| Lactotransferrin |
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Richardson diagram of recombinant human lactoferrin. Based on PDB: 1b0l .
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1B0L, 1BKA, 1CB6, 1DSN, 1EH3, 1FCK, 1H43, 1H44, 1H45, 1HSE, 1L5T, 1LCF, 1LCT, 1LFG, 1LFH, 1LFI, 1LGB, 1N76, 1SQY, 1U62, 1VFD, 1VFE, 1XV4, 1XV7, 1Z6V, 1Z6W, 2BJJ, 2DP4, 2GMC, 2GMD, 2HD4, 2PMS
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|
|
| Identifiers |
| Symbols |
LTF ; GIG12; HEL110; HLF2; LF |
| External IDs |
OMIM: 150210 MGI: 96837 HomoloGene: 1754 GeneCards: LTF Gene |
| EC number |
3.4.21.- |
| Gene ontology |
| Molecular function |
• DNA binding
• serine-type endopeptidase activity
• iron ion binding
• protein binding
• ferric iron binding
• heparin binding
• protein serine/threonine kinase activator activity
|
| Cellular component |
• extracellular region
• extracellular space
• nucleus
• secretory granule
• specific granule
• extracellular vesicular exosome
• phagocytic vesicle lumen
|
| Biological process |
• ossification
• regulation of cytokine production
• retina homeostasis
• innate immune response in mucosa
• transcription, DNA-templated
• proteolysis
• iron ion transport
• humoral immune response
• antibacterial humoral response
• antifungal humoral response
• negative regulation of lipopolysaccharide-mediated signaling pathway
• regulation of tumor necrosis factor production
• iron assimilation by chelation and transport
• positive regulation of osteoblast proliferation
• positive regulation of toll-like receptor 4 signaling pathway
• negative regulation of apoptotic process
• positive regulation of I-kappaB kinase/NF-kappaB signaling
• positive regulation of osteoblast differentiation
• positive regulation of NF-kappaB transcription factor activity
• interaction with host
• response to host immune response
• bone morphogenesis
• positive regulation of protein serine/threonine kinase activity
• phagosome maturation
• positive regulation of bone mineralization involved in bone maturation
• negative regulation of single-species biofilm formation in or on host organism
• positive regulation of chondrocyte proliferation
• negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
• negative regulation of osteoclast development
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| Sources: Amigo / QuickGO |
|
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
4057 |
17002 |
| Ensembl |
ENSG00000012223 |
ENSMUSG00000032496 |
| UniProt |
P02788 |
P08071 |
| RefSeq (mRNA) |
NM_001199149 |
NM_008522 |
| RefSeq (protein) |
NP_001186078 |
NP_032548 |
| Location (UCSC) |
Chr 3:
46.48 – 46.53 Mb |
Chr 9:
111.02 – 111.04 Mb |
| PubMed search |
[1] |
[2] |
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Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions. Lactoferrin is also present in secondary granules of PMN and is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum ("first milk") has the highest concentration, followed by human milk, then cow milk (150 mg/L).[1]
Lactoferrin is one of the components of the immune system of the body; it has antimicrobial activity (bacteriocide, fungicide) and is part of the innate defense, mainly at mucoses.[1] In particular, lactoferrin provides antibacterial activity to human infants.[2][3] Lactoferrin interacts with DNA and RNA, polysaccharides and heparin, and shows some of its biological functions in complexes with these ligands.
