Target Information

Target General Information

Target ID

T16144 (Former ID: TTDNC00463)

Target Name

B7-related protein 1 (B7RP1)

Synonyms

KIAA0653; ICOSL; ICOS ligand; CD275; B7related protein 1; B7like protein Gl50; B7RP-1; B7H2; B7-like protein Gl50; B7-H2; B7 homolog 2

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Gene Name

ICOSLG

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Lupus erythematosus [ICD-11: 4A40]

Sjogren syndrome [ICD-11: 4A43]

Function

Acts as a costimulatory signal for T-cell proliferation and cytokine secretion; induces also B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function. Ligand for the T-cell-specific cell surface receptor ICOS.

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BioChemical Class

Immunoglobulin

UniProt ID

ICOSL_HUMAN

Sequence

MRLGSPGLLFLLFSSLRADTQEKEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESK
TVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTPQDEQKFHCLVLSQSL
GFQEVLSVEVTLHVAANFSVPVVSAPHSPSQDELTFTCTSINGYPRPNVYWINKTDNSLL
DQALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVLLQQNLTVGSQTGNDIGERD
KITENPVSTGEKNAATWSILAVLCLLVVVAVAIGWVCRDRCLQHSYAGAWAVSPETELTG
HV

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3D Structure

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AlphaFold

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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). 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 Tissue Distribution 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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

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 Tissue Distribution

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Programmed cell death 1 ligand 2 (PD-L2)	PF08205	24.138 (63/261)	1.27E-08
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1)	PF07654	23.077 (48/208)	9.47E-05
Membrane glycoprotein OX2 (CD200)	PF00047	24.277 (42/173)	5.06E-04
Roundabout homolog 3 (ROBO3)	PF00041 ; PF07679 ; PF13927 More >>	27.612 (37/134)	4.00E-03


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Cell adhesion molecules	hsa04514	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Intestinal immune network for IgA production	hsa04672	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 2 KEGG Pathways

Cell adhesion molecules (CAMs)

Intestinal immune network for IgA production

Reactome

[+] 1 Reactome Pathways

Costimulation by the CD28 family

WikiPathways

[+] 1 WikiPathways

Costimulation by the CD28 family

References

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REF 1

Administration Of AMG 557, A Human Anti-B7RP-1 (ICOSL) Antibody, Leads To The Selective Inhibition Of Anti-KLH IgG Responses In Subjects With SLE: Results Of A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Sequential, Rising, Multiple-Dose Study. San Diego, CA October 25-30, 2013

REF 2

ClinicalTrials.gov (NCT02334306) A Phase 2a, Randomized, Placebo Controlled, Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Primary Sj ren's Syndrome. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04058028) Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE). U.S. National Institutes of Health.

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