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1.A.9.2.1
Serotonin (5-hydroxytryptamine)-activated cation-selective receptor/channel, 5-HT3R. Residues in TMS2 and the cytoplasmic loop linking TMSs 3 and 4 influence conductance, selectivity, gating and desensitization (Peters et al., 2010; McKinnon et al., 2011). Resveratrol enhances ion currents (Lee et al., 2011). Rings of charge within the extracellular vestibule influence ion permeation (Livesey et al., 2011).  Based on the 3-d structure, serotonin binding first induces distinct conformational fluctuations at the side chain of W156 in the highly conserved ligand-binding cage, followed by tilting-twisting movements of the extracellular domain which couple to the transmembrane TM2 helices, opening the hydrophobic gate at L260 and forming a continuous transmembrane water pathway (Yuan et al. 2016). There are 5 isoforms of 5-HT3A which include 5-HT3AB, 5-HT3AC, 5-HT3AD, and 5-HT3AE, all of which have similar but distinct pharmacological profiles compared to those of 5-HT3A receptors (Price et al. 2017). Trans-3-(4-methoxyphenyl)-N-(pentan-3-yl)acrylamide (TMPPAA) is a potent agonist with behavior different from that of 5-HT (Gasiorek et al. 2016).

Accession Number:P46098
Protein Name:5HT3 aka HTR3 aka HTR3A aka 5HT3R
Length:478
Molecular Weight:55280.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate inorganic cations

Cross database links:

Genevestigator: P46098
RefSeq: NP_000860.2    NP_001155244.1    NP_998786.2   
Entrez Gene ID: 3359   
Pfam: PF02931    PF02932   
Drugbank: Drugbank Link   
OMIM: 182139  gene
KEGG: hsa:3359   

Gene Ontology

GO:0030054 C:cell junction
GO:0005887 C:integral to plasma membrane
GO:0045211 C:postsynaptic membrane
GO:0051378 F:serotonin binding
GO:0004993 F:serotonin receptor activity
GO:0005232 F:serotonin-activated cation-selective channe...
GO:0007586 P:digestion
GO:0006811 P:ion transport
GO:0007268 P:synaptic transmission

References (12)

[1] “Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.”  Miyake A.et.al.   7565620
[2] “Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit.”  Belelli D.et.al.   8848005
[3] “Molecular cloning of alternatively spliced human 5HT3 receptor cDNAs.”  Bruess M.et.al.   9928262
[4] “Exon-intron organization of the human 5-HT3A receptor gene.”  Bruess M.et.al.   10670426
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “The 5-HT3B subunit is a major determinant of serotonin-receptor function.”  Davies P.A.et.al.   9950429
[7] “The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit.”  Dubin A.E.et.al.   10521471
[8] “A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.”  Kelley S.P.et.al.   12867984
[9] “Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3.”  Cheng A.et.al.   15809299
[10] “Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E.”  Niesler B.et.al.   17392525
[11] “Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients.”  Frank B.et.al.   15293096
[12] “Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression.”  Yamada K.et.al.   16487942

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MLLWVQQALL ALLLPTLLAQ GEARRSRNTT RPALLRLSDY LLTNYRKGVR PVRDWRKPTT 
61:	VSIDVIVYAI LNVDEKNQVL TTYIWYRQYW TDEFLQWNPE DFDNITKLSI PTDSIWVPDI 
121:	LINEFVDVGK SPNIPYVYIR HQGEVQNYKP LQVVTACSLD IYNFPFDVQN CSLTFTSWLH 
181:	TIQDINISLW RLPEKVKSDR SVFMNQGEWE LLGVLPYFRE FSMESSNYYA EMKFYVVIRR 
241:	RPLFYVVSLL LPSIFLMVMD IVGFYLPPNS GERVSFKITL LLGYSVFLII VSDTLPATAI 
301:	GTPLIGVYFV VCMALLVISL AETIFIVRLV HKQDLQQPVP AWLRHLVLER IAWLLCLREQ 
361:	STSQRPPATS QATKTDDCSA MGNHCSHMGG PQDFEKSPRD RCSPPPPPRE ASLAVCGLLQ 
421:	ELSSIRQFLE KRDEIREVAR DWLRVGSVLD KLLFHIYLLA VLAYSITLVM LWSIWQYA