Contents
- 1 History
- 2 Structure and properties
- 2.1 Molecular structure
- 2.2 Polymeric forms
- 3 Biological functions
- 3.1 Antibacterial activity
- 3.2 Antiviral activity
- 3.3 Antifungal activity
- 3.4 Bone activity
- 3.5 Interaction with nucleic acids
- 3.6 Enzymatic activity of lactoferrin
- 3.7 Anticarcinogenic activity
- 4 Genes of lactoferrin
- 5 Lactoferrin receptor
- 6 Cystic fibrosis
- 7 Nanotechnology
- 8 In Diagnosis
- 9 See also
- 10 References
- 11 External links
History
Occurrence of iron-containing red protein in bovine milk was reported as early as in 1939;[4] however, the protein could not be properly characterized because it could not be extracted with sufficient purity. Its first detailed studies were reported around 1960. They documented the molecular weight, isoelectric point, optical absorption spectra and presence of two iron atoms per protein molecule.[5][6] The protein was extracted from milk, contained iron and was structurally and chemically similar to serum transferrin. Therefore, it was named lactoferrin in 1961, though the name lactotransferrin was used in some earlier publications, and later studies demonstrated that the protein is not restricted to milk. The antibacterial action of lactoferrin was also documented in 1961, and was associated with its ability to bind iron.[7]
Structure and properties
Molecular structure
Lactoferrin is one of the transferrin proteins that transfer iron to the cells and control the level of free iron in the blood and external secretions. It is present in the milk of humans and other mammals,[6] in the blood plasma and neutrophils and is one of the major proteins of virtually all exocrine secretions of mammals, such as saliva, bile, tears and pancreas.[8] Concentration of lactoferrin in the milk varies from 7 g/L in the colostrum to 1 g/L in mature milk.
X-ray diffraction reveals that lactoferrin is based on one polypeptide chain that contains about 700 amino acids and forms two homologous globular domains named N-and C-lobes. N-lobe corresponds to amino acid residues 1–333 and C-lobe to 345–692, and the ends of those domains are connected by a short α-helix.[9][10] Each lobe consists of two subdomains, N1, N2 and C1, C2, and contains one iron binding site and one glycosylation site. The degree of glycosylation of the protein may be different and therefore the molecular weight of lactoferrin varies between 76 and 80 kDa. The stability of lactoferrin has been associated with the high glycosylation degree.[11]
Lactoferrin belongs to the basic proteins, its isoelectric point is 8.7. It exists in two forms: iron-rich hololactoferrin and iron-free apolactoferrin. Their tertiary structures are different; apolactoferrin is characterized by "open" conformation of the N-lobe and the "closed" conformation of the C-lobe, and both lobes are closed in the hololactoferrin.[12]
Each lactoferrin molecule can reversibly bind two ions of iron, zinc, copper or other metals.[13] The binding sites are localized in each of the two protein globules. There, each ion is bonded with six ligands: four from the polypeptide chain (two tyrosine residues, one histidine residue and one aspartic acid residue) and two from carbonate or bicarbonate ions.
Lactoferrin forms reddish complex with iron; its affinity for iron is 300 times higher than that of transferrin.[14] The affinity increases in weakly acidic medium. This facilitates the transfer of iron from transferrin to lactoferrin during inflammations, when the pH of tissues decreases due to accumulation of lactic and other acids.[15] The saturated iron concentration in lactoferrin in human milk is estimated as 10 to 30% (100% corresponds to all lactoferrin molecules containing 2 iron atoms). It is demonstrated that lactoferrin is involved not only in the transport of iron, zinc and copper, but also in the regulation of their intake.[16] Presence of loose ions of zinc and copper does not affect the iron binding ability of lactoferrin, and might even increase it.
Polymeric forms
Both in blood plasma and in secretory fluids lactoferrin can exist in different polymeric forms ranging from monomers to tetramers. Lactoferrin tends to polymerize both in vitro and in vivo, especially at high concentrations.[15] Several authors found that the dominant form of lactoferrin in physiological conditions is a tetramer, with the monomer:tetramer ratio of 1:4 at the protein concentrations of 10−5 M.[17][18][19]
It is suggested that the oligomer state of lactoferrin is determined by its concentration and that polymerization of lactoferrin is strongly affected by the presence of Ca2+ ions. In particular, monomers were dominant at concentrations below 10−10−10−11 M in the presence of Ca2+, but they converted into tetramers at lactoferrin concentrations above 10−9−10−10 M.[17][20] Titer of lactoferrin in the blood corresponds to this particular "transition concentration" and thus lactoferrin in the blood should be presented both as a monomer and tetramer. Many functional properties of lactoferrin depend on its oligomeric state. In particular, monomeric, but not tetrameric lactoferrin can strongly bind to DNA.
