10.1128/IAI.00500-12 |pmid=23132494 |pmc=3536124}}</ref> As such, BPIFA1 plays a role in [[Innate immune system|innate immune defense]] in the airways.
This gene is the human homolog of murine plunc, and like the mouse gene, is specifically expressed in the airways and [[nasopharyngeal]] regions. Plunc inhibits the [[epithelial sodium channel]] (ENaC),<ref name=GarciaCaballero2009>{{cite journal | vauthors = Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R | title = SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 27 | pages = 11412–7 | date = Jul 2009 | pmid = 19541605 | pmc = 2708735 | doi = 10.1073/pnas.0903609106 }}</ref> and also has anti-microbial functions.<ref>6</ref> As such, plunc is believed to play a role in [[Innate immune system|innate immune defense]] in the airways. PLUNC's ability to regulate ENaC is pH-sensitive and fails in acidic [[cystic fibrosis]] airways.<ref name=Garland2013>{{cite journal | vauthors = 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 | title = Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 40 | pages = 15973–8 | date = Oct 2013 | pmid = 24043776 | pmc = 3791714 | doi = 10.1073/pnas.1311999110 }}</ref> Thus, defective PLUNC1 function is thought to contribute to the development of lung pathology in cystic fibrosis patients.


BPIFA1/PLUNC's ability to regulate ENaC is pH-sensitive and fails in acidic [[cystic fibrosis]] airways.<ref name=Garland2013>{{cite journal | vauthors = 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 | title = Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 40 | pages = 15973–8 | date = Oct 2013 | pmid = 24043776 | pmc = 3791714 | doi = 10.1073/pnas.1311999110 | bibcode = 2013PNAS..11015973G | doi-access = free }}</ref> 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]].<ref name="entrez">{{cite web | title = Entrez Gene: PLUNC | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51297 | accessdate = }}</ref>

It may also serve as a potential molecular marker for detection of [[micrometastasis]] in [[non-small-cell lung cancer]].<ref name="entrez-PLUNC">{{cite web | title = Entrez Gene: PLUNC | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51297 }}</ref>


