Target Information

Target General Information

Target ID

T54902 (Former ID: TTDI02106)

Target Name

MHC class I NK cell receptor 2DL2 (CD158b1)

Synonyms

p58 natural killer cell receptor clone CL-43; p58 NK receptor CL-43; Natural killer-associated transcript 6; NKAT6; NKAT-6; Killer cell immunoglobulin-like receptor 2DL2; CD158B1; CD158 antigen-like family member B1

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Gene Name

KIR2DL2

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Acute myeloid leukaemia [ICD-11: 2A60]

Multiple myeloma [ICD-11: 2A83]

Function

Receptor on natural killer (NK) cells for HLA-Cw1, 3, 7, and 8 allotypes. Inhibits the activity of NK cells thus preventing cell lysis.

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BioChemical Class

Immunoglobulin

UniProt ID

KI2L2_HUMAN

Sequence

MSLMVVSMACVGFFLLQGAWPHEGVHRKPSLLAHPGRLVKSEETVILQCWSDVRFEHFLL
HREGKFKDTLHLIGEHHDGVSKANFSIGPMMQDLAGTYRCYGSVTHSPYQLSAPSDPLDI
VITGLYEKPSLSAQPGPTVLAGESVTLSCSSRSSYDMYHLSREGEAHECRFSAGPKVNGT
FQADFPLGPATHGGTYRCFGSFRDSPYEWSNSSDPLLVSVIGNPSNSWPSPTEPSSKTGN
PRHLHILIGTSVVIILFILLFFLLHRWCSNKKNAAVMDQESAGNRTANSEDSDEQDPQEV
TYTQLNHCVFTQRKITRPSQRPKTPPTDIIVYAELPNAESRSKVVSCP

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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

IPH-2101

Drug Info

Phase 2

Multiple myeloma

[2]

IPH-2102

Drug Info

Phase 2

Acute myeloid leukaemia

[3]

mab 1-7F9

Drug Info

Phase 2

Multiple myeloma

[4], [5]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 1 Modulator drugs

IPH-2101

Drug Info

[1], [6], [7]

Antagonist

[+] 1 Antagonist drugs

IPH-2102

Drug Info

[1]

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). Human Similarity Proteins Human Pathway Affiliation

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).

Human Similarity Proteins

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Leukocyte immunoglobulin-like receptor B2 (LILRB2)	PF13895	35.013 (132/377)	1.26E-47
Leukocyte immunoglobulin-like receptor subfamily B member 3 (LILRB3)	PF13895	36.152 (124/343)	3.02E-46
Leukocyte immunoglobulin-like receptor subfamily A member 5 (LILRA5)	PF13895	34.495 (99/287)	5.69E-39
Natural cytotoxic triggering receptor 1 (NCR1)		30.380 (96/316)	1.19E-33
Platelet glycoprotein VI (GP6)	PF13895	36.179 (89/246)	4.31E-28
Immunoglobulin alpha Fc receptor (FCAR)		38.129 (53/139)	2.11E-18
T-cell-interacting, activating receptor on myeloid cells protein 1 (TARM1)	PF13895	29.044 (79/272)	1.18E-16
Osteoclast-associated receptor (OSCAR)	PF13895	32.000 (72/225)	6.79E-16
Alpha-1B-glycoprotein (A1BG)	PF13895	26.923 (49/182)	1.98E-07
V-set and transmembrane domain-containing protein 1 (VSTM1)	PF13895	24.752 (50/202)	1.26E-06
Fc receptor-like protein 6 (FCRL6)	PF13895 ; PF13927	28.440 (31/109)	7.34E-06
Leukocyte-associated immunoglobulin-like receptor 2 (LAIR2)	PF13895	28.226 (35/124)	2.65E-05
Leukocyte-associated Ig-like receptor 1 (LAIR1)	PF13895	28.030 (74/264)	2.33E-04
B7 homolog 3 (CD276)	PF13927 ; PF07686	24.434 (54/221)	2.00E-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

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

Antigen processing and presentation

Natural killer cell mediated cytotoxicity

Graft-versus-host disease

NetPath Pathway

[+] 1 NetPath Pathways

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

Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide. Haematologica. 2015 Feb;100(2):263-8.

REF 2

ClinicalTrials.gov (NCT01222286) Study on the Anti-tumor Activity, Safety and Pharmacology of IPH2101 in Patients With Smoldering Multiple Myeloma. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT01687387) Efficacy Study of Anti-KIR Monoclonal Antibody as Maintenance Treatment in Acute Myeloid Leukemia (EFFIKIR). U.S. National Institutes of Health.

REF 4

Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12879-84.

REF 5

Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood. 2009 Sep 24;114(13):2667-77.

REF 6

IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. Curr Opin Mol Ther. 2010 Dec;12(6):724-33.

REF 7

A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma

REF 8

Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood. 2009 September 24; 114(13): 2667-2677.

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