Full text data of HBE1
HBE1
(HBE)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Hemoglobin subunit epsilon (Epsilon-globin; Hemoglobin epsilon chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Hemoglobin subunit epsilon (Epsilon-globin; Hemoglobin epsilon chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00217471
IPI00217471 Epsilon globin The epsilon chain is a beta-type chain of early mammalian embryonic hemoglobin. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00217471 Epsilon globin The epsilon chain is a beta-type chain of early mammalian embryonic hemoglobin. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P02100
ID HBE_HUMAN Reviewed; 147 AA.
AC P02100; Q6FH44;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 140.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF HB GOWER-2.
RX PubMed=9665850; DOI=10.1006/jmbi.1998.1868;
RA Sutherland-Smith A.J., Baker H.M., Hofmann O.M., Brittain T.,
RA Baker E.N.;
RT "Crystal structure of a human embryonic haemoglobin: the carbonmonoxy
RT form 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
CC mammalian embryonic hemoglobin.
CC -!- SUBUNIT: Heterotetramer of two alpha chains and two epsilon chains
CC in early embryonic hemoglobin Gower-2; two zeta chains and two
CC epsilon chains in early embryonic hemoglobin Gower-1.
CC -!- TISSUE SPECIFICITY: Red blood cells.
CC -!- SIMILARITY: Belongs to the globin family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A90802; HEHU.
DR RefSeq; NP_005321.1; NM_005330.3.
DR UniGene; Hs.655195; -.
DR PDB; 1A9W; X-ray; 2.90 A; E/F=2-147.
DR PDBsum; 1A9W; -.
DR ProteinModelPortal; P02100; -.
DR SMR; P02100; 2-146.
DR IntAct; P02100; 1.
DR STRING; 9606.ENSP00000292896; -.
DR PhosphoSite; P02100; -.
DR DMDM; 122726; -.
DR PaxDb; P02100; -.
DR PeptideAtlas; P02100; -.
DR PRIDE; P02100; -.
DR DNASU; 3046; -.
DR Ensembl; ENST00000292896; ENSP00000292896; ENSG00000213931.
DR Ensembl; ENST00000380237; ENSP00000369586; ENSG00000213931.
DR GeneID; 3046; -.
DR KEGG; hsa:3046; -.
DR UCSC; uc001mal.1; human.
DR CTD; 3046; -.
DR GeneCards; GC11M005289; -.
DR HGNC; HGNC:4830; HBE1.
DR MIM; 142100; gene.
DR neXtProt; NX_P02100; -.
DR PharmGKB; PA29205; -.
DR eggNOG; NOG325823; -.
DR HOGENOM; HOG000036868; -.
DR HOVERGEN; HBG009709; -.
DR InParanoid; P02100; -.
DR KO; K13825; -.
DR OMA; MDNLKGA; -.
DR OrthoDB; EOG7B8S5H; -.
DR PhylomeDB; P02100; -.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; P02100; -.
DR GeneWiki; HBE1; -.
DR GenomeRNAi; 3046; -.
DR NextBio; 12059; -.
DR PRO; PR:P02100; -.
DR ArrayExpress; P02100; -.
DR Bgee; P02100; -.
DR CleanEx; HS_HBE1; -.
DR Genevestigator; P02100; -.
DR GO; GO:0005833; C:hemoglobin complex; TAS:ProtInc.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen transporter activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like.
DR InterPro; IPR012292; Globin_dom.
DR InterPro; IPR002337; Haemoglobin_b.
DR PANTHER; PTHR11442:SF7; PTHR11442:SF7; 1.
DR Pfam; PF00042; Globin; 1.
DR PRINTS; PR00814; BETAHAEM.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing; Heme;
KW Iron; Metal-binding; Oxygen transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 147 Hemoglobin subunit epsilon.
FT /FTId=PRO_0000053212.
FT METAL 64 64 Iron (heme distal ligand).
FT METAL 93 93 Iron (heme proximal ligand).
FT CONFLICT 143 143 A -> G (in Ref. 5; AA sequence).
