ID HLAE_HUMAN Reviewed; 358 AA. AC P13747; E2G051; Q30169; Q6DU44; Q9BT83; Q9GIY7; Q9GIY8; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 05-DEC-2018, sequence version 4. DT 05-FEB-2025, entry version 225. DE RecName: Full=HLA class I histocompatibility antigen, alpha chain E; DE AltName: Full=MHC class I antigen E; DE Contains: DE RecName: Full=Soluble HLA class I histocompatibility antigen, alpha chain E; DE Short=sHLA-E {ECO:0000303|PubMed:17179229}; DE Flags: Precursor; GN Name=HLA-E {ECO:0000303|PubMed:9486650, ECO:0000312|HGNC:HGNC:4962}; GN Synonyms=HLA-6.2, HLAE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE E*01:01). RX PubMed=3131426; RA Mizuno S., Trapani J.A., Koller B.H., Dupont B., Yang S.Y.; RT "Isolation and nucleotide sequence of a cDNA clone encoding a novel HLA RT class I gene."; RL J. Immunol. 140:4024-4030(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELES E*01:01 AND E*01:03). RX PubMed=10064069; RX DOI=10.1002/(sici)1521-4141(199902)29:02<537::aid-immu537>3.0.co;2-6; RA Ulbrecht M., Courturier A., Martinozzi S., Pla M., Srivastava R., RA Peterson P.A., Weiss E.H.; RT "Cell surface expression of HLA-E: interaction with human beta-2 RT microglobulin and allelic differences."; RL Eur. J. Immunol. 29:537-547(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=3260916; RA Koller B.H., Geraghty D.E., Shimizu Y., Demars R., Orr H.T.; RT "HLA-E. A novel HLA class I gene expressed in resting T lymphocytes."; RL J. Immunol. 141:897-904(1988). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-203 (ALLELE E*01:04). RC TISSUE=Peripheral blood; RX PubMed=1977695; DOI=10.1007/bf02114975; RA Ohya K., Kondo K., Mizuno S.; RT "Polymorphism in the human class I MHC locus HLA-E in Japanese."; RL Immunogenetics 32:205-209(1990). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE E*01:03). RX PubMed=16702430; DOI=10.1534/genetics.106.057034; RA Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M., RA Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K., RA Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A., RA Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T., RA Inoko H., Bahram S.; RT "Rapid evolution of major histocompatibility complex class I genes in RT primates generates new disease alleles in humans via hitchhiking RT diversity."; RL Genetics 173:1555-1570(2006). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE E*01:03). RX PubMed=16570139; DOI=10.1007/s00251-005-0076-z; RA Pyo C.W., Williams L.M., Moore Y., Hyodo H., Li S.S., Zhao L.P., RA Sageshima N., Ishitani A., Geraghty D.E.; RT "HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype RT structure and variation spanning the nonclassical class I genes."; RL Immunogenetics 58:241-251(2006). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE E*01:03:01:03 AND ALLELE RP E*01:03:01:04). RX PubMed=28127896; DOI=10.1111/tan.12965; RA Olieslagers T.I., Voorter C.E., Groeneweg M., Xu Y., Wieten L., RA Tilanus M.G.; RT "New insights in HLA-E polymorphism by refined analysis of the full-length RT gene."; RL HLA 89:143-149(2017). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE E*01:03). RA He X., Xu L., Liu Y., Zeng Y.; RT "A new variant of HLA-E*010303 with three synonymous mutations."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE E*01:03). RA He X., Xu L., Liu Y., Zeng Y.; RT "Cloning of HLA-E cDNA from activated peripheral leukocytes."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE E*01:03). RA Xu Y., Wang S.; RT "Characterization of genomic full-length sequence of HLA-E in Chinese RT individuals."; RL Submitted (AUG-2016) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-295, AND VARIANT ARG-128. RA Veiga-Castelli L.C., Castelli E.C., Silva-Junior W.A., Donadi E.A.; RT "A new HLA-E allele in the Brazilian population."; RL Submitted (MAY-2010) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE E*01:01). RA Shiina S., Tamiya G., Oka A., Inoko H.; RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE E*01:01 AND ALLELE E*01:03). RC TISSUE=Lung, Ovarian adenocarcinoma, and Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [15] RP SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH B2M, AND INTERACTION WITH RP CALR AND TAP2. RX PubMed=9427624; DOI=10.1016/s0960-9822(98)70014-4; RA Braud V.M., Allan D.S., Wilson D., McMichael A.J.; RT "TAP- and tapasin-dependent HLA-E surface expression correlates with the RT binding of an MHC class I leader peptide."; RL Curr. Biol. 8:1-10(1998). RN [16] RP FUNCTION, AND SUBUNIT. RX PubMed=9754572; RX DOI=10.1002/(sici)1521-4141(199809)28:09<2854::aid-immu2854>3.0.co;2-w; RA Llano M., Lee N., Navarro F., Garcia P., Albar J.P., Geraghty D.E., RA Lopez-Botet M.; RT "HLA-E-bound peptides influence recognition by inhibitory and triggering RT CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer."; RL Eur. J. Immunol. 