== References ==
== References ==
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== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Zhang B, Nie X, Xiao B, Xiang J, Shen S, Gong J, Zhou M, Zhu S, Zhou J, Qian J, Lu H, He X, Li X, Hu G, Li G | title = Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray | journal = Genes, Chromosomes & Cancer | volume = 38 | issue = 1 | pages = 80–90 | date = Sep 2003 | pmid = 12874788 | doi = 10.1002/gcc.10247 }}
* {{cite journal | vauthors = Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R | title = SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 27 | pages = 11412–7 | date = Jul 2009 | pmid = 19541605 | pmc = 2708735 | doi = 10.1073/pnas.0903609106 | bibcode = 2009PNAS..10611412G | doi-access = free }}
* {{cite journal | vauthors = Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R | title = SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 27 | pages = 11412–7 | date = Jul 2009 | pmid = 19541605 | pmc = 2708735 | doi = 10.1073/pnas.0903609106 }}
* {{cite journal | vauthors = Zhang BC, Zhu SG, Xiang JJ, Zhou M, Nie XM, Xiao BY, Li XL, Li GY | title = [Analysis of splicing variants in NASG 3'UTR, down-regulated in nasopharyngeal carcinoma, and its expression in multiple cancer tissues] | journal = AI Zheng = Aizheng = Chinese Journal of Cancer | volume = 22 | issue = 5 | pages = 477–80 | date = May 2003 | pmid = 12753706 }}
* {{cite journal | vauthors = Zhang BC, Zhu SG, Xiang JJ, Zhou M, Nie XM, Xiao BY, Li XL, Li GY | title = [Analysis of splicing variants in NASG 3'UTR, down-regulated in nasopharyngeal carcinoma, and its expression in multiple cancer tissues] | journal = AI Zheng = Aizheng = Chinese Journal of Cancer | volume = 22 | issue = 5 | pages = 477–80 | date = May 2003 | pmid = 12753706 | doi = }}
* {{cite journal | vauthors = Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC | title = Determination of genetic predisposition to patent ductus arteriosus in preterm infants | journal = Pediatrics | volume = 123 | issue = 4 | pages = 1116–23 | date = Apr 2009 | pmid = 19336370 | pmc = 2734952 | doi = 10.1542/peds.2008-0313 }}
* {{cite journal | vauthors = Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC | title = Determination of genetic predisposition to patent ductus arteriosus in preterm infants | journal = Pediatrics | volume = 123 | issue = 4 | pages = 1116–23 | date = Apr 2009 | pmid = 19336370 | pmc = 2734952 | doi = 10.1542/peds.2008-0313 }}
* {{cite journal | vauthors = Bryborn M, Halldén C, Säll T, Cardell LO | title = CLC- a novel susceptibility gene for allergic rhinitis? | journal = Allergy | volume = 65 | issue = 2 | pages = 220–8 | date = Feb 2010 | pmid = 19650845 | doi = 10.1111/j.1398-9995.2009.02141.x }}
* {{cite journal | vauthors = Bryborn M, Halldén C, Säll T, Cardell LO | title = CLC- a novel susceptibility gene for allergic rhinitis? | journal = Allergy | volume = 65 | issue = 2 | pages = 220–8 | date = Feb 2010 | pmid = 19650845 | doi = 10.1111/j.1398-9995.2009.02141.x | s2cid = 29636426 }}
* {{cite journal | vauthors = Cheng M, Chen Y, Yu X, Tian Z, Wei H | title = Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer | journal = BMC Cancer | volume = 8 | issue = | pages = 156 | year = 2008 | pmid = 18513434 | pmc = 2424066 | doi = 10.1186/1471-2407-8-156 }}
* {{cite journal | vauthors = Cheng M, Chen Y, Yu X, Tian Z, Wei H | title = Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer | journal = BMC Cancer | volume = 8 | pages = 156 | year = 2008 | pmid = 18513434 | pmc = 2424066 | doi = 10.1186/1471-2407-8-156 | doi-access = free }}
* {{cite journal | vauthors = Zhou HD, Li GY, Yang YX, Li XL, Sheng SR, Zhang WL, Zhao J | title = Intracellular co-localization of SPLUNC1 protein with nanobacteria in nasopharyngeal carcinoma epithelia HNE1 cells depended on the bactericidal permeability increasing protein domain | journal = Molecular Immunology | volume = 43 | issue = 11 | pages = 1864–71 | date = Apr 2006 | pmid = 16364440 | doi = 10.1016/j.molimm.2005.10.021 }}
* {{cite journal | vauthors = Zhou HD, Li GY, Yang YX, Li XL, Sheng SR, Zhang WL, Zhao J | title = Intracellular co-localization of SPLUNC1 protein with nanobacteria in nasopharyngeal carcinoma epithelia HNE1 cells depended on the bactericidal permeability increasing protein domain | journal = Molecular Immunology | volume = 43 | issue = 11 | pages = 1864–71 | date = Apr 2006 | pmid = 16364440 | doi = 10.1016/j.molimm.2005.10.021 }}
* {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 }}
* {{cite journal | vauthors = Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY | title = A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration | journal = Cell | volume = 125 | issue = 4 | pages = 801–14 | date = May 2006 | pmid = 16713569 | doi = 10.1016/j.cell.2006.03.032 | s2cid = 13709685 | doi-access = free }}
* {{cite journal | vauthors = Zhou HD, Fan SQ, Zhao J, Huang DH, Zhou M, Liu HY, Zeng ZY, Yang YX, Huang H, Li XL, Shen SR, Li GY | title = Tissue distribution of the secretory protein, SPLUNC1, in the human fetus | journal = Histochemistry and Cell Biology | volume = 125 | issue = 3 | pages = 315–24 | date = Mar 2006 | pmid = 16195890 | doi = 10.1007/s00418-005-0070-4 }}
* {{cite journal | vauthors = Zhou HD, Fan SQ, Zhao J, Huang DH, Zhou M, Liu HY, Zeng ZY, Yang YX, Huang H, Li XL, Shen SR, Li GY | title = Tissue distribution of the secretory protein, SPLUNC1, in the human fetus | journal = Histochemistry and Cell Biology | volume = 125 | issue = 3 | pages = 315–24 | date = Mar 2006 | pmid = 16195890 | doi = 10.1007/s00418-005-0070-4 | s2cid = 20600762 }}
* {{cite journal | vauthors = Sentani K, Oue N, Sakamoto N, Arihiro K, Aoyagi K, Sasaki H, Yasui W | title = Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach | journal = Modern Pathology | volume = 21 | issue = 4 | pages = 464–75 | date = Apr 2008 | pmid = 18204429 | doi = 10.1038/modpathol.3801050 }}
