Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity, which depends on the extracellular cation concentration. 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. Can also prevent bacterial biofilm development in P.aeruginosa infection. Has weak antifungal activity against C.albicans. Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection. Can inhibit papillomavirus infections. Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with the lipopolysaccharide (LPS)-stimulated TLR4 signaling. Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells. Stimulates VEGFA-mediated endothelial cell migration and proliferation. Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs). Also binds specifically to pneumococcal surface protein A (pspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA. Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection. N-terminal region shows strong antifungal activity against C.albicans. Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site. Kaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes. Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors. The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity. Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites. Isoform DeltaLf: transcription factor with antiproliferative properties and ability to induce cell cycle arrest. Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters. Belongs to the transferrin family. High levels are found in saliva and tears, intermediate levels in serum and plasma, and low levels in urine. In kidney, detected in the distal collecting tubules in the medulla but not in the cortical region or in blood vessels. Detected in peripheral blood neutrophils (at protein level). Isoform 1 and isoform DeltaLf are expressed in breast, prostate, spleen, pancreas, kidney, small intestine, lung, skeletal muscle, uterus, thymus and fetal liver. Isoform 1 is expressed in brain, testis and peripheral blood leukocytes; isoform DeltaLf is barely detectable in these tissues. Isoform DeltaLf is expressed in placenta, liver and ovary; isoform 1 is barely detectable in these tissues. In kidney, isoform 1 is expressed at high levels in the collecting tubules of the medulla but at very low levels in the cortex. 2 human isoforms generated by alternative promoter usage have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 3.4.21.-; Protease; Secreted; Secreted, signal peptide
Cellular Component: cell surface; cytoplasm; extracellular region; extracellular space; other organism cell membrane; protein-containing complex; secretory granule; specific granule
Molecular Function: cysteine-type endopeptidase inhibitor activity; heparin binding; hydrolase activity; iron ion binding; lipopolysaccharide binding; metal ion binding; peptidase activity; protein serine/threonine kinase activator activity; serine-type endopeptidase activity; serine-type peptidase activity
Biological Process: antibacterial humoral response; antifungal humoral response; antimicrobial humoral immune response mediated by antimicrobial peptide; bone morphogenesis; defense response to Gram-negative bacterium; immune system process; innate immune response in mucosa; ion transport; iron ion homeostasis; killing of cells of other organism; membrane disruption in other organism; negative regulation by host of viral process; negative regulation of ATPase activity; negative regulation of cysteine-type endopeptidase activity; negative regulation of lipopolysaccharide-mediated signaling pathway; negative regulation of single-species biofilm formation in or on host organism; negative regulation of viral genome replication; negative regulation of viral process; ossification; 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; proteolysis; regulation of cytokine production; regulation of tumor necrosis factor production