28:2854-2863(1998). RN [17] RP FUNCTION, SUBUNIT, AND INTERACTION WITH KLRD1-KLRC1. RX PubMed=9486650; DOI=10.1038/35869; RA Braud V.M., Allan D.S., O'Callaghan C.A., Soederstroem K., D'Andrea A., RA Ogg G.S., Lazetic S., Young N.T., Bell J.I., Phillips J.H., Lanier L.L., RA McMichael A.J.; RT "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C."; RL Nature 391:795-799(1998). RN [18] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=10799855; DOI=10.4049/jimmunol.164.10.5019; RA Ulbrecht M., Martinozzi S., Grzeschik M., Hengel H., Ellwart J.W., Pla M., RA Weiss E.H.; RT "The human cytomegalovirus UL40 gene product contains a ligand for HLA-E RT and prevents NK cell-mediated lysis."; RL J. Immunol. 164:5019-5022(2000). RN [19] RP FUNCTION. RX PubMed=12461076; DOI=10.1084/jem.20020797; RA Michaelsson J., Teixeira de Matos C., Achour A., Lanier L.L., Kaerre K., RA Soederstroem K.; RT "A signal peptide derived from hsp60 binds HLA-E and interferes with RT CD94/NKG2A recognition."; RL J. Exp. Med. 196:1403-1414(2002). RN [20] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=15751767; DOI=10.1177/135965350501000107; RA Nattermann J., Nischalke H.D., Hofmeister V., Kupfer B., Ahlenstiel G., RA Feldmann G., Rockstroh J., Weiss E.H., Sauerbruch T., Spengler U.; RT "HIV-1 infection leads to increased HLA-E expression resulting in impaired RT function of natural killer cells."; RL Antivir. Ther. 10:95-107(2005). RN [21] RP TISSUE SPECIFICITY, INDUCTION BY PRO-INFLAMMATORY CYTOKINES, FUNCTION, PTM, RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=17179229; DOI=10.1182/blood-2006-06-030213; RA Coupel S., Moreau A., Hamidou M., Horejsi V., Soulillou J.P., Charreau B.; RT "Expression and release of soluble HLA-E is an immunoregulatory feature of RT endothelial cell activation."; RL Blood 109:2806-2814(2007). RN [22] RP FUNCTION, SUBUNIT, INTERACTION WITH KLRD1-KLRC1 AND KLRD1-KLRC2, AND RP MUTAGENESIS OF ARG-83; ARG-86; ASP-90; GLN-93; ARG-96; VAL-97; ARG-100; RP GLU-110; ARG-129; LYS-167; ASP-170; GLU-173; GLU-175; HIS-176; ASP-183; RP GLU-187 AND THR-235. RX PubMed=18083576; DOI=10.1016/j.immuni.2007.10.013; RA Sullivan L.C., Clements C.S., Beddoe T., Johnson D., Hoare H.L., Lin J., RA Huyton T., Hopkins E.J., Reid H.H., Wilce M.C., Kabat J., Borrego F., RA Coligan J.E., Rossjohn J., Brooks A.G.; RT "The heterodimeric assembly of the CD94-NKG2 receptor family and RT implications for human leukocyte antigen-E recognition."; RL Immunity 27:900-911(2007). RN [23] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-107. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [24] RP SUBUNIT, AND INTERACTION WITH HLA-F-B2M COMPLEX. RX PubMed=20483783; DOI=10.4049/jimmunol.1000078; RA Goodridge J.P., Burian A., Lee N., Geraghty D.E.; RT "HLA-F complex without peptide binds to MHC class I protein in the open RT conformer form."; RL J. Immunol. 184:6199-6208(2010). RN [25] RP FUNCTION. RX PubMed=20195504; DOI=10.1371/journal.ppat.1000782; RA Joosten S.A., van Meijgaarden K.E., van Weeren P.C., Kazi F., Geluk A., RA Savage N.D., Drijfhout J.W., Flower D.R., Hanekom W.A., Klein M.R., RA Ottenhoff T.H.; RT "Mycobacterium tuberculosis peptides presented by HLA-E molecules are RT targets for human CD8 T-cells with cytotoxic as well as regulatory RT activity."; RL PLoS Pathog. 6:e1000782-e1000782(2010). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [27] RP FUNCTION (MICROBIAL INFECTION), SUBUNIT, AND INTERACTION WITH KLRD1-KLRC2. RX PubMed=23335510; DOI=10.1074/jbc.m112.409672; RA Heatley S.L., Pietra G., Lin J., Widjaja J.M., Harpur C.M., Lester S., RA Rossjohn J., Szer J., Schwarer A., Bradstock K., Bardy P.G., Mingari M.C., RA Moretta L., Sullivan L.C., Brooks A.G.; RT "Polymorphism in human cytomegalovirus UL40 impacts on recognition of human RT leukocyte antigen-E (HLA-E) by natural killer cells."; RL J. Biol. Chem. 288:8679-8690(2013). RN [28] RP FUNCTION. RX PubMed=30134159; DOI=10.1016/j.celrep.2018.07.069; RA Roelle A., Meyer M., Calderazzo S., Jaeger D., Momburg F.; RT "Distinct HLA-E Peptide Complexes Modify Antibody-Driven Effector Functions RT of Adaptive NK Cells."; RL Cell Rep. 24:1967-1976(2018). RN [29] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=32859121; DOI=10.3390/cells9091975; RA Bortolotti D., Gentili V., Rizzo S., Rotola A., Rizzo R.; RT "SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the RT HLA-E/NKG2A Pathway."; RL Cells 9:0-0(2020). RN [30] RP FUNCTION. RX PubMed=34228645; DOI=10.1172/jci148979; RA Bansal A., Gehre M.N., Qin K., Sterrett S., Ali A., Dang Y., Abraham S., RA Costanzo M.C., Venegas L.A., Tang J., Manjunath N., Brockman M.A., RA Yang O.O., Kan-Mitchell J., Goepfert P.A.; RT "HLA-E-restricted HIV-1-specific CD8+ T cell responses in natural RT infection."; RL J. Clin. Invest. 