ID IGHE_HUMAN Reviewed; 546 AA. AC P01854; A0A286YES5; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 03-MAY-2023, sequence version 2. DT 27-MAR-2024, entry version 194. DE RecName: Full=Immunoglobulin heavy constant epsilon {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.22}; DE AltName: Full=Ig epsilon chain C region {ECO:0000305}; DE AltName: Full=Ig epsilon chain C region ND {ECO:0000305|Ref.1}; GN Name=IGHE {ECO:0000303|PubMed:11340299, ECO:0000303|Ref.22}; 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 PROTEIN SEQUENCE. RA Bennich H.H., Johansson S.G.O., von Bahr-Lindstroem H.; RL (In) Bach M.K. (eds.); RL Immediate hypersensitivity: modern concepts and developments, pp.1-36, RL Marcel Dekker, New York (1978). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-359. RX PubMed=6288268; DOI=10.1016/0092-8674(82)90185-4; RA Max E.E., Battey J., Ney R., Kirsch I.R., Leder P.; RT "Duplication and deletion in the human immunoglobulin epsilon genes."; RL Cell 29:691-699(1982). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE IGHE*02). RX PubMed=6234164; DOI=10.1002/j.1460-2075.1982.tb01223.x; RA Flanagan J.G., Rabbitts T.H.; RT "The sequence of a human immunoglobulin epsilon heavy chain constant region RT gene, and evidence for three non-allelic genes."; RL EMBO J. 1:655-660(1982). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE IGHE*01), AND VARIANT RP CYS-43. RX PubMed=6327276; DOI=10.1002/j.1460-2075.1982.tb01352.x; RA Ueda S., Nakai S., Nishida Y., Hisajima H., Honjo T.; RT "Long terminal repeat-like elements flank a human immunoglobulin epsilon RT pseudogene that lacks introns."; RL EMBO J. 1:1539-1544(1982). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (IMGT ALLELE IGHE*02). RX PubMed=6300763; DOI=10.1093/nar/11.3.719; RA Seno M., Kurokawa T., Ono Y., Onda H., Sasada R., Igarashi K., Kikuchi M., RA Sugino Y., Nishida Y., Honjo T.; RT "Molecular cloning and nucleotide sequencing of human immunoglobulin RT epsilon chain cDNA."; RL Nucleic Acids Res. 11:719-726(1983). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (IMGT ALLELE IGHE*04). RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40; 68-114 AND 427-428. RX PubMed=6815656; DOI=10.1073/pnas.79.21.6661; RA Kenten J.H., Molgaard H.V., Houghton M., Derbyshire R.B., Viney J., RA Bell L.O., Gould H.J.; RT "Cloning and sequence determination of the gene for the human RT immunoglobulin epsilon chain expressed in a myeloma cell line."; RL Proc. Natl. Acad. Sci. U.S.A. 79:6661-6665(1982). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 427-546 (ISOFORMS 2 AND 3), AND ALTERNATIVE RP SPLICING. RX PubMed=1727861; RA Peng C., Davis F.M., Sun L.K., Liou R.S., Kim Y.W., Chang T.W.; RT "A new isoform of human membrane-bound IgE."; RL J. Immunol. 148:129-136(1992). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 427-546 (ISOFORM 2), ALTERNATIVE RP SPLICING, AND TISSUE SPECIFICITY (ISOFORM 2). RX PubMed=1613458; DOI=10.1084/jem.176.1.233; RA Zhang K., Saxon A., Max E.E.; RT "Two unusual forms of human immunoglobulin E encoded by alternative RNA RT splicing of epsilon heavy chain membrane exons."; RL J. Exp. Med. 176:233-243(1992). RN [10] RP FUNCTION (ISOFORM 1). RX PubMed=2167225; DOI=10.1002/eji.1830200721; RA Pirron U., Schlunck T., Prinz J.C., Rieber E.P.; RT "IgE-dependent antigen focusing by human B lymphocytes is mediated by the RT low-affinity receptor for IgE."; RL Eur. J. Immunol. 