KLRG1

KLRG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3FF7
Identifiers
Aliases	KLRG1 , 2F1, CLEC15A, MAFA, MAFA-2F1, MAFA-L, MAFA-LIKE, killer cell lectin like receptor G1
External IDs	OMIM: 604874; MGI: 1355294; HomoloGene: 4244; GeneCards: KLRG1; OMA:KLRG1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12p13.31 Start 8,950,044 bp [1] End 9,010,760 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 F1|6 57.52 cM Start 122,247,555 bp [2] End 122,259,841 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte testicle blood gonad epithelium of colon lymph node spleen mucosa of ileum tibialis anterior muscle ganglionic eminence Top expressed in gastrula blood decidua embryo right ventricle tibiofemoral joint right lung facial motor nucleus lymph node spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding carbohydrate binding signaling receptor activity Cellular component plasma membrane membrane integral component of membrane intracellular membrane-bounded organelle Biological process innate immune response inflammatory response immune system process cellular defense response cell surface receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 6: 122.25 – 122.26 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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. GRCh38: Ensembl release 89: ENSG00000139187 – Ensembl, May 2017
2. 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. "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

• Ortega E, Schneider H, Pecht I (April 1991). "Possible interactions between the Fc epsilon receptor and a novel mast cell function-associated antigen". International Immunology. 3 (4): 333–42. doi:10.1093/intimm/3.4.333. PMID   1831652.
• Lamers MB, Lamont AG, Williams DH (August 1998). "Human MAFA has alternatively spliced variants". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1399 (2–3): 209–12. doi:10.1016/s0167-4781(98)00107-9. PMID   9765598.
• Voehringer D, Koschella M, Pircher H (November 2002). "Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)". Blood. 100 (10): 3698–702. doi: 10.1182/blood-2002-02-0657 . PMID   12393723.
• Matsuoka TA, Artner I, Henderson E, Means A, Sander M, Stein R (March 2004). "The MafA transcription factor appears to be responsible for tissue-specific expression of insulin". Proceedings of the National Academy of Sciences of the United States of America. 101 (9): 2930–3. Bibcode:2004PNAS..101.2930M. doi: 10.1073/pnas.0306233101 . PMC   365722 . PMID   14973194.
• Marcolino I, Przybylski GK, Koschella M, Schmidt CA, Voehringer D, Schlesier M, Pircher H (October 2004). "Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history". European Journal of Immunology. 34 (10): 2672–80. doi: 10.1002/eji.200425282 . PMID   15368283. S2CID   8599066.
• Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP (May 2005). "Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57". Journal of Immunology. 174 (10): 6088–94. doi: 10.4049/jimmunol.174.10.6088 . PMID   15879103.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Bengsch B, Spangenberg HC, Kersting N, Neumann-Haefelin C, Panther E, von Weizsäcker F, Blum HE, Pircher H, Thimme R (January 2007). "Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell subsets in the peripheral blood and liver". Journal of Virology. 81 (2): 945–53. doi:10.1128/JVI.01354-06. PMC   1797464 . PMID   17079288.
• Schwartzkopff S, Gründemann C, Schweier O, Rosshart S, Karjalainen KE, Becker KF, Pircher H (July 2007). "Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans". Journal of Immunology. 179 (2): 1022–9. doi: 10.4049/jimmunol.179.2.1022 . PMID   17617594.

External links

• KLRG1 human gene location in the UCSC Genome Browser .
• KLRG1 human gene details in the UCSC Genome Browser .
• Overview of all the structural information available in the PDB for UniProt : Q96E93 (Killer cell lectin-like receptor subfamily G member 1) at the PDBe-KB .