InnateDB Protein
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IDBP-30440.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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LTF
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Protein Name
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lactotransferrin
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Synonyms
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GIG12; HEL110; HLF2; LF;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000231751
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InnateDB Gene
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IDBG-30438 (LTF)
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Protein Structure
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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.
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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.
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Disease Associations |
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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}.
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Comments |
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Number of Interactions
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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]
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Protein-Protein |
21
[view]
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Protein-DNA |
6
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
3 [view]
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Molecular Function |
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Biological Process |
GO:0001503
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ossification
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GO:0001817
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regulation of cytokine production
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GO:0001895
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retina homeostasis
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GO:0002227
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innate immune response in mucosa
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GO:0006351
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transcription, DNA-templated
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GO:0006508
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proteolysis
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GO:0006826
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iron ion transport
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GO:0006879
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cellular iron ion homeostasis
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GO:0006959
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humoral immune response
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GO:0019731
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antibacterial humoral response
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GO:0019732
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antifungal humoral response
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GO:0031665
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negative regulation of lipopolysaccharide-mediated signaling pathway
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GO:0032680
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regulation of tumor necrosis factor production
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GO:0033214
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iron assimilation by chelation and transport
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GO:0033690
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positive regulation of osteoblast proliferation
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GO:0034145
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positive regulation of toll-like receptor 4 signaling pathway
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GO:0043066
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negative regulation of apoptotic process
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GO:0043123
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positive regulation of I-kappaB kinase/NF-kappaB signaling
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GO:0045669
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positive regulation of osteoblast differentiation
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GO:0051092
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positive regulation of NF-kappaB transcription factor activity
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GO:0051701
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interaction with host
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GO:0052572
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response to host immune response
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GO:0060349
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bone morphogenesis
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GO:0071902
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positive regulation of protein serine/threonine kinase activity
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GO:0090382
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phagosome maturation
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GO:1900159
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positive regulation of bone mineralization involved in bone maturation
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GO:1900229
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negative regulation of single-species biofilm formation in or on host organism
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GO:1902732
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positive regulation of chondrocyte proliferation
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GO:2000308
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negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
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GO:2001205
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negative regulation of osteoclast development
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Cellular Component |
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PDB ID |
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InterPro |
IPR001156
Transferrin-like domain
IPR016357
Transferrin
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PFAM |
PF00405
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PRINTS |
PR00422
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PIRSF |
PIRSF002549
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SMART |
SM00094
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TIGRFAMs |
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Modification |
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SwissProt |
P02788
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PhosphoSite |
PhosphoSite-P02788
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TrEMBL |
V9HWI4
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UniProt Splice Variant |
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Entrez Gene |
4057
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UniGene |
Hs.739670
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RefSeq |
NP_002334
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HUGO |
HGNC:6720
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OMIM |
150210
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CCDS |
CCDS33747
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HPRD |
01028
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IMGT |
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EMBL |
AC098613
AF332168
AK292813
AK298035
AY137470
AY165046
AY178998
AY493417
BC015822
BC015823
BC022347
EU622050
EU794669
M18642
M73700
M83202
M83205
M93150
S52659
U07643
U95626
X52941
X53961
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GenPept |
AAA36159
AAA58656
AAA59479
AAA59511
AAA86665
AAB24877
AAB57795
AAB60324
AAG48753
AAH15822
AAH15823
AAH22347
AAN11304
AAN63998
AAN75578
AAS72878
ACC95966
ACJ13723
BAF85502
BAH12708
CAA37116
CAA37914
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