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Aliases for LTF Gene

Aliases for LTF Gene

  • Lactotransferrin 2 3
  • Growth-Inhibiting Protein 12 3 4
  • Talalactoferrin 3 4
  • GIG12 3 4
  • LF 3 4
  • Epididymis Luminal Protein 110 3
  • Neutrophil Lactoferrin 3
  • Lactoferricin 3
  • Lactoferroxin 3
  • Lactoferrin 4
  • EC 3.4.21.- 4
  • Kaliocin-1 3
  • EC 3.4.21 63
  • HEL110 3
  • HLF2 3

External Ids for LTF Gene

Summaries for LTF Gene

Entrez Gene Summary for LTF Gene

  • This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. Antimicrobial, antiviral, antifungal and antiparasitic activity has been found for this protein and its peptides. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

GeneCards Summary for LTF Gene

LTF (Lactotransferrin) is a Protein Coding gene. Diseases associated with LTF include clostridium difficile colitis and inflammatory diarrhea. Among its related pathways are Disease and RNA Polymerase I Promoter Opening. GO annotations related to this gene include serine-type endopeptidase activity and ferric iron binding. An important paralog of this gene is MFI2.

UniProtKB/Swiss-Prot for LTF Gene

  • 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

Gene Wiki entry for LTF Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LTF Gene

Genomics for LTF Gene

Genomic Location for LTF Gene

Start:
46,435,645 bp from pter
End:
46,485,234 bp from pter
Size:
49,590 bases
Orientation:
Minus strand

Genomic View for LTF Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for LTF Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LTF Gene

Regulatory Elements for LTF Gene

Proteins for LTF Gene

  • Protein details for LTF Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P02788-TRFL_HUMAN
    Recommended name:
    Lactotransferrin
    Protein Accession:
    P02788
    Secondary Accessions:
    • A8K9U8
    • B2MV13
    • B7Z4X2
    • E7EQH5
    • O00756
    • Q16780
    • Q16785
    • Q16786
    • Q16789
    • Q5DSM0
    • Q8IU92
    • Q8IZH6
    • Q8TCD2
    • Q96KZ4
    • Q96KZ5
    • Q9H1Z3
    • Q9UCY5

    Protein attributes for LTF Gene

    Size:
    710 amino acids
    Molecular mass:
    78182 Da
    Quaternary structure:
    • Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1.

    Three dimensional structures from OCA and Proteopedia for LTF Gene

    Alternative splice isoforms for LTF Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LTF Gene

Proteomics data for LTF Gene at MOPED

Post-translational modifications for LTF Gene

  • Isoform DeltaLf: Ubiquitinated at Lys-379 and Lys-391
  • Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn156, Asn497, and Asn642

Other Protein References for LTF Gene

Domains for LTF Gene

Protein Domains for LTF Gene

Graphical View of Domain Structure for InterPro Entry

P02788

UniProtKB/Swiss-Prot:

TRFL_HUMAN
Domain:
  • Contains 2 transferrin-like domains.:
    • P02788
Family:
  • Belongs to the transferrin family.:
    • P02788
genes like me logo Genes that share domains with LTF: view

No data available for Gene Families for LTF Gene

Function for LTF Gene

Molecular function for LTF Gene

GENATLAS Biochemistry: lactotransferrin,80kDa,iron binding protein present in milk and a variety of secretions derived from glandular epithelium cells,also expressed in secondary granules of neutrophils,involved in iron transport,storage and chelation,and host defense mechanisms
UniProtKB/Swiss-Prot CatalyticActivity: Preferential at -Arg-Ser-Arg-Arg- - and -Arg-Arg-Ser-Arg- -, and of Z-Phe-Arg- -aminomethylcoumarin
UniProtKB/Swiss-Prot Function: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate
UniProtKB/Swiss-Prot Function: 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
UniProtKB/Swiss-Prot Function: 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
UniProtKB/Swiss-Prot Function: Kaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes
UniProtKB/Swiss-Prot Function: 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
UniProtKB/Swiss-Prot Function: 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
UniProtKB/Swiss-Prot Function: 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

Enzyme Numbers (IUBMB) for LTF Gene

Gene Ontology (GO) - Molecular Function for LTF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0004252 serine-type endopeptidase activity IEA --
GO:0005506 iron ion binding IDA 12037568
GO:0005515 protein binding IPI 12522210
GO:0008199 ferric iron binding --
genes like me logo Genes that share ontologies with LTF: view
genes like me logo Genes that share phenotypes with LTF: view

Animal Models for LTF Gene

MGI Knock Outs for LTF:

No data available for miRNA , Transcription Factor Targeting and HOMER Transcription for LTF Gene

Localization for LTF Gene

Subcellular locations from UniProtKB/Swiss-Prot for LTF Gene

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.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for LTF Gene COMPARTMENTS Subcellular localization image for LTF gene
Compartment Confidence
extracellular 5
nucleus 5
lysosome 3
vacuole 3
cytoskeleton 2
plasma membrane 2
cytosol 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for LTF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 16502470
GO:0005634 nucleus IDA 21630459
GO:0005737 cytoplasm IMP 25193851
GO:0030141 secretory granule IDA 11907569
genes like me logo Genes that share ontologies with LTF: view

Pathways for LTF Gene

SuperPathways for LTF Gene

Superpath Contained pathways
1 Disease
2 RNA Polymerase I Promoter Opening
.68
genes like me logo Genes that share pathways with LTF: view

