View source for HLA E

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
 | image = PBB_Protein_HLA-E_image.jpg
 | image_source = [[Protein_Data_Bank|PDB]] rendering based on 1kpr.
 | PDB = {{PDB2|1kpr}}, {{PDB2|1ktl}}, {{PDB2|1mhe}}, {{PDB2|2esv}}
 | Name = Major histocompatibility complex, class I, E
 | HGNCid = 4962
 | Symbol = HLA-E
 | AltSymbols =; DKFZp686P19218; EA1.2; EA2.1; HLA-6.2; MHC
 | OMIM = 143010
 | ECnumber =  
 | Homologene = 38064
 | MGIid = 95957
 | GeneAtlas_image1 = PBB_GE_HLA-E_200904_at_tn.png
 | GeneAtlas_image2 = PBB_GE_HLA-E_200905_x_at_tn.png
 | GeneAtlas_image3 = PBB_GE_HLA-E_217456_x_at_tn.png
 | Function = {{GNF_GO|id=GO:0032393 |text = MHC class I receptor activity}} 
 | Component = {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0042612 |text = MHC class I protein complex}} 
 | Process = {{GNF_GO|id=GO:0002474 |text = antigen processing and presentation of peptide antigen via MHC class I}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0019882 |text = antigen processing and presentation}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3133
    | Hs_Ensembl = ENSG00000204592
    | Hs_RefseqProtein = NP_005507
    | Hs_RefseqmRNA = NM_005516
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 6
    | Hs_GenLoc_start = 30565198
    | Hs_GenLoc_end = 30569950
    | Hs_Uniprot = P13747
    | Mm_EntrezGene = 15040
    | Mm_Ensembl = ENSMUSG00000067212
    | Mm_RefseqmRNA = XM_001004712
    | Mm_RefseqProtein = XP_001004712
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 35638029
    | Mm_GenLoc_end = 35640754
    | Mm_Uniprot = Q31130
  }}
}}

'''Major histocompatibility complex, class I, E''', also known as '''HLA-E''', is a human [[gene]].

<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title = 
| summary_text = HLA-E belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail.<ref>{{cite web | title = Entrez Gene: HLA-E major histocompatibility complex, class I, E| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3133| accessdate = }}</ref>
}}

HLA-E is a protein that is a member of the [[Human Leukocyte Antigen|HLA family]]. It is one of a family of molecules known as [[MHC class I|MHC class Ib]] and has a very specialized role in cell recognition by [[NK cells]] (Natural Killer). HLA-E is very highly conserved and presents a small repertoire of peptides of various origins.<ref>{{cite journal |author=Rodgers JR, Cook, RG|title=MHC CLASS IB MOLECULES BRIDGE INNATE AND ACQUIRED IMMUNITY |journal=Nat Rev Immunol. |volume=5 |issue=6 |pages=459-471|year=2005 |pmid=15928678 }}</ref> HLA-E is expressed ubiquitously. The primary peptides HLA-E binds are derived from the leader sequence of other HLA class Ia molecules, such as HLA-A, B, C, G.These proteins bind to the [[Peptide binding groove]] of the HLA-E molecule, and this allows it to be expressed on  on the [[Cell Membrane|surface]]. NK cells recognise bound HLA-E+Peptide combination using the heterodimeric inhibitory receptor [[CD94]]/[[NKG2]]A or the activating receptor NKG2C/CD94 . When CD94/NKG2A is stimulated, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis.

A number of viruses have evolved to express proteins that inhibit the expression of MHC I molecules on cell surface of cells they infect, thereby preventing [[Antigen presentation]] that would allow the [[Immune system]] to recognise infection. NK cells therefore identify cells that are exhibiting such characteristics of viral infection.

HLA E is also reported to interact with the T-cell receptor.<ref>{{cite journal |author=Hoare HL, Sullivan LC, Pietra G et al |title=Structural basis for a major histocompatibility complex class Ib-restricted T cell response |journal=Nat. Immunol. |volume=7 |issue=3 |pages=256-64 |year=2006 |pmid=16474394 |doi=10.1038/ni1312}}</ref> HLA-E presents a peptide (VMAPRTLIL) derived from the UL40 protein from cytomegalovirus. This peptide is highly similar to the leader peptides derived from other HLA molecules and acts as a surrogate "leader peptide" and interacts with CD94/NKG2 receptors. This engagement relays into an overall inhibitory effect on NK-cell meditated cytotoxicity.   