131:0-0(2021). RN [31] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=37264229; DOI=10.1038/s41590-023-01523-z; RA Lin Z., Bashirova A.A., Viard M., Garner L., Quastel M., Beiersdorfer M., RA Kasprzak W.K., Akdag M., Yuki Y., Ojeda P., Das S., Andresson T., RA Naranbhai V., Horowitz A., McMichael A.J., Hoelzemer A., Gillespie G.M., RA Garcia-Beltran W.F., Carrington M.; RT "HLA class I signal peptide polymorphism determines the level of CD94/NKG2- RT HLA-E-mediated regulation of effector cell responses."; RL Nat. Immunol. 24:1087-1097(2023). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 22-295, AND SUBUNIT. RX PubMed=9660937; DOI=10.1016/s1097-2765(00)80053-2; RA O'Callaghan C.A., Tormo J., Willcox B.E., Braud V.M., Jakobsen B.K., RA Stuart D.I., McMichael A.J., Bell J.I., Jones E.Y.; RT "Structural features impose tight peptide binding specificity in the RT nonclassical MHC molecule HLA-E."; RL Mol. Cell 1:531-541(1998). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 23-297, FUNCTION, AND SUBUNIT. RX PubMed=16474394; DOI=10.1038/ni1312; RA Hoare H.L., Sullivan L.C., Pietra G., Clements C.S., Lee E.J., Ely L.K., RA Beddoe T., Falco M., Kjer-Nielsen L., Reid H.H., McCluskey J., Moretta L., RA Rossjohn J., Brooks A.G.; RT "Structural basis for a major histocompatibility complex class Ib- RT restricted T cell response."; RL Nat. Immunol. 7:256-264(2006). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 22-297 IN COMPLEX WITH RP SELF-PEPTIDE, DISULFIDE BOND, FUNCTION, AND SUBUNIT. RX PubMed=18339401; DOI=10.1016/j.jmb.2008.01.098; RA Hoare H.L., Sullivan L.C., Clements C.S., Ely L.K., Beddoe T., RA Henderson K.N., Lin J., Reid H.H., Brooks A.G., Rossjohn J.; RT "Subtle changes in peptide conformation profoundly affect recognition of RT the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural RT killer cell receptors."; RL J. Mol. Biol. 377:1297-1303(2008). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 22-295 IN COMPLEX WITH RP PATHOGEN-DERIVED PEPTIDE, DISULFIDE BOND, FUNCTION, AND SUBUNIT. RX PubMed=30087334; DOI=10.1038/s41467-018-05459-z; RA Walters L.C., Harlos K., Brackenridge S., Rozbesky D., Barrett J.R., RA Jain V., Walter T.S., O'Callaghan C.A., Borrow P., Toebes M., Hansen S.G., RA Sacha J., Abdulhaqq S., Greene J.M., Frueh K., Marshall E., Picker L.J., RA Jones E.Y., McMichael A.J., Gillespie G.M.; RT "Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket RT tolerability and conformationally malleable peptide binding."; RL Nat. Commun. 9:3137-3137(2018). RN [36] RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 22-297 IN COMPLEX WITH RP PATHOGEN-DERIVED PEPTIDE, DISULFIDE BOND, FUNCTION, AND SUBUNIT. RX PubMed=35705051; DOI=10.1016/j.celrep.2022.110959; RA Walters L.C., Rozbesky D., Harlos K., Quastel M., Sun H., Springer S., RA Rambo R.P., Mohammed F., Jones E.Y., McMichael A.J., Gillespie G.M.; RT "Primary and secondary functions of HLA-E are determined by stability and RT conformation of the peptide-bound complexes."; RL Cell Rep. 39:110959-110964(2022). RN [37] RP POLYMORPHISM, AND QUESTIONING ON ALLELES E*01:02 AND E*01:04. RX PubMed=12445303; DOI=10.1034/j.1399-0039.2002.600302.x; RA Grimsley C., Kawasaki A., Gassner C., Sageshima N., Nose Y., Hatake K., RA Geraghty D.E., Ishitani A.; RT "Definitive high resolution typing of HLA-E allelic polymorphisms: RT identifying potential errors in existing allele data."; RL Tissue Antigens 60:206-212(2002). RN [38] RP POLYMORPHISM, AND QUESTIONING ON ALLELES E*01:02 AND E*01:04. RX PubMed=22665232; DOI=10.1007/978-1-61779-842-9_8; RA Lauterbach N., Voorter C.E., Tilanus M.G.; RT "Molecular typing of HLA-E."; RL Methods Mol. Biol. 882:143-158(2012). CC -!- FUNCTION: Non-classical major histocompatibility class Ib molecule CC involved in immune self-nonself discrimination. In complex with CC B2M/beta-2-microglobulin binds nonamer self-peptides derived from the CC signal sequence of classical MHC class Ia molecules (VL9 peptides CC - VMAPRT[V/L][L/V/I/F]L) (PubMed:18083576, PubMed:18339401, CC PubMed:35705051, PubMed:37264229, PubMed:9754572). Peptide-bound HLA-E- CC B2M heterotrimeric complex primarily functions as a ligand for natural CC killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to CC monitor the expression of other MHC class I molecules in healthy cells CC and to tolerate self (PubMed:17179229, PubMed:18083576, CC PubMed:37264229, PubMed:9486650, PubMed:9754572). Upon cellular stress, CC preferentially binds signal sequence-derived peptides from stress- CC induced chaperones and is no longer recognized by NK cell inhibitory CC receptor KLRD1-KLRC1, resulting in impaired protection from NK cells CC (PubMed:12461076). Binds signal sequence-derived peptides from non- CC classical MHC class Ib HLA-G molecules and acts as a ligand for NK cell