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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 19057895PubMed 19308295. Source: UniProtKB G-protein coupled receptor internalization Inferred from mutant phenotype PubMed 15625277. Source: UniProtKB cGMP biosynthetic process Inferred from direct assay PubMed 12970106. Source: UniProtKB calcium-mediated signaling Inferred from mutant phenotype PubMed 19057895PubMed 8882600. Source: UniProtKB cardiac muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB cellular response to calcium ion Inferred from mutant phenotype PubMed 19057895. 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 PubMed 7599919PubMed 9186750. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of autophagy Inferred from mutant phenotype PubMed 20099302. Source: UniProtKB neural crest cell migration Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype PubMed 16517693. Source: UniProtKB phosphatidylinositol biosynthetic process Inferred from mutant phenotype PubMed 19057895. Source: UniProtKB phosphorylation Inferred from mutant phenotype PubMed 19308295. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay PubMed 15625277. Source: UniProtKB positive regulation of cell division Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cytokine production Inferred from direct assay PubMed 19023134. 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 PubMed 19308295. Source: UniProtKB positive regulation of nitric-oxide synthase activity Inferred from direct assay PubMed 15625277. Source: UniProtKB protein kinase C signaling cascade Inferred from mutant phenotype PubMed 19057895PubMed 20099302. Source: UniProtKB protein kinase C-activating G-protein coupled receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of behavior Inferred from mutant phenotype Ref.11. Source: UniProtKB release of sequestered calcium ion into cytosol Inferred from direct assay PubMed 15862800. Source: UniProtKB response to drug Inferred from direct assay PubMed 15625277PubMed 15862800PubMed 18703043. Source: UniProtKB vasoconstriction Inferred from mutant phenotype PubMed 15625277. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay PubMed 15925089. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 12970106PubMed 15625277PubMed 15862800PubMed 18703043PubMed 19023134Ref.2. Source: UniProtKB
Molecular_function	G-protein alpha-subunit binding Inferred from mutant phenotype PubMed 15625277. Source: UniProtKB Ras GTPase activator activity Inferred from sequence or structural similarity. Source: UniProtKB calcium channel activity Inferred from mutant phenotype PubMed 8882600. Source: UniProtKB drug binding Inferred from direct assay PubMed 12970106PubMed 15625277PubMed 15831837PubMed 15862800PubMed 17609583PubMed 18703043PubMed 19307114Ref.2. Source: UniProtKB phosphatidylinositol phospholipase C activity Inferred from direct assay PubMed 12970106PubMed 19057895Ref.1. Source: UniProtKB serotonin binding Inferred from direct assay PubMed 15625277PubMed 15831837PubMed 15862800PubMed 17609583PubMed 19057895Ref.2. Source: UniProtKB serotonin receptor activity Inferred from direct assay PubMed 15862800Ref.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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4IB4	X-ray	2.70	A	36-405	[»]

ProteinModelPortal

P41595.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-444010.

STRING

9606.ENSP00000258400.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P41595.

Polymorphism databases

DMDM

1168220.

Proteomic databases

PaxDb

P41595.

PRIDE

P41595.

Protocols and materials databases

DNASU

3357.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258400; ENSP00000258400; ENSG00000135914.

GeneID

3357.

KEGG

hsa:3357.

UCSC

uc002vro.3. human.

Organism-specific databases

CTD

3357.

GeneCards

GC02M231936.

HGNC

HGNC:5294. HTR2B.

HPA

CAB011448.
HPA012867.

MIM

601122. gene.

neXtProt

NX_P41595.

PharmGKB

PA29554.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG247243.

HOGENOM

HOG000240378.

HOVERGEN

HBG107487.

InParanoid

P41595.

KO

K04157.

OMA

VWLISIG.

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. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]

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

BindingDB

P41595.

ChEMBL

CHEMBL1833.

DrugBank

DB01239. Chlorprothixene.
DB00216. Eletriptan.
DB00574. Fenfluramine.
DB01403. Methotrimeprazine.
DB00805. Minaprine.
DB01224. Quetiapine.
DB00669. Sumatriptan.
DB01079. Tegaserod.
DB00508. Triflupromazine.

GenomeRNAi

3357.

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:	May 1, 2013
This is version 127 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.