Lactoferrin (LTF)

HLF2; LF; GIG12; Lactotransferrin; Growth-inhibiting protein 12; Talalactoferrin; Lfcin-H; Kaliocin-1

SPN	W032
HGNC	6720
MGI	96837
PubMed	19519436
RGD	1305445
UniProt	P02788
Wiki	Lactoferrin

LTF, a globular multifunctional protein with antimicrobial activity (bacteriocide, fungicide), is part of the innate defense, mainly at mucoses. Lactoferrin is found in milk and many mucosal secretions such as tears and saliva. Lactoferrin is also present in secondary granules of PMN and also is secreted by some acinar cells. Human colostrum has the highest concentration, followed by human milk, then cow milk.

Lactoferrin belongs to the transferrin family proteins (TF, melanotransferrin, ovotransferin, etc.). Its molecular mass is 80,000 u (80 kDa).Lactoferrin antimicrobial activity is due partly to its high affinity for Fe (ferric state). LF proteolysis produces lactoferricin, kaliocin-1 small peptides with antimicrobial activity.

Reference

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Nucleic Acids Res. 18:5288-5288(1990) [PubMed] [Europe PMC] [Abstract]

"Cloning of human lactoferrin gene and its polymorphism in normal and cancer cells."
Thesis (1994), Genetic Engineering Research Institute, South Korea

"Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines."
Proc. Natl. Acad. Sci. U.S.A. 94:2198-2203(1997) [PubMed] [Europe PMC] [Abstract]

"cDNA cloning and sequence analysis of human lactoferrin."
Sheng Wu Gong Cheng Xue Bao 17:385-387(2001) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of human seminal diferric lactoferrin at 3.4 Angstrom resolution."
Indian J. Biochem. Biophys. 40:14-21(2003) [PubMed] [Europe PMC] [Abstract]

"One of two human lactoferrin variants exhibits increased antibacterial and transcriptional activation activities and is associated with localized juvenile periodontitis."
Infect. Immun. 71:6141-6147(2003) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse."
Mol. Endocrinol. 6:1969-1981(1992) [PubMed] [Europe PMC] [Abstract]

"Nucleotide sequence of human lactoferrin cDNA."
Nucleic Acids Res. 18:4013-4013(1990) [PubMed] [Europe PMC] [Abstract]

"Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins."
Eur. J. Biochem. 145:659-676(1984) [PubMed] [Europe PMC] [Abstract]

"The present state of the human lactotransferrin sequence. Study and alignment of the cyanogen bromide fragments and characterization of N- and C-terminal domains."
Biochim. Biophys. Acta 670:243-254(1981) [PubMed] [Europe PMC] [Abstract]

"Identification of the bactericidal domain of lactoferrin."
Biochim. Biophys. Acta 1121:130-136(1992) [PubMed] [Europe PMC] [Abstract]

"Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin."
J. Biol. Chem. 269:23661-23667(1994) [PubMed] [Europe PMC] [Abstract]

"Characterization of the 84-kDa protein with ABH activity in human seminal plasma."
Nihon Hoigaku Zasshi 49:281-293(1995) [PubMed] [Europe PMC] [Abstract]

"Human lactoferricin is partially folded in aqueous solution and is better stabilized in a membrane mimetic solvent."
Antimicrob. Agents Chemother. 49:3387-3395(2005) [PubMed] [Europe PMC] [Abstract]

"Isolation of lactoferrin cDNA from a human myeloid library and expression of mRNA during normal and leukemic myelopoiesis."
Blood 70:989-993(1987) [PubMed] [Europe PMC] [Abstract]

"An 88 amino acid long C-terminal sequence of human lactotransferrin."
FEBS Lett. 142:107-110(1982) [PubMed] [Europe PMC] [Abstract]

"Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation."
Infect. Immun. 35:792-799(1982) [PubMed] [Europe PMC] [Abstract]

"Ultrastructural localization of lactoferrin and myeloperoxidase in human neutrophils by immunogold."
Blood 65:423-432(1985) [PubMed] [Europe PMC] [Abstract]

"Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin."
Infect. Immun. 56:2774-2781(1988) [PubMed] [Europe PMC] [Abstract]

"Isolation and characterization of opioid antagonist peptides derived from human lactoferrin."
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"N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA."
Biochem. J. 328:145-151(1997) [PubMed] [Europe PMC] [Abstract]

"Candidacidal activities of human lactoferrin peptides derived from the N terminus."
Antimicrob. Agents Chemother. 44:3257-3263(2000) [PubMed] [Europe PMC] [Abstract]

"Expression of lactoferrin in the kidney: implications for innate immunity and iron metabolism."
Kidney Int. 57:2004-2010(2000) [PubMed] [Europe PMC] [Abstract]

"Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria."
Infect. Immun. 69:1469-1476(2001) [PubMed] [Europe PMC] [Abstract]

"A component of innate immunity prevents bacterial biofilm development."
Nature 417:552-555(2002) [PubMed] [Europe PMC] [Abstract]

"An intronic alternative promoter of the human lactoferrin gene is activated by Ets."
Biochem. Biophys. Res. Commun. 301:472-479(2003) [PubMed] [Europe PMC] [Abstract]

"Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane."
Biochemistry (Mosc.) 68:217-227(2003) [PubMed] [Europe PMC] [Abstract]

"Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites."
Mol. Microbiol. 47:607-617(2003) [PubMed] [Europe PMC] [Abstract]

"Expression of delta-lactoferrin induces cell cycle arrest."
BioMetals 17:325-329(2004) [PubMed] [Europe PMC] [Abstract]

"Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo."
Endocrinology 145:4366-4374(2004) [PubMed] [Europe PMC] [Abstract]

"Human lactoferrin upregulates expression of KDR/Flk-1 and stimulates VEGF-A-mediated endothelial cell proliferation and migration."
FEBS Lett. 580:4332-4336(2006) [PubMed] [Europe PMC] [Abstract]

"The anti-papillomavirus activity of human and bovine lactoferricin."
Antiviral Res. 75:258-265(2007) [PubMed] [Europe PMC] [Abstract]

"Characterization of an eppin protein complex from human semen and spermatozoa."
Biol. Reprod. 77:476-484(2007) [PubMed] [Europe PMC] [Abstract]

"Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells."
J. Virol. 81:954-963(2007) [PubMed] [Europe PMC] [Abstract]

"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry."
Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract]

"Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin."
J. Clin. Invest. 119:20-32(2009) [PubMed] [Europe PMC] [Abstract]

"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]

"Human lactoferrin activates NF-kappaB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling."
FEBS J. 277:2051-2066(2010) [PubMed] [Europe PMC] [Abstract]

"O-GlcNAcylation/phosphorylation cycling at Ser10 controls both transcriptional activity and stability of delta-lactoferrin."
J. Biol. Chem. 285:19205-19218(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor."
Biochem. Cell Biol. 90:307-319(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of human lactoferrin: crystallographic structure analysis and refinement at 2.8-A resolution."
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"Molecular replacement solution of the structure of apolactoferrin, a protein displaying large-scale conformational change."
Acta Crystallogr. B 47:998-1004(1991) [PubMed] [Europe PMC] [Abstract]

"Metal substitution in transferrins: the crystal structure of human copper-lactoferrin at 2.1-A resolution."
Biochemistry 31:4527-4533(1992) [PubMed] [Europe PMC] [Abstract]

"Structure of the recombinant N-terminal lobe of human lactoferrin at 2.0 A resolution."
J. Mol. Biol. 232:1084-1100(1993) [PubMed] [Europe PMC] [Abstract]

"Structure of copper- and oxalate-substituted human lactoferrin at 2.0 A resolution."
Acta Crystallogr. D 50:302-316(1994) [PubMed] [Europe PMC] [Abstract]

"Structures of a legume lectin complexed with the human lactotransferrin N2 fragment, and with an isolated biantennary glycopeptide: role of the fucose moiety."
Structure 2:209-219(1994) [PubMed] [Europe PMC] [Abstract]

