ID   HBE_HUMAN               Reviewed;         147 AA.
AC   P02100; Q6FH44;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   24-JAN-2024, entry version 211.
DE   RecName: Full=Hemoglobin subunit epsilon;
DE   AltName: Full=Epsilon-globin;
DE   AltName: Full=Hemoglobin epsilon chain;
GN   Name=HBE1; Synonyms=HBE;
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 [GENOMIC DNA].
RX   PubMed=6254663; DOI=10.1016/0092-8674(80)90425-0;
RA   Baralle F.E., Shoulders C.C., Proudfoot N.J.;
RT   "The primary structure of the human epsilon-globin gene.";
RL   Cell 21:621-626(1980).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [5]
RP   PROTEIN SEQUENCE OF 2-147.
RX   PubMed=6172865;
RA   Clegg J.B.;
RT   "Embryonic hemoglobin: sequence of the epsilon and zeta chains.";
RL   Tex. Rep. Biol. Med. 40:23-28(1980).
RN   [6]
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-51, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF HB GOWER-2 IN COMPLEX WITH HEME,
RP   AND SUBUNIT.
RX   PubMed=9665850; DOI=10.1006/jmbi.1998.1868;
RA   Sutherland-Smith A.J., Baker H.M., Hofmann O.M., Brittain T., Baker E.N.;
RT   "Crystal structure of a human embryonic haemoglobin: the carbonmonoxy form
RT   of Gower II (alpha2 epsilon2) haemoglobin at 2.9-A resolution.";
RL   J. Mol. Biol. 280:475-484(1998).
CC   -!- FUNCTION: The epsilon chain is a beta-type chain of early mammalian
CC       embryonic hemoglobin.
CC   -!- SUBUNIT: Heterotetramer of two alpha chains and two epsilon chains in
CC       early embryonic hemoglobin Gower-2; two zeta chains and two epsilon
CC       chains in early embryonic hemoglobin Gower-1.
CC       {ECO:0000269|PubMed:9665850}.
CC   -!- INTERACTION:
CC       P02100; P69905: HBA2; NbExp=4; IntAct=EBI-6190240, EBI-714680;
CC       P02100; P09105: HBQ1; NbExp=3; IntAct=EBI-6190240, EBI-10193656;
CC       P02100; P02008: HBZ; NbExp=6; IntAct=EBI-6190240, EBI-719843;
CC   -!- TISSUE SPECIFICITY: Red blood cells.
CC   -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00238}.
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DR   EMBL; U01317; AAA16330.1; -; Genomic_DNA.
DR   EMBL; V00508; CAA23766.1; -; Genomic_DNA.
DR   EMBL; CR541912; CAG46710.1; -; mRNA.
DR   EMBL; CH471064; EAW68802.1; -; Genomic_DNA.
DR   EMBL; BC015537; AAH15537.1; -; mRNA.
DR   CCDS; CCDS7756.1; -.
DR   PIR; A90802; HEHU.
DR   RefSeq; NP_005321.1; NM_005330.3.
DR   PDB; 1A9W; X-ray; 2.90 A; E/F=2-147.
DR   PDBsum; 1A9W; -.
DR   AlphaFoldDB; P02100; -.
DR   SMR; P02100; -.
DR   BioGRID; 109296; 14.
DR   ComplexPortal; CPX-2927; Hemoglobin E complex.
DR   ComplexPortal; CPX-2928; Embryonic hemoglobin Gower-1 complex.
DR   IntAct; P02100; 8.
DR   STRING; 9606.ENSP00000292896; -.
DR   iPTMnet; P02100; -.
DR   PhosphoSitePlus; P02100; -.
DR   BioMuta; HBE1; -.
DR   DMDM; 122726; -.
DR   jPOST; P02100; -.
DR   MassIVE; P02100; -.
DR   MaxQB; P02100; -.
DR   PaxDb; 9606-ENSP00000369586; -.
DR   PeptideAtlas; P02100; -.
DR   ProteomicsDB; 51516; -.
DR   Pumba; P02100; -.
DR   Antibodypedia; 42207; 208 antibodies from 25 providers.
DR   DNASU; 3046; -.
DR   Ensembl; ENST00000292896.3; ENSP00000292896.2; ENSG00000213931.7.
DR   Ensembl; ENST00000380237.5; ENSP00000369586.1; ENSG00000213931.7.
DR   Ensembl; ENST00000396895.3; ENSP00000380104.2; ENSG00000213931.7.
DR   GeneID; 3046; -.
DR   KEGG; hsa:3046; -.
DR   MANE-Select; ENST00000396895.3; ENSP00000380104.2; NM_005330.4; NP_005321.1.
DR   UCSC; uc001mal.2; human.