20:1547-1551(1990). RN [11] RP FUNCTION (ISOFORM 1). RX PubMed=8114916; DOI=10.1038/367183a0; RA Gounni A.S., Lamkhioued B., Ochiai K., Tanaka Y., Delaporte E., Capron A., RA Kinet J.P., Capron M.; RT "High-affinity IgE receptor on eosinophils is involved in defence against RT parasites."; RL Nature 367:183-186(1994). RN [12] RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND SUBUNIT (ISOFORM 1). RX PubMed=7995941; RA Batista F.D., Efremov D.G., Burrone O.R.; RT "Characterization and expression of alternatively spliced IgE heavy chain RT transcripts produced by peripheral blood lymphocytes."; RL J. Immunol. 154:209-218(1995). RN [13] RP FUNCTION (ISOFORM 1). RX PubMed=7544003; DOI=10.1073/pnas.92.17.7804; RA Vouldoukis I., Riveros-Moreno V., Dugas B., Ouaaz F., Becherel P., RA Debre P., Moncada S., Mossalayi M.D.; RT "The killing of Leishmania major by human macrophages is mediated by nitric RT oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7804-7808(1995). RN [14] RP FUNCTION (ISOFORM 1). RX PubMed=8551243; DOI=10.1084/jem.183.1.49; RA Fung-Leung W.P., De Sousa-Hitzler J., Ishaque A., Zhou L., Pang J., Ngo K., RA Panakos J.A., Chourmouzis E., Liu F.T., Lau C.Y.; RT "Transgenic mice expressing the human high-affinity immunoglobulin (Ig) E RT receptor alpha chain respond to human IgE in mast cell degranulation and in RT allergic reactions."; RL J. Exp. Med. 183:49-56(1996). RN [15] RP FUNCTION (ISOFORMS 2 AND 3), SUBUNIT (ISOFORMS 2 AND 3), AND SUBCELLULAR RP LOCATION (ISOFORMS 2 AND 3). RX PubMed=8976175; DOI=10.1084/jem.184.6.2197; RA Batista F.D., Anand S., Presani G., Efremov D.G., Burrone O.R.; RT "The two membrane isoforms of human IgE assemble into functionally distinct RT B cell antigen receptors."; RL J. Exp. Med. 184:2197-2205(1996). RN [16] RP INTERACTION WITH FCER2 (ISOFORM 1). RX PubMed=16172256; DOI=10.1084/jem.20050811; RA Hibbert R.G., Teriete P., Grundy G.J., Beavil R.L., Reljic R., Holers V.M., RA Hannan J.P., Sutton B.J., Gould H.J., McDonnell J.M.; RT "The structure of human CD23 and its interactions with IgE and CD21."; RL J. Exp. Med. 202:751-760(2005). RN [17] RP FUNCTION (ISOFORM 2), AND SUBCELLULAR LOCATION (ISOFORM 2). RX PubMed=20458139; DOI=10.1172/jci40141; RA Brightbill H.D., Jeet S., Lin Z., Yan D., Zhou M., Tan M., Nguyen A., RA Yeh S., Delarosa D., Leong S.R., Wong T., Chen Y., Ultsch M., Luis E., RA Ramani S.R., Jackman J., Gonzalez L., Dennis M.S., Chuntharapai A., RA DeForge L., Meng Y.G., Xu M., Eigenbrot C., Lee W.P., Refino C.J., RA Balazs M., Wu L.C.; RT "Antibodies specific for a segment of human membrane IgE deplete IgE- RT producing B cells in humanized mice."; RL J. Clin. Invest. 120:2218-2229(2010). RN [18] RP FUNCTION (ISOFORM 1). RX PubMed=25629393; DOI=10.1038/ncomms7174; RA Joulia R., Gaudenzio N., Rodrigues M., Lopez J., Blanchard N., RA Valitutti S., Espinosa E.; RT "Mast cells form antibody-dependent degranulatory synapse for dedicated RT secretion and defence."; RL Nat. Commun. 6:6174-6174(2015). RN [19] RP FUNCTION (ISOFORM 1). RX PubMed=30956175; DOI=10.1016/j.ebiom.2019.03.080; RA Pellizzari G., Hoskin C., Crescioli S., Mele S., Gotovina J., RA Chiaruttini G., Bianchini R., Ilieva K., Bax H.J., Papa S., Lacy K.E., RA Jensen-Jarolim E., Tsoka S., Josephs D.H., Spicer J.F., Karagiannis S.N.; RT "IgE re-programs alternatively-activated human macrophages towards pro- RT inflammatory anti-tumoural states."; RL EBioMedicine 43:67-81(2019). RN [20] RP FUNCTION (ISOFORM 1). RX PubMed=33840121; DOI=10.1111/all.14852; RA Starkl P., Gaudenzio N., Marichal T., Reber L.L., Sibilano R., RA Watzenboeck M.L., Fontaine F., Mueller A.C., Tsai M., Knapp S., Galli S.J.; RT "IgE antibodies increase honeybee venom responsiveness and detoxification RT efficiency of mast cells."; RL Allergy 77:499-512(2022). RN [21] RP NOMENCLATURE. RX PubMed=11340299; DOI=10.1159/000049189; RA Lefranc M.P.; RT "Nomenclature of the human immunoglobulin heavy (IGH) genes."; RL Exp. Clin. Immunogenet. 