O95264 (5HT3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-hydroxytryptamine receptor 3B
Short name=5-HT3-B
Short name=5-HT3B

Alternative name(s):
Serotonin receptor 3B

Gene names

Name:

HTR3B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	441 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses. It is a cation-specific, but otherwise relatively nonselective, ion channel. Ref.6
Subunit structure	Forms a pentaheteromeric complex with HTR3A. Not functional as a homomeric complex. Ref.2 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: Presumably retained within the endoplasmic reticulum unless complexed with HTR3A. Ref.8
Tissue specificity	Expressed in the brain cortex, in the caudate nucleus, the hyppocampus, the thalamus and the amygdala. Detected in the kidney and testis as well as in monocytes of the spleen, small and large intestine, uterus, prostate, ovary and placenta. Ref.1 Ref.2
Post-translational modification	N-glycosylation required for membrane localization.
Miscellaneous	The HA-stretch region of HTR3B seems to confer increased conductance to HTR3A/HTR3B heteromers compared to that of HTR3A homomers.
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3B sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Ionic channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: InterPro
Molecular function	serotonin receptor activity Traceable author statement. Source: ProtInc serotonin-activated cation-selective channel activity Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95264-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95264-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MLSSVMAPLWACILVAA → MIVYFP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 441	420	5-hydroxytryptamine receptor 3B		PRO_0000312289
Regions
	Topological domain	22 – 238	217	Extracellular Potential
	Transmembrane	239 – 259	21	Helical; Name=1; Potential
	Topological domain	260 – 268	9	Cytoplasmic Potential
	Transmembrane	269 – 286	18	Helical; Name=2; Potential
	Topological domain	287 – 303	17	Extracellular Potential
	Transmembrane	304 – 324	21	Helical; Name=3; Potential
	Topological domain	325 – 414	90	Cytoplasmic Potential
	Transmembrane	415 – 435	21	Helical; Name=4; Potential
	Topological domain	436 – 441	6	Extracellular Potential
	Region	381 – 413	33	HA-stretch
Amino acid modifications
	Glycosylation	52	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	96	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	138	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	168	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	203	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	287	1	N-linked (GlcNAc...) Potential
	Disulfide bond	155 ↔ 169		By similarity
Natural variations
	Alternative sequence	1 – 17	17	MLSSV…ILVAA → MIVYFP in isoform 2.		VSP_029796
	Natural variant	129	1	Y → S. Ref.3 Ref.9 Ref.10 Ref.11 Corresponds to variant rs1176744 [ dbSNP | Ensembl ].		VAR_037472
	Natural variant	143	1	I → T. Ref.11 Corresponds to variant rs34550504 [ dbSNP | Ensembl ].		VAR_037473
	Natural variant	156	1	S → R. Ref.9 Ref.10 Ref.12 Corresponds to variant rs72466469 [ dbSNP | Ensembl ].		VAR_037474
	Natural variant	183	1	V → I. Ref.9 Ref.10 Ref.11 Corresponds to variant rs17116138 [ dbSNP | Ensembl ].		VAR_037475
Experimental info
	Mutagenesis	52	1	N → S: Reduced molecular weight. Very little expression in the cell membrane. Ref.8
	Mutagenesis	96	1	N → S: Reduced molecular weight. Very little expression in the cell membrane. Ref.8
