InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LTF

Summary

InnateDB Protein

IDBP-374593.5

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

ENSP00000405719

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}.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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: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:0030141	secretory granule
GO:0042581	specific granule
GO:0070062	extracellular vesicular exosome
GO:0097013	phagocytic vesicle lumen