* {{cite journal | vauthors = Sentani K, Oue N, Sakamoto N, Arihiro K, Aoyagi K, Sasaki H, Yasui W | title = Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach | journal = Modern Pathology | volume = 21 | issue = 4 | pages = 464–75 | date = Apr 2008 | pmid = 18204429 | doi = 10.1038/modpathol.3801050 | doi-access = free }}
* {{cite journal | vauthors = Bingle CD, Gorr SU | title = Host defense in oral and airway epithelia: chromosome 20 contributes a new protein family | journal = The International Journal of Biochemistry & Cell Biology | volume = 36 | issue = 11 | pages = 2144–52 | date = Nov 2004 | pmid = 15313462 | doi = 10.1016/j.biocel.2004.05.002 }}
* {{cite journal | vauthors = Campos MA, Abreu AR, Nlend MC, Cobas MA, Conner GE, Whitney PL | title = Purification and characterization of PLUNC from human tracheobronchial secretions | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 30 | issue = 2 | pages = 184–92 | date = Feb 2004 | pmid = 12920053 | doi = 10.1165/rcmb.2003-0142OC }}
* {{cite journal | vauthors = Campos MA, Abreu AR, Nlend MC, Cobas MA, Conner GE, Whitney PL | title = Purification and characterization of PLUNC from human tracheobronchial secretions | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 30 | issue = 2 | pages = 184–92 | date = Feb 2004 | pmid = 12920053 | doi = 10.1165/rcmb.2003-0142OC }}
* {{cite journal | vauthors = He Y, Ding YQ, Huang ZX, Yao KT | title = [Association of the coding region single nucleotide polymorphisms in PLUNC gene with nasopharyngeal carcinoma] | journal = Zhonghua Yi Xue Za Zhi | volume = 87 | issue = 22 | pages = 1553–5 | date = Jun 2007 | pmid = 17785110 | doi = }}
* {{cite journal | vauthors = He Y, Ding YQ, Huang ZX, Yao KT | title = [Association of the coding region single nucleotide polymorphisms in PLUNC gene with nasopharyngeal carcinoma] | journal = Zhonghua Yi Xue Za Zhi | volume = 87 | issue = 22 | pages = 1553–5 | date = Jun 2007 | pmid = 17785110 }}
* {{cite journal | vauthors = Wang WB, Cui YG, Yao SY | title = [Message RNA expression of LUNX, CK19 and CEA genes in NSCLC with micrometastasis in lymph nodes] | journal = Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology] | volume = 30 | issue = 2 | pages = 121–4 | date = Feb 2008 | pmid = 18646695 | doi = }}
* {{cite journal | vauthors = Wang WB, Cui YG, Yao SY | title = [Message RNA expression of LUNX, CK19 and CEA genes in NSCLC with micrometastasis in lymph nodes] | journal = Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology] | volume = 30 | issue = 2 | pages = 121–4 | date = Feb 2008 | pmid = 18646695 }}
* {{cite journal | vauthors = Bartlett JA, Hicks BJ, Schlomann JM, Ramachandran S, Nauseef WM, McCray PB | title = PLUNC is a secreted product of neutrophil granules | journal = Journal of Leukocyte Biology | volume = 83 | issue = 5 | pages = 1201–6 | date = May 2008 | pmid = 18245229 | doi = 10.1189/jlb.0507302 }}
* {{cite journal | vauthors = Bartlett JA, Hicks BJ, Schlomann JM, Ramachandran S, Nauseef WM, McCray PB | title = PLUNC is a secreted product of neutrophil granules | journal = Journal of Leukocyte Biology | volume = 83 | issue = 5 | pages = 1201–6 | date = May 2008 | pmid = 18245229 | doi = 10.1189/jlb.0507302 | s2cid = 19196781 | doi-access = free }}
* {{cite journal | vauthors = Zhou HD, Li XL, Li GY, Zhou M, Liu HY, Yang YX, Deng T, Ma J, Sheng SR | title = Effect of SPLUNC1 protein on the Pseudomonas aeruginosa and Epstein-Barr virus | journal = Molecular and Cellular Biochemistry | volume = 309 | issue = 1–2 | pages = 191–7 | date = Feb 2008 | pmid = 18049866 | doi = 10.1007/s11010-007-9659-3 }}
* {{cite journal | vauthors = Zhou HD, Li XL, Li GY, Zhou M, Liu HY, Yang YX, Deng T, Ma J, Sheng SR | title = Effect of SPLUNC1 protein on the Pseudomonas aeruginosa and Epstein-Barr virus | journal = Molecular and Cellular Biochemistry | volume = 309 | issue = 1–2 | pages = 191–7 | date = Feb 2008 | pmid = 18049866 | doi = 10.1007/s11010-007-9659-3 | s2cid = 23343796 }}
* {{cite journal | vauthors = Ghafouri B, Kihlström E, Tagesson C, Lindahl M | title = PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide | journal = Biochimica et Biophysica Acta | volume = 1699 | issue = 1–2 | pages = 57–63 | date = Jun 2004 | pmid = 15158712 | doi = 10.1016/j.bbapap.2004.01.001 }}
* {{cite journal | vauthors = Bingle L, Barnes FA, Cross SS, Rassl D, Wallace WA, Campos MA, Bingle CD | title = Differential epithelial expression of the putative innate immune molecule SPLUNC1 in cystic fibrosis | journal = Respiratory Research | volume = 8 | pages = 79 | year = 2007 | issue = 1 | pmid = 17988392 | pmc = 2203987 | doi = 10.1186/1465-9921-8-79 | doi-access = free }}
* {{cite journal | vauthors = Bingle L, Barnes FA, Cross SS, Rassl D, Wallace WA, Campos MA, Bingle CD | title = Differential epithelial expression of the putative innate immune molecule SPLUNC1 in cystic fibrosis | journal = Respiratory Research | volume = 8 | issue = | pages = 79 | year = 2007 | pmid = 17988392 | pmc = 2203987 | doi = 10.1186/1465-9921-8-79 }}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|PLUNC+protein,+human}}

{{NLM content}}


* {{UCSC gene info|BPIFA1}}
* {{MeshName|PLUNC+protein,+human}}


[[Category:Human proteins]]
{{gene-20-stub}}
[[Category:Genes]]
[[Category:Genes on human chromosome 20]]

Latest revision as of 23:51, 21 March 2024

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; OMA:BPIFA1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

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]

Superfamily

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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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198183Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027483Ensembl, 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. ^ a b 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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