KLRG1 Products

Description

KLRG1 (killer cell lectin-like receptor G1), also known as CLEC15A and MAFA, belongs to the KLR family. KLRG1 is a lectin-like inhibitory receptor that is a single pass type II transmembrane protein (1). KLRG1 functions in innate immunity and has an inhibitory role on the function of natural killer (NK) cells and T cells that is induced by binding to their non-MHC ligands (1,2). The KLRG1 protein exists as both a monomer and homodimer and is expressed as an inhibitory receptor on NK cells as well as subsets of CD4+ and CD8+ T cells, gammadelta T cells, and alphabeta T cells (1,3,4). The human KLRG1 protein is 195 amino acids (aa) in length with a theoretical molecular weight (MW) of 21.8 kDa (2). Given KLRG1 protein glycosylation and disulfide bonds, the observed molecular weight often ranges from 30-38 kDa. The human KLRG1 protein consists of a cytoplasmic domain at 1-38 aa with one immunoreceptor tyrosine-based inhibitory motif (ITIM) at 5-10 aa, a transmembrane segment at 39-59 aa, and an extracellular domain (ECD) at 60-195 aa with one C-type lectin domain (CTLD) at 82-185 aa (2).

KLRG1's primary ligand is E-cadherin, which is expressed on non-neural epithelial tissues, but the KLRG1 receptor also recognizes both N- and R-cadherin expressed in nervous system tissues (1,3,5,6). E-cadherin binding of KLRG1 leads to ITIM triggering and, ultimately, either reduced T cell proliferation or decreased NK cell cytotoxicity (3,5,6). More precisely, upon differentiation of CD8+ T cells, cells switch from signaling through CD28 and instead signal through the inhibitory KLRG1 receptor molecule (3,4). Phosphorylation of KLRG1's ITIM causes recruitment of two phosphatases, SH2-containing inositol polyphosphate 5-phoshate (SHIP-1) and SH-2 containing protein-tyrosine phosphatase 2 (SHP-2) (3,5). The effectors SHIP-1 and SHP-2 degrade PIP3 to PIP2, preventing Akt phosphorylation and inhibiting proliferation (3,5,6). Conversely, when KLRG1 signaling is blocked in highly differentiated T cells, Akt signaling is restored and cell proliferation resumes (3). An increase in highly differentiated T cells is observed in many age-related infections such as meningitis, pneumonia, and influenza, which also correlates with elevated KLRG1 levels (3). This observation suggests that KLRG1 may be a potential immunotherapeutic target, especially for vaccinations which typically have decreased response in aged patients (3).

References

1. Li Y, Hofmann M, Wang Q, Teng L, Chlewicki LK, Pircher H, Mariuzza RA. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity. 2009 Jul 17;31(1):35-46. http://doi.org/10.1016/j.immuni.2009.04.019

2. Uniprot(Q96E93)

3. Henson SM, Akbar AN. KLRG1--more than a marker for T cell senescence. Age (Dordr). 2009 Dec;31(4):285-91. http://doi.org/10.1007/s11357-009-9100-9.

4. Thimme R, Appay V, Koschella M, Panther E, Roth E, Hislop AD, Rickinson AB, Rowland-Jones SL, Blum HE, Pircher H. Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. J Virol. 2005 Sep;79(18):12112-6.http://doi.org/10.1128/JVI.79.18.12112-12116.2005.

5. Borys SM, Bag AK, Brossay L, Adeegbe DO. The Yin and Yang of Targeting KLRG1+ Tregs and Effector Cells. Front Immunol. 2022 Apr 29;13:894508. http://doi.org10.3389/fimmu.2022.894508.

6. Van den Bossche J, Malissen B, Mantovani A, De Baetselier P, Van Ginderachter JA. Regulation and function of the E-cadherin/catenin complex in cells of the monocyte-macrophage lineage and DCs. Blood. 2012 Feb 16;119(7):1623-33. http://doi.org/10.1182/blood-2011-10-384289.

Bioinformatics

Entrez	10219 Human
Uniprot	NP_005801 Human NP_005801.3 Human
Product By Gene ID	10219
Alternate Names	2F1 CLEC15AMAFA-LIKE C-type lectin domain family 15 member A C-type lectin domain family 15, member A ITIM-containing receptor MAFA-L killer cell lectin-like receptor subfamily G member 1 killer cell lectin-like receptor subfamily G, member 1 MAFAL MAFA-L MAFA-like receptor MAFAMAFA-2F1 mast cell function-associated antigen (ITIM-containing) Mast cell function-associated antigen MGC13600

Research Areas for KLRG1

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Signal Transduction