Biological functions
Lactoferrin belongs to the innate immune system. Apart from its main biological function, namely binding and transport of iron ions, lactoferrin also has antibacterial, antiviral, antiparasitic, catalytic, anti-cancer, anti-allergic and radioprotecting functions and properties.[21]
Antibacterial activity
Lactoferrin's primary role is to sequester free iron, and in doing so remove essential substrate required for bacterial growth.[22] Antibacterial action of lactoferrin is also explained by the presence of specific receptors on the cell surface of microorganisms. Lactoferrin binds to lipopolysaccharide of bacterial walls, and the oxidized iron part of the lactoferrin oxidizes bacteria via formation of peroxides. This affects the membrane permeability and results in the cell breakdown (lysis).[22]
Although lactoferrin also has other antibacterial mechanisms not related to iron, such as stimulation of phagocytosis,[23] the interaction with the outer bacterial membrane described above is the most dominant and most studied.[24] Lactoferrin not only disrupts the membrane, but even penetrates into the cell. Its binding to the bacteria wall is associated with the specific peptide lactoferricin, which is located at the N-lobe of lactoferrin and is produced by in vitro cleavage of lactoferrin with another protein, trypsin.[25][26] A mechanism of the antimicrobial action of lactoferrin has been reported as lactoferrin targets H(+)-ATPase and interferes with proton translocation in the cell membrane, resulting in a lethal effect in vitro.[27]
Lactoferrin prevents the attachment of H. pylori in the stomach, which in turn, aids in reducing digestive system disorders. Bovine lactoferrin has more activity against H. pylori than human lactoferrin. [28]
Antiviral activity
Lactoferrin acts, mostly in vitro, on a wide range of human and animal viruses based on DNA and RNA genomes,[29] including the herpes simplex virus 1 and 2,[30][31] cytomegalovirus,[32] HIV,[31][33] hepatitis C virus,[34][35] hantaviruses, rotaviruses, poliovirus type 1,[36] human respiratory syncytial virus and murine leukemia viruses.[26]
The most studied mechanism of antiviral activity of lactoferrin is its diversion of virus particles from the target cells. Many viruses tend to bind to the lipoproteins of the cell membranes and then penetrate into the cell.[35] Lactoferrin binds to the same lipoproteins thereby repelling the virus particles. Iron-free apolactoferrin is more efficient in this function than hololactoferrin; and lactoferricin, which is responsible for antimicrobial properties of lactoferrin, shows almost no antiviral activity.[29]
Beside interacting with the cell membrane, lactoferrin also directly binds to viral particles, such as the hepatitis viruses.[35] This mechanism is also confirmed by the antiviral activity of lactoferrin against rotaviruses,[26] which act on different cell types.
Lactoferrin also suppresses virus replication after the virus penetrated into the cell.[26][33] Such an indirect antiviral effect is achieved by affecting natural killer cells, granulocytes and macrophages – cells, which play a crucial role in the early stages of viral infections, such as severe acute respiratory syndrome (SARS).[37]
Antifungal activity
Lactoferrin and lactoferricin inhibit in vitro growth of Trichophyton mentagrophytes, which are responsible for several skin diseases such as ringworm.[38] Lactoferrin also acts against the Candida albicans – a diploid fungus (a form of yeast) that causes opportunistic oral and genital infections in humans.[39][40] Fluconazole has long been used against Candida albicans, which resulted in emergence of strains resistant to this drug. However, a combination of lactoferrin with fluconazole can act against fluconazole-resistant strains of Candida albicans as well as other types of Candida: C. glabrata, C. krusei, C. parapsilosis and C. tropicalis.[39] Antifungal activity is observed for sequential incubation of Candida with lactoferrin and then with fluconazole, but not vice versa. The antifungal activity of lactoferricin exceeds that of lactoferrin. In particular, synthetic peptide 1–11 lactoferricin shows much greater activity against Candida albicans than native lactoferricin.[39]
Administration of lactoferrin through drinking water to mice with weakened immune systems and symptoms of aphthous ulcer reduced the number of Candida albicans strains in the mouth and the size of the damaged areas in the tongue.[41] Oral administration of lactoferrin to animals also reduced the number of pathogenic organisms in the tissues close to the gastrointestinal tract. Candida albicans could also be completely eradicated with a mixture containing lactoferrin, lysozyme and itraconazole in HIV-positive patients who were resistant to other antifungal drugs.[42] Such antifungal action when other drugs deem inefficient is characteristic of lactoferrin and is especially valuable for HIV-infected patients.[43] Contrary to the antiviral and antibacterial actions of lactoferrin, very little is known about the mechanism of its antifungal action. Lactoferrin seems to destroy the cell wall and bind the plasma membrane of C. albicans.[40]
Bone activity
Ribonuclease-enriched lactoferrin has been used to examine how lactoferrin affects bone. Lactoferrin has shown to have positive effects on bone turnover. It has aided in decreasing bone resorption and increasing bone formation. This was indicated by a decrease in the levels of two bone resorption markers (deoxypyridinoline and N-telopeptide) and an increase in the levels two bone formation markers (osteocalcin and alkaline phosphatase).[44] It has reduced osteoclast formation, which signifies a decrease in pro-inflammatory responses and an increase in anti-inflammatory responses [45] which indicates a reduction in bone resorption as well.