18:100-116(2001). RN [22] RP NOMENCLATURE. RA Lefranc M.P., Lefranc G.; RT "The Immunoglobulin FactsBook."; RL (In) Lefranc M.P., Lefranc G. (eds.); RL The Immunoglobulin FactsBook., pp.1-458, Academic Press, London. (2001). RN [23] RP REVIEW ON SOMATIC HYPERMUTATION. RX PubMed=17576170; DOI=10.1146/annurev.genet.41.110306.130340; RA Teng G., Papavasiliou F.N.; RT "Immunoglobulin somatic hypermutation."; RL Annu. Rev. Genet. 41:107-120(2007). RN [24] RP REVIEW ON IMMUNOGLOBULINS. RX PubMed=20176268; DOI=10.1016/j.jaci.2009.09.046; RA Schroeder H.W. Jr., Cavacini L.; RT "Structure and function of immunoglobulins."; RL J. Allergy Clin. Immunol. 125:S41-S52(2010). RN [25] RP REVIEW ON FUNCTION. RX PubMed=22158414; DOI=10.1038/nri3128; RA McHeyzer-Williams M., Okitsu S., Wang N., McHeyzer-Williams L.; RT "Molecular programming of B cell memory."; RL Nat. Rev. Immunol. 12:24-34(2012). RN [26] RP 3D-STRUCTURE MODELING. RX PubMed=3796618; DOI=10.1016/0161-5890(86)90005-2; RA Padlan E.A., Davies D.R.; RT "A model of the Fc of immunoglobulin E."; RL Mol. Immunol. 23:1063-1075(1986). RN [27] RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 211-428 IN COMPLEX WITH FCER1A RP (ISOFORM 1), DISULFIDE BOND, AND GLYCOSYLATION AT ASN-275. RX PubMed=10917520; DOI=10.1038/35018500; RA Garman S.C., Wurzburg B.A., Tarchevskaya S.S., Kinet J.P., Jardetzky T.S.; RT "Structure of the Fc fragment of human IgE bound to its high-affinity RT receptor Fc epsilonRI alpha."; RL Nature 406:259-266(2000). CC -!- FUNCTION: Constant region of immunoglobulin heavy chains. CC Immunoglobulins, also known as antibodies, are membrane-bound or CC secreted glycoproteins produced by B lymphocytes. In the recognition CC phase of humoral immunity, the membrane-bound immunoglobulins serve as CC receptors which, upon binding of a specific antigen, trigger the clonal CC expansion and differentiation of B lymphocytes into immunoglobulins- CC secreting plasma cells. Secreted immunoglobulins mediate the effector CC phase of humoral immunity, which results in the elimination of bound CC antigens (PubMed:22158414, PubMed:20176268). The antigen binding site CC is formed by the variable domain of one heavy chain, together with that CC of its associated light chain. Thus, each immunoglobulin has two CC antigen binding sites with remarkable affinity for a particular CC antigen. The variable domains are assembled by a process called V-(D)-J CC rearrangement and can then be subjected to somatic hypermutations CC which, after exposure to antigen and selection, allow affinity CC maturation for a particular antigen (PubMed:17576170, PubMed:20176268). CC {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, CC ECO:0000303|PubMed:22158414}. CC -!