Target Information

Target General Information

Target ID

T15783 (Former ID: TTDNC00520)

Target Name

NKG2-A/B-activating NK receptor (NKG2A)

Synonyms

NKG2A/NKG2B type II integral membrane protein; NKG2A/Bactivating NK receptor; NK cell receptor A; KLRC1; CD159a; CD159 antigenlike family member A

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Gene Name

KLRC1

Target Type

Clinical trial target

[1]

Disease

[+] 4 Target-related Diseases

Rheumatoid arthritis [ICD-11: FA20]

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

Mature B-cell leukaemia [ICD-11: 2A82]

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

Function

Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells.

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UniProt ID

NKG2A_HUMAN

Sequence

MDNQGVIYSDLNLPPNPKRQQRKPKGNKNSILATEQEITYAELNLQKASQDFQGNDKTYH
CKDLPSAPEKLIVGILGIICLILMASVVTIVVIPSTLIQRHNNSSLNTRTQKARHCGHCP
EEWITYSNSCYYIGKERRTWEESLLACTSKNSSLLSIDNEEEMKFLSIISPSSWIGVFRN
SSHHPWVTMNGLAFKHEIKDSDNAELNCAVLQVNRLKSAQCGSSIIYHCKHKL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

NN8765

Drug Info

Phase 2

Rheumatoid arthritis

[2]

BMS-986315

Drug Info

Phase 1/2

Solid tumour/cancer

[3]

Monalizumab

Drug Info

Phase 1/2

Chronic lymphocytic leukaemia

[4], [5]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

IM1240

Drug Info

Preclinical

Aggressive cancer

[6]

Mode of Action

[+] 3 Modes of Action

Modulator

[+] 1 Modulator drugs

NN8765

Drug Info

[1]

Inhibitor

[+] 1 Inhibitor drugs

BMS-986315

Drug Info

[3]

Antagonist

[+] 1 Antagonist drugs

Monalizumab

Drug Info

[4], [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). 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
NKG2-F type II integral membrane protein (KLRC4)		66.897 (97/145)	1.88E-64
Putative C-type lectin-like domain family 1 (CLECL1P)		24.771 (27/109)	5.00E-03

KEGG Pathway	Pathway ID	Affiliated Target
Antigen processing and presentation	hsa04612	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Natural killer cell mediated cytotoxicity	hsa04650	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	9	Degree centrality	9.67E-04	Betweenness centrality	8.09E-05
Closeness centrality	1.91E-01	Radiality	1.32E+01	Clustering coefficient	4.72E-01
Neighborhood connectivity	1.56E+01	Topological coefficient	2.13E-01	Eccentricity	12
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Target Affiliated Biological Pathways

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KEGG Pathway

[+] 3 KEGG Pathways

Antigen processing and presentation

Natural killer cell mediated cytotoxicity

Graft-versus-host disease

NetPath Pathway

[+] 2 NetPath Pathways

TCR Signaling Pathway

IL2 Signaling Pathway

Reactome

[+] 1 Reactome Pathways

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

WikiPathways

[+] 1 WikiPathways

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

References

Top

REF 1

Handbook of Therapeutic Antibodies. 2014. 1. Page(1098).

REF 2

Clinical pipeline report, company report or official report of Innate Pharma.

REF 3

ClinicalTrials.gov (NCT04349267) Study of BMS-986315 Alone and in Combination With Nivolumab or Cetuximab in Participants With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 4

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

REF 5

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

REF 6

Clinical pipeline report, company report or official report of Purple

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