Interaction with nucleic acids
One of the important properties of lactoferrin is its ability to bind with nucleic acids. The fraction of protein extracted from milk, contains 3.3% RNA,[17] besides, the protein preferably binds to the double-stranded than to the single-stranded DNA. The ability of lactoferrin to bind DNA is used for the isolation and purification of lactoferrin using affinity chromatography with columns containing immobilized DNA-containing sorbents, such as agarose with the immobilized single-stranded DNA.[46]
Enzymatic activity of lactoferrin
Lactoferrin hydrolyzes RNA and exhibits the properties of pyrimidine-specific secretory ribonucleases. In particular, by destroying the RNA genome, milk RNase inhibits reverse transcription of retroviruses that cause breast cancer in mice.[47] Parsi women in West India have the milk RNase level markedly lower than in other groups, and their breast cancer rate is three times higher than average.[48] Thus, ribonucleases of milk, and lactoferrin in particular, might play an important role in pathogenesis of diseases caused by various retroviruses.
Anticarcinogenic activity
The anticancer activity of bovine lactoferrin (bLF) has been demonstrated in experimental lung, bladder, tongue, colon, and liver carcinogeneses on rats, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2).[49] Also, in another experiment done on hamsters, bovine lactoferrin decreased the incidence of oral cancer by 50%.[50] Because bLF by far did not show any toxicity and because it's readily available in milk, bLF offers promise as a potential chemopreventive agent for oral cancer. Currently, bLF is used as an ingredient in yogurt, chewing gums, infant formulas, and cosmetics.[50]
Genes of lactoferrin
At least 60 gene sequences of lactoferrin have been characterized in 11 species of mammals.[51] In most species, stop codon is TAA, and TGA in Mus musculus. Deletions, insertions and mutations of stop codons affect the coding part and its length varies between 2,055 and 2,190 nucleotide pairs. Gene polymorphism between species is much more diverse than the intraspecific polymorphism of lactoferrin. There are differences in amino acid sequences: 8 in Homo sapiens, 6 in Mus musculus, 6 in Capra hircus, 10 in Bos taurus and 20 in Sus scrofa. This variation may indicate functional differences between different types of lactoferrin.[51]
In humans, lactoferrin gene LTF is located on the third chromosome in the locus 3q21-q23. In oxen, the coding sequence consists of 17 exons and has a length of about 34,500 nucleotide pairs. Exons of the lactoferrin gene in oxen have a similar size to the exons of other genes of the transferrin family, whereas the sizes of introns differ within the family. Similarity in the size of exons and their distribution in the domains of the protein molecule indicates that the evolutionary development of lactoferrin gene occurred by duplication.[52] Study of polymorphism of genes that encode lactoferrin helps selecting livestock breeds that are resistant to mastitis.[53]
Lactoferrin receptor
The lactoferrin receptor plays an important role in the internalization of lactoferrin; it also facilitates absorption of iron ions by lactoferrin. It was shown that gene expression increases with age in the duodenum and decreases in the jejunum.[54] The moonlighting glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been demonstrated to function as a receptor for lactoferrin.[55]
Cystic fibrosis