- FUNCTION: [Isoform 1]: Constant region of secreted IgE, also known as CC the Fc region of IgE antibody. Mediates IgE effector functions on CC myeloid and lymphoid cells primarily via two Fc receptors, the high- CC affinity IgE Fc receptor complex/FCER1A:MS4A2:FCGR1A and the low- CC affinity FCER2 receptor, which upon antigen/allergen cross-linking CC initiate signaling pathways that lead to immune cell activation and CC differentiation (PubMed:2167225, PubMed:8114916, PubMed:7544003, CC PubMed:8551243, PubMed:25629393, PubMed:33840121). Triggers the CC immediate hypersensitivity response to allergens as a host defense CC mechanism against helminth parasites, pathogenic bacteria and venom CC toxicity. When dysregulated, it can elicit harmful life-threatening CC allergic and anaphylactic reactions (PubMed:8114916, PubMed:7544003, CC PubMed:8551243, PubMed:25629393, PubMed:33840121). Stimulates the high- CC affinity IgE Fc receptor complex/FCER1A:MS4A2:FCGR1A on mast cells, CC basophils and eosinophils leading to secretion of vasoactive amines, CC lipid mediators and cytokines that contribute to inflammatory response, CC tissue remodeling and cytotoxicity against microbes (PubMed:8114916, CC PubMed:8551243, PubMed:25629393). On macrophages, cross-linking of CC FCER2 by IgE immune complexes induces intracellular killing of CC parasites through activation of L-Arginine-nitric oxide pathway CC (PubMed:7544003). Activates macrophages to kill tumor cells via CC antigen-specific antibody-dependent cytotoxicity (ADCC). Triggers CC differentiation of quiescent M0 macrophages toward M1 state and CC reprograms M2 macrophages toward a proinflammatory state with antitumor CC functions (PubMed:30956175). Stimulates FCER2 on B cells and initiates CC IgE-dependent antigen uptake and presentation to T cells CC (PubMed:2167225). {ECO:0000269|PubMed:2167225, CC ECO:0000269|PubMed:25629393, ECO:0000269|PubMed:30956175, CC ECO:0000269|PubMed:33840121, ECO:0000269|PubMed:7544003, CC ECO:0000269|PubMed:8114916, ECO:0000269|PubMed:8551243, CC ECO:0000303|PubMed:20176268, ECO:0000305|PubMed:10917520, CC ECO:0000305|PubMed:7995941}. CC -!- FUNCTION: [Isoform 2]: Constant region of membrane-bound IgE (long CC mIgE), part of the B cell receptor complex (BCR). Upon antigen cross- CC linking triggers quick BCR signaling, ensuring survival of IgE-switched CC B cells and differentiation into plasma cells, thus regulating both CC primary and memory IgE responses. {ECO:0000269|PubMed:20458139, CC ECO:0000269|PubMed:8976175}. CC -!- FUNCTION: [Isoform 3]: Constant region of membrane-bound IgE (short CC mIgE), part of the B cell receptor complex (BCR). Upon antigen cross- CC linking initiates slower but sustained BCR signaling that negatively CC regulates mature B cell proliferation. {ECO:0000269|PubMed:8976175}. CC -!- SUBUNIT: The basic structural unit of both sIgE and mIgE molecules CC consists of two identical heavy chains and two identical light chains; CC disulfide-linked. N-terminal variable regions of the heavy and light CC chains form the antigen binding sites, whereas the C-terminal constant CC regions of the heavy chains interact with immune receptors to mediate CC effector functions. {ECO:0000269|PubMed:7995941, CC ECO:0000269|PubMed:8976175}. CC -!- SUBUNIT: [Isoform 1]: Part of IgE antibody (PubMed:7995941). Interacts CC (via CH3) with the alpha chain/FCE1RA of IgE Fc receptor complex CC (PubMed:10917520). Interacts (via CH3 region) with FCER2 (via C-type CC lectin domain); this interaction regulates IgE homeostasis CC (PubMed:16172256). {ECO:0000269|PubMed:10917520, CC ECO:0000269|PubMed:16172256, ECO:0000269|PubMed:7995941}. CC -!- SUBUNIT: [Isoform 2]: Part of IgE B cell antigen receptor complex CC (BCR). The BCR complex consists of one mIgE molecule responsible for CC antigen binding, non-covalently associated with CD79A and CD79B CC signaling chains. {ECO:0000269|PubMed:8976175}. CC -!