FT HELIX 6 18
FT TURN 21 23
FT HELIX 24 35
FT HELIX 37 41
FT HELIX 44 46
FT HELIX 52 57
FT HELIX 59 76
FT STRAND 79 81
FT TURN 83 86
FT HELIX 87 94
FT TURN 95 97
FT HELIX 102 119
FT HELIX 120 122
FT HELIX 125 142
SQ SEQUENCE 147 AA; 16203 MW; 223388816EDDE8D5 CRC64;
MVHFTAEEKA AVTSLWSKMN VEEAGGEALG RLLVVYPWTQ RFFDSFGNLS SPSAILGNPK
VKAHGKKVLT SFGDAIKNMD NLKPAFAKLS ELHCDKLHVD PENFKLLGNV MVIILATHFG
KEFTPEVQAA WQKLVSAVAI ALAHKYH
//
ID HBE_HUMAN Reviewed; 147 AA.
AC P02100; Q6FH44;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 140.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF HB GOWER-2.
RX PubMed=9665850; DOI=10.1006/jmbi.1998.1868;
RA Sutherland-Smith A.J., Baker H.M., Hofmann O.M., Brittain T.,
RA Baker E.N.;
RT "Crystal structure of a human embryonic haemoglobin: the carbonmonoxy
RT form 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
CC mammalian embryonic hemoglobin.
CC -!- SUBUNIT: Heterotetramer of two alpha chains and two epsilon chains
CC in early embryonic hemoglobin Gower-2; two zeta chains and two
CC epsilon chains in early embryonic hemoglobin Gower-1.
CC -!- TISSUE SPECIFICITY: Red blood cells.
CC -!- SIMILARITY: Belongs to the globin family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A90802; HEHU.
DR RefSeq; NP_005321.1; NM_005330.3.
DR UniGene; Hs.655195; -.
DR PDB; 1A9W; X-ray; 2.90 A; E/F=2-147.
DR PDBsum; 1A9W; -.
DR ProteinModelPortal; P02100; -.
DR SMR; P02100; 2-146.
DR IntAct; P02100; 1.
DR STRING; 9606.ENSP00000292896; -.
DR PhosphoSite; P02100; -.
DR DMDM; 122726; -.
DR PaxDb; P02100; -.
DR PeptideAtlas; P02100; -.
DR PRIDE; P02100; -.
DR DNASU; 3046; -.
DR Ensembl; ENST00000292896; ENSP00000292896; ENSG00000213931.
DR Ensembl; ENST00000380237; ENSP00000369586; ENSG00000213931.
DR GeneID; 3046; -.
DR KEGG; hsa:3046; -.
DR UCSC; uc001mal.1; human.
DR CTD; 3046; -.
DR GeneCards; GC11M005289; -.
DR HGNC; HGNC:4830; HBE1.
DR MIM; 142100; gene.
DR neXtProt; NX_P02100; -.
DR PharmGKB; PA29205; -.
DR eggNOG; NOG325823; -.
DR HOGENOM; HOG000036868; -.
DR HOVERGEN; HBG009709; -.
DR InParanoid; P02100; -.
DR KO; K13825; -.
DR OMA; MDNLKGA; -.
DR OrthoDB; EOG7B8S5H; -.
DR PhylomeDB; P02100; -.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; P02100; -.
DR GeneWiki; HBE1; -.
DR GenomeRNAi; 3046; -.
DR NextBio; 12059; -.
DR PRO; PR:P02100; -.
DR ArrayExpress; P02100; -.
DR Bgee; P02100; -.
DR CleanEx; HS_HBE1; -.
DR Genevestigator; P02100; -.
DR GO; GO:0005833; C:hemoglobin complex; TAS:ProtInc.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen transporter activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR Gene3D; 1.10.490.10; -; 1.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like.
DR InterPro; IPR012292; Globin_dom.
DR InterPro; IPR002337; Haemoglobin_b.
DR PANTHER; PTHR11442:SF7; PTHR11442:SF7; 1.
DR Pfam; PF00042; Globin; 1.
DR PRINTS; PR00814; BETAHAEM.