==References==
{{reflist|2}}

==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Arnaiz-Villena A, Martinez-Laso J, Alvarez M, ''et al.'' |title=Primate Mhc-E and -G alleles. |journal=Immunogenetics |volume=46 |issue= 4 |pages= 251-66 |year= 1997 |pmid= 9218527 |doi=  }}
*{{cite journal  | author=Geyer M, Fackler OT, Peterlin BM |title=Structure--function relationships in HIV-1 Nef. |journal=EMBO Rep. |volume=2 |issue= 7 |pages= 580-5 |year= 2001 |pmid= 11463741 |doi= 10.1093/embo-reports/kve141 }}
*{{cite journal  | author=Greenway AL, Holloway G, McPhee DA, ''et al.'' |title=HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication. |journal=J. Biosci. |volume=28 |issue= 3 |pages= 323-35 |year= 2004 |pmid= 12734410 |doi=  }}
*{{cite journal  | author=Bénichou S, Benmerah A |title=[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway] |journal=Med Sci (Paris) |volume=19 |issue= 1 |pages= 100-6 |year= 2003 |pmid= 12836198 |doi=  }}
*{{cite journal  | author=Leavitt SA, SchOn A, Klein JC, ''et al.'' |title=Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm. |journal=Curr. Protein Pept. Sci. |volume=5 |issue= 1 |pages= 1-8 |year= 2004 |pmid= 14965316 |doi=  }}
*{{cite journal  | author=Tolstrup M, Ostergaard L, Laursen AL, ''et al.'' |title=HIV/SIV escape from immune surveillance: focus on Nef. |journal=Curr. HIV Res. |volume=2 |issue= 2 |pages= 141-51 |year= 2004 |pmid= 15078178 |doi=  }}
*{{cite journal  | author=Joseph AM, Kumar M, Mitra D |title=Nef: "necessary and enforcing factor" in HIV infection. |journal=Curr. HIV Res. |volume=3 |issue= 1 |pages= 87-94 |year= 2005 |pmid= 15638726 |doi=  }}
*{{cite journal  | author=Anderson JL, Hope TJ |title=HIV accessory proteins and surviving the host cell. |journal=Current HIV/AIDS reports |volume=1 |issue= 1 |pages= 47-53 |year= 2005 |pmid= 16091223 |doi=  }}
*{{cite journal  | author=Kozlowski S, Corr M, Takeshita T, ''et al.'' |title=Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules. |journal=J. Exp. Med. |volume=175 |issue= 6 |pages= 1417-22 |year= 1992 |pmid= 1316930 |doi=  }}
*{{cite journal  | author=Ulbrecht M, Honka T, Person S, ''et al.'' |title=The HLA-E gene encodes two differentially regulated transcripts and a cell surface protein. |journal=J. Immunol. |volume=149 |issue= 9 |pages= 2945-53 |year= 1992 |pmid= 1401923 |doi=  }}
*{{cite journal  | author=Truong MJ, Gruart V, Capron A, ''et al.'' |title=Cloning and expression of a cDNA encoding a non-classical MHC class I antigen (HLA-E) in eosinophils from hypereosinophilic patients. |journal=J. Immunol. |volume=148 |issue= 2 |pages= 627-32 |year= 1992 |pmid= 1530866 |doi=  }}
*{{cite journal  | author=Houlihan JM, Biro PA, Fergar-Payne A, ''et al.'' |title=Evidence for the expression of non-HLA-A,-B,-C class I genes in the human fetal liver. |journal=J. Immunol. |volume=149 |issue= 2 |pages= 668-75 |year= 1992 |pmid= 1624808 |doi=  }}
*{{cite journal  | author=Ohya K, Kondo K, Mizuno S |title=Polymorphism in the human class I MHC locus HLA-E in Japanese. |journal=Immunogenetics |volume=32 |issue= 3 |pages= 205-9 |year= 1990 |pmid= 1977695 |doi=  }}
*{{cite journal  | author=Wei XH, Orr HT |title=Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. |journal=Hum. Immunol. |volume=29 |issue= 2 |pages= 131-42 |year= 1991 |pmid= 2249951 |doi=  }}
*{{cite journal  | author=Srivastava R, Chorney MJ, Lawrance SK, ''et al.'' |title=Structure, expression, and molecular mapping of a divergent member of the class I HLA gene family. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 12 |pages= 4224-8 |year= 1987 |pmid= 2438694 |doi=  }}
*{{cite journal  | author=Pohla H, Kuon W, Tabaczewski P, ''et al.'' |title=Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles. |journal=Immunogenetics |volume=29 |issue= 5 |pages= 297-307 |year= 1989 |pmid= 2714852 |doi=  }}
*{{cite journal  | author=Takahashi H, Merli S, Putney SD, ''et al.'' |title=A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. |journal=Science |volume=246 |issue= 4926 |pages= 118-21 |year= 1989 |pmid= 2789433 |doi=  }}
*{{cite journal  | author=Carroll MC, Katzman P, Alicot EM, ''et al.'' |title=Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 23 |pages= 8535-9 |year= 1988 |pmid= 2825194 |doi=  }}
*{{cite journal  | author=Mizuno S, Trapani JA, Koller BH, ''et al.'' |title=Isolation and nucleotide sequence of a cDNA clone encoding a novel HLA class I gene. |journal=J. Immunol. |volume=140 |issue= 11 |pages= 4024-30 |year= 1988 |pmid= 3131426 |doi=  }}
*{{cite journal  | author=Koller BH, Geraghty DE, Shimizu Y, ''et al.'' |title=HLA-E. A novel HLA class I gene expressed in resting T lymphocytes. |journal=J. Immunol. |volume=141 |issue= 3 |pages= 897-904 |year= 1988 |pmid= 3260916 |doi=  }}
}}
{{refend}}

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{{Surface antigens}}
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