Tbio LTF Lactotransferrin

Protein Summary

Description

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. Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites. 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 SELENOH promoters. 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]

Uniprot Accession IDs

• P02788
• A8K9U8
• B2MV13
• B7Z4X2
• E7EQH5
• O00756
• Q16780
• Q16785
• Q16786
• Q16789
• Q5DSM0
• Q8IU92
• Q8IZH6
• Q8TCD2
• Q96KZ4
• Q96KZ5
• Q9H1Z3
• Q9UCY5
• Lactoferrin

Gene Name

• LTF

Ensembl ID

• ENST00000231751
• ENSP00000231751
• ENSG00000012223
• ENST00000426532
• ENSP00000405719

Symbol

• GIG12
• LF
• LF
• HLF2
• GIG12
• HEL110

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
PubMedID	1
biological term	0.97
molecular function	0.96
small molecule perturbation	0.86

Protein Classes

PANTHER Classes

Protein / Transfer/carrier Protein / Lactotransferrin

Protein / Receptor / Lactotransferrin

Protein / ... / Serine Protease / Lactotransferrin

DTO Classes

Protein / Enzyme / Protease / Serine Protease / Lactotransferrin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1072.98   (req: < 5)

Gene RIFs: 185   (req: <= 3)

Antibodies: 1219   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1072.98   (req: >= 5)

Gene RIFs: 185   (req: > 3)

Antibodies: 1219   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 45

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (165)

Explore Interacting Targets

1 – 10 of 165

• See Interactions on String-DB

DDX31

Tbio

Family:  Enzyme

Novelty:  2.84646195

p_int:  0.999997774

p_ni:  0.000002226

Data Source:  BioPlex

SNX27

Tbio

Novelty:  0.02419724

p_int:  0.999965689

p_ni:  0.000034311

Data Source:  BioPlex

HBM

Tdark

Novelty:  0.02658671

p_int:  0.999801173

p_ni:  0.000198827

Score:  0.2

Data Source:  BioPlex,STRINGDB

ICE2

Tbio

Novelty:  0.03407933

p_int:  0.999658439

p_ni:  0.000341561

Data Source:  BioPlex

CCDC148

Tdark

Novelty:  2.81805259

p_int:  0.999161952

p_ni:  0.000838047

Score:  0.196

Data Source:  BioPlex,STRINGDB

FRMD1

Tdark

Novelty:  0.96833141

p_int:  0.998384769

p_ni:  0.001615231

Data Source:  BioPlex

POLL

Tbio

Family:  Enzyme

Novelty:  0.00244645

p_int:  0.994555369

p_ni:  0.005444631

Score:  0.17

Data Source:  BioPlex,STRINGDB

FN3KRP

Tbio

Family:  Kinase

Novelty:  0.10259418

p_int:  0.97039602

p_ni:  0.02960398

Score:  0.235

Data Source:  BioPlex,STRINGDB

CDK15

Tchem

Family:  Kinase

Novelty:  0.3870338

p_int:  0.968423716

p_ni:  0.031576279

p_wrong:  5e-9

Data Source:  BioPlex

TMEM237

Tbio

Novelty:  0.27005874

p_int:  0.960652736

p_ni:  0.039347264

Score:  0.175

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (84)

Reactome (11)

WikiPathways (73)

Amyloid fiber formation (R-HSA-977225)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Amyloid fiber formation	79 targets	R-HSA-977225
Reactome	Antimicrobial peptides	89 targets	R-HSA-6803157
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Infectious disease	408 targets	R-HSA-5663205

Name	Explore in Pharos	Explore in Source
Amyloid fiber formation	79 targets	R-HSA-977225
Antimicrobial peptides	89 targets	R-HSA-6803157
Disease	1105 targets	R-HSA-1643685
Immune System	2246 targets	R-HSA-168256
Infectious disease	408 targets	R-HSA-5663205

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (58)

Functions (7)

Components (13)

Processes (38)

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1 – 7 of 7

GO Term	Evidence	Assigned by
cysteine-type endopeptidase inhibitor activity	Inferred from Direct Assay (IDA)	CAFA
heparin binding	Inferred from Direct Assay (IDA)	MGI
iron ion binding	Inferred from Direct Assay (IDA)	UniProtKB
lipopolysaccharide binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activator activity	Inferred from Direct Assay (IDA)	UniProtKB
serine-type endopeptidase activity	Traceable Author Statement (TAS)	ProtInc
DNA binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (19)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 19

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	15	10	15		98.2
monocyte count	EFO_0005091	7	6	7		95.5
Oral ulcer	HP_0000155	1	2	0	1.1	92.1
CCL2 measurement	EFO_0004749	3	4	4		91
macrophage inflammatory protein 1b measurement	EFO_0008219	1	3	3		87.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 19

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	15		98.2
monocyte count	EFO_0005091	7		95.5
Oral ulcer	HP_0000155	0	1.1	92.1
CCL2 measurement	EFO_0004749	4		91
macrophage inflammatory protein 1b measurement	EFO_0008219	3		87.5

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UniProt Keyword Find Similar Targets

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3D-structure
Alternative promoter usage
Antibiotic
Antimicrobial
Complete proteome
Cytoplasm
Direct protein sequencing
Disulfide bond
DNA-binding
Glycoprotein

GWAS Trait Find Similar Targets

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alkaline phosphatase measurement
blood protein measurement
blood urea nitrogen measurement
CCL2 measurement
CCL4 measurement
celiac disease
eosinophil count
eotaxin measurement
granulocyte percentage of myeloid white cells
inflammatory bowel disease

MGI Phenotype Find Similar Targets

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cellular phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
neoplasm

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	lactotransferrin	VGNC:1866	460325
Macaque	lactotransferrin		713115
Mouse	lactotransferrin	MGI:96837	17002
Rat	lactotransferrin	RGD:1305445	301034
Dog	lactotransferrin	VGNC:42861	484787

Species	Name	OMA	EggNOG	Inparanoid
Chimp	lactotransferrin
Macaque	lactotransferrin
Mouse	lactotransferrin
Rat	lactotransferrin
Dog	lactotransferrin

Publication Statistics

PubMed Score 1072.98

PubMed score by year

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PubTator Score 214.74

PubTator score by year

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Related Publications

Text Mined References (285)

GeneRif Annotations (185)

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PMID	Year	Title