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Gene Review

LTF  -  lactotransferrin

Homo sapiens

Synonyms: GIG12, Growth-inhibiting protein 12, HEL110, HLF2, LF, ...
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Disease relevance of LTF


Psychiatry related information on LTF


High impact information on LTF

  • Particular emphasis is put on milk proteins such as lactoferrin, casein, and whey proteins, but phytate in soy formula is also discussed [10].
  • Lactoferrin deficiency associated with altered granulocyte function [11].
  • Lactoferrin, an iron-binding glycoprotein found in high concentrations in human milk and other epithelial secretions and in the secondary (specific) granules of neutrophils, is thought to be responsible for primary defence against microbial infection, mainly as a result of lactoferrin sequestration of iron required for microbial growth [12].
  • Why diabetes is associated with abnormally high susceptibility to infection remains unknown, although two major antibacterial proteins, lysozyme and lactoferrin, have now been shown to specifically bind glucose-modified proteins bearing advanced glycation end products (AGEs) [13].
  • Many other functions have been attributed to lactoferrin, including immunomodulation and cell growth regulation (reviewed in ref. 4). Some of these functions appear to be at least in part independent of the iron-binding activity of lactoferrin [12].

Chemical compound and disease context of LTF


Biological context of LTF


Anatomical context of LTF


Associations of LTF with chemical compounds


Physical interactions of LTF


Enzymatic interactions of LTF


Co-localisations of LTF


Regulatory relationships of LTF


Other interactions of LTF

  • Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%) [36].
  • The binding affinity for lactoferrin (83 nM) was about 4-fold lower than for transferrin (21 nM) [23].
  • ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides [37].
  • Lactoferrin, another protein with a high affinity for mammalian LRP/alpha 2MR, also binds to OVR and abolishes its interaction with yolk precursors [26].
  • Fe acquisition by M.tb within hereditary hemochromatosis macrophages was decreased by 84% from Tf and 92% from Lf relative to that in healthy control macrophages [38].