- SUBUNIT: [Isoform 3]: Part of IgE B cell antigen receptor complex CC (BCR). The BCR complex consists of one mIgE molecule responsible for CC antigen binding, non-covalently associated with CD79A and CD79B CC signaling chains. {ECO:0000269|PubMed:8976175}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted CC {ECO:0000269|PubMed:7995941}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane CC {ECO:0000269|PubMed:20458139, ECO:0000269|PubMed:7995941, CC ECO:0000269|PubMed:8976175}; Single-pass type I membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane CC {ECO:0000269|PubMed:8976175}; Single-pass type I membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=2; Synonyms=Membrane-bound, long mIgE CC {ECO:0000303|PubMed:1727861}; CC IsoId=P01854-2; Sequence=Displayed; CC Name=1; Synonyms=Secreted, sIgE {ECO:0000303|PubMed:7995941}; CC IsoId=P01854-1; Sequence=VSP_061835, VSP_061836; CC Name=3; Synonyms=Membrane-bound, short mIgE CC {ECO:0000303|PubMed:1727861}; CC IsoId=P01854-3; Sequence=VSP_061834; CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in B lymphocytes stimulated CC with IL4 and CD40. {ECO:0000269|PubMed:1613458}. CC -!- POLYMORPHISM: There are several alleles. The sequence shown is that of CC IMGT allele IGHE*04. {ECO:0000305}. CC -!- CAUTION: For an example of a full-length immunoglobulin epsilon heavy CC chain see AC P0DOX4. CC -!- SEQUENCE CAUTION: CC Sequence=AAB59395.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAB59424.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; L00022; AAB59424.1; ALT_INIT; Genomic_DNA. DR EMBL; J00222; AAB59395.1; ALT_INIT; Genomic_DNA. DR EMBL; AL928742; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X63693; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A22771; EHHU. DR PDB; 1F6A; X-ray; 3.50 A; B/D=211-428. DR PDB; 1FP5; X-ray; 2.30 A; A=211-428. DR PDB; 1G84; NMR; -; A=106-208. DR PDB; 1O0V; X-ray; 2.60 A; A/B=104-427. DR PDB; 2WQR; X-ray; 1.90 A; A/B=105-427. DR PDB; 2Y7Q; X-ray; 3.40 A; B/D=104-428. DR PDB; 3H9Y; X-ray; 2.23 A; A/B/E=209-428. DR PDB; 3H9Z; X-ray; 2.45 A; A/B/C/D=209-428. DR PDB; 3HA0; X-ray; 2.80 A; A/B/C/D/E/F=209-428. DR PDB; 4EZM; X-ray; 3.10 A; A/B/C/D/E/F=209-428. DR PDB; 4GKO; X-ray; 3.30 A; A/B/C/D/E/F=209-428. DR PDB; 4GRG; X-ray; 4.24 A; C/D=210-428. DR PDB; 4GT7; X-ray; 2.61 A; A/B/C/D=210-426. DR PDB; 4J4P; X-ray; 2.91 A; A/B=105-427. DR PDB; 4KI1; X-ray; 3.20 A; A/B/C/D=209-428. DR PDB; 5ANM; X-ray; 2.85 A; E/F/G=211-428. DR PDB; 5HYS; X-ray; 2.50 A; G/I/J/K=209-428. DR PDB; 5LGJ; X-ray; 2.60 A; A=108-426, B=108-427. DR PDB; 5LGK; X-ray; 3.50 A; A/B/C/D=114-421. DR PDB; 5MOI; X-ray; 2.20 A; A/B/C/D/E/F=209-428. DR PDB; 5MOJ; X-ray; 2.26 A; A/B=209-428. DR PDB; 5MOK; X-ray; 2.00 A; A/B/C/D=209-428. DR PDB; 5MOL; X-ray; 1.75 A; A/B=104-428. DR PDB; 5NQW; X-ray; 3.40 A; A/B=215-426. DR PDB; 6EYO; X-ray; 3.70 A; A/B=104-428. DR PDB; 6UQR; X-ray; 3.65 A; B/D=209-426. DR PDB; 7MXI; X-ray; 2.80 A; A/B=209-426. DR PDB; 7SHT; EM; 7.29 A; B/D=109-428. DR PDB; 7SHU; X-ray; 2.75 A; A/B=209-426. DR PDB; 7SHY; X-ray; 3.00 A; A/B/G/H=209-426. DR PDB; 7SHZ; X-ray; 3.00 A; A/B/G/H=209-426. DR PDB; 7SI0; X-ray; 3.00 A; A/B/G/H=209-426. DR PDB; 8C1B; EM; 3.80 A; H/X=108-423. DR PDB; 8C1C; EM; 4.10 A; H/X=1-423. DR PDBsum; 1F6A; -. DR PDBsum; 1FP5; -. DR PDBsum; 1G84; -. DR PDBsum; 1O0V; -. DR PDBsum; 2WQR; -. DR PDBsum; 2Y7Q; -. DR PDBsum; 