CC activating receptor KLRD1-KLRC2, likely playing a role in the CC generation and effector functions of adaptive NK cells and in maternal- CC fetal tolerance during pregnancy (PubMed:30134159, PubMed:37264229, CC PubMed:9754572). Besides self-peptides, can also bind and present CC pathogen-derived peptides conformationally similar to VL9 peptides to CC alpha-beta T cell receptor (TCR) on unconventional CD8-positive CC cytotoxic T cells, ultimately triggering antimicrobial immune response CC (PubMed:16474394, PubMed:20195504, PubMed:30087334, PubMed:34228645). CC Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant CC KALGPAATL epitopes) predominantly to CD8-positive T cell clones CC expressing a TRAV17-containing TCR, triggering HLA-E-restricted T cell CC responses (PubMed:34228645). Presents mycobacterial peptides to HLA-E- CC restricted CD8-positive T cells eliciting both cytotoxic and CC immunoregulatory functions (PubMed:20195504, PubMed:35705051). CC {ECO:0000269|PubMed:12461076, ECO:0000269|PubMed:16474394, CC ECO:0000269|PubMed:17179229, ECO:0000269|PubMed:18083576, CC ECO:0000269|PubMed:18339401, ECO:0000269|PubMed:20195504, CC ECO:0000269|PubMed:30087334, ECO:0000269|PubMed:30134159, CC ECO:0000269|PubMed:34228645, ECO:0000269|PubMed:35705051, CC ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9486650, CC ECO:0000269|PubMed:9754572}. CC -!- FUNCTION: (Microbial infection) Viruses like human cytomegalovirus have CC evolved an escape mechanism whereby virus-induced down-regulation of CC host MHC class I molecules is coupled to the binding of viral peptides CC to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK CC cell immune tolerance to infected cells. {ECO:0000269|PubMed:10799855, CC ECO:0000269|PubMed:23335510}. CC -!- FUNCTION: (Microbial infection) May bind HIV-1 gag/Capsid protein p24- CC derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell CC cytotoxicity, a mechanism that allows HIV-1 to escape immune CC recognition. {ECO:0000269|PubMed:15751767}. CC -!- FUNCTION: (Microbial infection) Upon SARS-CoV-2 infection, may CC contribute to functional exhaustion of cytotoxic NK cells and CD8- CC positive T cells (PubMed:32859121). Binds SARS-CoV-2 S/Spike protein CC S1-derived peptide (LQPRTFLL) expressed on the surface of lung CC epithelial cells, inducing NK cell exhaustion and dampening of CC antiviral immune surveillance (PubMed:32859121). CC {ECO:0000269|PubMed:32859121}. CC -!- SUBUNIT: Forms a heterotrimer with B2M and a self- or a pathogen- CC derived peptide (peptide-bound HLA-E-B2M) (PubMed:18339401, CC PubMed:30087334, PubMed:35705051). Similarly to MHC class Ia assembly, CC HLA-E-B2M heterodimer interacts with components of the antigen CC processing machinery TAPBP and TAP1-TAP2 complex; this interaction is CC required for peptide loading and translocation to the cell surface CC (PubMed:9427624). Interacts with CALCR; this interaction is required CC for appropriate folding (PubMed:9427624). The optimum binding peptide CC is a nonamer (VL9) that is primarily derived from amino-acid residues CC 3-11 of the signal sequences of most HLA-A, -B, -C and -G molecules CC (PubMed:18083576, PubMed:18339401, PubMed:9660937, PubMed:9754572). The CC VL9 peptide anchors to five main sites in the peptide-binding groove of CC HLA-E (PubMed:18339401). Peptide-bound HLA-E-B2M complex interacts with CC KLRD1-KLRC1 receptor on NK cells (PubMed:18083576, PubMed:9486650). CC Binds with lower affinity to activating KLRD1-KLRC2 (PubMed:18083576, CC PubMed:23335510). The common subunit KLRC1 plays a prominent role in CC directly interacting with HLA-E (PubMed:18083576). Peptide-bound HLA-E- CC B2M interacts with the alpha-beta TCR on unconventional CD8+ T cells CC (PubMed:16474394). Peptide-free HLA-E interacts with HLA-F-B2M complex; CC this interaction may regulate the intracellular trafficking and the CC stability of peptide-free MHC class I open conformers (OCs). CC {ECO:0000269|PubMed:16474394, ECO:0000269|PubMed:18083576, CC ECO:0000269|PubMed:18339401, ECO:0000269|PubMed:20483783, CC ECO:0000269|PubMed:23335510, ECO:0000269|PubMed:30087334, CC ECO:0000269|PubMed:35705051, ECO:0000269|PubMed:9427624, CC ECO:0000269|PubMed:9486650, ECO:0000269|PubMed:9660937, CC ECO:0000269|PubMed:9754572}. CC -!- INTERACTION: CC P13747; P30511: HLA-F; NbExp=4; IntAct=EBI-726583, EBI-2811134; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17179229, CC ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9427624}; Single-pass CC type I membrane protein. Golgi apparatus membrane CC {ECO:0000269|PubMed:17179229}. CC -!- SUBCELLULAR LOCATION: [Soluble HLA class I histocompatibility antigen, CC alpha chain E]: Secreted {ECO:0000269|PubMed:17179229}. CC -!