Lactotransferrin (LTF)
The protein contains 710 amino acids for an estimated molecular weight of 78182 Da.
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.', 'Major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Has antimicrobial activity, which depends on the extracellular cation concentration (PubMed:6802759). Antimicrobial properties include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Can also prevent bacterial biofilm development in P.aeruginosa infection (PubMed:12037568). Has weak antifungal activity against C.albicans (PubMed:11083624). Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth (PubMed:15166119). Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection (PubMed:17079302). Can inhibit papillomavirus infections (PubMed:17481742). Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with (updated: Feb. 10, 2021)
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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Amyloid fibril formation
Antibacterial humoral response
Antifungal humoral response
Antimicrobial humoral immune response mediated by antimicrobial peptide
Antimicrobial humoral response
Biological process involved in interaction with host
Bone morphogenesis
Cellular protein metabolic process
Defense response to Gram-negative bacterium
Defense response to Gram-positive bacterium
Humoral immune response
Innate immune response
Innate immune response in mucosa
Ion transport
Iron ion transport
Killing of cells of other organism
Membrane disruption in other organism
Negative regulation by host of viral process
Negative regulation of apoptotic process
Negative regulation of ATPase activity
Negative regulation of cysteine-type endopeptidase activity
Negative regulation of lipopolysaccharide-mediated signaling pathway
Negative regulation of membrane potential
Negative regulation of osteoclast development
Negative regulation of single-species biofilm formation in or on host organism
Negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
Negative regulation of viral genome replication
Negative regulation of viral process
Neutrophil degranulation
Ossification
Phagosome maturation
Positive regulation of bone mineralization involved in bone maturation
Positive regulation of chondrocyte proliferation
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of osteoblast differentiation
Positive regulation of osteoblast proliferation
Positive regulation of protein serine/threonine kinase activity
Positive regulation of toll-like receptor 4 signaling pathway
Regulation of cytokine production
Regulation of tumor necrosis factor production
Response to host immune response
Retina homeostasis
Siderophore-dependent iron import into cell
Transcription, DNA-templated
Cellular Component
Cell surface
Cytoplasm
Early endosome
Extracellular exosome
Extracellular region
Extracellular space
Nucleus
Obsolete cell
Other organism cell membrane
Phagocytic vesicle lumen
Plasma membrane
Protein complex
Protein-containing complex
Recycling endosome
Secretory granule
Specific granule
Specific granule lumen
Tertiary granule lumen
The reference OMIM entry for this protein is 150210
Lactotransferrin; ltf
Lactoferrin; lf
DESCRIPTION
Lactoferrin is an iron-binding glycoprotein of the transferrin (TF; 190000) family that is expressed in most biologic fluids and is a major component of mammals' innate immune system (Legrand et al., 2008).CLONING
Yang et al. (1983) cloned human cDNA for lactotransferrin. Powell and Ogden (1990) reported the nucleotide sequence of human lactoferrin cDNA. The deduced protein contains 709 amino acids, including a 17-amino acid putative signal peptide. In a review, Legrand et al. (2008) stated that the mature LF protein contains 690 amino acids and is highly basic. It has a positively charged N terminus that shares 40% sequence identity with the C terminus. LF shares 60% amino acid identity with TF.GENE FUNCTION
Gallin (1990) doubted that the structural gene for lactoferrin is the site of mutation causing neutrophil lactoferrin deficiency (245480) because the disorder appears to involve abnormal packaging of all neutrophil-specific granule contents. Bezault et al. (1994) found that Lf inhibited solid tumor growth and tumor metastasis in mice. Natural killer cells appeared to be involved in Lf antimetastatic activity in mouse tumor models. Haemophilus influenzae is a major cause of otitis media and other respiratory tract disease in children. The pathogenesis of the disease begins with colonization of the upper respiratory mucosa, a process that involves evasion of local immune mechanisms and adherence to epithelial cells. Several studies demonstrated that human milk is protective against H. influenzae colonization and disease. Qiu et al. (1998) examined the effect of human milk on 2 autotransported proteins of H. influenzae that are presumed to facilitate colonization: IgA1 protease and Hap adhesin. They found that human milk lactoferrin efficiently extracted the IgA1 protease preprotein from the bacterial outer membrane. In addition, lactoferrin specifically degraded the Hap adhesin and abolished Hap-mediated adherence. The results suggested that human milk lactoferrin attenuates the pathogenic potential of H. influenzae by selectively inactivating IgA1 protease and Hap, thereby interfering with colonization. They suggested that future studies should examine the therapeutic potential of lactoferrin, perhaps as a supplement in infant formulas. Human T-cell leukemia virus-1 (HTLV-1) causes T-cell leukemia and lymphoma and is clustered in certain geographic areas. Like HIV-1 infection, HTLV-1 infection can be transmitted vertically through breast milk. Refraining from breast feeding was found to efficiently block mother-to-infant transmission in southwestern Japan. Moriuchi and Moriuchi (2001) observed a dose-dependent enhancement of HTLV-1 replication by transactivating the viral long terminal repeat in cells stimulated with human or bovine lactoferrin. Lactoferrin also accelerated transmission to uninfected cord blood mononuclear cells. Moriuchi and Moriuchi (2001) confirmed that lactoferrin inhibits HIV-1 replication and showed that it does so by nonspecifically blocking viral fusion to cells. Singh et al. (2002) hypothesized that the innate immune system possesses specific activity to protect against biofilm infections and demonstrated that lactoferrin, a ubiquitous and abundant constituent of human external secretions, blocks biofilm development by the opportunistic pathogen Pseudomonas aeruginosa. This occurs at lactoferrin concentrations below those that kill or prevent growth. By chelati ... More on the omim web site
Feb. 16, 2021: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 150210 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed