LTF
Lactotransferrin
Also known as: HLF2, TRFL_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P02788
- Gene
- LTF
- Ensembl
- ENSG00000012223
- Chromosome
- 3
- Canonical length
- 710 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
OverviewNCBI 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. Activity against both DNA and RNA viruses has been found, including activity against SARS-CoV-2, and HIV. [provided by RefSeq, Jul 2021]
Canonical amino-acid sequenceUniProt
710 residues, UniProt reviewed canonical sequence.
>P02788|LTF
1 MKLVFLVLLF LGALGLCLAG RRRSVQWCAV SQPEATKCFQ WQRNMRKVRG PPVSCIKRDS
61 PIQCIQAIAE NRADAVTLDG GFIYEAGLAP YKLRPVAAEV YGTERQPRTH YYAVAVVKKG
121 GSFQLNELQG LKSCHTGLRR TAGWNVPIGT LRPFLNWTGP PEPIEAAVAR FFSASCVPGA
181 DKGQFPNLCR LCAGTGENKC AFSSQEPYFS YSGAFKCLRD GAGDVAFIRE STVFEDLSDE
241 AERDEYELLC PDNTRKPVDK FKDCHLARVP SHAVVARSVN GKEDAIWNLL RQAQEKFGKD
301 KSPKFQLFGS PSGQKDLLFK DSAIGFSRVP PRIDSGLYLG SGYFTAIQNL RKSEEEVAAR
361 RARVVWCAVG EQELRKCNQW SGLSEGSVTC SSASTTEDCI ALVLKGEADA MSLDGGYVYT
421 AGKCGLVPVL AENYKSQQSS DPDPNCVDRP VEGYLAVAVV RRSDTSLTWN SVKGKKSCHT
481 AVDRTAGWNI PMGLLFNQTG SCKFDEYFSQ SCAPGSDPRS NLCALCIGDE QGENKCVPNS
541 NERYYGYTGA FRCLAENAGD VAFVKDVTVL QNTDGNNNEA WAKDLKLADF ALLCLDGKRK
601 PVTEARSCHL AMAPNHAVVS RMDKVERLKQ VLLHQQAKFG RNGSDCPDKF CLFQSETKNL
661 LFNDNTECLA RLHGKTTYEK YLGPQYVAGI TNLKKCSTSP LLEACEFLRKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against LTF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.23
- Highest tissue expression
- 4,021 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 4,021 nTPM
- salivary gland: 1,063 nTPM
- cervix: 619 nTPM
- seminal vesicle: 358 nTPM
- tonsil: 323 nTPM
- stomach: 313 nTPM
Single-cell type
- lacrimal acinar cells: 29,240 nCPM
- breast lactating cells: 12,230 nCPM
- neutrophil progenitors: 6,129 nCPM
- submucosal glandular cells: 3,406 nCPM
- salivary acinar cells: 3,274 nCPM
- breast secretory cells: 1,334 nCPM
Immune cell
- total PBMC: 30 nTPM
- non-classical monocyte: 17 nTPM
- neutrophil: 5.4 nTPM
- plasmacytoid DC: 0.4 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
Brain region
- midbrain: 40 nTPM
- thalamus: 27 nTPM
- medulla oblongata: 23 nTPM
- white matter: 19 nTPM
- spinal cord: 13 nTPM
- hypothalamus: 11 nTPM
ReferencesPubMed · IEDB
Publications for LTF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
1 publication
- Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.
2017 · Sci Rep · RCR 1.1 · 29 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.16
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.23
- DepMap mean gene effect
- -0.28
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antibacterial humoral response
- antifungal humoral response
- antimicrobial humoral immune response mediated by antimicrobial peptide
- bone morphogenesis
- defense response to Gram-negative bacterium
- host-mediated suppression of viral proces
- humoral immune response
- innate immune response in mucosa
- iron ion transport
- killing of cells of another organism
- negative regulation of apoptotic process
- negative regulation of ATP-dependent activity
- negative regulation of lipopolysaccharide-mediated signaling pathway
- negative regulation of osteoclast development
- negative regulation of single-species biofilm formation in or on host organism
- negative regulation of viral genome replication
- negative regulation of viral process
- ossification
- positive regulation of bone mineralization involved in bone maturation
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of chondrocyte proliferation
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of osteoblast differentiation
- positive regulation of osteoblast proliferation
- positive regulation of protein serine/threonine kinase activity
- positive regulation of toll-like receptor 4 signaling pathway
- proteolysis
- regulation of cytokine production
- regulation of tumor necrosis factor production
- negative regulation of tumor necrosis factor (ligand) superfamily member 11 production
Molecular functions
- cysteine-type endopeptidase inhibitor activity
- DNA binding
- heparin binding
- iron ion binding
- lipopolysaccharide binding
- membrane destabilizing activity
- protein serine/threonine kinase activator activity
- serine-type endopeptidase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
- Alternative promoter usage
- Antibiotic
- Antimicrobial
- Cytoplasm
- Disulfide bond
- DNA-binding
- Glycoprotein
- Heparin-binding
- Hydrolase
- Immunity
- Ion transport
- Iron
- Iron transport
- Isopeptide bond
- Metal-binding
- Nucleus
- Osteogenesis
- Protease
- Repeat
- Secreted
- Serine protease
- Signal
- Transcription
- Transcription regulation
- Transport
- Ubl conjugation
InteractionsUniProt · HPA
Protein binding partners of LTF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads LTF as an antibody target. Whether an autoantibody or antibody against LTF could matter depends on whether native LTF is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
LTF is annotated as secreted, so native LTF circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label LTF as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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