Analytical, diagnostic and therapeutic context of LTF


  1. Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. Nozaki, A., Ikeda, M., Naganuma, A., Nakamura, T., Inudoh, M., Tanaka, K., Kato, N. J. Biol. Chem. (2003) [Pubmed]
  2. Specificity of the lactoferrin and transferrin receptors in Neisseria gonorrhoeae. Lee, B.C., Schryvers, A.B. Mol. Microbiol. (1988) [Pubmed]
  3. Characterization of the human transferrin and lactoferrin receptors in Haemophilus influenzae. Schryvers, A.B. Mol. Microbiol. (1988) [Pubmed]
  4. Analysis of the immunological responses to transferrin and lactoferrin receptor proteins from Moraxella catarrhalis. Yu, R.H., Bonnah, R.A., Ainsworth, S., Schryvers, A.B. Infect. Immun. (1999) [Pubmed]
  5. An intronic alternative promoter of the human lactoferrin gene is activated by Ets. Liu, D., Wang, X., Zhang, Z., Teng, C.T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  6. Variability of the parahippocampal surface of the transverse fissure in the human brain. Berdel, B., Morys, J., Maciejewska, B., Kowalewska, J., Narkiewicz, O. Folia morphologica. (1994) [Pubmed]
  7. Nasal airway changes assessed by acoustic rhinometry and mediator release during immediate and late reactions to allergen challenge. Zweiman, B., Getsy, J., Kalenian, M., Lane, A., Schwartz, L.B., Doty, R., Lanza, D. J. Allergy Clin. Immunol. (1997) [Pubmed]
  8. The iron-binding protein lactotransferrin is present in pathologic lesions in a variety of neurodegenerative disorders: a comparative immunohistochemical analysis. Leveugle, B., Spik, G., Perl, D.P., Bouras, C., Fillit, H.M., Hof, P.R. Brain Res. (1994) [Pubmed]
  9. The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Goldenberg, R.L., Andrews, W.W., Guerrant, R.L., Newman, M., Mercer, B., Iams, J., Meis, P., Moawad, A., Das, A., VanDorsten, J.P., Caritis, S.N., Thurnau, G., Bottoms, S., Miodovnik, M., McNellis, D., Roberts, J.M. Am. J. Obstet. Gynecol. (2000) [Pubmed]
  10. Effects of milk and milk components on calcium, magnesium, and trace element absorption during infancy. Lönnerdal, B. Physiol. Rev. (1997) [Pubmed]
  11. Lactoferrin deficiency associated with altered granulocyte function. Boxer, L.A., Coates, T.D., Haak, R.A., Wolach, J.B., Hoffstein, S., Baehner, R.L. N. Engl. J. Med. (1982) [Pubmed]
  12. Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA. He, J., Furmanski, P. Nature (1995) [Pubmed]
  13. Antibacterial activity of lysozyme and lactoferrin is inhibited by binding of advanced glycation-modified proteins to a conserved motif. Li, Y.M., Tan, A.X., Vlassara, H. Nat. Med. (1995) [Pubmed]
  14. Human lactoferrin interacts with soluble CD14 and inhibits expression of endothelial adhesion molecules, E-selectin and ICAM-1, induced by the CD14-lipopolysaccharide complex. Baveye, S., Elass, E., Fernig, D.G., Blanquart, C., Mazurier, J., Legrand, D. Infect. Immun. (2000) [Pubmed]
  15. Lactoferrin immunoexpression in endometrial carcinomas: relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival. Giuffrè, G., Arena, F., Scarfì, R., Simone, A., Todaro, P., Tuccari, G. Oncol. Rep. (2006) [Pubmed]
  16. Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers. Iijima, H., Tomizawa, Y., Iwasaki, Y., Sato, K., Sunaga, N., Dobashi, K., Saito, R., Nakajima, T., Minna, J.D., Mori, M. Int. J. Cancer (2006) [Pubmed]
  17. Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites. Hendrixson, D.R., Qiu, J., Shewry, S.C., Fink, D.L., Petty, S., Baker, E.N., Plaut, A.G., St Geme, J.W. Mol. Microbiol. (2003) [Pubmed]
  18. Lactoferrin-lipopolysaccharide interaction: involvement of the 28-34 loop region of human lactoferrin in the high-affinity binding to Escherichia coli 055B5 lipopolysaccharide. Elass-Rochard, E., Roseanu, A., Legrand, D., Trif, M., Salmon, V., Motas, C., Montreuil, J., Spik, G. Biochem. J. (1995) [Pubmed]
  19. Ultrastructural localization of lactoferrin and myeloperoxidase in human neutrophils by immunogold. Cramer, E., Pryzwansky, K.B., Villeval, J.L., Testa, U., Breton-Gorius, J. Blood (1985) [Pubmed]
  20. Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-alpha. Srivastava, C.H., Rado, T.A., Bauerle, D., Broxmeyer, H.E. J. Immunol. (1991) [Pubmed]
  21. Bactericidal capacity of phorbol myristate acetate-treated human polymorphonuclear leukocytes. Wang-Iverson, P., Pryzwansky, K.B., Spitznagel, J.K., Cooney, M.H. Infect. Immun. (1978) [Pubmed]
