Target Information

Target General Information

Top

Target ID

T78381 (Former ID: TTDI02296)

Target Name

Interleukin-29 (IL29)

Synonyms

ZCYTO21; Interleukin29; Interferon lambda1; Interferon lambda-1; IL-29; IFNlambda1; IFN-lambda-1; Cytokine Zcyto21

Click to Show/Hide

Gene Name

IFNL1

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Acute myeloid leukaemia [ICD-11: 2A60]

Function

Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression. Cytokine with antiviral, antitumour and immunomodulatory activities.

Click to Show/Hide

BioChemical Class

Cytokine: interleukin

UniProt ID

IFNL1_HUMAN

Sequence

MAAAWTVVLVTLVLGLAVAGPVPTSKPTTTGKGCHIGRFKSLSPQELASFKKARDALEES
LKLKNWSCSSPVFPGNWDLRLLQVRERPVALEAELALTLKVLEAAAGPALEDVLDQPLHT
LHHILSQLQACIQPQPTAGPRPRGRLHHWLHRLQEAPKKESAGCLEASVTFNLFRLLTRD
LKYVADGNLCLRTSTHPEST

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

Peginterferon lambda-1a

Drug Info

Phase 3

Acute myeloid leukaemia

[2]

PEG-Interferon lambda (IL-29)

Drug Info

Phase 1

Virus infection

[3]

Mode of Action

[+] 1 Modes of Action

Agonist

[+] 2 Agonist drugs

Peginterferon lambda-1a

Drug Info

[1]

PEG-Interferon lambda (IL-29)

Drug Info

[1]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.64E-01	Radiality	1.25E+01	Clustering coefficient	1.00E+00
Neighborhood connectivity	8.00E+00	Topological coefficient	7.27E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 2 KEGG Pathways

Cytokine-cytokine receptor interaction

Jak-STAT signaling pathway

WikiPathways

[+] 1 WikiPathways

Type III interferon signaling

References

Top

REF 1

Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C. J Interferon Cytokine Res. 2010 Aug;30(8):591-5.

REF 2

ClinicalTrials.gov (NCT01866930) Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naive Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT00565539) Study of PEG-rIL-29 (or PEG-IFN Lambda) in Subjects With Chronic Hepatitis C Virus Infection. U.S. National Institutes of Health.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN