Lipopolysaccharide binding protein

Last updated
LBP
LBP protein.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases LBP , BPIFD2, lipopolysaccharide binding protein
External IDs OMIM: 151990 MGI: 1098776 HomoloGene: 3055 GeneCards: LBP
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004139

NM_008489

RefSeq (protein)

NP_004130

NP_032515

Location (UCSC) Chr 20: 38.35 – 38.38 Mb Chr 2: 158.15 – 158.17 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Lipopolysaccharide binding protein (LBP) is a protein that in humans is encoded by the LBP gene. [5] [6]

Contents

LBP is a soluble acute-phase protein that binds to bacterial lipopolysaccharide (or LPS) to elicit immune responses by presenting the LPS to important cell surface pattern recognition receptors called CD14 and TLR4. [7]

The protein encoded by this gene is involved in the acute-phase immunologic response to gram-negative bacterial infections. Gram-negative bacteria contain a glycolipid, lipopolysaccharide (LPS), on their outer cell wall. Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation. This protein is part of a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Finally, this gene is found on chromosome 20, immediately downstream of the BPI gene. [6]

Clinical significance

LPS exposure induces LBP production. [8] LBP is synthesized by the liver, adipose tissue, and intestinal cells. [8] Dietary glucose and saturated fats acutely increase plasma LBP. [8]

The proinflammatory activity of plasma LPS is increased by LBP, which is higher in obesity. [9]

Plasma LBP is used as a better biomarker of plasma LPS than LPS itself due to the short half-life of LPS. [8]

Interactions

Lipopolysaccharide-binding protein has been shown to interact with CD14, TLR2, TLR4 and the co-receptor MD-2. [10] [11] [12]

Related Research Articles

<span class="mw-page-title-main">Lipopolysaccharide</span> Class of molecules found in the outer membrane of Gram-negative bacteria

Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by covalent bonds, and are found in the bacterial capsule, the outermost membrane of cell envelope of Gram-negative bacteria, such as E. coli and Salmonella. Today, the term endotoxin is often used synonymously with LPS, although there are a few endotoxins that are not related to LPS, such as the so-called delta endotoxin proteins produced by Bacillus thuringiensis.

<span class="mw-page-title-main">Toll-like receptor</span> Pain receptors and inflammation

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.

<span class="mw-page-title-main">CD14</span> Mammalian protein found in Homo sapiens

CD14 is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).

<span class="mw-page-title-main">MYD88</span> Protein-coding gene in the species Homo sapiens

Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.

Bactericidal permeability-increasing protein (BPI) is a 456-residue (~50kDa) protein that is part of the innate immune system, coded for in the human by the BPI gene. It belongs to the family of lipid-binding serum glycoproteins.

<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">Toll-like receptor 4</span> Protein-coding gene in the species Homo sapiens

Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an intracellular signaling pathway NF-κB and inflammatory cytokine production which is responsible for activating the innate immune system.

<span class="mw-page-title-main">Lymphocyte antigen 96</span> Protein-coding gene in the species Homo sapiens

Lymphocyte antigen 96, also known as "Myeloid Differentiation factor 2 (MD-2)," is a protein that in humans is encoded by the LY96 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">AOAH</span> Protein-coding gene in the species Homo sapiens

Acyloxyacyl hydrolase, also known as AOAH, is a eukaryotic protein encoded by the AOAH gene. AOAH is produced by macrophages, dendritic cells, NK cells, ILC1 cells, neutrophils and renal proximal tubule cells.

<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">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: ENSG00000129988 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016024 - 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. Gray PW, Corcorran AE, Eddy RL Jr, Byers MG, Shows TB (March 1993). "The genes for the lipopolysaccharide binding protein (LBP) and the bactericidal permeability increasing protein (BPI) are encoded in the same region of human chromosome 20". Genomics. 15 (1): 188–90. doi:10.1006/geno.1993.1030. PMID   8432532.
  6. 1 2 "Entrez Gene: LBP lipopolysaccharide binding protein".
  7. Muta T, Takeshige K (2001). "Essential roles of CD14 and lipopolysaccharide-binding protein for activation of toll-like receptor (TLR)2 as well as TLR4 Reconstitution of TLR2- and TLR4-activation by distinguishable ligands in LPS preparations". Eur. J. Biochem. 268 (16): 4580–9. doi:10.1046/j.1432-1327.2001.02385.x. PMID   11502220.
  8. 1 2 3 4 Djuric Z (2017). "Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state". Translational Research . 179: 155–167. doi:10.1016/j.trsl.2016.07.017. PMC   5164980 . PMID   27522986.
  9. Tuomi K, Logomarsino JV (2016). "Bacterial Lipopolysaccharide, Lipopolysaccharide-Binding Protein, and Other Inflammatory Markers in Obesity and After Bariatric Surgery". Metabolic Syndrome and Related Disorders . 14 (6): 279–288. doi:10.1089/met.2015.0170. PMID   27228236.
  10. Thomas CJ, Kapoor Mili, Sharma Shilpi, Bausinger Huguette, Zyilan Umit, Lipsker Dan, Hanau Daniel, Surolia Avadhesha (November 2002). "Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response". FEBS Lett. 531 (2): 184–8. doi:10.1016/S0014-5793(02)03499-3. ISSN   0014-5793. PMID   12417309. S2CID   25135963.
  11. Yu B, Wright S D (1995). "LPS-dependent interaction of Mac-2-binding protein with immobilized CD14". J. Inflamm. 45 (2): 115–25. ISSN   1078-7852. PMID   7583357.
  12. Erridge C, Pridmore A, Eley A, Stewart J, Poxton IR (2004). "Lipopolysaccharides of Bacteroides fragilis, Chlamydia trachomatis and Pseudomonas aeruginosa signal via toll-like receptor 2". Journal of Medical Microbiology. 53 (Pt 8): 735–40. doi: 10.1099/jmm.0.45598-0 . PMID   15272059.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.