3H9Y; -. DR PDBsum; 3H9Z; -. DR PDBsum; 3HA0; -. DR PDBsum; 4EZM; -. DR PDBsum; 4GKO; -. DR PDBsum; 4GRG; -. DR PDBsum; 4GT7; -. DR PDBsum; 4J4P; -. DR PDBsum; 4KI1; -. DR PDBsum; 5ANM; -. DR PDBsum; 5HYS; -. DR PDBsum; 5LGJ; -. DR PDBsum; 5LGK; -. DR PDBsum; 5MOI; -. DR PDBsum; 5MOJ; -. DR PDBsum; 5MOK; -. DR PDBsum; 5MOL; -. DR PDBsum; 5NQW; -. DR PDBsum; 6EYO; -. DR PDBsum; 6UQR; -. DR PDBsum; 7MXI; -. DR PDBsum; 7SHT; -. DR PDBsum; 7SHU; -. DR PDBsum; 7SHY; -. DR PDBsum; 7SHZ; -. DR PDBsum; 7SI0; -. DR PDBsum; 8C1B; -. DR PDBsum; 8C1C; -. DR AlphaFoldDB; P01854; -. DR EMDB; EMD-16377; -. DR EMDB; EMD-16378; -. DR EMDB; EMD-25136; -. DR SMR; P01854; -. DR ComplexPortal; CPX-6969; IgE - Ig kappa immunoglobulin complex, constant regions. DR ComplexPortal; CPX-6970; IgE - Ig lambda 1 immunoglobulin complex, constant regions. DR ComplexPortal; CPX-6971; IgE - Ig lambda 2 immunoglobulin complex, constant regions. DR ComplexPortal; CPX-6972; IgE - Ig lambda 3 immunoglobulin complex, constant regions. DR ComplexPortal; CPX-6973; IgE - Ig lambda 6 immunoglobulin complex, constant regions. DR ComplexPortal; CPX-6974; IgE - Ig lambda 7 immunoglobulin complex, constant regions. DR DIP; DIP-6167N; -. DR ChEMBL; CHEMBL1834; -. DR DrugBank; DB11856; Ligelizumab. DR DrugCentral; P01854; -. DR GuidetoPHARMACOLOGY; 2741; -. DR IMGT_GENE-DB; IGHE; -. DR GlyConnect; 2970; 39 N-Linked glycans. DR GlyConnect; 2971; 38 N-Linked glycans. DR GlyConnect; 765; 104 N-Linked glycans (7 sites). DR GlyCosmos; P01854; 7 sites, 126 glycans. DR GlyGen; P01854; 8 sites, 126 N-linked glycans (8 sites). DR iPTMnet; P01854; -. DR PhosphoSitePlus; P01854; -. DR BioMuta; IGHE; -. DR DMDM; 119512; -. DR jPOST; P01854; -. DR MassIVE; P01854; -. DR PeptideAtlas; P01854; -. DR ProteomicsDB; 51493; -. DR ABCD; P01854; 81 sequenced antibodies. DR Ensembl; ENST00000390541.2; ENSP00000374983.2; ENSG00000211891.6. [P01854-1] DR Ensembl; ENST00000610670.2; ENSP00000481089.1; ENSG00000276192.2. [P01854-1] DR Ensembl; ENST00000641420.1; ENSP00000492979.1; ENSG00000211891.6. [P01854-3] DR UCSC; uc059gcp.1; human. [P01854-2] DR AGR; HGNC:5522; -. DR GeneCards; IGHE; -. DR HGNC; HGNC:5522; IGHE. DR HPA; ENSG00000211891; Not detected. DR MIM; 147180; gene. DR neXtProt; NX_P01854; -. DR OpenTargets; ENSG00000211891; -. DR VEuPathDB; HostDB:ENSG00000211891; -. DR GeneTree; ENSGT00940000163076; -. DR HOGENOM; CLU_030625_0_2_1; -. DR InParanoid; P01854; -. DR OMA; ITQGQWV; -. DR PhylomeDB; P01854; -. DR TreeFam; TF334176; -. DR PathwayCommons; P01854; -. DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling. DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR SignaLink; P01854; -. DR EvolutionaryTrace; P01854; -. DR Pharos; P01854; Tclin. DR PRO; PR:P01854; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P01854; Protein. DR Bgee; ENSG00000211891; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 73 other cell types or tissues. DR ExpressionAtlas; P01854; baseline and differential. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0071744; C:IgE B cell receptor complex; IDA:UniProtKB. DR GO; GO:0071742; C:IgE immunoglobulin complex; NAS:ComplexPortal. DR GO; GO:0042571; C:immunoglobulin complex, circulating; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0003823; F:antigen binding; IBA:GO_Central. DR GO; GO:0034987; F:immunoglobulin receptor binding; IDA:UniProtKB. DR GO; GO:0090716; P:adaptive immune memory response; IMP:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; NAS:ComplexPortal. DR GO; GO:0019731; P:antibacterial humoral response; IBA:GO_Central. DR GO; GO:0001788; P:antibody-dependent cellular cytotoxicity; IDA:UniProtKB. DR GO; GO:0002450; P:B cell antigen processing and presentation; IDA:UniProtKB. DR GO; GO:0042100; P:B cell proliferation; IDA:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006958; P:complement activation, classical pathway; IBA:GO_Central. DR GO; GO:0043308; P:eosinophil degranulation; IDA:UniProtKB. DR GO; GO:0160006; P:Fc receptor-mediated immune complex endocytosis; IDA:UniProtKB. DR GO; GO:0006955; P:immune response; NAS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0042116; P:macrophage activation; IDA:UniProtKB. DR GO; GO:0030225; P:macrophage differentiation; IDA:UniProtKB. DR GO; GO:0043303; P:mast cell degranulation; IDA:UniProtKB. DR GO; GO:0090720; P:primary adaptive immune response; IMP:UniProtKB. DR GO; GO:0042092; P:type 2 immune response; IDA:UniProtKB. DR GO; GO:0016068; P:type I hypersensitivity; IDA:UniProtKB. DR CDD; cd21817; IgC1_CH1_IgEG; 1. DR CDD; cd05847; IgC1_CH2_IgE; 1. DR CDD; cd07696; IgC1_CH3_IgAEM_CH2_IgG; 1. DR CDD; cd05768; IgC1_CH3_IgAGD_CH4_IgAEM; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. 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 PANTHER; PTHR23411:SF30; IMMUNOGLOBULIN HEAVY CONSTANT EPSILON; 1. DR PANTHER; PTHR23411; TAPASIN; 1. DR Pfam; PF07654; C1-set; 4. DR SMART; SM00407; IGc1; 4. DR SUPFAM; SSF48726; Immunoglobulin; 4. DR PROSITE; PS50835; IG_LIKE; 4. DR PROSITE; PS00290; IG_MHC; 3. DR Genevisible; P01854; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin; Immunoglobulin domain; Inflammatory response; Membrane; KW Reference proteome; Repeat; Secreted; Transmembrane; Transmembrane helix. FT CHAIN <1..546 FT /note="Immunoglobulin heavy constant epsilon" FT /id="PRO_0000153574" FT TOPO_DOM 1..499 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 500..520 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 521..546 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT DOMAIN 6..103 FT /note="Ig-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DOMAIN 112..210 FT /note="Ig-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DOMAIN 214..318 FT /note="Ig-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DOMAIN 324..423 FT /note="Ig-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT CARBOHYD 21 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 49 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 99 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 146 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 252 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 264 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 275 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:10917520" FT DISULFID 14 FT /note="Interchain (with a light chain)" FT DISULFID 15..105 FT DISULFID 29..85 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 121 FT /note="Interchain (with a heavy chain)" FT DISULFID 135..193 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 209 FT /note="Interchain (with a heavy chain)" FT DISULFID 239..299 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10917520" FT DISULFID 345..405 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:10917520" FT VAR_SEQ 426..477 FT /note="Missing (in isoform 3)" FT /id="VSP_061834" FT VAR_SEQ 428 FT /note="L -> K (in isoform 1)" FT /id="VSP_061835" FT VAR_SEQ 429..546 FT /note="Missing (in isoform 1)" FT /id="VSP_061836" FT