Homo sapiens Protein: LTF
InnateDB Protein IDBP-30440.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol LTF
Protein Name lactotransferrin
Synonyms GIG12; HEL110; HLF2; LF;
Species Homo sapiens
Ensembl Protein ENSP00000231751
InnateDB Gene IDBG-30438 (LTF)
Protein Structure
UniProt Annotation
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 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.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 SELH promoters.
Subcellular Localization Isoform 1: Secreted. Cytoplasmic granule. Note=Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.Isoform DeltaLf: Cytoplasm. Nucleus. Note=Mainly localized in the cytoplasm.
Disease Associations
Tissue Specificity 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. {ECO:0000269PubMed:10792619, ECO:0000269PubMed:2981589, ECO:0000269PubMed:9122171}.
Number of Interactions This gene and/or its encoded proteins are associated with 27 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 27 [view]
Protein-Protein 21 [view]
Protein-DNA 6 [view]
Protein-RNA 0
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0004252 serine-type endopeptidase activity
GO:0005506 iron ion binding
GO:0005515 protein binding
GO:0008199 ferric iron binding
GO:0008201 heparin binding
GO:0008233 peptidase activity
GO:0043539 protein serine/threonine kinase activator activity
Biological Process
GO:0001503 ossification
GO:0001817 regulation of cytokine production
GO:0001895 retina homeostasis
GO:0002227 innate immune response in mucosa
GO:0006351 transcription, DNA-templated
GO:0006508 proteolysis
GO:0006826 iron ion transport
GO:0006879 cellular iron ion homeostasis
GO:0006959 humoral immune response
GO:0019731 antibacterial humoral response
GO:0019732 antifungal humoral response
GO:0031665 negative regulation of lipopolysaccharide-mediated signaling pathway
GO:0032680 regulation of tumor necrosis factor production
GO:0033214 iron assimilation by chelation and transport
GO:0033690 positive regulation of osteoblast proliferation
GO:0034145 positive regulation of toll-like receptor 4 signaling pathway
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045669 positive regulation of osteoblast differentiation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051701 interaction with host
GO:0052572 response to host immune response
GO:0060349 bone morphogenesis
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090382 phagosome maturation
GO:1900159 positive regulation of bone mineralization involved in bone maturation
GO:1900229 negative regulation of single-species biofilm formation in or on host organism
GO:1902732 positive regulation of chondrocyte proliferation
GO:2000308 negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
GO:2001205 negative regulation of osteoclast development
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0030141 secretory granule
GO:0042581 specific granule
GO:0070062 extracellular vesicular exosome
GO:0097013 phagocytic vesicle lumen
Protein Structure and Domains
InterPro IPR001156 Transferrin-like domain
IPR016357 Transferrin
PFAM PF00405
Post-translational Modifications
SwissProt P02788
PhosphoSite PhosphoSite-P02788
UniProt Splice Variant
Entrez Gene 4057
UniGene Hs.739670
RefSeq NP_002334
OMIM 150210
HPRD 01028
EMBL AC098613 AF332168 AK292813 AK298035 AY137470 AY165046 AY178998 AY493417 BC015822 BC015823 BC022347 EU622050 EU794669 M18642 M73700 M83202 M83205 M93150 S52659 U07643 U95626 X52941 X53961
GenPept AAA36159 AAA58656 AAA59479 AAA59511 AAA86665 AAB24877 AAB57795 AAB60324 AAG48753 AAH15822 AAH15823 AAH22347 AAN11304 AAN63998 AAN75578 AAS72878 ACC95966 ACJ13723 BAF85502 BAH12708 CAA37116 CAA37914