O77811 · TRFL_HORSE

Function

function

Transferrins are iron binding transport proteins which can bind two Fe3+ 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. 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.
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.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site66Fe3+ 1 (UniProtKB | ChEBI)
Active site79
Binding site98Fe3+ 1 (UniProtKB | ChEBI)
Binding site123hydrogencarbonate 1 (UniProtKB | ChEBI)
Binding site127hydrogencarbonate 1 (UniProtKB | ChEBI)
Binding site129hydrogencarbonate 1 (UniProtKB | ChEBI)
Binding site130hydrogencarbonate 1 (UniProtKB | ChEBI)
Binding site198Fe3+ 1 (UniProtKB | ChEBI)
Binding site259Fe3+ 1 (UniProtKB | ChEBI)
Active site265Nucleophile
Binding site401Fe3+ 2 (UniProtKB | ChEBI)
Binding site436D-glucose (UniProtKB | ChEBI)
Binding site439Fe3+ 2 (UniProtKB | ChEBI)
Binding site465hydrogencarbonate 2 (UniProtKB | ChEBI)
Binding site469hydrogencarbonate 2 (UniProtKB | ChEBI)
Binding site471hydrogencarbonate 2 (UniProtKB | ChEBI)
Binding site472hydrogencarbonate 2 (UniProtKB | ChEBI)
Binding site532Fe3+ 2 (UniProtKB | ChEBI)
Binding site600D-glucose (UniProtKB | ChEBI)
Binding site601Fe3+ 2 (UniProtKB | ChEBI)
Binding site666D-glucose (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentearly endosome
Cellular Componentextracellular space
Cellular Componentplasma membrane
Cellular Componentrecycling endosome
Cellular Componentspecific granule
Molecular Functionmetal ion binding
Molecular Functionserine-type peptidase activity
Biological Processantibacterial humoral response
Biological Processantifungal humoral response
Biological Processbone morphogenesis
Biological Processinnate immune response in mucosa
Biological Processiron ion transport
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of lipopolysaccharide-mediated signaling pathway
Biological Processnegative regulation of osteoclast development
Biological Processnegative regulation of single-species biofilm formation in or on host organism
Biological Processnegative regulation of tumor necrosis factor (ligand) superfamily member 11 production
Biological Processossification
Biological Processpositive regulation of bone mineralization involved in bone maturation
Biological Processpositive regulation of chondrocyte proliferation
Biological Processpositive regulation of osteoblast differentiation
Biological Processpositive regulation of osteoblast proliferation
Biological Processproteolysis
Biological Processregulation of cytokine production
Biological Processregulation of tumor necrosis factor production

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Lactotransferrin
  • EC number
  • Short names
    Lactoferrin

Gene names

    • Name
      LTF

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Perissodactyla > Equidae > Equus

Accessions

  • Primary accession
    O77811

Proteomes

Subcellular Location

Cytoplasmic granule
Note: Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils (By similarity).

Keywords

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-6
ChainPRO_00000357317-695Lactotransferrin
Disulfide bond15↔51
Disulfide bond25↔42
Disulfide bond121↔204
Glycosylation143N-linked (GlcNAc...) asparagine
Disulfide bond163↔179
Disulfide bond166↔189
Disulfide bond176↔187
Disulfide bond237↔251
Glycosylation287N-linked (GlcNAc...) asparagine
Disulfide bond354↔386
Disulfide bond364↔377
Disulfide bond411↔690
Disulfide bond431↔653
Disulfide bond463↔538
Glycosylation482N-linked (GlcNAc...) asparagine
Disulfide bond487↔681
Disulfide bond497↔511
Disulfide bond508↔521
Disulfide bond579↔593
Disulfide bond631↔636

Post-translational modification

Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.

Keywords

Proteomic databases

PTM databases

Interaction

Subunit

Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1. Found in a complex with MPO and LTF; interacts directly with CP, allows Fe3+ incorporation into LTF and activation of CP ferroxidase activity.

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain12-339Transferrin-like 1
Domain351-680Transferrin-like 2

Sequence similarities

Belongs to the transferrin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Fragment
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    695
  • Mass (Da)
    75,991
  • Last updated
    1998-11-01 v1
  • Checksum
    07BB84D50E1B165D
LGLCLAAPRKSVRWCTISPAEAAKCAKFQRNMKKVRGPSVSCIRKTSSFECIQAIAANKADAVTLDGGLVYEAGLHPYKLRPVAAEVYQTRGKPQTRYYAVAVVKKGSGFQLNQLQGVKSCHTGLGRSAGWNIPIGTLRPYLNWTGPPEPLQKAVANFFSASCVPCADGKQYPNLCRLCAGTEADKCACSSQEPYFGYSGAFKCLENGAGDVAFVKDSTVFENLPDEADRDKYELLCPDNTRKPVDAFKECHLARVPSHAVVARSVDGREDLIWRLLHRAQEEFGRNKSSAFQLFKSTPENKDLLFKDSALGFVRIPSQIDSGLYLGANYLTATQNLRETAAEVAARRERVVWCAVGPEEERKCKQWSDVSNRKVACASASTTEECIALVLKGEADALNLDGGFIYVAGKCGLVPVLAENQKSQNSNAPDCVHRPPEGYLAVAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTECLAELQGKTTYEQYLGSEYVTSITNLRRCSSSPLLEACAFLRA

Features

Showing features for non-terminal residue.

TypeIDPosition(s)Description
Non-terminal residue1

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AJ010930
EMBL· GenBank· DDBJ
CAA09407.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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