Target Information

Target General Information

Target ID

T53669 (Former ID: TTDI02048)

Target Name

Thymic stromal lymphoprotein receptor (CRLF2)

Synonyms

Thymic stromal lymphopoietin protein receptor; TSLP receptor; ILXR; Cytokine receptorlike factor 2; Cytokine receptorlike 2; CRLF2

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Gene Name

CRLF2

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Asthma [ICD-11: CA23]

Function

Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2. Implicated in the development of the hematopoietic system.

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BioChemical Class

Cytokine receptor

UniProt ID

CRLF2_HUMAN

Sequence

MGRLVLLWGAAVFLLGGWMALGQGGAAEGVQIQIIYFNLETVQVTWNASKYSRTNLTFHY
RFNGDEAYDQCTNYLLQEGHTSGCLLDAEQRDDILYFSIRNGTHPVFTASRWMVYYLKPS
SPKHVRFSWHQDAVTVTCSDLSYGDLLYEVQYRSPFDTEWQSKQENTCNVTIEGLDAEKC
YSFWVRVKAMEDVYGPDTYPSDWSEVTCWQRGEIRDACAETPTPPKPKLSKFILISSLAI
LLMVSLLLLSLWKLWRVKKFLIPSVPDPKSIFPGLFEIHQGNFQEWITDTQNVAHLHKMA
GAEQESGPEEPLVVQLAKTEAESPRMLDPQTEEKEASGGSLQLPHQPLQGGDVVTIGGFT
FVMNDRSYVAL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

UPB-101

Drug Info

Phase 1

Asthma

[2]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

UPB-101

Drug Info

[3]

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

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Thymic stromal lymphoprotein receptor (CRLF2)		100.000 (371/371)	0.00E+00
Cytokine receptor common subunit gamma (IL2RG)	PF09240	24.727 (68/275)	1.47E-10
Interleukin-9 receptor (IL9R)		26.344 (49/186)	3.18E-04

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	3	Degree centrality	3.22E-04	Betweenness centrality	1.28E-04
Closeness centrality	2.01E-01	Radiality	1.35E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	2.67E+01	Topological coefficient	3.42E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

CRLF2 expression associates with ICN1 stabilization in T-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2019 Jun;58(6):396-401.

REF 2

ClinicalTrials.gov (NCT05448651) A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending-Dose Study to Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Pharmacodynamics of UPB-101 in Subjects With Asthma. U.S.National Institutes of Health.

REF 3

Clinical pipeline report, company report or official report of Upstream Biosciences

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