  22. Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Suzuki, K., Nakaji, S., Yamada, M., Liu, Q., Kurakake, S., Okamura, N., Kumae, T., Umeda, T., Sugawara, K. Medicine and science in sports and exercise. (2003) [Pubmed]
  23. Binding of lactoferrin and transferrin to the human promonocytic cell line U937. Effect on iron uptake and release. Ismail, M., Brock, J.H. J. Biol. Chem. (1993) [Pubmed]
  24. Immobilized lactoferrin is a stimulus for eosinophil activation. Thomas, L.L., Xu, W., Ardon, T.T. J. Immunol. (2002) [Pubmed]
  25. Hydroxyl radical formation and iron-binding proteins. Stimulation by the purple acid phosphatases. Sibille, J.C., Doi, K., Aisen, P. J. Biol. Chem. (1987) [Pubmed]
  26. The chicken oocyte receptor for yolk precursors as a model for studying the action of receptor-associated protein and lactoferrin. Hiesberger, T., Hermann, M., Jacobsen, L., Novak, S., Hodits, R.A., Bujo, H., Meilinger, M., Hüttinger, M., Schneider, W.J., Nimpf, J. J. Biol. Chem. (1995) [Pubmed]
  27. Identification and characterization of the human lactoferrin-binding protein from Neisseria meningitidis. Schryvers, A.B., Morris, L.J. Infect. Immun. (1988) [Pubmed]
  28. Interaction of lactoferrin with ceruloplasmin. Zakharova, E.T., Shavlovski, M.M., Bass, M.G., Gridasova, A.A., Pulina, M.O., De Filippis, V., Beltramini, M., Di Muro, P., Salvato, B., Fontana, A., Vasilyev, V.B., Gaitskhoki, V.S. Arch. Biochem. Biophys. (2000) [Pubmed]
  29. CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter. Khanna-Gupta, A., Zibello, T., Kolla, S., Neufeld, E.J., Berliner, N. Blood (1997) [Pubmed]
  30. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Sørensen, O., Arnljots, K., Cowland, J.B., Bainton, D.F., Borregaard, N. Blood (1997) [Pubmed]
  31. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Volck, B., Price, P.A., Johansen, J.S., Sørensen, O., Benfield, T.L., Nielsen, H.J., Calafat, J., Borregaard, N. Proc. Assoc. Am. Physicians (1998) [Pubmed]
  32. Promoter and species specific differential estrogen-mediated gene transcription in the uterus and cultured cells using structurally altered agonists. Curtis, S.W., Shi, H., Teng, C., Korach, K.S. J. Mol. Endocrinol. (1997) [Pubmed]
  33. Molecular interactions between human lactotransferrin and the phytohemagglutinin-activated human lymphocyte lactotransferrin receptor lie in two loop-containing regions of the N-terminal domain I of human lactotransferrin. Legrand, D., Mazurier, J., Elass, A., Rochard, E., Vergoten, G., Maes, P., Montreuil, J., Spik, G. Biochemistry (1992) [Pubmed]
  34. The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Grey, A., Banovic, T., Zhu, Q., Watson, M., Callon, K., Palmano, K., Ross, J., Naot, D., Reid, I.R., Cornish, J. Mol. Endocrinol. (2004) [Pubmed]
  35. Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways. Curran, C.S., Demick, K.P., Mansfield, J.M. Cell. Immunol. (2006) [Pubmed]
  36. Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells. Scheinecker, C., Strobl, H., Fritsch, G., Csmarits, B., Krieger, O., Majdic, O., Knapp, W. Blood (1995) [Pubmed]
  37. Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. Characterization and clinical correlations. Mulder, A.H., Horst, G., van Leeuwen, M.A., Limburg, P.C., Kallenberg, C.G. Arthritis Rheum. (1993) [Pubmed]
  38. Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis within human macrophages. Olakanmi, O., Schlesinger, L.S., Britigan, B.E. J. Leukoc. Biol. (2007) [Pubmed]
  39. Neutrophil degranulation inhibits potential hydroxyl-radical formation. Relative impact of myeloperoxidase and lactoferrin release on hydroxyl-radical production by iron-supplemented neutrophils assessed by spin-trapping techniques. Britigan, B.E., Hassett, D.J., Rosen, G.M., Hamill, D.R., Cohen, M.S. Biochem. J. (1989) [Pubmed]
  40. The value of indirect immunofluorescence and solid phase techniques for ANCA detection. A report on the first phase of an international cooperative study on the standardization of ANCA assays. EEC/BCR Group for ANCA Assay Standardization. Hagen, E.C., Andrassy, K., Chernok, E., Daha, M.R., Gaskin, G., Gross, W., Lesavre, P., Lüdemann, J., Pusey, C.D., Rasmussen, N. J. Immunol. Methods (1993) [Pubmed]
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