P41595 (5HT2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-hydroxytryptamine receptor 2B
Short name=5-HT-2B
Short name=5-HT2B

Alternative name(s):
Serotonin receptor 2B

Gene names

Name:

HTR2B

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	481 AA.
Sequence status	Complete.
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 mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Plays a role in the regulation of impulsive behavior.
Subunit structure	Interacts with MPDZ. Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in brain. Higher levels of expression are observed in the cerebellum, occipital cortex and frontal cortex. Ref.11
Polymorphism	A variation at a single nucleotide base, which results in an erroneous stop codon and affects Gln-20, triggers non-sense mediated RNA decay, such that no HTR2B-receptor protein is expressed. It is associated with impulsive behavior and co-segregates with disorders characterized by impulsivity. However, the presence of this variant is not in itself sufficient to cause impulsive behavior: male sex, testosterone level, alcohol and stress exposure are other factors playing important roles.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ERK1 and ERK2 cascade Inferred from mutant phenotype. Source: UniProtKB G-protein coupled receptor internalization Inferred from mutant phenotype. Source: UniProtKB activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB cGMP biosynthetic process Inferred from direct assay. Source: UniProtKB calcium-mediated signaling Inferred from mutant phenotype. Source: UniProtKB cardiac muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB cellular response to calcium ion Inferred from mutant phenotype. Source: UniProtKB cellular response to temperature stimulus Inferred from sequence or structural similarity. Source: UniProtKB embryonic morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB heart morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB intestine smooth muscle contraction Inferred from mutant phenotype. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of autophagy Inferred from mutant phenotype. Source: UniProtKB neural crest cell migration Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype. Source: UniProtKB phosphatidylinositol biosynthetic process Inferred from mutant phenotype. Source: UniProtKB phosphorylation Inferred from mutant phenotype. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay. Source: UniProtKB positive regulation of cell division Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cytokine production Inferred from direct assay. Source: UniProtKB positive regulation of cytokine secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of endothelial cell proliferation Inferred from mutant phenotype. Source: UniProtKB positive regulation of nitric-oxide synthase activity Inferred from direct assay. Source: UniProtKB protein kinase C signaling cascade Inferred from mutant phenotype. Source: UniProtKB regulation of behavior Inferred from mutant phenotype Ref.11. Source: UniProtKB release of sequestered calcium ion into cytosol Inferred from direct assay. Source: UniProtKB response to drug Inferred from direct assay. Source: UniProtKB vasoconstriction Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.2. Source: UniProtKB
Molecular function	G-protein alpha-subunit binding Inferred from mutant phenotype. Source: UniProtKB Ras GTPase activator activity Inferred from sequence or structural similarity. Source: UniProtKB calcium channel activity Inferred from mutant phenotype. Source: UniProtKB drug binding Inferred from direct assay Ref.2. Source: UniProtKB phosphatidylinositol phospholipase C activity Inferred from direct assay Ref.1. Source: UniProtKB serotonin binding Inferred from direct assay Ref.2. Source: UniProtKB serotonin receptor activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 481	481	5-hydroxytryptamine receptor 2B		PRO_0000068953
Regions
	Topological domain	1 – 56	56	Extracellular By similarity
	Transmembrane	57 – 79	23	Helical; Name=1; By similarity
	Topological domain	80 – 91	12	Cytoplasmic By similarity
	Transmembrane	92 – 113	22	Helical; Name=2; By similarity
	Topological domain	114 – 129	16	Extracellular By similarity
	Transmembrane	130 – 151	22	Helical; Name=3; By similarity
	Topological domain	152 – 171	20	Cytoplasmic By similarity
	Transmembrane	172 – 192	21	Helical; Name=4; By similarity
	Topological domain	193 – 216	24	Extracellular By similarity
	Transmembrane	217 – 239	23	Helical; Name=5; By similarity
	Topological domain	240 – 324	85	Cytoplasmic By similarity
	Transmembrane	325 – 345	21	Helical; Name=6; By similarity
	Topological domain	346 – 360	15	Extracellular By similarity
	Transmembrane	361 – 383	23	Helical; Name=7; By similarity
	Topological domain	384 – 481	98	Cytoplasmic By similarity
	Motif	479 – 481	3	PDZ-binding
Amino acid modifications
	Lipidation	397	1	S-palmitoyl cysteine Potential
	Glycosylation	30	1	N-linked (GlcNAc...) Potential
	Disulfide bond	128 ↔ 207		By similarity
Natural variations
	Natural variant	45	1	Q → E. Ref.11 Corresponds to variant rs78484969 [ dbSNP | Ensembl ].		VAR_064574
	Natural variant	173	1	F → L. Ref.11 Corresponds to variant rs77570025 [ dbSNP | Ensembl ].		VAR_064575
	Natural variant	388	1	R → W. Ref.11 Corresponds to variant rs77982984 [ dbSNP | Ensembl ].		VAR_064576
	Natural variant	421	1	M → V. Corresponds to variant rs6736017 [ dbSNP | Ensembl ].		VAR_055907
Experimental info
	Sequence conflict	452	1	T → P in CAA85319. Ref.2
	Sequence conflict	477	1	Q → R in AAH63123. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P41595 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: CDA4447ECDBA3B46	FASTA	481	54,298
	10 20 30 40 50 60 MALSYRVSEL QSTIPEHILQ STFVHVISSN WSGLQTESIP EEMKQIVEEQ GNKLHWAALL 70 80 90 100 110 120 ILMVIIPTIG GNTLVILAVS LEKKLQYATN YFLMSLAVAD LLVGLFVMPI ALLTIMFEAM 130 140 150 160 170 180 WPLPLVLCPA WLFLDVLFST ASIMHLCAIS VDRYIAIKKP IQANQYNSRA TAFIKITVVW 190 200 210 220 230 240 LISIGIAIPV PIKGIETDVD NPNNITCVLT KERFGDFMLF GSLAAFFTPL AIMIVTYFLT 250 260 270 280 290 300 IHALQKKAYL VKNKPPQRLT WLTVSTVFQR DETPCSSPEK VAMLDGSRKD KALPNSGDET 310 320 330 340 350 360 LMRRTSTIGK KSVQTISNEQ RASKVLGIVF FLFLLMWCPF FITNITLVLC DSCNQTTLQM 370 380 390 400 410 420 LLEIFVWIGY VSSGVNPLVY TLFNKTFRDA FGRYITCNYR ATKSVKTLRK RSSKIYFRNP 430 440 450 460 470 480 MAENSKFFKK HGIRNGINPA MYQSPMRLRS STIQSSSIIL LDTLLLTENE GDKTEEQVSY V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional characterization of the human 5-HT2B serotonin receptor." Schmuck K., Ullmer C., Engels P., Luebbert H. FEBS Lett. 342:85-90(1994) [PubMed: 8143856] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors." Choi D.S., Birraux G., Launay J.-M., Maroteaux L. FEBS Lett. 352:393-399(1994) [PubMed: 7926008] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor." Kursar J.D., Nelson D.L., Wainscott D.B., Baez M. Mol. Pharmacol. 46:227-234(1994) [PubMed: 8078486] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Uterus.
[4]	"Mutation screening of human 5-HT(2B) receptor gene in early-onset obsessive-compulsive disorder." Kim S.J., Veenstra-VanderWeele J., Hanna G.L., Gonen D., Leventhal B.L., Cook E.H. Jr. Mol. Cell. Probes 14:47-52(2000) [PubMed: 10722792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[6]	"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].
[7]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[10]	"Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1." Becamel C., Figge A., Poliak S., Dumuis A., Peles E., Bockaert J., Luebbert H., Ullmer C. J. Biol. Chem. 276:12974-12982(2001) [PubMed: 11150294] [Abstract] Cited for: INTERACTION WITH MPDZ.
[11]	"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: INVOLVEMENT IN IMPULSIVE BEHAVIOR, TISSUE SPECIFICITY, POLYMORPHISM, VARIANTS GLU-45; LEU-173 AND TRP-388.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

