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5-HT3B

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Target id: 374

Nomenclature: 5-HT3B

Family: 5-HT3 receptors

Contents:

Quaternary Structure: Complexes
5-HT3AB
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 441 11q23.2 HTR3B 5-hydroxytryptamine receptor 3B 4,6
Mouse 4 437 9 A5.3 Htr3b 5-hydroxytryptamine (serotonin) receptor 3B 8
Rat 4 437 8q23 Htr3b 5-hydroxytryptamine receptor 3B 8
Previous and Unofficial Names Click here for help
serotonin receptor 3B | 5-HT3 receptor subunit B | 5-hydroxytryptamine (serotonin) receptor 3B, ionotropic
Database Links Click here for help
Alphafold O95264 (Hs), Q9JHJ5 (Mm), Q9JJ16 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL3895 (Hs), CHEMBL3781 (Mm), CHEMBL2094116 (Rn)
Ensembl Gene ENSG00000149305 (Hs), ENSMUSG00000008590 (Mm), ENSRNOG00000006920 (Rn)
Entrez Gene 9177 (Hs), 57014 (Mm), 58963 (Rn)
Human Protein Atlas ENSG00000149305 (Hs)
KEGG Gene hsa:9177 (Hs), mmu:57014 (Mm), rno:58963 (Rn)
OMIM 604654 (Hs)
Pharos O95264 (Hs)
RefSeq Nucleotide NM_006028 (Hs), NM_020274 (Mm), NM_022189 (Rn)
RefSeq Protein NP_006019 (Hs), NP_064670 (Mm), NP_071525 (Rn)
UniProtKB O95264 (Hs), Q9JHJ5 (Mm), Q9JJ16 (Rn)
Wikipedia HTR3B (Hs)
Functional Characteristics Click here for help
γ = 0.4-0.8 pS [+ 5-HT3B, γ = 16 pS]; inwardly rectifying current [+ 5-HT3B, rectification reduced]; nH 2-3 [+ 5-HT3B 1-2]; relative permeability to divalent cations reduced by co-expression of the 5-HT3B subunit
Natural/Endogenous Ligands Click here for help
5-hydroxytryptamine
Tissue Distribution Click here for help
Amygdala, hippocampus, caudate nucleus, small intestine, colon and kidney.
Species:  Human
Technique:  RT-PCR
References:  20
Amygdala, caudate nucleus, hippocampus, thalamus.
Species:  Human
Technique:  Northern Blot
References:  4
Pyramidal neurones in the CA2, CA3 and to a lesser extent CA1 fields of the hippocampus. Large neurones in the hilus (CA4) of the hippocampus.
Species:  Human
Technique:  Immunohistochemistry
References:  3
Submucous plexus neurones.
Species:  Human
Technique:  Immunohistochemistry
References:  13
Cerebral cortex including occipital, frontal and temporal regions, amygdala, hippocampus and testis.
Species:  Human
Technique:  PCR-based detection
References:  6
Nodose, trigeminal, superior cervical and dorsal root ganglia.
Species:  Mouse
Technique:  Immunohistochemistry
References:  5
Brain, small intestine, colon.
Species:  Mouse
Technique:  RT-PCR
References:  11
Neurones of the myenteric and submucous plexus, mucosal epithelial cells of the intestinal crypts.
Species:  Mouse
Technique:  In situ hybridisation
References:  13
Hippocampal interneurones.
Species:  Rat
Technique:  Immunohistochemistry
References:  14
Restricted subpopulation of neurones in the pyramidal and molecular layers of the hippocampus.
Species:  Rat
Technique:  Immunohistochemistry
References:  16
Hippocampus (CA1 and dentate gyrus) and cerebral cortex.
Species:  Rat
Technique:  Immunohistochemistry
References:  5
Nodose, trigeminal, superior cervical and dorsal root ganglia.
Species:  Rat
Technique:  Immunohistochemistry
References:  5
The 5-HT3B subunit is co-expressed with the 5-HT3A subunit in a subpopulation of superior cervical, nodose and dorsal root ganglion neurones. Nodose and dorsal root ganglion neurones co-expressing the 5-HT3A and 5-HT3B subunits have been demonstrated to project centrally to the nucleus tractus solitarius and superficial layers of the spinal cord, respectively.
Species:  Rat
Technique:  In situ hybridisation
References:  15
Physiological Consequences of Altering Gene Expression Click here for help
