Target Information

Target General Information

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Target ID

T47610 (Former ID: TTDS00501)

Target Name

Interleukin 11 receptor alpha (IL11RA)

Synonyms

Interleukin-11 receptor subunit alpha; IL-11RA; IL-11R-alpha; IL-11R subunit alpha; IL-11 receptor subunit alpha

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Gene Name

IL11RA

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Thrombocytopenia [ICD-11: 3B64]

Function

The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. Essential for the normal development of craniofacial bones and teeth. Restricts suture fusion and tooth number. Receptor for interleukin-11.

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BioChemical Class

Cytokine receptor

UniProt ID

I11RA_HUMAN

Sequence

MSSSCSGLSRVLVAVATALVSASSPCPQAWGPPGVQYGQPGRSVKLCCPGVTAGDPVSWF
RDGEPKLLQGPDSGLGHELVLAQADSTDEGTYICQTLDGALGGTVTLQLGYPPARPVVSC
QAADYENFSCTWSPSQISGLPTRYLTSYRKKTVLGADSQRRSPSTGPWPCPQDPLGAARC
VVHGAEFWSQYRINVTEVNPLGASTRLLDVSLQSILRPDPPQGLRVESVPGYPRRLRASW
TYPASWPCQPHFLLKFRLQYRPAQHPAWSTVEPAGLEEVITDAVAGLPHAVRVSARDFLD
AGTWSTWSPEAWGTPSTGTIPKEIPAWGQLHTQPEVEPQVDSPAPPRPSLQPHPRLLDHR
DSVEQVAVLASLGILSFLGLVAGALALGLWLRLRRGGKDGSPKPGFLASVIPVDRRPGAP
NL

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3D Structure

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PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Oprelvekin

Drug Info

Approved

Thrombocytopenia

[2], [3]

Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

UNI-rhIL-11

Drug Info

Phase 3

Thrombocytopenia

[4]

BMTP-11

Drug Info

Phase 1

Prostate cancer

[5]

Mode of Action

[+] 2 Modes of Action

Binder

[+] 1 Binder drugs

Oprelvekin

Drug Info

[1]

Modulator

[+] 2 Modulator drugs

UNI-rhIL-11

Drug Info

[6]

BMTP-11

Drug Info

[7]

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). 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

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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).

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Interleukin 11 receptor alpha (IL11RA)		100.000 (422/422)	0.00E+00
Ciliary neurotrophic factor receptor alpha (CNTFR)	PF00041	33.677 (98/291)	1.20E-35
Interleukin-6 receptor subunit alpha (IL6R)	PF00047 ; PF09240	29.512 (121/410)	6.94E-26
Interleukin-35 (IL35)	PF00041	31.579 (66/209)	3.78E-19
Cytokine receptor-like factor 1 (CRLF1)	PF09067 ; PF00041	26.337 (64/243)	3.49E-12
Prolactin receptor (PRLR)	PF09067	28.302 (60/212)	1.59E-10
Interleukin-12 beta (IL12B)	PF10420	20.645 (64/310)	2.91E-07
Interleukin-6 receptor subunit beta (IL6ST)	PF00041 ; PF09240 ; PF06328 More >>	22.685 (49/216)	4.18E-07
Interleukin 31 receptor (IL31R)	PF00041 ; PF09240	25.225 (56/222)	6.78E-06
Leukemia inhibitory factor receptor (LIFR)	PF00041 ; PF17971 ; PF18207 More >>	22.857 (40/175)	1.83E-05
Myomesin-2 (MYOM2)	PF00041 ; PF07679	29.565 (34/115)	1.63E-04
Immunoglobulin superfamily member 22 (IGSF22)	PF00041 ; PF07679 ; PF18362 More >>	26.250 (42/160)	3.97E-04
Roundabout homolog 4 (ROBO4)	PF00041 ; PF07679 ; PF13927 More >>	44.444 (20/45)	6.85E-04
Obscurin-like protein 1 (OBSL1)	PF07679 ; PF13927	34.118 (29/85)	2.00E-03
Immunoglobulin lambda variable 1-40 (IGLV1-40)	PF07686	28.723 (27/94)	3.00E-03
Leptin receptor (LEPR)	PF06328 ; PF18589	23.377 (54/231)	5.00E-03
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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
Hematopoietic cell lineage	hsa04640	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.56E-01	Radiality	1.22E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	3.00E+00	Topological coefficient	1.00E+00	Eccentricity	14
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 3 KEGG Pathways

Cytokine-cytokine receptor interaction

Jak-STAT signaling pathway

Hematopoietic cell lineage

Panther Pathway

[+] 1 Panther Pathways

Interleukin signaling pathway

WikiPathways

[+] 1 WikiPathways

Interleukin-11 Signaling Pathway

References

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REF 1

Oprelvekin: a review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia. BioDrugs. 1998 Aug;10(2):159-71.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6971).

REF 3

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 4

ClinicalTrials.gov (NCT01663441) A Phase Study of Genetically Modified Recombinant Human Interleukin-11. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT00872157) BMTP-11 in Patients With Castrate-Resistant Prostate Cancer With Bone Mets. U.S. National Institutes of Health.

REF 6

Clinical study of rhIL-11 for prevention and treatment of chemotherapy-induced thrombocytopenia. Ai Zheng. 2002 Aug;21(8):892-5.

REF 7

Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens. Clin Cancer Res. 2015 Jul 1;21(13):3041-51.

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