LTF
This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. Antimicrobial, antiviral, antifungal and antiparasitic activity has been found for this protein and its peptides. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
Function
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.
Lactotransferrin
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 the lipopolysaccharide (LPS)-stimulated TLR4 signaling (PubMed:20345905).
Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells (PubMed:19033648).
Stimulates VEGFA-mediated endothelial cell migration and proliferation (PubMed:16842782).
Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs) (PubMed:9359845).
Also binds specifically to pneumococcal surface protein A (PspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA (PubMed:9359845).
Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection (PubMed:17481742).
N-terminal region shows strong antifungal activity against C.albicans (PubMed:11083624).
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.
Lactoferroxin-A
Has opioid antagonist activity (PubMed:1369293).
Shows preference for mu-receptor (PubMed:1369293).
Lactoferroxin-B
Has opioid antagonist activity (PubMed:1369293).
Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293).
Lactoferroxin-C
Has opioid antagonist activity (PubMed:1369293).
Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293).
The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions (PubMed:12535064).
This function contributes to the antimicrobial activity (PubMed:12535064).
Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites (PubMed:12535064).
Isoform DeltaLf
Transcription factor with antiproliferative properties and ability to induce cell cycle arrest (PubMed:15222485).
Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters (PubMed:22320386).
Biological Process
Antibacterial humoral responseManual Assertion Based On ExperimentIDA:UniProtKB
Antifungal humoral responseManual Assertion Based On ExperimentIDA:UniProtKB
Antimicrobial humoral immune response mediated by antimicrobial peptideManual Assertion Based On ExperimentIMP:UniProtKB
Bone morphogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Defense response to Gram-negative bacteriumManual Assertion Based On ExperimentIMP:UniProtKB
Defense response to Gram-positive bacteriumIMP:UniProtKB
Humoral immune responseManual Assertion Based On ExperimentTAS:ProtInc
Innate immune responseIMP:UniProtKB
Innate immune response in mucosaManual Assertion Based On ExperimentIDA:UniProtKB
Iron ion homeostasisIEA:UniProtKB-KW
Iron ion transportManual Assertion Based On ExperimentIBA:GO_Central
Killing of cells of another organismManual Assertion Based On ExperimentIDA:UniProtKB
Membrane disruption in another organismManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation by host of viral processManual Assertion Based On ExperimentIMP:AgBase
Negative regulation of apoptotic processISS:UniProtKB
Negative regulation of ATP-dependent activityManual Assertion Based On ExperimentIMP:AgBase
Negative regulation of cysteine-type endopeptidase activityManual Assertion Based On ExperimentIDA:CAFA
Negative regulation of lipopolysaccharide-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of membrane potentialIMP:UniProtKB
Negative regulation of osteoclast developmentISS:UniProtKB
Negative regulation of single-species biofilm formation in or on host organismManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of tumor necrosis factor (ligand) superfamily member 11 productionISS:UniProtKB
Negative regulation of viral genome replicationManual Assertion Based On ExperimentIMP:AgBase
Negative regulation of viral processManual Assertion Based On ExperimentIMP:AgBase
OssificationIEA:UniProtKB-KW
Positive regulation of bone mineralization involved in bone maturationISS:UniProtKB
Positive regulation of chondrocyte proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of osteoblast differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of osteoblast proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of toll-like receptor 4 signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cytokine productionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:UniProtKB
Retina homeostasisManual Assertion Based On ExperimentHEP:UniProtKB
PTM
Isoform DeltaLf
Phosphorylation at Ser-10 activates the transcriptional activity (PubMed:20404350).
Phosphorylation at Ser-10 also promotes proteasomal degradation (PubMed:20404350).
Alternatively can undergo O-GlcNAcylation at Ser-10 (PubMed:20404350).
Isoform DeltaLf
O-GlcNAcylation at Ser-10 inhibits DNA binding and negatively regulates the transcriptional activity (PubMed:20404350).
Alternatively can undergo phosphorylation at Ser-10 (PubMed:20404350).
Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.
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Datasheet