Despite the existence of 5-HT3B subunit mRNA in neuroblastoma cell lines, the introduction of the rat 5-HT3B subunit by transient transfection of mouse NB41A3 cells causes 5-HT to become less potent as an activator of 5-HT3 receptors native to the cell line and alters the kinetics of 5-HT activated currents. Introduction of the 5-HT3B subunit also abolishes the 5-HT induced increase in intracellular Ca2+ concentration seen in untransfected NB41A3 cells.
Species:  Mouse
Tissue:  NB41A3 cells
Technique:  Transient transfection of the rat 5-HT3B subunit
References:  17
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Emesis
Comments:  This deletion variant in the promotor region of the HTR3B gene increases promoter activity in vitro and has been associated with an increased incidence of paroxetine-induced nausea, and with an increased frequency of vomiting caused by chemotherapy in patients receiving 5-HT3 receptor antagonists as anti-emetic therapy.
References:  12,18-19
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human 100_102delAAG 18-19
Disease:  Major affective disorder 1; MAFD1
Synonyms: Bipolar affective disorder
Manic depressive-psychosis
OMIM: 125480
Comments:  This deletion in the promotor region of the HTR3B gene is underrepresented in a sample of patients suffering from bipolar depression.
References:  7
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human 100_102delAAG 7
Disease:  Major depressive disorder; MDD
Disease Ontology: DOID:1470
OMIM: 608516
Role:  5-HT3B has been associated with major female depression in genetic analyses.
Comments:  This polymorphism occurs at a significantly reduced frequency in female patients suffering from major depression and also patients with bipolar disorder, consistent with a protective influence of the variant allele.
References:  22
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human Y129S 22
Gene Expression and Pathophysiology Click here for help
Downregulation of mRNA encoding the 5-HT3B subunit as a consequence of the knockout of SERT.
Tissue or cell type:  Myenteric neurones
Pathophysiology:  Downregulation of mRNA encoding the 5-HT3B subunit as a consequence of the knockout of SERT is associated with an increase in the EC50 for 5-HT in myenteric neurones.
Species:  Mouse
Technique:  Whole cell patch clamp.
References:  11
Biologically Significant Variants Click here for help
Type:  Missense mutation
Species:  Human
Description:  The human 5-HT3B(Y129S) polymorphism causes decreased desensitisation, decreased inactivation rate, and a 7-fold increase in the mean channel open time of heteromeric 5-HT3AB receptors compared to receptors incorporating the Y129 variant.
References:  9
Type:  Missense mutation
Species:  Human
Description:  The human 5-HT3B(S156R) polymorphism causes enhanced functional responses to 5-HT mediated by heteromeric 5-HT3AB receptors.
References:  21
Type:  Missense mutation
Species:  Human
Description:  The human 5-HT3B(I143T) polymorphism causes reduced functional responses to 5-HT mediated by heteromeric 5-HT3AB receptors and is associated with decreased cell surface expression.
References:  10
General Comments
The 5-HT3B subunit does not function as a homo-oligomer in recombinant expression systems and is retained in the endoplasmic reticulum [2]. Association with the 5-HT3A subunit facilitates trafficking of 5-HT3B to the plasma membrane as a heteromeric complex [2] with the suggested stoichiometry (5-HT3A)2(5-HT3B)3 [1]. Variants of the human 5-HT3B subunit canonical form have been postulated to exist in the intestine (the canonical form) and brain due to alternative promoters with the HTR3B gene that initiate transcription at different start sites [20]. One brain specific isoform (brain transcript 1) is predicted to differ from the canonical 5-HT3B subunit only within the signal peptide, whereas the second (brain transcript 2) is predicted to lack a large section of the extracellular N-terminal domain [20].

