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 28-JUN-2023, entry version 216.
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 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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 22-297 IN COMPLEX WITH
RP SELF-PEPTIDE, DISULFIDE BOND, SUBUNIT, AND FUNCTION.
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 [32]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 22-295 IN COMPLEX WITH
RP PATHOGEN-DERIVED PEPTIDE, DISULFIDE BOND, SUBUNIT, AND FUNCTION.
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 [33]
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 [34]
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 (PubMed:9754572, PubMed:18083576, PubMed:18339401). Peptide-bound HLA-
CC E-B2M heterotrimeric complex primarily functions as a ligand for
CC natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK
CC cells to monitor the expression of other MHC class I molecules in
CC healthy cells and to tolerate self (PubMed:9754572, PubMed:9486650,
CC PubMed:17179229, PubMed:18083576). Upon cellular stress, preferentially
CC binds signal sequence-derived peptides from stress-induced chaperones
CC and is no longer recognized by NK cell inhibitory receptor KLRD1-KLRC1,
CC resulting in impaired protection from NK cells (PubMed:12461076). Binds
CC signal sequence-derived peptides from non-classical MHC class Ib HLA-G
CC molecules and acts as a ligand for NK cell activating receptor KLRD1-
CC KLRC2, likely playing a role in the generation and effector functions
CC of adaptive NK cells and in maternal-fetal tolerance during pregnancy
CC (PubMed:9754572, PubMed:30134159). Besides self-peptides, can also bind
CC and present pathogen-derived peptides conformationally similar to VL9
CC peptides to alpha-beta T cell receptor (TCR) on unconventional CD8+
CC cytotoxic T cells, ultimately triggering antimicrobial immune response
CC (PubMed:16474394, PubMed:30087334). {ECO:0000269|PubMed:12461076,
CC ECO:0000269|PubMed:16474394, ECO:0000269|PubMed:17179229,
CC ECO:0000269|PubMed:18083576, ECO:0000269|PubMed:18339401,
CC ECO:0000269|PubMed:30087334, ECO:0000269|PubMed:30134159,
CC ECO:0000269|PubMed:9486650, 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 antiviral
CC immune surveillance (PubMed:32859121). {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). Similarly to MHC class Ia assembly, HLA-E-B2M
CC heterodimer interacts with components of the antigen processing
CC machinery TAPBP and TAP1-TAP2 complex; this interaction is required for
CC peptide loading and translocation to the cell surface (PubMed:9427624).
CC Interacts with CALCR; this interaction is required for appropriate
CC folding (PubMed:9427624). The optimum binding peptide is a nonamer
CC (VL9) that is primarily derived from amino-acid residues 3-11 of the
CC signal sequences of most HLA-A, -B, -C and -G molecules
CC (PubMed:9754572, PubMed:18083576, PubMed:9660937, PubMed:18339401). 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:9486650, PubMed:18083576).
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:9427624, ECO:0000269|PubMed:9486650,
CC ECO:0000269|PubMed:9660937, ECO:0000269|PubMed:9754572}.
CC -!- INTERACTION:
CC P13747; P30511: HLA-F; NbExp=2; IntAct=EBI-726583, EBI-2811134;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17179229,
CC ECO:0000269|PubMed:9427624}; Single-pass type I membrane protein. Golgi
CC apparatus membrane {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 -!- 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:3131426, PubMed:10064069, PubMed:16702430, PubMed:16570139,
CC PubMed:28127896). 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:3260916, PubMed:1977695). Allele E*01:02 was found
CC to be identical to HLA E*01:01 (PubMed:3260916, PubMed:22665232). The
CC existence of allele E*01:04 is uncertain as it could not be confirmed
CC in further studies (PubMed:1977695, PubMed:12445303). The sequence
CC shown is that of E*01:03 (PubMed:10064069, PubMed:16702430,
CC PubMed:16570139, 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}.
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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 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 AlphaFoldDB; P13747; -.
DR SMR; P13747; -.
DR BioGRID; 109378; 107.
DR DIP; DIP-32N; -.
DR IntAct; P13747; 57.
DR MINT; P13747; -.
DR STRING; 9606.ENSP00000365817; -.
DR GlyConnect; 1330; 1 N-Linked glycan (1 site).
DR GlyCosmos; P13747; 1 site, 1 glycan.
DR GlyGen; P13747; 3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P13747; -.
DR PhosphoSitePlus; P13747; -.
DR SwissPalm; P13747; -.
DR BioMuta; HLA-E; -.
DR DMDM; 34395942; -.
DR EPD; P13747; -.
DR jPOST; P13747; -.
DR MassIVE; P13747; -.
DR PaxDb; P13747; -.
DR PeptideAtlas; P13747; -.
DR ProteomicsDB; 52981; -.
DR ProteomicsDB; 66256; -.
DR TopDownProteomics; P13747; -.
DR Antibodypedia; 26293; 909 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; ENSGT00980000198488; -.
DR HOGENOM; CLU_047501_1_1_1; -.
DR InParanoid; P13747; -.
DR OMA; CVEWLHT; -.
DR OrthoDB; 3840485at2759; -.
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 97 other 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:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; 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: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 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; 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; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
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 344..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 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="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 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 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 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 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"
FT DISULFID 224..280
FT /evidence="ECO:0000269|PubMed:18339401,
FT ECO:0000269|PubMed:30087334"
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
//