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killer cell lectin like receptor C1 (CD159a)

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2849

Nomenclature: killer cell lectin like receptor C1 (CD159a)

Abbreviated Name: NKG2A

Systematic Nomenclature: CD159a

Family: CD molecules

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 233 12p13 KLRC1 killer cell lectin like receptor C1 5
Mouse - 244 6 G1-2 Klrc1 killer cell lectin-like receptor subfamily C, member 1
Rat - 236 4q42 Klrc1 killer cell lectin like receptor C1
Previous and Unofficial Names Click here for help
killer cell lectin-like receptor subfamily C | killer cell lectin-like receptor subfamily C, member 1 | NKG2-1/B activating NK receptor | NKG2-A
Database Links Click here for help
Alphafold P26715 (Hs)
CATH/Gene3D 3.10.100.10
ChEMBL Target CHEMBL4630892 (Hs)
Ensembl Gene ENSG00000134545 (Hs), ENSMUSG00000030167 (Mm), ENSRNOG00000055196 (Rn)
Entrez Gene 3821 (Hs), 16641 (Mm), 29683 (Rn)
Human Protein Atlas ENSG00000134545 (Hs)
KEGG Gene hsa:3821 (Hs), mmu:16641 (Mm), rno:29683 (Rn)
OMIM 161555 (Hs)
Pharos P26715 (Hs)
RefSeq Nucleotide NM_002259 (Hs), NM_001136068 (Mm), NM_001037441 (Rn)
RefSeq Protein NP_002250 (Hs), NP_001129540 (Mm), NP_001032518 (Rn)
UniProtKB P26715 (Hs)
Wikipedia KLRC1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
monalizumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding ~10.6 pKd 1
⤷ pKd ~10.6 (Kd ~2.7x10-11 M) [1]
Immunopharmacology Comments
NKG2A (KLRC1; CD159a) acts as an inhibitory checkpoint receptor for HLA-E. NKG2A forms functional heterodimers with CD94 (KLRD1) to form a human leukocyte antigen E (HLA-E) recognition complex on a subset of natural killer (NK) cells and cytotoxic T cells. NKG2A/CD94/HLA-E binding suppresses immune vigilance, and overexpression of HLA-E is used by cancer cells to evade immune recognition and destruction [3,6-7,9]. As a result NKG2A is being investigated as a molecular target for the development of novel cancer immunotherapeutics.

Novel anti-NKG2A monoclonals such as Innate Pharma's antibody monalizumab (code named IPH2201), block NKG2A/CD94 activation, and re-establish NK and T cell-driven destruction of cancer cells, even in the presence of HLA-E [2,4]. This therapeutic effect could be used to complement first-generation immuno-oncology agents, such as the PD-1/PD-L1 checkpoint inhibitors.
Cell Type Associations
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
Comment:  Expression has been reported on NK and T cells from many human cancers.
References:  2,8
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0001915 negative regulation of T cell mediated cytotoxicity IDA
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway IBA
GO:0002305 CD8-positive, gamma-delta intraepithelial T cell differentiation IDA
GO:0002769 natural killer cell inhibitory signaling pathway IDA
GO:0032814 regulation of natural killer cell activation NAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0001915 negative regulation of T cell mediated cytotoxicity IDA
GO:0002223 stimulatory C-type lectin receptor signaling pathway IBA
GO:0002769 natural killer cell inhibitory signaling pathway IDA
GO:0032814 regulation of natural killer cell activation NAS
GO:0045953 negative regulation of natural killer cell mediated cytotoxicity IDA
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity IBA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0002305 CD8-positive, gamma-delta intraepithelial T cell differentiation IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway IBA
GO:0045953 negative regulation of natural killer cell mediated cytotoxicity IDA
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity IBA
click arrow to show/hide IEA associations
GO:0045087 innate immune response IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0001915 negative regulation of T cell mediated cytotoxicity IDA
GO:0002305 CD8-positive, gamma-delta intraepithelial T cell differentiation IDA
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA

References

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1. Andre P, Blery M, Paturel C, Soulas C, Wagtmann N. (2016) Treatment regimens using anti-nkg2a antibodies. Patent number: WO2016041947. Assignee: Innate Pharma. Priority date: 16/09/2014. Publication date: 24/03/2016.

2. André P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T, Bléry M, Bonnafous C, Gauthier L, Morel A et al.. (2018) Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell, 175 (7): 1731-1743.e13. [PMID:30503213]

3. Derré L, Corvaisier M, Charreau B, Moreau A, Godefroy E, Moreau-Aubry A, Jotereau F, Gervois N. (2006) Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of cytotoxic effector cells. J Immunol, 177 (5): 3100-7. [PMID:16920947]

4. Godal R, Bachanova V, Gleason M, McCullar V, Yun GH, Cooley S, Verneris MR, McGlave PB, Miller JS. (2010) Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade. Biol Blood Marrow Transplant, 16 (5): 612-21. [PMID:20139023]

5. Houchins JP, Yabe T, McSherry C, Bach FH. (1991) DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. J Exp Med, 173 (4): 1017-20. [PMID:2007850]

6. Levy EM, Bianchini M, Von Euw EM, Barrio MM, Bravo AI, Furman D, Domenichini E, Macagno C, Pinsky V, Zucchini C et al.. (2008) Human leukocyte antigen-E protein is overexpressed in primary human colorectal cancer. Int J Oncol, 32 (3): 633-41. [PMID:18292941]

7. Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J, Castellano R, Gonçalves A, André P, Romagné F, Thibault G et al.. (2011) Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest, 121 (9): 3609-22. [PMID:21841316]

8. Mariotti FR, Quatrini L, Munari E, Vacca P, Moretta L. (2019) Innate Lymphoid Cells: Expression of PD-1 and Other Checkpoints in Normal and Pathological Conditions. Front Immunol, 10: 910. [PMID:31105707]

9. Silva TG, Crispim JC, Miranda FA, Hassumi MK, de Mello JM, Simões RT, Souto F, Soares EG, Donadi EA, Soares CP. (2011) Expression of the nonclassical HLA-G and HLA-E molecules in laryngeal lesions as biomarkers of tumor invasiveness. Histol Histopathol, 26 (12): 1487-97. [PMID:21972088]

How to cite this page

CD molecules: killer cell lectin like receptor C1 (CD159a). Last modified on 25/02/2021. Accessed on 02/07/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2849.