References

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1. Barrera NP, Herbert P, Henderson RM, Martin IL, Edwardson JM. (2005) Atomic force microscopy reveals the stoichiometry and subunit arrangement of 5-HT3 receptors. Proc Natl Acad Sci USA, 102 (35): 12595-600. [PMID:16116092]

2. Boyd GW, Low P, Dunlop JI, Robertson LA, Vardy A, Lambert JJ, Peters JA, Connolly CN. (2002) Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins. Mol Cell Neurosci, 21 (1): 38-50. [PMID:12359150]

3. Brady CA, Dover TJ, Massoura AN, Princivalle AP, Hope AG, Barnes NM. (2007) Identification of 5-HT3A and 5-HT3B receptor subunits in human hippocampus. Neuropharmacology, 52 (5): 1284-90. [PMID:17327132]

4. Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF. (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature, 397 (6717): 359-63. [PMID:9950429]

5. Doucet E, Latrémolière A, Darmon M, Hamon M, Emerit MB. (2007) Immunolabelling of the 5-HT 3B receptor subunit in the central and peripheral nervous systems in rodents. Eur J Neurosci, 26 (2): 355-66. [PMID:17650111]

6. Dubin AE, Huvar R, D'Andrea MR, Pyati J, Zhu JY, Joy KC, Wilson SJ, Galindo JE, Glass CA, Luo L et al.. (1999) The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit. J Biol Chem, 274 (43): 30799-810. [PMID:10521471]

7. Frank B, Niesler B, Nöthen MM, Neidt H, Propping P, Bondy B, Rietschel M, Maier W, Albus M, Rappold G. (2004) Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet, 131B (1): 1-5. [PMID:15389765]

8. Hanna MC, Davies PA, Hales TG, Kirkness EF. (2000) Evidence for expression of heteromeric serotonin 5-HT(3) receptors in rodents. J Neurochem, 75 (1): 240-7. [PMID:10854267]

9. Krzywkowski K, Davies PA, Feinberg-Zadek PL, Bräuner-Osborne H, Jensen AA. (2008) High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor. Proc Natl Acad Sci USA, 105 (2): 722-7. [PMID:18184810]

10. Krzywkowski K, Davies PA, Irving AJ, Bräuner-Osborne H, Jensen AA. (2008) Characterization of the effects of four HTR3B polymorphisms on human 5-HT3AB receptor expression and signalling. Pharmacogenet Genomics, 18 (12): 1027-40. [PMID:19008750]

11. Liu MT, Rayport S, Jiang Y, Murphy DL, Gershon MD. (2002) Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter. Am J Physiol Gastrointest Liver Physiol, 283 (6): G1398-411. [PMID:12388212]

12. Meineke C, Tzvetkov MV, Bokelmann K, Oetjen E, Hirsch-Ernst K, Kaiser R, Brockmöller J. (2008) Functional characterization of a -100_-102delAAG deletion-insertion polymorphism in the promoter region of the HTR3B gene. Pharmacogenet Genomics, 18 (3): 219-30. [PMID:18300944]

13. Michel K, Zeller F, Langer R, Nekarda H, Kruger D, Dover TJ, Brady CA, Barnes NM, Schemann M. (2005) Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors. Gastroenterology, 128 (5): 1317-26. [PMID:15887114]

14. Monk SA, Desai K, Brady CA, Williams JM, Lin L, Princivalle A, Hope AG, Barnes NM. (2001) Generation of a selective 5-HT3B subunit-recognising polyclonal antibody; identification of immunoreactive cells in rat hippocampus. Neuropharmacology, 41 (8): 1013-6. [PMID:11747906]

15. Morales M, Wang SD. (2002) Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system. J Neurosci, 22 (15): 6732-41. [PMID:12151552]

16. Reeves DC, Lummis SC. (2006) Detection of human and rodent 5-HT3B receptor subunits by anti-peptide polyclonal antibodies. BMC Neurosci, 7: 27. [PMID:16571125]

17. Stewart A, Davies PA, Kirkness EF, Safa P, Hales TG. (2003) Introduction of the 5-HT3B subunit alters the functional properties of 5-HT3 receptors native to neuroblastoma cells. Neuropharmacology, 44 (2): 214-23. [PMID:12623220]

18. Tanaka M, Kobayashi D, Murakami Y, Ozaki N, Suzuki T, Iwata N, Haraguchi K, Ieiri I, Kinukawa N, Hosoi M, Ohtani H, Sawada Y, Mine K. (2008) Genetic polymorphisms in the 5-hydroxytryptamine type 3B receptor gene and paroxetine-induced nausea. Int J Neuropsychopharmacol, 11 (2): 261-7. [PMID:17697394]

19. Tremblay PB, Kaiser R, Sezer O, Rosler N, Schelenz C, Possinger K, Roots I, Brockmoller J. (2003) Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients. J Clin Oncol, 21 (11): 2147-55. [PMID:12775740]

20. Tzvetkov MV, Meineke C, Oetjen E, Hirsch-Ernst K, Brockmöller J. (2007) Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine. Gene, 386 (1-2): 52-62. [PMID:17010535]

21. Walstab J, Hammer C, Bönisch H, Rappold G, Niesler B. (2008) Naturally occurring variants in the HTR3B gene significantly alter properties of human heteromeric 5-hydroxytryptamine-3A/B receptors. Pharmacogenet Genomics, 18 (9): 793-802. [PMID:18698232]

22. Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Takao H, Minabe Y, Nakatani N, Higuchi T et al.. (2006) Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression. Biol Psychiatry, 60 (2): 192-201. [PMID:16487942]

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