- TISSUE SPECIFICITY: Expressed in secretory endometrial cells during CC pregnancy (at protein level). The expression in nonlymphoid tissues is CC restricted to endothelial cells from all types of vessels, including CC arteries, veins, capillaries, and lymphatics (at protein level). In CC lymphoid organs, it is mainly expressed in endothelial venules, B and T CC cells, monocytes, macrophages, NK cells and megakaryocytes (at protein CC level). {ECO:0000269|PubMed:17179229}. CC -!- DEVELOPMENTAL STAGE: Expressed in extravillous trophoblast (at protein CC level). {ECO:0000269|PubMed:17179229}. CC -!- INDUCTION: Pro-inflammatory cytokines including TNF, IL1B and IFNG up- CC regulate membrane bound HLA-E expression on endothelial and NK cells CC and induce the release of soluble HLA-E (sHLA-E) in the extracellular CC compartment. {ECO:0000269|PubMed:17179229, CC ECO:0000269|PubMed:37264229}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:17179229}. CC -!- PTM: The soluble form (sHLA-E) can be partly produced by proteolytic CC cleavage at the cell surface (shedding) by a matrix metalloproteinase. CC Alternative splicing is also suggested as a mechanism for generation of CC sHLA-E, although it remains to be proved. CC {ECO:0000269|PubMed:17179229}. CC -!- POLYMORPHISM: The following alleles are known: E*01:01 and E*01:03 CC (PubMed:10064069, PubMed:16570139, PubMed:16702430, PubMed:28127896, CC PubMed:3131426). The frequency of E*01:01 and E*01:03 alleles in the CC population is about equal suggesting balanced selection in diverse CC populations. Evolutionary studies suggest that E*01:03 is the original CC allele (PubMed:12445303). Two other alleles has been described E*01:02 CC and E*01:04 (PubMed:1977695, PubMed:3260916). Allele E*01:02 was found CC to be identical to HLA E*01:01 (PubMed:22665232, PubMed:3260916). The CC existence of allele E*01:04 is uncertain as it could not be confirmed CC in further studies (PubMed:12445303, PubMed:1977695). The sequence CC shown is that of E*01:03 (PubMed:10064069, PubMed:16570139, CC PubMed:16702430, PubMed:28127896). {ECO:0000269|PubMed:10064069, CC ECO:0000269|PubMed:12445303, ECO:0000269|PubMed:16570139, CC ECO:0000269|PubMed:16702430, ECO:0000269|PubMed:1977695, CC ECO:0000269|PubMed:22665232, ECO:0000269|PubMed:28127896, CC ECO:0000269|PubMed:3131426, ECO:0000269|PubMed:3260916}. CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M20022; AAA52655.1; -; mRNA. DR EMBL; AJ293263; CAC07212.1; -; mRNA. DR EMBL; AJ293264; CAC07213.1; -; mRNA. DR EMBL; M21533; AAA59835.1; -; Genomic_DNA. DR EMBL; M32508; AAA63225.1; -; Genomic_DNA. DR EMBL; AB103600; BAF31260.1; -; Genomic_DNA. DR EMBL; AF523274; AAM74969.1; -; Genomic_DNA. DR EMBL; AF523275; AAM74970.1; -; Genomic_DNA. DR EMBL; AF523276; AAM74971.1; -; Genomic_DNA. DR EMBL; AF523277; AAM74972.1; -; Genomic_DNA. DR EMBL; AF523278; AAM74973.1; -; Genomic_DNA. DR EMBL; AF523279; AAM74974.1; -; Genomic_DNA. DR EMBL; AF523280; AAM74975.1; -; Genomic_DNA. DR EMBL; AF523281; AAM74976.1; -; Genomic_DNA. DR EMBL; AF523282; AAM74977.1; -; Genomic_DNA. DR EMBL; AF523283; AAM74978.1; -; Genomic_DNA. DR EMBL; AY645727; AAT73210.1; -; Genomic_DNA. DR EMBL; AY645731; AAT73214.1; -; Genomic_DNA. DR EMBL; AY645733; AAT73216.1; -; Genomic_DNA. DR EMBL; AY645736; AAT73219.1; -; Genomic_DNA. DR EMBL; AY645737; AAT73220.1; -; Genomic_DNA. DR EMBL; AY645738; AAT73221.1; -; Genomic_DNA. DR EMBL; AY645740; AAT73223.1; -; Genomic_DNA. DR EMBL; AY645741; AAT73224.1; -; Genomic_DNA. DR EMBL; LM654512; CDX10595.1; -; Genomic_DNA. DR EMBL; LT618796; SCQ83612.1; -; Genomic_DNA. DR EMBL; AY221103; AAO34408.1; -; mRNA. DR EMBL; AY216681; AAO37688.1; -; mRNA. DR EMBL; KX709624; ASU09661.1; -; Genomic_DNA. DR EMBL; HM231277; ADN38247.1; -; Genomic_DNA. DR EMBL; BA000025; BAB63328.1; -; Genomic_DNA. DR EMBL; BC002578; AAH02578.1; -; mRNA. DR EMBL; BC040479; AAH40479.1; -; mRNA. DR EMBL; BC004297; AAH04297.1; -; mRNA. DR EMBL; AL662873; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS34379.1; -. DR PIR; A28834; A28834. DR RefSeq; NP_005507.3; NM_005516.5. DR PDB; 1KPR; X-ray; 2.80 A; A/C=22-295. DR PDB; 1KTL; X-ray; 3.10 A; A/C=22-295. DR PDB; 1MHE; X-ray; 2.85 A; A/C=22-295. DR PDB; 2ESV; X-ray; 2.60 A; A=23-297. DR PDB; 3AM8; X-ray; 2.80 A; A/B=22-297. DR PDB; 3BZE; X-ray; 2.50 A; A/C/E/G=23-295. DR PDB; 3BZF; X-ray; 2.50 A; A/C=22-297. DR PDB; 3CDG; X-ray; 3.40 A; A/C=23-295. DR PDB; 3CII; X-ray; 4.41 A; A/D=23-295. DR PDB; 5W1V; X-ray; 3.31 A; A/F/K/P=22-299. DR PDB; 5W1W; X-ray; 3.10 A; A/F/K/P=22-299. DR PDB; 6GGM; X-ray; 2.73 A; A/C=22-295. DR PDB; 6GH1; X-ray; 2.10 A; A/C/E/G=22-295. DR PDB; 6GH4; X-ray; 2.16 A; A/C/E/G=22-295. DR PDB; 6GHN; X-ray; 2.54 A; A/C=22-295. DR PDB; 6GL1; X-ray; 2.62 A; A/C/E/G=22-295. DR PDB; 6ZKW; X-ray; 2.26 A; A=22-297. DR PDB; 6ZKX; X-ray; 2.17 A; A=22-297. DR PDB; 6ZKY; X-ray; 2.65 A; A=22-297. DR PDB; 6ZKZ; X-ray; 2.30 A; A=22-297. DR PDB; 