The human lung and saliva contain a wide range of antimicrobial compound including lactoperoxidase system, producing hypothiocyanite and lactoferrin, with hypothiocyanite missing in cystic fibrosis patients.[56] Lactoferrin, a component of innate immunity, prevents bacterial biofilm development.[57][58] The loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity is observed in patients with cystic fibrosis.[59] These findings demonstrate the important role of lactoferrin in human host defense and especially in lung.[60]
Lactoferrin with hypothiocyanite has been granted orphan drug status by the EMEA[61] and the FDA.[62]
Nanotechnology
Lactotransferrin has been used in the synthesis of fluorescent gold quantum clusters, which has potential applications in nanotechnology.[63]
In Diagnosis
Lactoferrin levels in tear fluid have been shown to decrease in dry eye diseases such as Sjogren's syndrome.[64] A rapid, portable test utilizing microfluidic technology has been developed to enable measurement of lactoferrin levels in human tear fluid at the point-of-care with the aim of improving diagnosis of Sjogren's syndrome and other forms of dry eye disease.[65]
See also
- Respiratory tract antimicrobial defense system
References
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- ^ Takakura N, Wakabayashi H, Ishibashi H, Teraguchi S, Tamura Y, Yamaguchi H, Abe S (2003). "Oral lactoferrin treatment of experimental oral candidiasis in mice". Antimicrob. Agents Chemother. 47 (8): 2619–23. doi:10.1128/AAC.47.8.2619-2623.2003. PMC 166093. PMID 12878528.
- ^ Masci JR (October 2000). "Complete response of severe, refractory oral candidiasis to mouthwash containing lactoferrin and lysozyme". AIDS 14 (15): 2403–4. doi:10.1097/00002030-200010200-00023. PMID 11089630.
- ^ Kuipers ME, de Vries HG, Eikelboom MC, Meijer DK, Swart PJ (1999). "Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates". Antimicrob. Agents Chemother. 43 (11): 2635–41. PMC 89536. PMID 10543740.
- ^ Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS (September 2009). "Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women". Osteoporos Int 20 (9): 1603–11. doi:10.1007/s00198-009-0839-8. PMID 19172341.
- ^ Bharadwaj S, Naidu TA, Betageri GV, Prasadarao NV, Naidu AS (November 2010). "Inflammatory responses improve with milk ribonuclease-enriched lactoferrin supplementation in postmenopausal women". Inflamm. Res. 59 (11): 971–8. doi:10.1007/s00011-010-0211-7. PMID 20473630.
- ^ Rosenmund A, Kuyas C, Haeberli A (1986). "Oxidative radioiodination damage to human lactoferrin". Biochem. J. 240 (1): 239–45. PMC 1147399. PMID 3827843.
- ^ McCormick JJ, Larson LJ, Rich MA (1974). "RNase inhibition of reverse transcriptase activity in human milk". Nature 251 (5477): 737–40. doi:10.1038/251737a0. PMID 4139659.
- ^ Das MR, Padhy LC, Koshy R, Sirsat SM, Rich MA (1976). "Human milk samples from different ethnic groups contain RNase that inhibits, and plasma membrane that stimulates, reverse transcription". Nature 262 (5571): 802–5. doi:10.1038/262802a0. PMID 60710.
- ^ Tsuda H, Sekine K, Fujita K, Ligo M (2002). "Cancer prevention by bovine lactoferrin and underlying mechanisms--a review of experimental and clinical studies". Biochem. Cell Biol. 80 (1): 131–6. doi:10.1139/o01-239. PMID 11908637.
- ^ a b Chandra Mohan KV, Kumaraguruparan R, Prathiba D, Nagini S (September 2006). "Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactoferrin". Nutrition 22 (9): 940–6. doi:10.1016/j.nut.2006.05.017. PMID 16928475.
- ^ a b Jing-Fen Kang, Xiang-Long Li, Rong-Yan Zhou, Lan-Hui Li, Fu-Jun Feng and Xiu -Li Guo (2008). "Bioinformatics Analysis of Lactoferrin Gene for Several Species". Biochemical Genetics 46 (5–6): 312–322. doi:10.1007/s10528-008-9147-9. PMID 18228129.
- ^ Seyfert HM, Tuckoricz A, Interthal H, Koczan D, Hobom G (1994). "Structure of the bovine lactoferrin-encoding gene and its promoter". Gene 143 (2): 265–9. doi:10.1016/0378-1119(94)90108-2. PMID 8206385.