DR SUPFAM; SSF46458; SSF46458; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing; Heme;
KW Iron; Metal-binding; Oxygen transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 147 Hemoglobin subunit epsilon.
FT /FTId=PRO_0000053212.
FT METAL 64 64 Iron (heme distal ligand).
FT METAL 93 93 Iron (heme proximal ligand).
FT CONFLICT 143 143 A -> G (in Ref. 5; AA sequence).
FT HELIX 6 18
FT TURN 21 23
FT HELIX 24 35
FT HELIX 37 41
FT HELIX 44 46
FT HELIX 52 57
FT HELIX 59 76
FT STRAND 79 81
FT TURN 83 86
FT HELIX 87 94
FT TURN 95 97
FT HELIX 102 119
FT HELIX 120 122
FT HELIX 125 142
SQ SEQUENCE 147 AA; 16203 MW; 223388816EDDE8D5 CRC64;
MVHFTAEEKA AVTSLWSKMN VEEAGGEALG RLLVVYPWTQ RFFDSFGNLS SPSAILGNPK
VKAHGKKVLT SFGDAIKNMD NLKPAFAKLS ELHCDKLHVD PENFKLLGNV MVIILATHFG
KEFTPEVQAA WQKLVSAVAI ALAHKYH
//
MIM
142100
*RECORD*
*FIELD* NO
142100
*FIELD* TI
*142100 HEMOGLOBIN--EPSILON LOCUS; HBE1
*FIELD* TX
The epsilon locus determines the epsilon, or non-alpha, chain of
read moreembryonic hemoglobin (originally known as Gower-2). No mutations
affecting the epsilon chain have yet been identified. Gower-1 is a
tetramer of epsilon chains. The epsilon locus may be linked to the
delta-beta complex. The amino acid sequence of the epsilon chain is
similar to those of the delta and beta chains. Furthermore, the
homologous chain in the mouse is linked to the beta locus (Gilman and
Smithies, 1968). Shen and Smithies (1982) determined the complete
nucleotide sequence of the 3.4-kb stretch of DNA 5-prime to the epsilon
gene where a pseudogene (psi-beta-2) was thought to reside (Fritsch et
al., 1980). They concluded that no globin-related gene exists there and
provided a possible explanation for the earlier contrary conclusion. By
studies in transgenic mice, Raich et al. (1992) demonstrated that
deletion of a 'negative element' located between -182 and -467 bp
upstream of the HBE gene cap site resulted in continuation of HBE gene
expression in the definitive erythroblasts of the fetal liver and in the
red blood cells of adult animals. The findings provided direct in vivo
evidence that cis-acting silencing elements are involved in the
developmental control of the HBE gene.
Bailey et al. (1992) used the epsilon-globin gene to examine the debate
as to whether all bats fall into a monophyletic order (Chiroptera) or
have diphyletic origins with the megabats actually being 'flying
primates.' Results of parsimony analysis supported bat monophyly.
He and Russell (2002) analyzed the anti-sickling properties of HBE both
in vitro as well as in vivo in a well-established mouse model of sickle
cell anemia (603903). These animals, expressing 100% of human Hb S
(141900.0243), display a chronic hemolytic anemia with compensatory
marrow and extramedullary erythropoiesis, abundant circulating sickled
erythrocytes, and chronic tissue damage evidenced by parallel
histopathologic and functional deficits. By comparison, related mice
that coexpress Hb S as well as HBE exhibited normal physiologic,
morphologic, histologic, and functional attributes. Subsequent in vitro
analyses substantiated results from whole-animal studies, indicating
that the polymerization of deoxygenated Hb S can be significantly slowed
by relatively small quantities of HBE. Together, the in vivo and in
vitro analyses suggested that reactivation of epsilon-globin gene
expression would be therapeutically beneficial to adults with sickle
phenotypes, and provide a rationale for detailed investigations into the
molecular basis for its developmental silencing.