"Structure of human diferric lactoferrin refined at 2.2-A resolution."
Acta Crystallogr. D 51:629-646(1995) [PubMed] [Europe PMC] [Abstract]

"Anion binding by transferrins: importance of second-shell effects revealed by the crystal structure of oxalate-substituted diferric lactoferrin."
Biochemistry 35:9007-9013(1996) [PubMed] [Europe PMC] [Abstract]

"Mutation of arginine 121 in lactoferrin destabilizes iron binding by disruption of anion binding: crystal structures of R121S and R121E mutants."
Biochemistry 35:14473-14479(1996) [PubMed] [Europe PMC] [Abstract]

"Altered domain closure and iron binding in transferrins: the crystal structure of the Asp60Ser mutant of the amino-terminal half-molecule of human lactoferrin."
J. Mol. Biol. 256:352-363(1996) [PubMed] [Europe PMC] [Abstract]

"Mutagenesis of the histidine ligand in human lactoferrin: iron binding properties and crystal structure of the histidine-253-->methionine mutant."
Biochemistry 36:341-346(1997) [PubMed] [Europe PMC] [Abstract]

"Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of ligand-induced conformational change."
Acta Crystallogr. D 54:1319-1335(1998) [PubMed] [Europe PMC] [Abstract]

"Structure of recombinant human lactoferrin expressed in Aspergillus awamori."
Acta Crystallogr. D 55:403-407(1999) [PubMed] [Europe PMC] [Abstract]

"Crystal structure and iron-binding properties of the R210K mutant of the N-lobe of human lactoferrin: implications for iron release from transferrins."
Biochemistry 39:6625-6633(2000) [PubMed] [Europe PMC] [Abstract]

"Metal substitution in transferrins: specific binding of cerium(IV) revealed by the crystal structure of cerium-substituted human lactoferrin."
J. Biol. Inorg. Chem. 5:692-698(2000) [PubMed] [Europe PMC] [Abstract]

"Structure of a domain-opened mutant (R121D) of the human lactoferrin N-lobe refined from a merohedrally twinned crystal form."
Acta Crystallogr. D 58:955-962(2002) [PubMed] [Europe PMC] [Abstract]

"'Dilysine trigger' in transferrins probed by mutagenesis of lactoferrin: crystal structures of the R210G, R210E, and R210L mutants of human lactoferrin."
Biochemistry 41:14167-14175(2002) [PubMed] [Europe PMC] [Abstract]

"Structure of human diferric lactoferrin at 2.5A resolution using crystals grown at pH 6.5."
Submitted (MAR-2004) to the PDB data bank

"Structural origin of endotoxin neutralization and antimicrobial activity of a lactoferrin-based peptide."
J. Biol. Chem. 280:16955-16961(2005) [PubMed] [Europe PMC] [Abstract]

"The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin."
Transgenic Res. 14:397-405(2005) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the complex formed between proteinase K and a human lactoferrin fragment at 2.9 A resolution."
Submitted (MAY-2006) to the PDB data bank

"Crystal structure of proteinase K inhibited by a lactoferrin octapeptide Gly-Asp-Glu-Gln-Gly-Glu-Asn-Lys at 2.15 A resolution."
Submitted (JUN-2006) to the PDB data bank

"The acyl group as the central element of the structural organization of antimicrobial lipopeptide."
J. Am. Chem. Soc. 129:1022-1023(2007) [PubMed] [Europe PMC] [Abstract]

"Structure of a complex of human lactoferrin N-lobe with pneumococcal surface protein a provides insight into microbial defense mechanism."
J. Mol. Biol. 370:701-713(2007) [PubMed] [Europe PMC] [Abstract]

"Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene."
Mol. Vis. 4:31-32(1998) [PubMed] [Europe PMC] [Abstract]

"Functional polymorphisms in the LTF gene and risk of coronary artery stenosis."
Hum. Immunol. 73:554-559(2012) [PubMed] [Europe PMC] [Abstract]