7BH8; X-ray; 1.80 A; A/C=22-297. DR PDB; 7NDQ; X-ray; 2.55 A; AAA=22-297. DR PDB; 7NDT; X-ray; 3.00 A; AAA/FFF=22-297. DR PDB; 7NDU; X-ray; 2.90 A; AAA=22-297. DR PDB; 7P49; X-ray; 2.05 A; A/C/E/G=22-297. DR PDB; 7P4B; X-ray; 1.72 A; A/C/E/G=22-297. DR PDB; 8QFY; X-ray; 2.33 A; AAA/FFF=22-297. DR PDB; 8RLT; X-ray; 2.25 A; A/F=22-297. DR PDB; 8RLU; X-ray; 2.35 A; A/F=22-297. DR PDB; 8RLV; X-ray; 2.61 A; A/F=22-297. DR PDBsum; 1KPR; -. DR PDBsum; 1KTL; -. DR PDBsum; 1MHE; -. DR PDBsum; 2ESV; -. DR PDBsum; 3AM8; -. DR PDBsum; 3BZE; -. DR PDBsum; 3BZF; -. DR PDBsum; 3CDG; -. DR PDBsum; 3CII; -. DR PDBsum; 5W1V; -. DR PDBsum; 5W1W; -. DR PDBsum; 6GGM; -. DR PDBsum; 6GH1; -. DR PDBsum; 6GH4; -. DR PDBsum; 6GHN; -. DR PDBsum; 6GL1; -. DR PDBsum; 6ZKW; -. DR PDBsum; 6ZKX; -. DR PDBsum; 6ZKY; -. DR PDBsum; 6ZKZ; -. DR PDBsum; 7BH8; -. DR PDBsum; 7NDQ; -. DR PDBsum; 7NDT; -. DR PDBsum; 7NDU; -. DR PDBsum; 7P49; -. DR PDBsum; 7P4B; -. DR PDBsum; 8QFY; -. DR PDBsum; 8RLT; -. DR PDBsum; 8RLU; -. DR PDBsum; 8RLV; -. DR AlphaFoldDB; P13747; -. DR SMR; P13747; -. DR BioGRID; 109378; 110. DR DIP; DIP-32N; -. DR IntAct; P13747; 75. DR MINT; P13747; -. DR STRING; 9606.ENSP00000365817; -. DR TCDB; 9.A.75.1.3; the mhc ii receptor (mhc2r) family. DR GlyConnect; 1330; 1 N-Linked glycan (1 site). DR GlyCosmos; P13747; 1 site, 1 glycan. DR GlyGen; P13747; 3 sites, 7 N-linked glycans (1 site), 2 O-linked glycans (1 site). DR iPTMnet; P13747; -. DR PhosphoSitePlus; P13747; -. DR SwissPalm; P13747; -. DR BioMuta; HLA-E; -. DR DMDM; 34395942; -. DR jPOST; P13747; -. DR MassIVE; P13747; -. DR PaxDb; 9606-ENSP00000365817; -. DR PeptideAtlas; P13747; -. DR ProteomicsDB; 52981; -. DR ProteomicsDB; 66256; -. DR Pumba; P13747; -. DR TopDownProteomics; P13747; -. DR Antibodypedia; 26293; 990 antibodies from 30 providers. DR CPTC; P13747; 1 antibody. DR DNASU; 3133; -. DR Ensembl; ENST00000376630.5; ENSP00000365817.4; ENSG00000204592.9. DR Ensembl; ENST00000383597.6; ENSP00000373091.4; ENSG00000206493.7. DR Ensembl; ENST00000415289.4; ENSP00000409910.2; ENSG00000229252.6. DR Ensembl; ENST00000415649.4; ENSP00000390707.2; ENSG00000233904.6. DR Ensembl; ENST00000425603.4; ENSP00000402694.2; ENSG00000236632.5. DR Ensembl; ENST00000427936.4; ENSP00000397420.2; ENSG00000230254.7. DR Ensembl; ENST00000444683.4; ENSP00000400458.2; ENSG00000225201.6. DR GeneID; 3133; -. DR KEGG; hsa:3133; -. DR MANE-Select; ENST00000376630.5; ENSP00000365817.4; NM_005516.6; NP_005507.3. DR UCSC; uc003nqg.4; human. DR AGR; HGNC:4962; -. DR CTD; 3133; -. DR DisGeNET; 3133; -. DR GeneCards; HLA-E; -. DR HGNC; HGNC:4962; HLA-E. DR HPA; ENSG00000204592; Low tissue specificity. DR MIM; 143010; gene. DR neXtProt; NX_P13747; -. DR OpenTargets; ENSG00000204592; -. DR PharmGKB; PA35081; -. DR VEuPathDB; HostDB:ENSG00000204592; -. DR eggNOG; ENOG502RQEK; Eukaryota. DR GeneTree; ENSGT01120000271826; -. DR HOGENOM; CLU_047501_1_1_1; -. DR InParanoid; P13747; -. DR OMA; CVEWLHT; -. DR OrthoDB; 8936120at2759; -. DR PhylomeDB; P13747; -. DR TreeFam; TF336617; -. DR PathwayCommons; P13747; -. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-2172127; DAP12 interactions. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC. DR SignaLink; P13747; -. DR SIGNOR; P13747; -. DR BioGRID-ORCS; 3133; 15 hits in 1148 CRISPR screens. DR ChiTaRS; HLA-E; human. DR EvolutionaryTrace; P13747; -. DR GeneWiki; HLA-E; -. DR GenomeRNAi; 3133; -. DR Pharos; P13747; Tbio. DR PRO; PR:P13747; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P13747; protein. DR Bgee; ENSG00000204592; Expressed in blood and 99 other cell types or tissues. DR ExpressionAtlas; P13747; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0098553; C:lumenal side of endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0042612; C:MHC class I protein complex; IDA:UniProtKB. DR GO; GO:0032398; C:MHC class Ib protein complex; IDA:UniProtKB. DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; TAS:Reactome. DR GO; GO:0030881; F:beta-2-microglobulin binding; IDA:UniProtKB. DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB. DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; IPI:UniProtKB. DR GO; GO:0042605; F:peptide antigen binding; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0042608; F:T cell receptor binding; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IDA:UniProtKB. DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB. DR GO; GO:0002486; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent; IBA:GO_Central. DR GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IDA:UniProtKB. DR GO; GO:0002477; P:antigen processing and presentation of exogenous peptide antigen via MHC class Ib; IDA:UniProtKB. DR GO; GO:0036037; P:CD8-positive, alpha-beta T cell activation; IDA:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0002519; P:natural killer cell tolerance induction; IDA:UniProtKB. DR GO; GO:0032815; P:negative regulation of natural killer cell activation; IDA:UniProtKB. DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB. DR GO; GO:0042130; P:negative regulation of T cell proliferation; IDA:UniProtKB. DR GO; GO:0001815; P:positive regulation of antibody-dependent cellular cytotoxicity; IDA:UniProtKB. DR GO; GO:2001187; P:positive regulation of CD8-positive, alpha-beta T cell activation; IDA:UniProtKB. DR GO; GO:2000566; P:positive regulation of CD8-positive, alpha-beta T cell proliferation; IDA:UniProtKB. