Lipopolysaccharide-binding protein (LBP)
The protein contains 481 amino acids for an estimated molecular weight of 53384 Da.
Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:7517398, PubMed:24120359). Acts as an affinity enhancer for CD14, facilitating its association with LPS. Promotes the release of cytokines in response to bacterial lipopolysaccharide (PubMed:7517398, PubMed:24120359). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Acute-phase response
Cellular defense response
Cellular response to lipopolysaccharide
Cellular response to lipoteichoic acid
Cytokine-mediated signaling pathway
Defense response to Gram-negative bacterium
Defense response to Gram-positive bacterium
Detection of molecule of bacterial origin
Innate immune response
Leukocyte chemotaxis involved in inflammatory response
Lipopolysaccharide transport
Lipopolysaccharide-mediated signaling pathway
Macromolecule localization
Macrophage activation involved in immune response
Negative regulation of tumor necrosis factor production
Obsolete negative regulation of growth of symbiont in host
Opsonization
Positive regulation of chemokine production
Positive regulation of cytolysis
Positive regulation of interleukin-6 production
Positive regulation of interleukin-8 production
Positive regulation of macrophage activation
Positive regulation of neutrophil chemotaxis
Positive regulation of respiratory burst involved in inflammatory response
Positive regulation of toll-like receptor 4 signaling pathway
Positive regulation of tumor necrosis factor biosynthetic process
Positive regulation of tumor necrosis factor production
Response to lipopolysaccharide
Toll-like receptor 4 signaling pathway
Toll-like receptor signaling pathway
Cellular Component
Cell surface
Extracellular exosome
Extracellular region
Extracellular space
Membrane
The reference OMIM entry for this protein is 151990
Lipopolysaccharide-binding protein; lbp
Lps-binding protein
DESCRIPTION
Lipopolysaccharide-binding protein is an acute-phase reactant produced during gram-negative bacterial infections. Higher eukaryotes have evolved several mechanisms for protecting against such infections. Gram-negative bacteria express lipopolysaccharide (LPS; endotoxin) on their outer cell wall, and mammals respond rapidly to the presence of LPS in serum. LBP and another acute-phase reactant, bactericidal permeability-increasing protein (BPI; 109195), bind LPS with high affinity. LBP is made in the liver during the acute phase of infections and is thought to function as a carrier for LPS and to help control LPS-dependent monocyte responses. See CD14 (158120) for information on the receptor for the lipopolysaccharide binding protein/lipopolysaccharide complex.CLONING
By screening a human liver cDNA library with an oligonucleotide derived from the rabbit LBP protein sequence, Schumann et al. (1990) isolated cDNAs encoding LBP. The predicted human LBP protein consists of a 25-amino acid signal sequence followed by a 452-amino acid mature protein containing 4 cysteine residues and 5 potential glycosylation sites. Human LBP shares 69% amino acid identity with rabbit LBP, 44% identity with human BPI, and 23% identity with human CETP (118470). In rabbits, Schumann et al. (1990) found that LBP functions as a carrier protein for LPS in plasma and controls LPS-dependent monocytic responses.GENE STRUCTURE
Hubacek et al. (1997) found that the LBP gene spans approximately 28.5 kb of DNA and contains 14 exons. Comparison of the genomic structures of LBP, BPI, PLTP (172425), and CETP, which constitute a family of functionally related proteins, revealed a remarkable conservation of exon/intron junctions and exon size.GENE FUNCTION
LPS interacts with LBP and CD14 to present LPS to TLR4 (603030), which activates inflammatory gene expression through NF-kappa-B (see 164011) and MAPK signaling. Bochkov et al. (2002) demonstrated that oxidized phospholipids inhibit LPS-induced but not TNF-alpha (191160)-induced or interleukin-1-beta (147720)-induced NF-kappa-B-mediated upregulation of inflammatory genes by blocking the interaction of LPS with LBP and CD14. Moreover, in LPS-injected mice, oxidized phospholipids inhibited inflammation and protected mice from lethal endotoxin shock. Thus, in severe gram-negative bacterial infection, endogenously formed oxidized phospholipids may function as a negative feedback to blunt innate immune responses. Furthermore, Bochkov et al. (2002) identified chemical structures capable of inhibiting the effects of endotoxins such as LPS that could be used for the development of new drugs for treatment of sepsis. Weber et al. (2003) found that LBP was present in the cerebrospinal fluid of patients with pneumococcal meningitis. Injection of living pneumococci or pneumococcal cell wall (PCW) into spinal canals of Lbp +/- mice resulted in leukocyte influx and severe meningitis. In contrast, injection into Lbp -/- mice produced no meningeal inflammation. Lbp enhanced PCW-induced signaling and Tnf release in rodent cell lines, and Lbp bound to PCW multimers independently of the phosphorylcholine and teichoic acid components of PCW. Experiments using human LBP suggested that the binding site for PCW may overlap with that for LPS. Weber et al. (2003) concluded that LBP is also involved in gram-positive infections.BIOCHEMICAL FEATURES
- Crystal Structure Eckert et al. ( ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for LBP
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 151990 was added.