BPIFA2

Last updated
BPIFA2
Identifiers
Aliases BPIFA2 , C20orf70, PSP, SPLUNC2, bA49G10.1, BPI fold containing family A member 2
External IDs MGI: 97787 HomoloGene: 69034 GeneCards: BPIFA2
Orthologs
SpeciesHumanMouse
Entrez

140683

19194

Ensembl

ENSG00000131050

ENSMUSG00000042459

UniProt

Q96DR5

P07743

RefSeq (mRNA)

NM_080574
NM_001319164

NM_008953

RefSeq (protein)

NP_001306093
NP_542141

NP_032979

Location (UCSC) Chr 20: 33.16 – 33.18 Mb Chr 2: 153.85 – 153.86 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] 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. [6]

Contents

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. [7] This superfamily is also known as the BPI/LBP/PLUNC family or the BPI/LPB/CETP family. [8] 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 BPIFfamily-BPIF-A2.png
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. [9] [10] 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. [11] It had been identified shortly before as human PSP [12] and nearly a decade and half earlier as the mouse PSP gene. [13]

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. [14] 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. [15] For example, BPIFA2 protein was shown to inhibit the growth of Pseudomonas aeruginosa, although it did not cause agglutination of these bacteria. [16]

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. [17] 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.

Related Research Articles

<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">BPIFA1</span> Protein-coding gene in the species Homo sapiens

BPI fold containing family A, member 1 (BPIFA1), also known as Palate, lung, and nasal epithelium clone (PLUNC), is a protein that in humans is encoded by the BPIFA1 gene. It was also formerly known as "Secretory protein in upper respiratory tracts" (SPURT). The BPIFA1 gene sequence predicts 4 transcripts ; 3 mRNA variants have been well characterized. The resulting BPIFA1 is a secreted protein, expressed at very high levels in mucosa of the airways 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 and pancreas. The protein can be detected on the apical side of epithelial cells and in airway surface liquid, nasal mucus, and sputum.

<span class="mw-page-title-main">CST4</span> Protein-coding gene in humans

Cystatin-S is a protein that in humans is encoded by the CST4 gene.

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

Statherin is a protein in humans that is encoded by the STATH gene. It prevents the precipitation of calcium phosphate in saliva, maintaining a high calcium level in saliva available for remineralisation of tooth enamel and high phosphate levels for buffering.

<span class="mw-page-title-main">Carbonic anhydrase VI</span> Enzyme found in humans

Carbonic anhydrase 6 is an enzyme that in humans is encoded by the CA6 gene. It is also called 'gustin' because of its presence in saliva, and lower-than-normal levels of salivary zinc in individuals with hypogeusia.

<span class="mw-page-title-main">CST1</span> Protein-coding gene in the species Homo sapiens

Cystatin-SN is a protein that in humans is encoded by the CST1 gene.

<span class="mw-page-title-main">CST2</span> Protein-coding gene in the species Homo sapiens

Cystatin-SA is a protein that in humans is encoded by the CST2 gene.

<span class="mw-page-title-main">PRB1</span> Protein-coding gene in the species Homo sapiens

Basic salivary proline-rich protein 1 is a protein that in humans is encoded by the PRB1 gene.

<span class="mw-page-title-main">Histatin 1</span> Protein-coding gene in the species Homo sapiens

Histatin-1 is a protein that in humans is encoded by the HTN1 gene.

<span class="mw-page-title-main">CST5</span> Protein-coding gene in the species Homo sapiens

Cystatin-D is a protein that in humans is encoded by the CST5 gene.

<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">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">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">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: ENSG00000131050 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042459 - 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. ↑ "BPIFA2 BPI fold containing family A member 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  6. ↑ "Gene : BPIFA2 - ENSG00000131050". bgee.org. The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals.
  7. ↑ 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.
  8. ↑ "CDD Conserved Protein Domain Family: BPI". www.ncbi.nlm.nih.gov.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ "Homo sapiens parotid secretory protein mRNA, complete cds". NLM NCBI. 7 November 2001. Retrieved 17 February 2023.
  13. ↑ Madsen HO, Hjorth J (1985). "Molecular cloning of mouse PSP mRNA". Nucleic Acids Research. 13 (1): 1–13. doi:10.1093/nar/13.1.1. PMC   340970 . PMID   2582349.
  14. ↑ Bingle L, Barnes FA, Lunn H, Musa M, Webster S, Douglas CW, et al. (September 2009). "Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein". Histochemistry and Cell Biology. 132 (3): 339–349. doi:10.1007/s00418-009-0610-4. PMID   19499239. S2CID   24708348 . Retrieved 17 February 2023.
  15. ↑ Gorr S, Abdolhosseini M, Shelar A, Sotsky J (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. PMC   3417823 . PMID   21787342.
  16. ↑ 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.
  17. ↑ Nandula SR, Huxford I, Wheeler TT, Aparicio C, Gorr S (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. PMC   9484039 . PMID   32390232.
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