O77811 · TRFL_HORSE
- ProteinLactotransferrin
- GeneLTF
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids695 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 66 | Fe3+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 79 | |||||
Sequence: K | ||||||
Binding site | 98 | Fe3+ 1 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 123 | hydrogencarbonate 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 127 | hydrogencarbonate 1 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 129 | hydrogencarbonate 1 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 130 | hydrogencarbonate 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 198 | Fe3+ 1 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 259 | Fe3+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Active site | 265 | Nucleophile | ||||
Sequence: S | ||||||
Binding site | 401 | Fe3+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 436 | D-glucose (UniProtKB | ChEBI) | ||||
Sequence: P | ||||||
Binding site | 439 | Fe3+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 465 | hydrogencarbonate 2 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 469 | hydrogencarbonate 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 471 | hydrogencarbonate 2 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 472 | hydrogencarbonate 2 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 532 | Fe3+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 600 | D-glucose (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 601 | Fe3+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 666 | D-glucose (UniProtKB | ChEBI) | ||||
Sequence: Y |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLactotransferrin
- EC number
- Short namesLactoferrin
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Perissodactyla > Equidae > Equus
Accessions
- Primary accessionO77811
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-6 | |||||
Sequence: LGLCLA | ||||||
Chain | PRO_0000035731 | 7-695 | Lactotransferrin | |||
Sequence: APRKSVRWCTISPAEAAKCAKFQRNMKKVRGPSVSCIRKTSSFECIQAIAANKADAVTLDGGLVYEAGLHPYKLRPVAAEVYQTRGKPQTRYYAVAVVKKGSGFQLNQLQGVKSCHTGLGRSAGWNIPIGTLRPYLNWTGPPEPLQKAVANFFSASCVPCADGKQYPNLCRLCAGTEADKCACSSQEPYFGYSGAFKCLENGAGDVAFVKDSTVFENLPDEADRDKYELLCPDNTRKPVDAFKECHLARVPSHAVVARSVDGREDLIWRLLHRAQEEFGRNKSSAFQLFKSTPENKDLLFKDSALGFVRIPSQIDSGLYLGANYLTATQNLRETAAEVAARRERVVWCAVGPEEERKCKQWSDVSNRKVACASASTTEECIALVLKGEADALNLDGGFIYVAGKCGLVPVLAENQKSQNSNAPDCVHRPPEGYLAVAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTECLAELQGKTTYEQYLGSEYVTSITNLRRCSSSPLLEACAFLRA | ||||||
Disulfide bond | 15↔51 | |||||
Sequence: CTISPAEAAKCAKFQRNMKKVRGPSVSCIRKTSSFEC | ||||||
Disulfide bond | 25↔42 | |||||
Sequence: CAKFQRNMKKVRGPSVSC | ||||||
Disulfide bond | 121↔204 | |||||
Sequence: CHTGLGRSAGWNIPIGTLRPYLNWTGPPEPLQKAVANFFSASCVPCADGKQYPNLCRLCAGTEADKCACSSQEPYFGYSGAFKC | ||||||
Glycosylation | 143 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 163↔179 | |||||
Sequence: CVPCADGKQYPNLCRLC | ||||||
Disulfide bond | 166↔189 | |||||
Sequence: CADGKQYPNLCRLCAGTEADKCAC | ||||||
Disulfide bond | 176↔187 | |||||
Sequence: CRLCAGTEADKC | ||||||
Disulfide bond | 237↔251 | |||||
Sequence: CPDNTRKPVDAFKEC | ||||||
Glycosylation | 287 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 354↔386 | |||||
Sequence: CAVGPEEERKCKQWSDVSNRKVACASASTTEEC | ||||||
Disulfide bond | 364↔377 | |||||
Sequence: CKQWSDVSNRKVAC | ||||||
Disulfide bond | 411↔690 | |||||
Sequence: CGLVPVLAENQKSQNSNAPDCVHRPPEGYLAVAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTECLAELQGKTTYEQYLGSEYVTSITNLRRCSSSPLLEAC | ||||||
Disulfide bond | 431↔653 | |||||
Sequence: CVHRPPEGYLAVAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTEC | ||||||
Disulfide bond | 463↔538 | |||||
Sequence: CHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRC | ||||||
Glycosylation | 482 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 487↔681 | |||||
Sequence: CKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTECLAELQGKTTYEQYLGSEYVTSITNLRRC | ||||||
Disulfide bond | 497↔511 | |||||
Sequence: CAPGADPQSSLCALC | ||||||
Disulfide bond | 508↔521 | |||||
Sequence: CALCVGNNENENKC | ||||||
Disulfide bond | 579↔593 | |||||
Sequence: CLDGTRKPVAEAESC | ||||||
Disulfide bond | 631↔636 | |||||
Sequence: CPGKFC |
Post-translational modification
Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-339 | Transferrin-like 1 | ||||
Sequence: VRWCTISPAEAAKCAKFQRNMKKVRGPSVSCIRKTSSFECIQAIAANKADAVTLDGGLVYEAGLHPYKLRPVAAEVYQTRGKPQTRYYAVAVVKKGSGFQLNQLQGVKSCHTGLGRSAGWNIPIGTLRPYLNWTGPPEPLQKAVANFFSASCVPCADGKQYPNLCRLCAGTEADKCACSSQEPYFGYSGAFKCLENGAGDVAFVKDSTVFENLPDEADRDKYELLCPDNTRKPVDAFKECHLARVPSHAVVARSVDGREDLIWRLLHRAQEEFGRNKSSAFQLFKSTPENKDLLFKDSALGFVRIPSQIDSGLYLGANYLTATQNLRE | ||||||
Domain | 351-680 | Transferrin-like 2 | ||||
Sequence: VVWCAVGPEEERKCKQWSDVSNRKVACASASTTEECIALVLKGEADALNLDGGFIYVAGKCGLVPVLAENQKSQNSNAPDCVHRPPEGYLAVAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKDVTVLQNTDGKNSEPWAKDLKQEDFELLCLDGTRKPVAEAESCHLARAPNHAVVSQSDRAQHLKKVLFLQQDQFGGNGPDCPGKFCLFKSETKNLLFNDNTECLAELQGKTTYEQYLGSEYVTSITNLRR |
Sequence similarities
Belongs to the transferrin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusFragment
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length695
- Mass (Da)75,991
- Last updated1998-11-01 v1
- Checksum07BB84D50E1B165D
Features
Showing features for non-terminal residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Non-terminal residue | 1 | |||||
Sequence: L |
Keywords
- Technical term