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MGP001846

UniProt Annotations

Entry Information
Gene Namelactotransferrin
Protein EntryTRFL_HUMAN
UniProt IDP02788
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative promoter usage; Named isoforms=2; Name=1; IsoId=P02788-1; Sequence=Displayed; Name=DeltaLf; Synonyms=Delta-lactoferrin; IsoId=P02788-2; Sequence=VSP_044308; Note=Contains a phosphoserine at position 10. Glycosylated at Ser-10. O-GlcNAcylation at Ser-10 inhibits DNA binding and negatively regulates DeltaLf transcriptional activity, whereas phosphorylation activates it. Phosphorylation at Ser-10 also promotes proteasomal degradation.;
Catalytic ActivityPreferential at -Arg-Ser-Arg-Arg-|- and -Arg- Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin.
FunctionIsoform 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.
FunctionKaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes.
FunctionLactoferricin 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.
FunctionLactoferroxins 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.
FunctionLactotransferrin 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.
FunctionThe 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.
FunctionTransferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.
InteractionP27958:- (xeno); NbExp=3; IntAct=EBI-1058602, EBI-6904259; P62157:CALM (xeno); NbExp=2; IntAct=EBI-1058602, EBI-397403;
Mass SpectrometryMass=5737.8; Method=Electrospray; Range=20-67; Evidence={ECO:0000269|PubMed:16048952};
PolymorphismThe sequence shown corresponds to the reference genome sequence and is likely to represent the minor allele, whereas most publications refer to the longer sequence containing variant Arg-22 ins. Insertion of the additional arginine in variant Arg-22 ins creates an N-terminal basic cluster of four arginines, all of which appear to be important for the full functionality of the protein, including bactericidal and antifungal activities as well as binding to glycosaminoglycans, pspA, LPS, lysozyme and DNA.
PtmIsoform DeltaLf: Ubiquitinated at Lys-379 and Lys-391.
PtmPoly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.
SimilarityBelongs to the transferrin family. {ECO:0000255|PROSITE-ProRule:PRU00741}.
SimilarityContains 2 transferrin-like domains. {ECO:0000255|PROSITE-ProRule:PRU00741}.
Subcellular LocationIsoform 1: Secreted. Cytoplasmic granule. Note=Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.
Subcellular LocationIsoform DeltaLf: Cytoplasm. Nucleus. Note=Mainly localized in the cytoplasm.
SubunitMonomer. Found in a complex with LTF, CLU, EPPIN and SEMG1. {ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299444, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:15687491, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:17567961, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.69, ECO:0000269|Ref.72, ECO:0000269|Ref.73}.
Tissue SpecificityHigh 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:0000269|PubMed:10792619, ECO:0000269|PubMed:2981589, ECO:0000269|PubMed:9122171}.
Web ResourceName=Wikipedia; Note=Lactotransferrin entry; URL="http://en.wikipedia.org/wiki/Lactotransferrin";
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