KLRG1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKLRG1, 2F1, CLEC15A, MAFA, MAFA-2F1, MAFA-L, MAFA-LIKE, killer cell lectin like receptor G1
External IDsOMIM: 604874 MGI: 1355294 HomoloGene: 4244 GeneCards: KLRG1
Orthologs
SpeciesHumanMouse
Entrez

10219

50928

Ensembl

ENSG00000139187

ENSMUSG00000030114

UniProt

Q96E93

O88713

RefSeq (mRNA)

NM_001329099
NM_001329101
NM_001329102
NM_001329103
NM_005810

NM_016970

RefSeq (protein)

NP_001316028
NP_001316030
NP_001316031
NP_001316032
NP_005801

NP_058666

Location (UCSC)Chr 12: 8.95 – 9.01 MbChr 6: 122.25 – 122.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.[5][6][7][8][9]

Function

Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules.[9]

KLRG1 is a lymphocyte co-inhibitory, or immune checkpoint, receptor expressed predominantly on late-differentiated effector and effector memory CD8+ T and NK cells. Its ligands are E-cadherin and N-cadherin with similar affinities,[10] respective markers of epithelial and mesenchymal cells.[11] Targeting of other co-inhibitory receptors for applications in oncology has gained widespread interest[12][13][14] (e.g., CTLA-4, PD-1, and its ligand PD-L1). Unlike the obvious enhanced immune activation present in CTLA-4 and PD-1 gene knockout mice,[15][16] KLRG1 knockout mice initially were found to have no abnormal features,[17] though were subsequently found to have enhanced immunity in a tuberculosis challenge model.[18]

The characterization of KLRG1 as a “senescent” marker, but other co-inhibitory receptors as “exhaustion” markers,[19][20][21] has contributed to relatively fewer studies on this molecule.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000139187 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030114 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Hanke T, Corral L, Vance RE, Raulet DH (December 1998). "2F1 antigen, the mouse homolog of the rat "mast cell function-associated antigen", is a lectin-like type II transmembrane receptor expressed by natural killer cells". European Journal of Immunology. 28 (12): 4409–17. doi:10.1002/(SICI)1521-4141(199812)28:12<4409::AID-IMMU4409>3.0.CO;2-3. PMID 9862378.
  6. ↑ Butcher S, Arney KL, Cook GP (November 1998). "MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells". European Journal of Immunology. 28 (11): 3755–62. doi:10.1002/(SICI)1521-4141(199811)28:11<3755::AID-IMMU3755>3.0.CO;2-3. PMID 9842918.
  7. ↑ Ito M, Maruyama T, Saito N, Koganei S, Yamamoto K, Matsumoto N (February 2006). "Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity". The Journal of Experimental Medicine. 203 (2): 289–95. doi:10.1084/jem.20051986. PMC 2118217. PMID 16461340.
  8. ↑ Thimme R, Appay V, Koschella M, Panther E, Roth E, Hislop AD, Rickinson AB, Rowland-Jones SL, Blum HE, Pircher H (September 2005). "Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation". Journal of Virology. 79 (18): 12112–6. doi:10.1128/JVI.79.18.12112-12116.2005. PMC 1212638. PMID 16140789.
  9. 1 2 "Entrez Gene: KLRG1 killer cell lectin-like receptor subfamily G, member 1".
  10. ↑ Nakamura S, Kuroki K, Ohki I, Sasaki K, Kajikawa M, Maruyama T, Ito M, Kameda Y, Ikura M, Yamamoto K, Matsumoto N, Maenaka K (October 2009). "Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)". The Journal of Biological Chemistry. 284 (40): 27327–35. doi:10.1074/jbc.M109.038802. PMC 2785660. PMID 19654330.
  11. ↑ Rosshart S, Hofmann M, Schweier O, Pfaff AK, Yoshimoto K, Takeuchi T, Molnar E, Schamel WW, Pircher H (December 2008). "Interaction of KLRG1 with E-cadherin: new functional and structural insights". European Journal of Immunology. 38 (12): 3354–64. doi:10.1002/eji.200838690. PMID 19009530. S2CID 21597777.
  12. ↑ Pauken KE, Wherry EJ (April 2015). "Overcoming T cell exhaustion in infection and cancer". Trends in Immunology. 36 (4): 265–76. doi:10.1016/j.it.2015.02.008. PMC 4393798. PMID 25797516.
  13. ↑ Mahoney KM, Rennert PD, Freeman GJ (August 2015). "Combination cancer immunotherapy and new immunomodulatory targets". Nature Reviews. Drug Discovery. 14 (8): 561–84. doi:10.1038/nrd4591. PMID 26228759. S2CID 2220735.
  14. ↑ Anderson AC, Joller N, Kuchroo VK (May 2016). "Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation". Immunity. 44 (5): 989–1004. doi:10.1016/j.immuni.2016.05.001. PMC 4942846. PMID 27192565.
  15. ↑ Nishimura H, Nose M, Hiai H, Minato N, Honjo T (August 1999). "Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor". Immunity. 11 (2): 141–51. doi:10.1016/s1074-7613(00)80089-8. PMID 10485649.
  16. ↑ Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH (November 1995). "Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4". Immunity. 3 (5): 541–7. doi:10.1016/1074-7613(95)90125-6. PMID 7584144.
  17. ↑ Gründemann C, Schwartzkopff S, Koschella M, Schweier O, Peters C, Voehringer D, Pircher H (May 2010). "The NK receptor KLRG1 is dispensable for virus-induced NK and CD8+ T-cell differentiation and function in vivo". European Journal of Immunology. 40 (5): 1303–14. doi:10.1002/eji.200939771. PMID 20201037.
  18. ↑ Cyktor JC, Carruthers B, Stromberg P, Flaño E, Pircher H, Turner J (April 2013). "Killer cell lectin-like receptor G1 deficiency significantly enhances survival after Mycobacterium tuberculosis infection". Infection and Immunity. 81 (4): 1090–9. doi:10.1128/IAI.01199-12. PMC 3639586. PMID 23340310.
  19. ↑ Melis L, Van Praet L, Pircher H, Venken K, Elewaut D (June 2014). "Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α production by interaction with its soluble E-cadherin ligand in chronically inflamed joints". Annals of the Rheumatic Diseases. 73 (6): 1223–31. doi:10.1136/annrheumdis-2013-203881. PMID 23740233. S2CID 206850050.
  20. ↑ Akbar AN, Henson SM (April 2011). "Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?". Nature Reviews. Immunology. 11 (4): 289–95. doi:10.1038/nri2959. PMID 21436838. S2CID 13364819.
  21. ↑ Henson SM, Akbar AN (December 2009). "KLRG1--more than a marker for T cell senescence". Age (Dordrecht, Netherlands). 31 (4): 285–91. doi:10.1007/s11357-009-9100-9. PMC 2813054. PMID 19479342.

Further reading


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