VARIANT 43 FT /note="W -> C (in IMGT allele IGHE*01)" FT /evidence="ECO:0000269|PubMed:6327276" FT /id="VAR_044229" FT VARIANT 359 FT /note="W -> L" FT /evidence="ECO:0000269|PubMed:6288268" FT /id="VAR_003885" FT CONFLICT 1..5 FT /note="ASTQS -> GAWTL (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 53..54 FT /note="Missing (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 93..94 FT /note="Missing (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 124 FT /note="G -> L (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 166..168 FT /note="TQE -> ESQ (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="Q -> E (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 177 FT /note="E -> Q (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 203 FT /note="E -> Q (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 398..399 FT /note="EQ -> QE (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT NON_TER 1 FT STRAND 115..119 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:1G84" FT STRAND 129..140 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 145..151 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:5LGJ" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 161..168 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 171..181 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 182..186 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 191..197 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 200..206 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 218..221 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 226..230 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 236..244 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 252..257 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 269..272 FT /evidence="ECO:0007829|PDB:5MOL" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:3H9Y" FT STRAND 278..285 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 288..292 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 297..302 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 310..314 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 325..330 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 335..338 FT /evidence="ECO:0007829|PDB:1FP5" FT STRAND 340..353 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 356..361 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 368..370 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 371..373 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 380..393 FT /evidence="ECO:0007829|PDB:5MOL" FT HELIX 394..399 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 403..408 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 410..412 FT /evidence="ECO:0007829|PDB:1F6A" FT TURN 413..415 FT /evidence="ECO:0007829|PDB:5MOL" FT STRAND 416..422 FT /evidence="ECO:0007829|PDB:5MOL" SQ SEQUENCE 546 AA; 59539 MW; 844D72B12B737FB9 CRC64; ASTQSPSVFP LTRCCKNIPS NATSVTLGCL ATGYFPEPVM VTWDTGSLNG TTMTLPATTL TLSGHYATIS LLTVSGAWAK QMFTCRVAHT PSSTDWVDNK TFSVCSRDFT PPTVKILQSS CDGGGHFPPT IQLLCLVSGY TPGTINITWL EDGQVMDVDL STASTTQEGE LASTQSELTL SQKHWLSDRT YTCQVTYQGH TFEDSTKKCA DSNPRGVSAY LSRPSPFDLF IRKSPTITCL VVDLAPSKGT VNLTWSRASG KPVNHSTRKE EKQRNGTLTV TSTLPVGTRD WIEGETYQCR VTHPHLPRAL MRSTTKTSGP RAAPEVYAFA TPEWPGSRDK RTLACLIQNF MPEDISVQWL HNEVQLPDAR HSTTQPRKTK GSGFFVFSRL EVTRAEWEQK DEFICRAVHE AASPSQTVQR AVSVNPGLAG GSAQSQRAPD RVLCHSGQQQ GLPRAAGGSV PHPRCHCGAG RADWPGPPEL DVCVEEAEGE APWTWTGLCI FAALFLLSVS YSAAITLLMV QRFLSATRQG RPQTSLDYTN VLQPHA //