LTF lactotransferrin [Homo sapiens (human)] - Gene

Summary

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

Location:: 3p21.31

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (46435645..46485234, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (46451475..46501054, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (46477136..46526724, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures.
Title: Lactoferrin Modulates Induction of Transcription Factor c-Fos in Neuronal Cultures.
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.
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.
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.
The Lactoferrin Phenomenon-A Miracle Molecule.
Title: The Lactoferrin Phenomenon-A Miracle Molecule.
Lactoferrin as a Human Genome ""Guardian""-An Overall Point of View.
Title: Lactoferrin as a Human Genome "Guardian"-An Overall Point of View.
Effect of human lactoferrin on Candida albicans infection and host response interactions in experimental oral candidiasis in mice.
Title: Effect of human lactoferrin on Candida albicans infection and host response interactions in experimental oral candidiasis in mice.
Lactoferrin modified by hypohalous acids: Partial loss in activation of human neutrophils.
Title: Lactoferrin modified by hypohalous acids: Partial loss in activation of human neutrophils.

Submit: New GeneRIF Correction See all GeneRIFs (217)

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 EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D3S1478 (e-PCR)
- UniSTS:148256

RH119558 (e-PCR)
- UniSTS:132641

GDB:181215 (e-PCR)
- UniSTS:155183

G59627 (e-PCR)
- UniSTS:136783

D3S4169 (e-PCR)
- UniSTS:22917

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	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 defense response to Gram-negative 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 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 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 more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	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 more info	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

EC 3.4.21.-

NP_001308050.1

EC 3.4.21.-

NP_001308051.1

EC 3.4.21.-

NP_002334.2

EC 3.4.21.-

NCBI Reference Sequences (RefSeq)

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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

NG_023257.2 RefSeqGene

Range

25330..54590

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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