Target Information

Target General Information

Target ID

T28217 (Former ID: TTDI02397)

Target Name

MHC class I NK cell receptor 3DL2 (CD158k)

Synonyms

p70 natural killer cell receptor clone CL5; p70 NK receptor CL5; Natural killerassociated transcript 4; NKAT4; KIR3DL2; CD158k; CD158 antigenlike family member K

Click to Show/Hide

Gene Name

KIR3DL2

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Mature T-cell lymphoma [ICD-11: 2A90]

Function

Receptor on natural killer (NK) cells for HLA-A alleles. Inhibits the activity of NK cells thus preventing cell lysis.

Click to Show/Hide

BioChemical Class

Immunoglobulin

UniProt ID

KI3L2_HUMAN

Sequence

MSLTVVSMACVGFFLLQGAWPLMGGQDKPFLSARPSTVVPRGGHVALQCHYRRGFNNFML
YKEDRSHVPIFHGRIFQESFIMGPVTPAHAGTYRCRGSRPHSLTGWSAPSNPLVIMVTGN
HRKPSLLAHPGPLLKSGETVILQCWSDVMFEHFFLHREGISEDPSRLVGQIHDGVSKANF
SIGPLMPVLAGTYRCYGSVPHSPYQLSAPSDPLDIVITGLYEKPSLSAQPGPTVQAGENV
TLSCSSWSSYDIYHLSREGEAHERRLRAVPKVNRTFQADFPLGPATHGGTYRCFGSFRAL
PCVWSNSSDPLLVSVTGNPSSSWPSPTEPSSKSGICRHLHVLIGTSVVIFLFILLLFFLL
YRWCSNKKNAAVMDQEPAGDRTVNRQDSDEQDPQEVTYAQLDHCVFIQRKISRPSQRPKT
PLTDTSVYTELPNAEPRSKVVSCPRAPQSGLEGVF

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

IPH4102

Drug Info

Phase 2

T-cell lymphoma

[2]

Mode of Action

[+] 1 Modes of Action

Antagonist

[+] 1 Antagonist drugs

IPH4102

Drug Info

[1], [3]

Cell-based Target Expression Variations

Top

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
Leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3)	PF13895	39.693 (181/456)	1.19E-78
Leukocyte immunoglobulin-like receptor B2 (LILRB2)	PF13895	36.253 (178/491)	1.67E-71
Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5)	PF13895	35.741 (94/263)	1.31E-35
Platelet glycoprotein VI (GP6)	PF13895	32.258 (100/310)	5.04E-26
Natural cytotoxic triggering receptor 1 (NCR1)		32.813 (84/256)	7.13E-26
Osteoclast-associated receptor (OSCAR)	PF13895	35.897 (70/195)	9.34E-22
Immunoglobulin alpha Fc receptor (FCAR)		33.673 (66/196)	1.21E-19
T-cell-interacting, activating receptor on myeloid cells protein 1 (TARM1)	PF13895	31.839 (71/223)	1.21E-11
Alpha-1B-glycoprotein (A1BG)	PF13895	26.119 (70/268)	3.46E-10
Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2)	PF13895	29.032 (36/124)	3.77E-06
B7 homolog 3 (CD276)	PF13927 ; PF07686	22.222 (94/423)	6.88E-06
V-set and transmembrane domain-containing protein 1 (VSTM1)	PF13895	27.461 (53/193)	1.42E-05
Leukocyte-associated Ig-like receptor 1 (LAIR1)	PF13895	25.681 (66/257)	2.01E-05
Fc receptor-like protein 6 (FCRL6)	PF13895 ; PF13927	26.016 (32/123)	4.29E-04
Sialoadhesin (SIGLEC1)	PF08205 ; PF07679 ; PF13895 ; PF07686 More >>	23.108 (58/251)	1.00E-03
Fc receptor-like A (FCRLA)	PF13895	23.474 (50/213)	3.00E-03
Click to Show/Hide the Information of Human Similarity Proteins

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	4	Degree centrality	4.30E-04	Betweenness centrality	3.30E-09
Closeness centrality	1.70E-01	Radiality	1.27E+01	Clustering coefficient	8.33E-01
Neighborhood connectivity	1.48E+01	Topological coefficient	5.46E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

References

Top

REF 1

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

REF 2

ClinicalTrials.gov (NCT03902184) IPH4102 Alone or in Combination With Chemotherapy in Patients With Advanced T Cell Lymphoma (TELLOMAK). U.S. National Institutes of Health.

REF 3

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

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Feng ZHU

Prof. Yuzong CHEN