| Post Translational Modifications | N-glycosylated. The soluble form (sHLA-E) can be partly produced by proteolytic cleavage at the cell surface (shedding) by a matrix metalloproteinase. Alternative splicing is also suggested as a mechanism for generation of sHLA-E, although it remains to be proved. |
| Function | Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination. In complex with B2M/beta-2-microglobulin binds nonamer self-peptides derived from the signal sequence of classical MHC class Ia molecules (VL9 peptides - VMAPRTV/LL/V/I/FL). Peptide-bound HLA-E-B2M heterotrimeric complex primarily functions as a ligand for natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to monitor the expression of other MHC class I molecules in healthy cells and to tolerate self. Upon cellular stress, preferentially binds signal sequence-derived peptides from stress-induced chaperones and is no longer recognized by NK cell inhibitory receptor KLRD1-KLRC1, resulting in impaired protection from NK cells. Binds signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules and acts as a ligand for NK cell activating receptor KLRD1-KLRC2, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy. Besides self-peptides, can also bind and present pathogen-derived peptides conformationally similar to VL9 peptides to alpha-beta T cell receptor (TCR) on unconventional CD8-positive cytotoxic T cells, ultimately triggering antimicrobial immune response. Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV17-containing TCR, triggering HLA-E-restricted T cell responses. Presents mycobacterial peptides to HLA-E-restricted CD8-positive T cells eliciting both cytotoxic and immunoregulatory functions. (Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells. (Microbial infection) May bind HIV-1 gag/Capsid protein p24-derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell cytotoxicity, a mechanism that allows HIV-1 to escape immune recognition. (Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8-positive T cells. Binds SARS-CoV-2 S/Spike protein S1-derived peptide (LQPRTFLL) expressed on the surface of lung epithelial cells, inducing NK cell exhaustion and dampening of antiviral immune surveillance. |
| Protein Name | Hla Class I Histocompatibility Antigen - Alpha Chain EMhc Class I Antigen E Cleaved Into - Soluble Hla Class I Histocompatibility Antigen - Alpha Chain EShla-E |
| Database Links | Reactome: R-HSA-1236974Reactome: R-HSA-1236977Reactome: R-HSA-198933Reactome: R-HSA-2172127Reactome: R-HSA-2424491Reactome: R-HSA-877300Reactome: R-HSA-909733Reactome: R-HSA-9705671Reactome: R-HSA-983170 |
| Cellular Localisation | Cell MembraneSingle-Pass Type I Membrane ProteinGolgi Apparatus MembraneSoluble Hla Class I Histocompatibility AntigenAlpha Chain E: Secreted |
| Alternative Protein Names | Hla Class I Histocompatibility Antigen - Alpha Chain E proteinMhc Class I Antigen E Cleaved Into - Soluble Hla Class I Histocompatibility Antigen - Alpha Chain E proteinShla-E proteinHLA-E proteinHLA-6.2 proteinHLAE protein |
Information sourced from Uniprot.org
