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    LTF lactotransferrin [ Homo sapiens (human) ]

    Gene ID: 4057, updated on 15-Apr-2019

    Summary

    Official Symbol
    LTFprovided by HGNC
    Official Full Name
    lactotransferrinprovided by HGNC
    Primary source
    HGNC:HGNC:6720
    See related
    Ensembl:ENSG00000012223 MIM:150210
    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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
    Expression
    Biased expression in bone marrow (RPKM 1214.2), salivary gland (RPKM 176.0) and 2 other tissues See more
    Orthologs

    Genomic context

    See LTF in Genome Data Viewer
    Location:
    3p21.31
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (46436005..46485234, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (46477496..46506598, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2009 Neighboring gene C-C motif chemokine receptor like 2 Neighboring gene receptor transporter protein 3 Neighboring gene leucine rich repeat containing 2 Neighboring gene LRRC2 antisense RNA 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    NHGRI GWAS Catalog

    Description
    Genome-wide association study implicates PARD3B-based AIDS restriction.
    NHGRI GWA 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.
    NHGRI GWA Catalog

    HIV-1 interactions

    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 BioSystems

    • Amyloid fiber formation, organism-specific biosystem (from REACTOME)
      Amyloid fiber formation, organism-specific biosystemAmyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloi...
    • Antimicrobial peptides, organism-specific biosystem (from REACTOME)
      Antimicrobial peptides, organism-specific biosystemAntimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majo...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Infectious disease, organism-specific biosystem (from REACTOME)
      Infectious disease, organism-specific biosystem
      Infectious disease
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystem (from REACTOME)
      Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystemInfection by Mycobacterium tuberculosis (Mtb) is soon countered by the host's immune system, the organism is however almost never eradicated; ten per cent of infections will develop into "open tuberc...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Metal sequestration by antimicrobial proteins, organism-specific biosystem (from REACTOME)
      Metal sequestration by antimicrobial proteins, organism-specific biosystemMetals are necessary for all forms of life including microorganisms, evidenced by the fact that metal cations are constituents of approximately 40% of all proteins crystallized to date (Waldron KJ et...
    • Mtb iron assimilation by chelation, organism-specific biosystem (from REACTOME)
      Mtb iron assimilation by chelation, organism-specific biosystemUptake of iron in Mtb, especially when the bacterium is in the host, strongly depends on siderophores. Humans, through secretion of lactoferrin, maintain an iron concentration of 10^(-18) M within ma...
    • Neutrophil degranulation, organism-specific biosystem (from REACTOME)
      Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
    • Response of Mtb to phagocytosis, organism-specific biosystem (from REACTOME)
      Response of Mtb to phagocytosis, organism-specific biosystemMtb encounters a vastly changed environment, soon after it gets internalized by macrophages. The compartment it resides in, the phagosome, is acidified and devoid of important metal ions. It is flood...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    cysteine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    heparin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    iron ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    lipopolysaccharide binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    serine-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    antibacterial humoral response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antifungal humoral response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antimicrobial humoral immune response mediated by antimicrobial peptide IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    antimicrobial humoral response TAS
    Traceable Author Statement
    more info
     
    bone morphogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular protein metabolic process TAS
    Traceable Author Statement
    more info
     
    defense response to Gram-negative bacterium IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    humoral immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    innate immune response in mucosa IDA
    Inferred from Direct Assay
    more info
    PubMed 
    iron assimilation by chelation and transport TAS
    Traceable Author Statement
    more info
     
    killing of cells of other organism IDA
    Inferred from Direct Assay
    more info
    PubMed 
    killing of cells of other organism IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    membrane disruption in other organism IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation by host of viral process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of ATPase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of lipopolysaccharide-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of osteoclast development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of single-species biofilm formation in or on host organism IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of tumor necrosis factor (ligand) superfamily member 11 production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of viral process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    neutrophil degranulation TAS
    Traceable Author Statement
    more info
     
    ossification IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of bone mineralization involved in bone maturation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of chondrocyte proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of osteoblast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of osteoblast proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of toll-like receptor 4 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    proteolysis IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of cytokine production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of tumor necrosis factor production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    retina homeostasis HEP PubMed 
    Component Evidence Code Pubs
    cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasm IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    extracellular exosome HDA PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space HDA PubMed 
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleus HDA PubMed 
    other organism cell membrane IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    phagocytic vesicle lumen TAS
    Traceable Author Statement
    more info
     
    protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    secretory granule IDA
    Inferred from Direct Assay
    more info
    PubMed 
    specific granule IDA
    Inferred from Direct Assay
    more info
    PubMed 
    specific granule lumen TAS
    Traceable Author Statement
    more info
     
    tertiary granule lumen TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    lactotransferrin
    Names
    epididymis luminal protein 110
    growth-inhibiting protein 12
    kaliocin-1
    lactoferricin
    lactoferroxin
    neutrophil lactoferrin
    talalactoferrin

    NCBI Reference Sequences (RefSeq)

    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
      25072..54230
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001199149.1NP_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)
      AK298035, BC015822
      Consensus CDS
      CCDS56251.1
      UniProtKB/Swiss-Prot
      P02788
      Related
      ENSP00000405719.2, ENST00000426532.6
      Conserved Domains (4) summary
      smart00094
      Location:320651
      TR_FER; Transferrin
      cd13617
      Location:317650
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:1307
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:1308
      Transferrin; Transferrin
    2. NM_001321121.1NP_001308050.1  lactotransferrin isoform 3 preproprotein

      Status: REVIEWED

      Source sequence(s)
      AY360320, BP342557, EU794669, X52941, X53961
      Consensus CDS
      CCDS82763.1
      UniProtKB/Swiss-Prot
      P02788
      UniProtKB/TrEMBL
      E7ER44, Q2TUW9, V9HWI4
      Related
      ENSP00000405546.1, ENST00000417439.5
      Conserved Domains (4) summary
      smart00094
      Location:364693
      TR_FER; Transferrin
      cd13617
      Location:361692
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:24351
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:25352
      Transferrin; Transferrin
    3. NM_001321122.1NP_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/Swiss-Prot
      P02788
      UniProtKB/TrEMBL
      B3KSL2, V9HWI4
      Related
      ENSP00000397427.1, ENST00000443496.5
      Conserved Domains (4) summary
      smart00094
      Location:351682
      TR_FER; Transferrin
      cd13617
      Location:348681
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:11338
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:12339
      Transferrin; Transferrin
    4. NM_002343.5NP_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)
      BP342557, EU794669, X52941, X53961
      Consensus CDS
      CCDS33747.1
      UniProtKB/Swiss-Prot
      P02788
      UniProtKB/TrEMBL
      V9HWI4
      Related
      ENSP00000231751.4, ENST00000231751.8
      Conserved Domains (4) summary
      smart00094
      Location:364695
      TR_FER; Transferrin
      cd13617
      Location:361694
      PBP2_transferrin_C; The C-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      cd13618
      Location:24351
      PBP2_transferrin_N; The N-lobe of transferrin, a member of the type 2 periplasmic binding protein fold superfamily
      pfam00405
      Location:25352
      Transferrin; Transferrin

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

      Range
      46436005..46485234 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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