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IDA:UniProtKB. DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IDA:UniProtKB. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:UniProtKB. DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IDA:UniProtKB. DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IDA:UniProtKB. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB. DR GO; GO:0002717; P:positive regulation of natural killer cell mediated immunity; IDA:UniProtKB. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:UniProtKB. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:UniProtKB. DR GO; GO:0032759; P:positive regulation of TRAIL production; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB. DR GO; GO:0042270; P:protection from natural killer cell mediated cytotoxicity; IDA:UniProtKB. DR GO; GO:0002715; P:regulation of natural killer cell mediated immunity; IDA:UniProtKB. DR CDD; cd21024; IgC1_MHC_Ib_HLA-E; 1. DR FunFam; 2.60.40.10:FF:000014; H-2 class I histocompatibility antigen, alpha chain; 1. DR FunFam; 3.30.500.10:FF:000001; H-2 class I histocompatibility antigen, alpha chain; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 3.30.500.10; MHC class I-like antigen recognition-like; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003006; Ig/MHC_CS. DR InterPro; IPR003597; Ig_C1-set. DR InterPro; IPR050208; MHC_class-I_related. DR InterPro; IPR011161; MHC_I-like_Ag-recog. DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf. DR InterPro; IPR011162; MHC_I/II-like_Ag-recog. DR InterPro; IPR001039; MHC_I_a_a1/a2. DR InterPro; IPR010579; MHC_I_a_C. DR PANTHER; PTHR16675:SF164; HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, ALPHA CHAIN E; 1. DR PANTHER; PTHR16675; MHC CLASS I-RELATED; 1. DR Pfam; PF07654; C1-set; 1. DR Pfam; PF00129; MHC_I; 1. DR Pfam; PF06623; MHC_I_C; 1. DR PRINTS; PR01638; MHCCLASSI. DR SMART; SM00407; IGc1; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR SUPFAM; SSF54452; MHC antigen-recognition domain; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00290; IG_MHC; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; KW Glycoprotein; Golgi apparatus; Host-virus interaction; Immunity; KW Innate immunity; Membrane; MHC I; Phosphoprotein; KW Proteomics identification; Reference proteome; Secreted; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..358 FT /note="HLA class I histocompatibility antigen, alpha chain FT E" FT /id="PRO_0000018882" FT CHAIN 22..? FT /note="Soluble HLA class I histocompatibility antigen, FT alpha chain E" FT /id="PRO_0000445757" FT TOPO_DOM 22..305 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 306..329 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 330..358 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 206..294 FT /note="Ig-like C1-type" FT REGION 22..111 FT /note="Alpha-1" FT REGION 112..203 FT /note="Alpha-2" FT REGION 204..295 FT /note="Alpha-3" FT REGION 296..305 FT /note="Connecting peptide" FT REGION 333..358 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 348..358 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 28 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:30087334, FT ECO:0000269|PubMed:35705051, ECO:0007744|PDB:7P4B" FT BINDING 84 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P49, ECO:0007744|PDB:7P4B" FT BINDING 87 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P4B" FT BINDING 98 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P49, ECO:0007744|PDB:7P4B" FT BINDING 98 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 105 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P49, ECO:0007744|PDB:7P4B" FT BINDING 105 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 164 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:30087334, FT ECO:0000269|PubMed:35705051, ECO:0007744|PDB:7P49, FT ECO:0007744|PDB:7P4B" FT BINDING 164 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 167 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:30087334, FT ECO:0000269|PubMed:35705051, ECO:0007744|PDB:7P49, FT ECO:0007744|PDB:7P4B" FT BINDING 167 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 177 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 180 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:30087334, FT