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Gene Review

HTR1E  -  5-hydroxytryptamine (serotonin) receptor...

Homo sapiens

Synonyms: 5-HT-1E, 5-HT1E, 5-hydroxytryptamine receptor 1E, S31, Serotonin receptor 1E
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Disease relevance of HTR1E


High impact information on HTR1E

  • Here, we demonstrate by both MS and biochemical methods that this serine is phosphorylated (S31P) during mitosis in mammalian cells [4].
  • Additionally, H3.3 S31P forms a speckled staining pattern on the metaphase plate, whereas H3 S10 and H3 S28 phosphorylation localizes to the outer regions of condensed DNA [4].
  • Histone H3.3 contains a serine (S) to alanine (A) replacement at amino acid position 31 (S31) [4].
  • Furthermore, in contrast to phosphorylated general H3, H3.3 S31P is localized in distinct chromosomal regions immediately adjacent to centromeres [4].
  • In contrast to H3 S10 and H3 S28, which first become phosphorylated in prophase, H3.3 S31 phosphorylation is observed only in late prometaphase and metaphase and is absent in anaphase [4].

Biological context of HTR1E


Anatomical context of HTR1E


Associations of HTR1E with chemical compounds

  • Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype [6].
  • However, 5-carboxamidotryptamine demonstrated low affinity (pKi = 5.15) compared with serotonin (pKi = 8.14), consistent with the observed binding of the putative 5HT1E receptor [6].
  • Fluorescence titration experiments indicated that S31 bound the substrate H2folate 10-fold tighter and the coenzyme NADPH 2-fold tighter than the wild-type human dihydrofolate reductase [14].
  • Using oligonucleotide-directed mutagenesis and a bacterial expression system producing the wild-type and mutant human dihydrofolate reductases at levels of 10% of the bacterial protein, we have constructed, expressed, and purified a serine 31 (S31) mutant and a serine 34 (S34) mutant [14].
  • The serine 34 mutant had much greater alterations in its properties than S31; specifically, S34 had a 3-fold reduction in the Km for NADPH, a 24-fold increase in the Km for H2folate, a 3-fold reduction in the overall reaction rate kcat, and an 80,000-fold increase in the Kd for methotrexate [14].

Other interactions of HTR1E

  • 5-HT1A, 5-HT1D, and 5-HT1E mRNAs were detected in only some patients [15].
  • Specific binding at 5-HT1E/F and high-affinity 5-HT2A sites was too low for characterization [16].
  • MR77 thus represents a 5-HT receptor of the 5-HT1 class, and we propose that, based on the pharmacological characterization, MR77 represents an additional 5-HT1E-like receptor [17].
  • Competition studies with nonradioactive drugs indicated that, of the drugs tested, 5-CT and ergotamine displayed the highest selectivity for the 5-HT1D site versus the 5-HT1E site.(ABSTRACT TRUNCATED AT 250 WORDS)[18]
  • No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors) [13].

Analytical, diagnostic and therapeutic context of HTR1E


  1. Assignment of the gene encoding the 5-HT1E serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15. Levy, F.O., Holtgreve-Grez, H., Taskén, K., Solberg, R., Ried, T., Gudermann, T. Genomics (1994) [Pubmed]
  2. Serotonin receptors in human neuroblastoma: a possible biologic tumor marker. Pranzatelli, M.R., Balletti, J. Exp. Neurol. (1992) [Pubmed]
  3. Expression of serotonin receptors in human fetal astrocytes and glioma cell lines: a possible role in glioma cell proliferation and migration. Merzak, A., Koochekpour, S., Fillion, M.P., Fillion, G., Pilkington, G.J. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  4. Serine 31 phosphorylation of histone variant H3.3 is specific to regions bordering centromeres in metaphase chromosomes. Hake, S.B., Garcia, B.A., Kauer, M., Baker, S.P., Shabanowitz, J., Hunt, D.F., Allis, C.D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. beta-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation. Jeffries, A.R., Mungall, A.J., Dawson, E., Halls, K., Langford, C.F., Murray, R.M., Dunham, I., Powell, J.F. Mol. Psychiatry (2003) [Pubmed]
  6. Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype. McAllister, G., Charlesworth, A., Snodin, C., Beer, M.S., Noble, A.J., Middlemiss, D.N., Iversen, L.L., Whiting, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor. Zgombick, J.M., Schechter, L.E., Macchi, M., Hartig, P.R., Branchek, T.A., Weinshank, R.L. Mol. Pharmacol. (1992) [Pubmed]
  8. Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclase. Levy, F.O., Gudermann, T., Birnbaumer, M., Kaumann, A.J., Birnbaumer, L. FEBS Lett. (1992) [Pubmed]
  9. Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. Amlaiky, N., Ramboz, S., Boschert, U., Plassat, J.L., Hen, R. J. Biol. Chem. (1992) [Pubmed]
  10. 5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex. Lowther, S., Katona, C.L., Crompton, M.R., Horton, R.W. Mol. Psychiatry (1997) [Pubmed]
  11. Identification of 5-hydroxytryptamine1D binding sites in sheep caudate nucleus membranes. Pauwels, P.J., Palmier, C., Briley, M. Biochem. Pharmacol. (1993) [Pubmed]
  12. The distribution of 5-HT1D and 5-HT1E binding sites in human brain. Lowther, S., De Paermentier, F., Crompton, M.R., Horton, R.W. Eur. J. Pharmacol. (1992) [Pubmed]
  13. Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5-HT, in frontal cortex and the hippocampal region of the human brain. Barone, P., Jordan, D., Atger, F., Kopp, N., Fillion, G. Brain Res. (1994) [Pubmed]
  14. Probing the role of two hydrophobic active site residues in the human dihydrofolate reductase by site-directed mutagenesis. Schweitzer, B.I., Srimatkandada, S., Gritsman, H., Sheridan, R., Venkataraghavan, R., Bertino, J.R. J. Biol. Chem. (1989) [Pubmed]
  15. Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. Ishida, T., Hirata, K., Sakoda, T., Kawashima, S., Akita, H., Yokoyama, M. Cardiovasc. Res. (1999) [Pubmed]
  16. Human brainstem serotonin receptors: characterization and implications for subcortical myoclonus. Pranzatelli, M.R., Galvan, I., Tailor, P.T. Clinical neuropharmacology. (1996) [Pubmed]
  17. Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Lovenberg, T.W., Erlander, M.G., Baron, B.M., Racke, M., Slone, A.L., Siegel, B.W., Craft, C.M., Burns, J.E., Danielson, P.E., Sutcliffe, J.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  18. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. Leonhardt, S., Herrick-Davis, K., Titeler, M. J. Neurochem. (1989) [Pubmed]
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