DR   AGR; HGNC:4830; -.
DR   CTD; 3046; -.
DR   DisGeNET; 3046; -.
DR   GeneCards; HBE1; -.
DR   HGNC; HGNC:4830; HBE1.
DR   HPA; ENSG00000213931; Low tissue specificity.
DR   MIM; 142100; gene.
DR   neXtProt; NX_P02100; -.
DR   OpenTargets; ENSG00000213931; -.
DR   PharmGKB; PA29205; -.
DR   VEuPathDB; HostDB:ENSG00000213931; -.
DR   eggNOG; KOG3378; Eukaryota.
DR   GeneTree; ENSGT00940000157809; -.
DR   HOGENOM; CLU_003827_10_0_1; -.
DR   InParanoid; P02100; -.
DR   OMA; INGLWSK; -.
DR   OrthoDB; 5356926at2759; -.
DR   PhylomeDB; P02100; -.
DR   TreeFam; TF333268; -.
DR   PathwayCommons; P02100; -.
DR   Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR   SignaLink; P02100; -.
DR   SIGNOR; P02100; -.
DR   BioGRID-ORCS; 3046; 13 hits in 1152 CRISPR screens.
DR   ChiTaRS; HBE1; human.
DR   EvolutionaryTrace; P02100; -.
DR   GeneWiki; HBE1; -.
DR   GenomeRNAi; 3046; -.
DR   Pharos; P02100; Tbio.
DR   PRO; PR:P02100; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P02100; Protein.
DR   Bgee; ENSG00000213931; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 90 other cell types or tissues.
DR   ExpressionAtlas; P02100; baseline and differential.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0031838; C:haptoglobin-hemoglobin complex; IBA:GO_Central.
DR   GO; GO:0005833; C:hemoglobin complex; IPI:ComplexPortal.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   GO; GO:0031721; F:hemoglobin alpha binding; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0043177; F:organic acid binding; IBA:GO_Central.
DR   GO; GO:0019825; F:oxygen binding; IBA:GO_Central.
DR   GO; GO:0005344; F:oxygen carrier activity; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0015670; P:carbon dioxide transport; NAS:ComplexPortal.
DR   GO; GO:0098869; P:cellular oxidant detoxification; IEA:GOC.
DR   GO; GO:0042744; P:hydrogen peroxide catabolic process; IBA:GO_Central.
DR   GO; GO:0015671; P:oxygen transport; IDA:ComplexPortal.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   CDD; cd08925; Hb-beta-like; 1.
DR   Gene3D; 1.10.490.10; Globins; 1.
DR   InterPro; IPR000971; Globin.
DR   InterPro; IPR009050; Globin-like_sf.
DR   InterPro; IPR012292; Globin/Proto.
DR   InterPro; IPR002337; Hemoglobin_b.
DR   PANTHER; PTHR11442; HEMOGLOBIN FAMILY MEMBER; 1.
DR   PANTHER; PTHR11442:SF7; HEMOGLOBIN SUBUNIT EPSILON; 1.
DR   Pfam; PF00042; Globin; 1.
DR   PRINTS; PR00814; BETAHAEM.
DR   SUPFAM; SSF46458; Globin-like; 1.
DR   PROSITE; PS01033; GLOBIN; 1.
DR   Genevisible; P02100; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Heme; Iron; Metal-binding;
KW   Oxygen transport; Phosphoprotein; Reference proteome; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:6172865"
FT   CHAIN           2..147
FT                   /note="Hemoglobin subunit epsilon"
FT                   /id="PRO_0000053212"
FT   BINDING         64
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="distal binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P80044"
FT   BINDING         93
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="proximal binding residue"
FT                   /evidence="ECO:0000269|PubMed:9665850,
FT                   ECO:0007744|PDB:1A9W"
FT   MOD_RES         14
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         51
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   CONFLICT        143
FT                   /note="A -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           6..18
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   TURN            21..23
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           24..35
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           37..41
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           44..46
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           52..57
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           59..76
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   STRAND          79..81
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   TURN            83..86
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           87..94
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   TURN            95..97
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           102..119
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           120..122
FT                   /evidence="ECO:0007829|PDB:1A9W"
FT   HELIX           125..142
FT                   /evidence="ECO:0007829|PDB:1A9W"
SQ   SEQUENCE   147 AA;  16203 MW;  223388816EDDE8D5 CRC64;
     MVHFTAEEKA AVTSLWSKMN VEEAGGEALG RLLVVYPWTQ RFFDSFGNLS SPSAILGNPK
     VKAHGKKVLT SFGDAIKNMD NLKPAFAKLS ELHCDKLHVD PENFKLLGNV MVIILATHFG
     KEFTPEVQAA WQKLVSAVAI ALAHKYH
//