Target Information

Target General Information

Target ID

T48429 (Former ID: TTDI02093)

Target Name

Interleukin 15 receptor alpha (IL15RA)

Synonyms

sIL15Ralpha; sIL15RA; sIL15 receptor subunit alpha; Soluble interleukin15 receptor subunit alpha; Interleukin-15 receptor subunit alpha; IL15Ralpha; IL15 receptor subunit alpha; IL-15RA; IL-15R-alpha; IL-15 receptor subunit alpha; CD215

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Gene Name

IL15RA

Target Type

Clinical trial target

[1]

Disease

[+] 10 Target-related Diseases

Acute myeloid leukaemia [ICD-11: 2A60]

Bladder cancer [ICD-11: 2C94]

Colorectal cancer [ICD-11: 2B91]

Head and neck cancer [ICD-11: 2D42]

Lung cancer [ICD-11: 2C25]

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Human immunodeficiency virus disease [ICD-11: 1C60-1C62]

Multiple myeloma [ICD-11: 2A83]

Pancreatic cancer [ICD-11: 2C10]

Function

Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells. In neutrophils, binds and activates kinase SYK in response to IL15 stimulation. In neutrophils, required for IL15-induced phagocytosis in a SYK-dependent manner. Expression of different isoforms may alter or interfere with signal transduction. High-affinity receptor for interleukin-15.

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BioChemical Class

Cytokine receptor

UniProt ID

I15RA_HUMAN

Sequence

MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICN
SGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPPSTVTTAGVTPQPE
SLSPSGKEPAASSPSSNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTA
KNWELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLKSRQTPPLASVE
MEAMEALPVTWGTSSRDEDLENCSHHL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

ALT-803

Drug Info

Phase 2

Bladder cancer

[1], [2]

NKTR-255

Drug Info

Phase 1/2

Colorectal cancer

[3]

Mode of Action

[+] 1 Modes of Action

Agonist

[+] 2 Agonist drugs

ALT-803

Drug Info

[4]

NKTR-255

Drug Info

[5]

Cell-based Target Expression Variations

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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). Human Similarity Proteins Human Pathway Affiliation

Different Human System Profiles of Target

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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).

Human Similarity Proteins

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Interleukin 15 receptor alpha (IL15RA)		100.000 (267/267)	0.00E+00

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
Intestinal immune network for IgA production	hsa04672	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 4 KEGG Pathways

Cytokine-cytokine receptor interaction

Jak-STAT signaling pathway

Intestinal immune network for IgA production

HTLV-I infection

NetPath Pathway

[+] 2 NetPath Pathways

TCR Signaling Pathway

IL1 Signaling Pathway

Panther Pathway

[+] 1 Panther Pathways

Interleukin signaling pathway

WikiPathways

[+] 1 WikiPathways

TCR Signaling Pathway

References

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REF 1

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

ClinicalTrials.gov (NCT04616196) Study of NKTR 255 in Combination With Cetuximab in Solid Tumors. U.S. National Institutes of Health.

REF 4

Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor alphaSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Cancer Res. 2013 May 15;73(10):3075-86.

REF 5

Clinical pipeline report, company report or official report of Nektar Therapeutics.

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