- ^ O'Halloran F, Bahar B, Buckley F, O'Sullivan O, Sweeney T, Giblin L. (2009). "Characterisation of single nucleotide polymorphisms identified in the bovine lactoferrin gene sequences across a range of dairy cow breeds". Biochimie 91 (1): 68–75. doi:10.1016/j.biochi.2008.05.011. PMID 18554515.
- ^ Liao Y, Lopez V, Shafizadeh TB, Halsted CH, Lönnerdal B (2007). "Cloning of a pig homologue of the human lactoferrin receptor: expression and localization during intestinal maturation in piglets". Comp Biochem Physiol a Mol Integr Physiol 148 (3): 584–90. doi:10.1016/j.cbpa.2007.08.001. PMC 2265088. PMID 17766154.
- ^ The multifunctional glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a novel macrophage lactoferrin receptor. Pooja Rawat, Santosh Kumar, Navdeep Sheokand, Chaaya Iyengar Raje and Manoj Raje. Biochemistry and Cell Biology; 2012, 90(3): 329–338.
- ^ Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB, Nauseef WM, Dupuy C, Bánfi B (2007). "A novel host defense system of airways is defective in cystic fibrosis". Am. J. Respir. Crit. Care Med. 175 (2): 174–83. doi:10.1164/rccm.200607-1029OC. PMC 2720149. PMID 17082494.
- ^ Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP (2000). "Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms". Nature 407 (6805): 762–4. doi:10.1038/35037627. PMID 11048725.
- ^ Singh PK, Parsek MR, Greenberg EP, Welsh MJ (2002). "A component of innate immunity prevents bacterial biofilm development". Nature 417 (6888): 552–5. doi:10.1038/417552a. PMID 12037568.
- ^ Rogan MP, Taggart CC, Greene CM, Murphy PG, O'Neill SJ, McElvaney NG (2004). "Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis". J. Infect. Dis. 190 (7): 1245–53. doi:10.1086/423821. PMID 15346334.
- ^ Rogan MP, Geraghty P, Greene CM, O'Neill SJ, Taggart CC, McElvaney NG (2006). "Antimicrobial proteins and polypeptides in pulmonary innate defence". Respir. Res. 7 (1): 29. doi:10.1186/1465-9921-7-29. PMC 1386663. PMID 16503962.
- ^ "Public summary of positive opinion for orphan designation of hypothiocyanite/lactoferrin for the treatment of cystic fibrosis" (PDF). Pre-authorisation Evaluation of Medicines for Human Use. European Medicines Agency. 2009-09-07. Retrieved 2010-01-23.
- ^ "Meveol: orphan drug status granted by the FDA for the treatment of cystic fibrosis". United States Food and Drug Administration. 2009-11-05. Retrieved 2010-01-23.
- ^ Xavier PL, Chaudhari K, Verma PK, Pal SK, Pradeep T (2010). "Luminescent quantum clusters of gold in transferrin family protein, lactoferrin exhibiting FRET" (PDF). Nanoscale 12 (12): 2769–76. doi:10.1039/C0NR00377H. PMID 20882247.
- ^ Ohashi, Yoshiki; Reiko Ishida; Takashi Kojima; Eiki Goto; Yukihiro Matsumoto; Katsuhiko Watanabe; Naruhiro Ishida; Katsuhiko Nakata; Tsutomu Takeuchi; Kazuo Tsubota (August 2003). "Abnormal Protein Profiles in Tears with Dry Eye Syndrome". American Journal of Ophthalmology 136 (2): 291–9. doi:10.1016/S0002-9394(03)00203-4. PMID 12888052.
- ^ Karns, Kelly; Herr, Amy E (November 2011). "Human Tear Protein Analysis Enabled by an Alkaline Microfluidic Homogeneous Immunoassay". Analytical Chemistry 83 (21): 8115–22. doi:10.1021/ac202061v. PMID 21910436.
External links
- Uniprot
- LTF on the National Center for Biotechnology Information
- FDA Lactoferrin Considered Safe to Fight E. Coli.
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PDB gallery
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1b0l: RECOMBINANT HUMAN DIFERRIC LACTOFERRIN
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1bka: OXALATE-SUBSTITUTED DIFERRIC LACTOFERRIN
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1cb6: STRUCTURE OF HUMAN APOLACTOFERRIN AT 2.0 A RESOLUTION.
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1dsn: D60S N-TERMINAL LOBE HUMAN LACTOFERRIN
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1eh3: R210K N-TERMINAL LOBE HUMAN LACTOFERRIN
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1fck: STRUCTURE OF DICERIC HUMAN LACTOFERRIN
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1h43: R210E N-TERMINAL LOBE HUMAN LACTOFERRIN
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1h44: R210L N-TERMINAL LOBE HUMAN LACTOFERRIN
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1h45: R210G N-TERMINAL LOBE HUMAN LACTOFERRIN
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1hse: H253M N TERMINAL LOBE OF HUMAN LACTOFERRIN
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1l5t: Crystal Structure of a Domain-Opened Mutant (R121D) of the Human Lactoferrin N-lobe Refined From a Merohedrally-Twinned Crystal Form.
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1lcf: CRYSTAL STRUCTURE OF COPPER-AND OXALATE-SUBSTITUTED HUMAN LACTOFERRIN AT 2.0 ANGSTROMS RESOLUTION
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1lct: STRUCTURE OF THE RECOMBINANT N-TERMINAL LOBE OF HUMAN LACTOFERRIN AT 2.0 ANGSTROMS RESOLUTION
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1lfg: MOLECULAR REPLACEMENT SOLUTION OF THE STRUCTURE OF APOLACTOFERRIN, A PROTEIN DISPLAYING LARGE-SCALE CONFORMATIONAL CHANGE
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1lfh: MOLECULAR REPLACEMENT SOLUTION OF THE STRUCTURE OF APOLACTOFERRIN, A PROTEIN DISPLAYING LARGE-SCALE CONFORMATIONAL CHANGE
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1lfi: METAL SUBSTITUTION IN TRANSFERRINS: THE CRYSTAL STRUCTURE OF HUMAN COPPER-LACTOFERRIN AT 2.1 ANGSTROMS RESOLUTION
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1lgb: INTERACTION OF A LEGUME LECTIN WITH THE N2 FRAGMENT OF HUMAN LACTOTRANSFERRIN OR WITH THE ISOLATED BIANTENNARY GLYCOPEPTIDE: ROLE OF THE FUCOSE MOIETY
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1n76: CRYSTAL STRUCTURE OF HUMAN SEMINAL LACTOFERRIN AT 3.4 A RESOLUTION
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1sqy: Structure of human diferric lactoferrin at 2.5A resolution using crystals grown at pH 6.5
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1vfd: HUMAN LACTOFERRIN, N-TERMINAL LOBE MUTANT WITH ARG 121 REPLACED BY GLU (R121E)
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1vfe: HUMAN LACTOFERRIN, N-TERMINAL LOBE MUTANT WITH ARG 121 REPLACED BY SER (R121S)
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1z6v: Human lactoferricin
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1z6w: Human Lactoferricin
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2bjj: STRUCTURE OF RECOMBINANT HUMAN LACTOFERRIN PRODUCED IN THE MILK OF TRANSGENIC COWS
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Proteins: Globular proteins
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| Serum globulins |
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Alpha globulins
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serpins:
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- alpha-1 (Alpha 1-antichymotrypsin, Alpha 1-antitrypsin)
- alpha-2 (Alpha 2-antiplasmin)
- Antithrombin (Heparin cofactor II)
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carrier proteins:
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- alpha-1 (Transcortin)
- alpha-2 (Ceruloplasmin)
- Retinol binding protein
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other:
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- alpha-1 (Orosomucoid)
- alpha-2 (alpha-2-Macroglobulin, Haptoglobin)
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Beta globulins
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carrier proteins:
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- Sex hormone-binding globulin
- Transferrin
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other:
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- Angiostatin
- Hemopexin
- Beta-2 microglobulin
- Factor H
- Plasminogen
- Properdin
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Gamma globulin
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Other
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- Fibronectin (fFN: Fetal fibronectin)
- Macroglobulin/Microglobulin
- Transcobalamin
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| Other globulins |
- Beta-lactoglobulin
- Thyroglobulin
- Alpha-lactalbumin
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| Albumins |
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Egg white
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- Conalbumin
- Ovalbumin
- Avidin
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Serum albumin
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- Human serum albumin
- Bovine serum albumin
- Prealbumin
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Other