*FIELD* SA
Baralle et al. (1980); Gale et al. (1979); Huehns et al. (1964); Huehns
et al. (1961); Ramsay et al. (1986)
*FIELD* RF
1. Bailey, W. J.; Slightom, J. L.; Goodman, M.: Rejection of the
'flying primate' hypothesis by phylogenetic evidence from the epsilon-globin
gene. Science 256: 86-89, 1992. Note: Erratum: Science 260: 608
only, 1993.
2. Baralle, F. E.; Shoulders, C. C.; Proudfoot, N. J.: The primary
structure of the human epsilon-globin gene. Cell 21: 621-626, 1980.
3. Fritsch, E. F.; Lawn, R. M.; Maniatis, T.: Molecular cloning and
characterization of the human beta-like globin gene cluster. Cell 19:
959-972, 1980.
4. Gale, R. E.; Clegg, J. B.; Huehns, E. R.: Human embryonic haemoglobins
Gower 1 and Gower 2. Nature 280: 162-164, 1979.
5. Gilman, J. G.; Smithies, O.: Fetal hemoglobin variants in mice. Science 160:
885-886, 1968.
6. He, Z.; Russell, J. E.: A human embryonic hemoglobin inhibits
Hb S polymerization in vitro and restores a normal phenotype to mouse
models of sickle cell disease. Proc. Nat. Acad. Sci. 99: 10635-10640,
2002.
7. Huehns, E. R.; Dance, N.; Beaven, G. H.; Hecht, F.; Motulsky, A.
G.: Human embryonic hemoglobin. Nature 201: 1095-1097, 1964.
8. Huehns, E. R.; Flynn, F. V.; Butler, E. A.; Beaven, G. H.: Two
new hemoglobin variants in a very young human embryo. Nature 189:
496-497, 1961.
9. Raich, N.; Papayannopoulou, T.; Stamatoyannopoulos, G.; Enver,
T.: Demonstration of a human epsilon-globin gene silencer with studies
in transgenic mice. Blood 79: 861-864, 1992.
10. Ramsay, M.; Thomson, J. A.; Jenkins, T.: A new epsilon globin
HincII variant fragment length in a South African Negroid family. J.
Med. Genet. 23: 145-150, 1986.
11. Shen, S.-H.; Smithies, O.: Human globin psi-beta-2 is not a globin-related
sequence. Nucleic Acids Res. 10: 7809-7818, 1982.
*FIELD* CN
Victor A. McKusick - updated: 9/27/2002
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 04/01/2013
alopez: 5/27/2004
terry: 5/21/2004
cwells: 10/1/2002
carol: 9/27/2002
alopez: 8/1/1997
mimadm: 9/24/1994
terry: 5/9/1994
carol: 8/11/1992
carol: 5/11/1992
carol: 5/1/1992
supermim: 3/16/1992
*RECORD*
*FIELD* NO
142100
*FIELD* TI
*142100 HEMOGLOBIN--EPSILON LOCUS; HBE1
*FIELD* TX
The epsilon locus determines the epsilon, or non-alpha, chain of
read moreembryonic hemoglobin (originally known as Gower-2). No mutations
affecting the epsilon chain have yet been identified. Gower-1 is a
tetramer of epsilon chains. The epsilon locus may be linked to the
delta-beta complex. The amino acid sequence of the epsilon chain is
similar to those of the delta and beta chains. Furthermore, the
homologous chain in the mouse is linked to the beta locus (Gilman and
Smithies, 1968). Shen and Smithies (1982) determined the complete
nucleotide sequence of the 3.4-kb stretch of DNA 5-prime to the epsilon
gene where a pseudogene (psi-beta-2) was thought to reside (Fritsch et
al., 1980). They concluded that no globin-related gene exists there and
provided a possible explanation for the earlier contrary conclusion. By
studies in transgenic mice, Raich et al. (1992) demonstrated that
deletion of a 'negative element' located between -182 and -467 bp
upstream of the HBE gene cap site resulted in continuation of HBE gene
expression in the definitive erythroblasts of the fetal liver and in the
red blood cells of adult animals. The findings provided direct in vivo
evidence that cis-acting silencing elements are involved in the
developmental control of the HBE gene.