On the spur of a whim - Issue 127 of March 2011

Cross-references

Sequence databases
EMBL GenBank DDBJ	X77307 mRNA. Translation: CAA54513.1. Z36748 mRNA. Translation: CAA85319.1. AF156160, AF156158, AF156159 Genomic DNA. Translation: AAD39259.1. AY136751 mRNA. Translation: AAN01277.1. AC009407 Genomic DNA. Translation: AAX93128.1. AK313741 mRNA. Translation: BAG36482.1. CH471063 Genomic DNA. Translation: EAW70949.1. BC063123 mRNA. Translation: AAH63123.1.
IPI	IPI00015134.
PIR	S43687. S49442.
RefSeq	NP_000858.3. NM_000867.4.
UniGene	Hs.421649.
3D structure databases
ProteinModelPortal	P41595.
SMR	P41595. Positions 57-395.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-444010.
STRING	P41595.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	1168220.
Proteomic databases
PRIDE	P41595.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258400; ENSP00000258400; ENSG00000135914.
GeneID	3357.
KEGG	hsa:3357.
Organism-specific databases
CTD	3357.
GeneCards	GC02M231936.
H-InvDB	HIX0029887.
HGNC	HGNC:5294. HTR2B.
HPA	CAB011448. HPA012867.
MIM	601122. gene.
neXtProt	NX_P41595.
PharmGKB	PA29554.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17666.
GeneTree	ENSGT00580000081527.
HOGENOM	HBG445348.
HOVERGEN	HBG107487.
InParanoid	P41595.
OMA	FTPLAIM.
OrthoDB	EOG41ZF9R.
PhylomeDB	P41595.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P41595.
Bgee	P41595.
CleanEx	HS_HTR2B.
Genevestigator	P41595.
GermOnline	ENSG00000135914. Homo sapiens.
Family and domain databases
InterPro	IPR000482. 5HT2B_rcpt. IPR002231. 5HT_rcpt. IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
KO	K04157.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00651. 5HT2BRECEPTR. PR01101. 5HTRECEPTOR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB01239. Chlorprothixene. DB00216. Eletriptan. DB00574. Fenfluramine. DB01403. Methotrimeprazine. DB00805. Minaprine. DB01224. Quetiapine. DB00669. Sumatriptan. DB01079. Tegaserod. DB00508. Triflupromazine.
NextBio	13274.
SOURCE	Search...

Entry information

Entry name

5HT2B_HUMAN

Accession

Primary (citable) accession number: P41595
Secondary accession number(s): B2R9D5 , Q53TI1, Q62221, Q6P523

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 114 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.