ECO:0000269|PubMed:35705051, ECO:0007744|PDB:7P49, FT ECO:0007744|PDB:7P4B" FT BINDING 180 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT BINDING 192 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="1" FT /ligand_note="pathogen-derived peptide antigen" FT /evidence="ECO:0000269|PubMed:30087334, FT ECO:0000269|PubMed:35705051, ECO:0007744|PDB:7P49" FT BINDING 192 FT /ligand="a peptide antigen" FT /ligand_id="ChEBI:CHEBI:166823" FT /ligand_label="2" FT /ligand_note="self-peptide antigen" FT /evidence="ECO:0000269|PubMed:18339401" FT MOD_RES 353 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P01900" FT CARBOHYD 107 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT DISULFID 122..185 FT /evidence="ECO:0000269|PubMed:18339401, FT ECO:0000269|PubMed:30087334, ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P49" FT DISULFID 224..280 FT /evidence="ECO:0000269|PubMed:18339401, FT ECO:0000269|PubMed:30087334, ECO:0000269|PubMed:35705051, FT ECO:0007744|PDB:7P49" FT VARIANT 98 FT /note="N -> K (in dbSNP:rs1059510)" FT /id="VAR_059510" FT VARIANT 128 FT /note="G -> R (in allele E*01:01; dbSNP:rs1264457)" FT /evidence="ECO:0000269|Ref.11" FT /id="VAR_016651" FT VARIANT 178 FT /note="R -> G (in allele E*01:04; dbSNP:rs41562314)" FT /id="VAR_016652" FT MUTAGEN 83 FT /note="R->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 86 FT /note="R->A: Reduces the affinity for KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 90 FT /note="D->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 93 FT /note="Q->A: Impairs the recognition by KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 96 FT /note="R->A: Abolishes the recognition by KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 97 FT /note="V->A: Impairs the recognition by KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 100 FT /note="R->A: Reduces the affinity for KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 110 FT /note="E->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 129 FT /note="R->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 167 FT /note="K->A: Impairs folding." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 170 FT /note="D->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 173 FT /note="E->A: Impairs the recognition by KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 175 FT /note="E->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 176 FT /note="H->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 183 FT /note="D->A: Impairs the recognition by KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 187 FT /note="E->A: Reduces the affinity for KLRD1-KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT MUTAGEN 235 FT /note="T->A: Has no impact on the affinity for KLRD1- FT KLRC1." FT /evidence="ECO:0000269|PubMed:18083576" FT CONFLICT 10 FT /note="L -> S (in Ref. 1; AAA52655)" FT /evidence="ECO:0000305" FT CONFLICT 104 FT /note="G -> R (in Ref. 3; AAA59835)" FT /evidence="ECO:0000305" FT STRAND 24..33 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 42..49 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 52..58 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 67..70 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 71..75 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 78..105 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:7BH8" FT STRAND 115..124 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 128..139 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 142..147 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 159..170 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 173..182 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 184..195 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 197..200 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 207..214 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 216..232 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 235..240 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:6GH1" FT STRAND 248..251 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 258..260 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 262..271 FT /evidence="ECO:0007829|PDB:7P4B" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 278..283 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:7P4B" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:7P4B" SQ SEQUENCE 358 AA; 40058 MW; 6B3001CA9F3B7FE3 CRC64; MVDGTLLLLL SEALALTQTW AGSHSLKYFH TSVSRPGRGE PRFISVGYVD DTQFVRFDND AASPRMVPRA PWMEQEGSEY WDRETRSARD TAQIFRVNLR TLRGYYNQSE AGSHTLQWMH GCELGPDGRF LRGYEQFAYD GKDYLTLNED LRSWTAVDTA AQISEQKSND ASEAEHQRAY LEDTCVEWLH KYLEKGKETL LHLEPPKTHV THHPISDHEA TLRCWALGFY PAEITLTWQQ DGEGHTQDTE LVETRPAGDG TFQKWAAVVV PSGEEQRYTC HVQHEGLPEP VTLRWKPASQ PTIPIVGIIA GLVLLGSVVS GAVVAAVIWR KKSSGGKGGS YSKAEWSDSA QGSESHSL //