	Mutagenesis	138	1	N → S: Reduced molecular weight. Very little expression in the cell membrane. Ref.8
	Mutagenesis	168	1	N → S: Reduced molecular weight and cell membrane expression. Ref.8
	Mutagenesis	203	1	N → S: Reduced molecular weight. Very little expression in the cell membrane. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 2ED59E4E11400648	FASTA	441	50,292
	10 20 30 40 50 60 MLSSVMAPLW ACILVAAGIL ATDTHHPQDS ALYHLSKQLL QKYHKEVRPV YNWTKATTVY 70 80 90 100 110 120 LDLFVHAILD VDAENQILKT SVWYQEVWND EFLSWNSSMF DEIREISLPL SAIWAPDIII 130 140 150 160 170 180 NEFVDIERYP DLPYVYVNSS GTIENYKPIQ VVSACSLETY AFPFDVQNCS LTFKSILHTV 190 200 210 220 230 240 EDVDLAFLRS PEDIQHDKKA FLNDSEWELL SVSSTYSILQ SSAGGFAQIQ FNVVMRRHPL 250 260 270 280 290 300 VYVVSLLIPS IFLMLVDLGS FYLPPNCRAR IVFKTSVLVG YTVFRVNMSN QVPRSVGSTP 310 320 330 340 350 360 LIGHFFTICM AFLVLSLAKS IVLVKFLHDE QRGGQEQPFL CLRGDTDADR PRVEPRAQRA 370 380 390 400 410 420 VVTESSLYGE HLAQPGTLKE VWSQLQSISN YLQTQDQTDQ QEAEWLVLLS RFDRLLFQSY 430 440 LFMLGIYTIT LCSLWALWGG V
	Isoform 2 [UniParc]. Checksum: 8C69BE27437D6D03	FASTA	430	49,285
	10 20 30 40 50 60 MIVYFPGILA TDTHHPQDSA LYHLSKQLLQ KYHKEVRPVY NWTKATTVYL DLFVHAILDV 70 80 90 100 110 120 DAENQILKTS VWYQEVWNDE FLSWNSSMFD EIREISLPLS AIWAPDIIIN EFVDIERYPD 130 140 150 160 170 180 LPYVYVNSSG TIENYKPIQV VSACSLETYA FPFDVQNCSL TFKSILHTVE DVDLAFLRSP 190 200 210 220 230 240 EDIQHDKKAF LNDSEWELLS VSSTYSILQS SAGGFAQIQF NVVMRRHPLV YVVSLLIPSI 250 260 270 280 290 300 FLMLVDLGSF YLPPNCRARI VFKTSVLVGY TVFRVNMSNQ VPRSVGSTPL IGHFFTICMA 310 320 330 340 350 360 FLVLSLAKSI VLVKFLHDEQ RGGQEQPFLC LRGDTDADRP RVEPRAQRAV VTESSLYGEH 370 380 390 400 410 420 LAQPGTLKEV WSQLQSISNY LQTQDQTDQQ EAEWLVLLSR FDRLLFQSYL FMLGIYTITL 430 CSLWALWGGV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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., Huvar R., D'Andrea M.R., Pyati J., Zhu J.Y., Joy K.C., Wilson S.J., Galindo J.E., Glass C.A., Luo L., Jackson M.R., Lovenberg T.W., Erlander M.G. J. Biol. Chem. 274:30799-30810(1999) [PubMed: 10521471] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Small intestine.
[2]	"The 5-HT3B subunit is a major determinant of serotonin-receptor function." Davies P.A., Pistis M., Hanna M.C., Peters J.A., Lambert J.J., Hales T.G., Kirkness E.F. Nature 397:359-363(1999) [PubMed: 9950429] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBUNIT.
[3]	"Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine." Tzvetkov M.V., Meineke C., Oetjen E., Hirsch-Ernst K., Brockmoller J. Gene 386:52-62(2007) [PubMed: 17010535] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-129. Tissue: Brain.
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"A cytoplasmic region determines single-channel conductance in 5-HT3 receptors." Kelley S.P., Dunlop J.I., Kirkness E.F., Lambert J.J., Peters J.A. Nature 424:321-324(2003) [PubMed: 12867984] [Abstract] Cited for: FUNCTION, REGION.
[7]	"Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E." Niesler B., Walstab J., Combrink S., Moeller D., Kapeller J., Rietdorf J., Boenisch H., Goethert M., Rappold G., Bruess M. Mol. Pharmacol. 72:8-17(2007) [PubMed: 17392525] [Abstract] Cited for: SUBUNIT.
[8]	"The identification of N-glycosylated residues of the human 5-HT3B receptor subunit: importance for cell membrane expression." Massoura A.N., Dover T.J., Newman A.S., Barnes N.M. J. Neurochem. 116:975-983(2011) [PubMed: 21138434] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203, MUTAGENESIS OF ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203.