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- C-reactive protein
- Lactalbumin (Alpha-lactalbumin)
- Parvalbumin
- Ricin
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- see also disorders of globin and globulin proteins
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Index of proteins
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| Description |
- Proteins
- Membrane
- Globular
- Antibodies
- Fibrous
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Carrier proteins, metalloproteins: iron-binding proteins
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| heme |
- Ferritin (Bacterioferritin)
- Lactoferrin
- Transferrin
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| nonheme |
- Hemerythrin
- Inositol oxygenase
- Iron-sulfur protein
- Lipoxygenase
- Tyrosine hydroxylase
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Protein, glycoconjugate: glycoproteins and glycopeptides
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| Mucoproteins |
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Mucin
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- CD43
- CD164
- MUC1
- MUC2
- MUC3A
- MUC3B
- MUC4
- MUC5AC
- MUC5B
- MUC6
- MUC7
- MUC8
- MUC12
- MUC13
- MUC15
- MUC16
- MUC17
- MUC19
- MUC20
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Other
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- Haptoglobin
- Intrinsic factor
- Orosomucoid
- Peptidoglycan
- Phytohaemagglutinin
- Ovomucin
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| Proteoglycans |
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CS/DS
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- Decorin
- Biglycan
- Versican
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HS/CS
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CS
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- Chondroitin sulfate proteoglycans: Aggrecan
- Neurocan
- Brevican
- CD44
- CSPG4
- CSPG5
- Platelet factor 4
- Structural maintenance of chromosomes 3
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KS
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- Fibromodulin
- Lumican
- Keratocan
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HS
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| Other |
- Activin and inhibin
- ADAM
- Alpha 1-antichymotrypsin
- Apolipoprotein H
- CD70
- Asialoglycoprotein
- Avidin
- B-cell activating factor
- 4-1BB ligand
- Cholesterylester transfer protein
- Clusterin
- Colony-stimulating factor
- Hemopexin
- Lactoferrin
- Membrane glycoproteins
- Myelin protein zero
- Osteonectin
- Protein C
- Protein S
- Serum amyloid P component
- Sialoglycoprotein
- CD43
- Glycophorin
- Glycophorin C
- Thrombopoietin
- Thyroglobulin
- Thyroxine-binding proteins
- Transcortin
- Tumor necrosis factor alpha
- Uteroglobin
- Vitronectin
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Index of inborn errors of metabolism
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| Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
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| Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
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| Treatment |
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Index of biochemical families
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| Carbohydrates |
- Alcohols
- Glycoproteins
- Glycosides
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| Lipids |
- Eicosanoids
- Fatty acids
- Glycerides
- Phospholipids
- Sphingolipids
- Steroids
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| Nucleic acids |
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| Proteins |
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| Other |
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Antimicrobial peptides: Granulocyte granule contents
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| Azurophilic granules (1°) |
- Myeloperoxidase
- Defensins
- neutral serine proteases (Proteinase 3)
- Lysozyme
- Bactericidal/permeability-increasing protein
- Collagenase
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| Specific granules (2°) |
| Neutrophil |
- Alkaline phosphatase
- Lactoferrin
- Lysozyme
- NADPH oxidase
- Collagenase
- Cathelicidin
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| Eosinophil |
- Cathepsin
- Major basic protein
- Eosinophil cationic protein
- Eosinophil peroxidase
- Eosinophil-derived neurotoxin
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| Basophil |
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- see also platelet alpha-granule, dense granule
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Index of cells from bone marrow
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| Description |
- Immune system
- Cells
- Physiology
- coagulation
- proteins
- granule contents
- colony-stimulating
- heme and porphyrin
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| Disease |
- Red blood cell
- Monocyte and granulocyte
- Neoplasms and cancer
- Histiocytosis
- Symptoms and signs
- Blood tests
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| Treatment |
- Transfusion
- Drugs
- thrombosis
- bleeding
- other
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