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    LTF lactotransferrin [ Homo sapiens (human) ]

    Gene ID: 4057, updated on 3-Nov-2024

    Summary

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    Official Symbol
    LTFprovided by HGNC
    Official Full Name
    lactotransferrinprovided by HGNC
    Primary source
    HGNC:HGNC:6720
    See related
    Ensembl:ENSG00000012223 MIM:150210; AllianceGenome:HGNC:6720
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LF; HLF2; GIG12; HEL110
    Summary
    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. Activity against both DNA and RNA viruses has been found, including activity against SARS-CoV-2, and HIV. [provided by RefSeq, Jul 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Biased expression in bone marrow (RPKM 1214.2), salivary gland (RPKM 176.0) and 2 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LTF in Genome Data Viewer
    Location:
    3p21.31
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (46435645..46485234, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (46451475..46501054, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (46477136..46526724, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene C-C motif chemokine receptor like 2 Neighboring gene long intergenic non-protein coding RNA 2009 Neighboring gene Sharpr-MPRA regulatory region 12992 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46484307-46484808 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:46491889-46492388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46497203-46497704 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46497705-46498204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46511713-46512212 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:46519415-46519916 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:46519917-46520416 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46530070-46530846 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:46530847-46531621 Neighboring gene receptor transporter protein 3 Neighboring gene Sharpr-MPRA regulatory region 6156 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:46561999-46563198 Neighboring gene leucine rich repeat containing 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19797 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:46585952-46586496 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:46598181-46598782 Neighboring gene LRRC2 antisense RNA 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Risk of nasopharyngeal carcinoma associated with polymorphic lactotransferrin haplotypes. Zhou Y, et al. Med Oncol, 2012 Sep. PMID 22011934
    2. Crystal structure of human seminal diferric lactoferrin at 3.4 Angstrom resolution. Kumar J, et al. Indian J Biochem Biophys, 2003 Feb. PMID 22900286
    3. Human lactoferrin increases Helicobacter pylori internalisation into AGS cells. Coray DS, et al. World J Microbiol Biotechnol, 2012 May. PMID 22806010
    4. Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients. Waszkiewicz N, et al. Folia Histochem Cytobiol, 2012 Jul 4. PMID 22763972
    5. Lactoferrin regulates an axis involving CD11b and CD49d integrins and the chemokines MIP-1α and MCP-1 in GM-CSF-treated human primary eosinophils. Curran CS, et al. J Interferon Cytokine Res, 2012 Oct. PMID 22731992, Free PMC Article

    See all (407) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma.
      Title: METTL16-SENP3-LTF axis confers ferroptosis resistance and facilitates tumorigenesis in hepatocellular carcinoma.
    2. Association between LTF/MMP20/CA6/TAS1R2 polymorphisms and susceptibility to dental caries.
      Title: Association between LTF/MMP20/CA6/TAS1R2 polymorphisms and susceptibility to dental caries.
    3. Lactoferrin mediates epithelial-mesenchymal transformation by regulating the PI3K/AKT/mTOR pathway to inhibit nasopharyngeal carcinoma metastasis.
      Title: Lactoferrin mediates epithelial-mesenchymal transformation by regulating the PI3K/AKT/mTOR pathway to inhibit nasopharyngeal carcinoma metastasis.
    4. Ceruloplasmin Reduces the Lactoferrin/Oleic Acid Antitumor Complex-Mediated Release of Heme-Containing Proteins from Blood Cells.
      Title: Ceruloplasmin Reduces the Lactoferrin/Oleic Acid Antitumor Complex-Mediated Release of Heme-Containing Proteins from Blood Cells.
    5. Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures.
      Title: Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures.
    6. Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.
      Title: Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.
    7. The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.
      Title: The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.
    8. Evaluation of faecal lactoferrin as a morbidity biomarker in Schistosoma mansoni infection.
      Title: Evaluation of faecal lactoferrin as a morbidity biomarker in Schistosoma mansoni infection.
    9. The Lactoferrin Phenomenon-A Miracle Molecule.
      Title: The Lactoferrin Phenomenon-A Miracle Molecule.
    10. Lactoferrin as a Human Genome ""Guardian""-An Overall Point of View.
      Title: Lactoferrin as a Human Genome "Guardian"-An Overall Point of View.
    Submit: New GeneRIF Correction See all GeneRIFs (219)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study implicates PARD3B-based AIDS restriction.
    EBI GWAS Catalog
    Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 is inhibited by TNC (tenascin C), MUC1, and LTF (lactoferrin) as shown through neutralization assays in TZM-bl cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Native lactoferrin (LF) and acylated LF from milk strongly bind to the V3 domain of the HIV-1 envelope protein gp120, resulting in inhibition of the virus-cell fusion and entry of the virus in CD4+ cells PubMed
    reverse transcriptase gag-pol A peptide derived from human lactoferricin inhibits HIV-1 RT activity in a dose-dependent manner PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cysteine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables heparin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables iron ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables lipopolysaccharide binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables lipopolysaccharide binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables membrane destabilizing activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in antibacterial humoral response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in antibacterial humoral response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in antifungal humoral response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in antimicrobial humoral immune response mediated by antimicrobial peptide IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in bone morphogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cytolysis by host of symbiont cells IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in defense response to Gram-negative bacterium IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in defense response to Gram-positive bacterium IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in humoral immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in innate immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in innate immune response in mucosa IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in iron ion transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in killing of cells of another organism IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in killing of cells of another organism IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation by host of viral process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of ATP-dependent activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of lipopolysaccharide-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of membrane potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of osteoclast development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of single-species biofilm formation in or on host organism IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of tumor necrosis factor (ligand) superfamily member 11 production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of viral process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of bone mineralization involved in bone maturation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of chondrocyte proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of osteoblast differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of osteoblast proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of toll-like receptor 4 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cytokine production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of tumor necrosis factor production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in early endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus HDA PubMed 
    located_in phagocytic vesicle lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in recycling endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in secretory granule IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in specific granule IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in specific granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in tertiary granule lumen TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    lactotransferrin
    Names
    epididymis luminal protein 110
    growth-inhibiting protein 12
    kaliocin-1
    lactoferricin
    lactoferroxin
    neutrophil lactoferrin
    talalactoferrin
    NP_001186078.1
    NP_001308050.1
    NP_001308051.1
    NP_002334.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_023257.2 RefSeqGene