[9]	"Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients." Frank B., Niesler B., Noethen M.M., Neidt H., Propping P., Bondy B., Rietschel M., Maier W., Albus M., Rappold G. Am. J. Med. Genet. B Neuropsychiatr. Genet. 131:1-5(2004) [PubMed: 15389765] [Abstract] Cited for: VARIANTS SER-129; ARG-156 AND ILE-183.
[10]	"Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients." Frank B., Niesler B., Bondy B., Spaeth M., Pongratz D.E., Ackenheil M., Fischer C., Rappold G. Clin. Rheumatol. 23:338-344(2004) [PubMed: 15293096] [Abstract] Cited for: VARIANTS SER-129; ARG-156 AND ILE-183.
[11]	"Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression." Yamada K., Hattori E., Iwayama Y., Ohnishi T., Ohba H., Toyota T., Takao H., Minabe Y., Nakatani N., Higuchi T., Detera-Wadleigh S.D., Yoshikawa T. Biol. Psychiatry 60:192-201(2006) [PubMed: 16487942] [Abstract] Cited for: VARIANTS SER-129; THR-143 AND ILE-183.
[12]	"A population-specific HTR2B stop codon predisposes to severe impulsivity." Bevilacqua L., Doly S., Kaprio J., Yuan Q., Tikkanen R., Paunio T., Zhou Z., Wedenoja J., Maroteaux L., Diaz S., Belmer A., Hodgkinson C.A., Dell'osso L., Suvisaari J., Coccaro E., Rose R.J., Peltonen L., Virkkunen M., Goldman D. Nature 468:1061-1066(2010) [PubMed: 21179162] [Abstract] Cited for: VARIANT ARG-156.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF169255 mRNA. Translation: AAF03691.1. AF080582 mRNA. Translation: AAD12242.1. AM293589 mRNA. Translation: CAL25321.1. EF444985 Genomic DNA. Translation: ACA06001.1. AK314268 mRNA. Translation: BAG36930.1.
IPI	IPI00005673. IPI00876974.
RefSeq	NP_006019.1. NM_006028.4.
UniGene	Hs.241377.
3D structure databases
HSSP	HSSP built from PDB template 2BG9 based on UniProtKB P02711.
ProteinModelPortal	O95264.
SMR	O95264. Positions 30-434.
ModBase	Search...
Protein-protein interaction databases
STRING	O95264.
Proteomic databases
PRIDE	O95264.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000260191; ENSP00000260191; ENSG00000149305.
GeneID	9177.
KEGG	hsa:9177.
UCSC	uc001pok.1. human. uc001pol.1. human.
Organism-specific databases
CTD	9177.
GeneCards	GC11P113809.
H-InvDB	HIX0035859.
HGNC	HGNC:5298. HTR3B.
HPA	HPA039559.
MIM	604654. gene.
neXtProt	NX_O95264.
PharmGKB	PA29556.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18756.
GeneTree	ENSGT00570000078866.
HOGENOM	HBG714660.
HOVERGEN	HBG106638.
InParanoid	O95264.
OMA	RSREDIK.
OrthoDB	EOG4N8R4Z.
PhylomeDB	O95264.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O95264.
Bgee	O95264.
CleanEx	HS_HTR3B.
Genevestigator	O95264.
Family and domain databases
InterPro	IPR008132. 5HT3_rcpt. IPR008134. 5HT3_rcpt_B. IPR006202. Neur_chan_lig-bd. IPR006201. Neur_channel. IPR006029. Neurotrans-gated_channel_TM. [Graphical view]
Gene3D	G3DSA:2.70.170.10. Neur_chan_lig_bd. 1 hit.
KO	K04819.
PANTHER	PTHR18945. Neur_channel. 1 hit.
Pfam	PF02931. Neur_chan_LBD. 1 hit. PF02932. Neur_chan_memb. 1 hit. [Graphical view]
PRINTS	PR01710. 5HT3BRECEPTR. PR01708. 5HT3RECEPTOR. PR00252. NRIONCHANNEL.
SUPFAM	SSF90112. Neu_channel_TM. 1 hit. SSF63712. Neur_chan_LBD. 1 hit.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	34409.
SOURCE	Search...

Entry information

Entry name

5HT3B_HUMAN

Accession

Primary (citable) accession number: O95264
Secondary accession number(s): B0YJ23, Q0VJC3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 4, 2007
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.