killer cell lectin like receptor C1 (CD159a)
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  |
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| 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 |
| 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 |
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| 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) |
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| 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. |
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References
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 02/10/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2849.
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