      Range
      25330..54590
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001199149.2 → NP_001186078.1  lactotransferrin isoform 2

      See identical proteins and their annotated locations for NP_001186078.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as delta LF) represents use of an alternate promoter and initiates translation at a downstream start codon compared to variant 1. The resulting isoform (2) has a shorter N-terminus than isoform 1.
      Source sequence(s)
      AC098613, AK298035, BC015822
      Consensus CDS
      CCDS56251.1
      UniProtKB/TrEMBL
      B7ZAL5
      Related
      ENSP00000405719.2, ENST00000426532.6
      Conserved Domains (4) summary
      smart00094
      Location:320 → 651
      TR_FER; Transferrin
      cd13617
      Location:317 → 650
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:1 → 307
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:1 → 308
      Transferrin; Transferrin

    2. NM_001321121.2 → NP_001308050.1  lactotransferrin isoform 3 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AC098613, AY360320, BP342557, EU794669, X52941
      Consensus CDS
      CCDS82763.1
      UniProtKB/TrEMBL
      A0A161I202, E7ER44
      Related
      ENSP00000405546.1, ENST00000417439.5
      Conserved Domains (4) summary
      smart00094
      Location:364 → 693
      TR_FER; Transferrin
      cd13617
      Location:361 → 692
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:24 → 351
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:25 → 352
      Transferrin; Transferrin

    3. NM_001321122.2 → NP_001308051.1  lactotransferrin isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' exon structure and initiates translation at an alternate start codon compared to variant 1. The encoded isoform (4) has a distinct, shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC098613, AK093852, EU794669, X52941
      UniProtKB/TrEMBL
      E7EQB2
      Related
      ENSP00000397427.1, ENST00000443496.5
      Conserved Domains (4) summary
      smart00094
      Location:351 → 682
      TR_FER; Transferrin
      cd13617
      Location:348 → 681
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:11 → 338
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:12 → 339
      Transferrin; Transferrin

    4. NM_002343.6 → NP_002334.2  lactotransferrin isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_002334.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC098613, BP342557, EU794669, X52941
      Consensus CDS
      CCDS33747.1
      UniProtKB/Swiss-Prot
      A8K9U8, B2MV13, B7Z4X2, E7EQH5, O00756, P02788, Q16780, Q16785, Q16786, Q16789, Q5DSM0, Q8IU92, Q8IZH6, Q8TCD2, Q96KZ4, Q96KZ5, Q9H1Z3, Q9UCY5
      UniProtKB/TrEMBL
      A0A161I202, V9HWI4
      Related
      ENSP00000231751.4, ENST00000231751.9
      Conserved Domains (4) summary
      smart00094
      Location:364 → 695
      TR_FER; Transferrin
      cd13617
      Location:361 → 694
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:24 → 351
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:25 → 352
      Transferrin; Transferrin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      46435645..46485234 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      46451475..46501054 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P02788.6 GenPept UniProtKB/Swiss-Prot:P02788

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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