Pathways by source for LTF Gene

2 Reactome pathways for LTF Gene

Gene Ontology (GO) - Biological Process for LTF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001503 ossification IEA --
GO:0001817 regulation of cytokine production IDA 20345905
GO:0001895 retina homeostasis IEP 23580065
GO:0002227 innate immune response in mucosa IDA 12037568
GO:0006351 transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with LTF: view

Compounds for LTF Gene

(2) HMDB Compounds for LTF Gene

Compound Synonyms Cas Number PubMed IDs
Hydrogen carbonate
  • Bicarbonate
71-52-3
Iron
  • Armco iron
7439-89-6

(7) Drugbank Compounds for LTF Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
2-(4-(2-HYDROXY-3-(ISOPROPYLAMINO)PROPOXY)PHENYL)ETHANAMIDE
target
3h-Indole-5,6-Diol
3131-52-0 target
Alpha-D-Fucose
target
Alpha-D-Mannose
3458-28-4 target
Nimesulide
51803-78-2 target

(151) Novoseek inferred chemical compound relationships for LTF Gene

Compound -log(P) Hits PubMed IDs
iron 79.1 333
whey 70.6 47
l-bpa 68.5 6
ipabc 68.4 3
hypothiocyanite 67.1 9
genes like me logo Genes that share compounds with LTF: view

Transcripts for LTF Gene

Unigene Clusters for LTF Gene

Lactotransferrin:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for LTF Gene

No ASD Table

Relevant External Links for LTF Gene

GeneLoc Exon Structure for
LTF
ECgene alternative splicing isoforms for
LTF

Expression for LTF Gene

mRNA expression in normal human tissues for LTF Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for LTF Gene

This gene is overexpressed in Minor Salivary Gland (18.9), Whole Blood (13.3), Kidney - Cortex (6.1), and Breast - Mammary Tissue (4.5).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for LTF Gene

SOURCE GeneReport for Unigene cluster for LTF Gene Hs.529517

mRNA Expression by UniProt/SwissProt for LTF Gene

P02788-TRFL_HUMAN
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.
genes like me logo Genes that share expressions with LTF: view

Orthologs for LTF Gene

This gene was present in the common ancestor of animals.

Orthologs for LTF Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LTF 35
  • 98.83 (n)
  • 98.03 (a)
LTF 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia LTF 35
  • 77.44 (n)
  • 69.86 (a)
LTF 36
  • 70 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LTF 35
  • 80.46 (n)
  • 73.87 (a)
LTF 36
  • 74 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ltf 35
  • 76.53 (n)
  • 71.57 (a)
Ltf 16
Ltf 36
  • 71 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 58 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 58 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Ltf 35
  • 71.79 (n)
  • 62.66 (a)
chicken
(Gallus gallus)
Aves TF 36
  • 51 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 51 (a)
OneToMany
African clawed frog
(Xenopus laevis)
Amphibia MGC64306 35
zebrafish
(Danio rerio)
Actinopterygii -- 35
tfa 36
  • 41 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Tsf2 36
  • 26 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.4617 36
  • 29 (a)
ManyToMany
Species with no ortholog for LTF:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for LTF Gene

ENSEMBL:
Gene Tree for LTF (if available)
TreeFam:
Gene Tree for LTF (if available)

Paralogs for LTF Gene

Paralogs for LTF Gene

Selected SIMAP similar genes for LTF Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with LTF: view

Variants for LTF Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for LTF Gene

P02788-TRFL_HUMAN
The 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

Sequence variations from dbSNP and Humsavar for LTF Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type MAF
rs9110 -- 46,439,310(-) AGGTG(A/C/G/T)TGCTC missense, synonymous-codon, reference
rs17135 -- 46,454,226(+) GGAAT(C/T)TAATT intron-variant
rs743658 -- 46,446,997(+) GGCCC(A/G)AGAGC intron-variant
rs743659 -- 46,447,524(-) TTGAA(C/T)AGTCC intron-variant
rs762787 -- 46,447,445(+) CATCC(C/T)GTCCT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for LTF Gene

Variant ID Type Subtype PubMed ID
esv2725234 CNV Deletion 23290073

Relevant External Links for LTF Gene

HapMap Linkage Disequilibrium report
LTF
Human Gene Mutation Database (HGMD)
LTF

Disorders for LTF Gene

(98) Novoseek inferred disease relationships for LTF Gene

Disease -log(P) Hits PubMed IDs
specific granule deficiency 72.2 3
inflammation 58.6 134
colitis ulcerative 58.1 40
inflammatory bowel diseases 51.4 39
amyloidosis, corneal 50.3 1

Relevant External Links for LTF

Genetic Association Database (GAD)
LTF
Human Genome Epidemiology (HuGE) Navigator
LTF
genes like me logo Genes that share disorders with LTF: view

No data available for UniProtKB/Swiss-Prot for LTF Gene

Publications for LTF Gene

  1. Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. (PMID: 9122171) Siebert P.D. … Huang B.C. (Proc. Natl. Acad. Sci. U.S.A. 1997) 3 4 23
  2. N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. (PMID: 9359845) van Berkel P.H. … Nuijens J.H. (Biochem. J. 1997) 3 4 23
  3. Identification of the bactericidal domain of lactoferrin. (PMID: 1599934) Bellamy W. … Tomita M. (Biochim. Biophys. Acta 1992) 3 4 23
  4. Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene. (PMID: 9873069) Klintworth G.K. … Teng C.T. (Mol. Vis. 1998) 3 4 23
  5. Candidacidal activities of human lactoferrin peptides derived from the N terminus. (PMID: 11083624) Lupetti A. … Nibbering P.H. (Antimicrob. Agents Chemother. 2000) 3 4 23

Products for LTF Gene

Sources for LTF Gene

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