Bailey et al. (1992) used the epsilon-globin gene to examine the debate
as to whether all bats fall into a monophyletic order (Chiroptera) or
have diphyletic origins with the megabats actually being 'flying
primates.' Results of parsimony analysis supported bat monophyly.
He and Russell (2002) analyzed the anti-sickling properties of HBE both
in vitro as well as in vivo in a well-established mouse model of sickle
cell anemia (603903). These animals, expressing 100% of human Hb S
(141900.0243), display a chronic hemolytic anemia with compensatory
marrow and extramedullary erythropoiesis, abundant circulating sickled
erythrocytes, and chronic tissue damage evidenced by parallel
histopathologic and functional deficits. By comparison, related mice
that coexpress Hb S as well as HBE exhibited normal physiologic,
morphologic, histologic, and functional attributes. Subsequent in vitro
analyses substantiated results from whole-animal studies, indicating
that the polymerization of deoxygenated Hb S can be significantly slowed
by relatively small quantities of HBE. Together, the in vivo and in
vitro analyses suggested that reactivation of epsilon-globin gene
expression would be therapeutically beneficial to adults with sickle
phenotypes, and provide a rationale for detailed investigations into the
molecular basis for its developmental silencing.
*FIELD* SA
Baralle et al. (1980); Gale et al. (1979); Huehns et al. (1964); Huehns
et al. (1961); Ramsay et al. (1986)
*FIELD* RF
1. Bailey, W. J.; Slightom, J. L.; Goodman, M.: Rejection of the
'flying primate' hypothesis by phylogenetic evidence from the epsilon-globin
gene. Science 256: 86-89, 1992. Note: Erratum: Science 260: 608
only, 1993.
2. Baralle, F. E.; Shoulders, C. C.; Proudfoot, N. J.: The primary
structure of the human epsilon-globin gene. Cell 21: 621-626, 1980.
3. Fritsch, E. F.; Lawn, R. M.; Maniatis, T.: Molecular cloning and
characterization of the human beta-like globin gene cluster. Cell 19:
959-972, 1980.
4. Gale, R. E.; Clegg, J. B.; Huehns, E. R.: Human embryonic haemoglobins
Gower 1 and Gower 2. Nature 280: 162-164, 1979.
5. Gilman, J. G.; Smithies, O.: Fetal hemoglobin variants in mice. Science 160:
885-886, 1968.
6. He, Z.; Russell, J. E.: A human embryonic hemoglobin inhibits
Hb S polymerization in vitro and restores a normal phenotype to mouse
models of sickle cell disease. Proc. Nat. Acad. Sci. 99: 10635-10640,
2002.
7. Huehns, E. R.; Dance, N.; Beaven, G. H.; Hecht, F.; Motulsky, A.
G.: Human embryonic hemoglobin. Nature 201: 1095-1097, 1964.
8. Huehns, E. R.; Flynn, F. V.; Butler, E. A.; Beaven, G. H.: Two
new hemoglobin variants in a very young human embryo. Nature 189:
496-497, 1961.
9. Raich, N.; Papayannopoulou, T.; Stamatoyannopoulos, G.; Enver,
T.: Demonstration of a human epsilon-globin gene silencer with studies
in transgenic mice. Blood 79: 861-864, 1992.
10. Ramsay, M.; Thomson, J. A.; Jenkins, T.: A new epsilon globin
HincII variant fragment length in a South African Negroid family. J.
Med. Genet. 23: 145-150, 1986.
11. Shen, S.-H.; Smithies, O.: Human globin psi-beta-2 is not a globin-related
sequence. Nucleic Acids Res. 10: 7809-7818, 1982.
*FIELD* CN
Victor A. McKusick - updated: 9/27/2002
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 04/01/2013
alopez: 5/27/2004
terry: 5/21/2004
cwells: 10/1/2002
carol: 9/27/2002
alopez: 8/1/1997
mimadm: 9/24/1994
terry: 5/9/1994
carol: 8/11/1992
carol: 5/11/1992
carol: 5/1/1992
supermim: 3/16/1992