Reviewed, UniProtKB/Swiss-Prot P28223 (5HT2A_HUMAN)

Names and origin

Protein names

Recommended name:
    5-hydroxytryptamine receptor 2A
      Short name=5-HT-2A
      Short name=5-HT-2
Alternative name(s):
    Serotonin receptor 2A

Gene names

Name:	HTR2A
Synonyms:	HTR2

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	471 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production.
Subunit structure	Interacts with MPDZ and INADL. May interact with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2. Ref.9 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Note: Localizes to the post-synaptic thickening of axo-dendritic synapses By similarity.
Domain	The PDZ domain-binding motif is involved in the interaction with INADL, CASK, APBA1, DLG1 and DLG4.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	serotonin binding Inferred from direct assay. Source: MGI serotonin receptor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 471	471	5-hydroxytryptamine receptor 2A		PRO_0000068946
Regions
	Topological domain	1 – 75	75	Extracellular By similarity
	Transmembrane	76 – 99	24	1 By similarity
	Topological domain	100 – 110	11	Cytoplasmic By similarity
	Transmembrane	111 – 132	22	2 By similarity
	Topological domain	133 – 147	15	Extracellular By similarity
	Transmembrane	148 – 171	24	3 By similarity
	Topological domain	172 – 191	20	Cytoplasmic By similarity
	Transmembrane	192 – 215	24	4 By similarity
	Topological domain	216 – 233	18	Extracellular By similarity
	Transmembrane	234 – 254	21	5 By similarity
	Topological domain	255 – 324	70	Cytoplasmic By similarity
	Transmembrane	325 – 346	22	6 By similarity
	Topological domain	347 – 362	16	Extracellular By similarity
	Transmembrane	363 – 384	22	7 By similarity
	Topological domain	385 – 471	87	Cytoplasmic By similarity
	Motif	469 – 471	3	PDZ-binding
Amino acid modifications
	Glycosylation	8	1	N-linked (GlcNAc...) Potential
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Glycosylation	51	1	N-linked (GlcNAc...) Potential
	Glycosylation	54	1	N-linked (GlcNAc...) Potential
	Disulfide bond	148 ↔ 227		By similarity
Natural variations
	Natural variant	25	1	T → N: dbSNP rs1805055. Ref.11 Ref.12		VAR_003448
	Natural variant	197	1	I → V: dbSNP rs6304. Ref.13		VAR_013901
	Natural variant	447	1	A → V: dbSNP rs6308. Ref.13		VAR_013902
	Natural variant	452	1	H → Y: dbSNP rs6314. Ref.11 Ref.12 Ref.13		VAR_003449
Experimental info
	Mutagenesis	463	1	G → V: Loss of interaction with INADL. Ref.10
	Mutagenesis	465	1	N → S: No effect on interaction with INADL. Acquires the binding properties of HTR2C; when associated with S-470. Ref.10
	Mutagenesis	470	1	C → S: No effect on interaction with INADL. Acquires the binding properties of HTR2C; when associated with S-465. Ref.10
	Mutagenesis	471	1	V → A: Loss of interaction with INADL, CASK, APBA1, DLG1 and DLG4. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	P28223-1 [UniParc]. Last modified June 1, 1994. Version 2. Checksum: EF8AAC0BC5379DA2	FASTA	471	52,603
	10 20 30 40 50 60 MDILCEENTS LSSTTNSLMQ LNDDTRLYSN DFNSGEANTS DAFNWTVDSE NRTNLSCEGC 70 80 90 100 110 120 LSPSCLSLLH LQEKNWSALL TAVVIILTIA GNILVIMAVS LEKKLQNATN YFLMSLAIAD 130 140 150 160 170 180 MLLGFLVMPV SMLTILYGYR WPLPSKLCAV WIYLDVLFST ASIMHLCAIS LDRYVAIQNP 190 200 210 220 230 240 IHHSRFNSRT KAFLKIIAVW TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF 250 260 270 280 290 300 VSFFIPLTIM VITYFLTIKS LQKEATLCVS DLGTRAKLAS FSFLPQSSLS SEKLFQRSIH 310 320 330 340 350 360 REPGSYTGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK ESCNEDVIGA 370 380 390 400 410 420 LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK ENKKPLQLIL VNTIPALAYK 430 440 450 460 470 SSQLQMGQKK NSKQDAKTTD NDCSMVALGK QHSEEASKDN SDGVNEKVSC V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes." Saltzman A.G., Morse B., Whitman M.M., Ivanshchenko Y., Jaye M., Felder S. Biochem. Biophys. Res. Commun. 181:1469-1478(1991) [PubMed: 1722404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain stem.
[2]	"The human 5-HT2 receptor is encoded by a multiple intron-exon gene." Chen K., Yang W., Grimsby J., Shih J.C. Brain Res. Mol. Brain Res. 14:20-26(1992) [PubMed: 1323014] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor." Cook E.H. Jr., Fletcher K.E., Wainwright M., Marks N., Yan S.Y., Leventhal B.L. J. Neurochem. 63:465-469(1994) [PubMed: 8035173] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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 (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Lung.
[7]	"Cloning and nucleotide sequence of the human(5HT) type 2 receptor." Tritch R.J., Robinson D.L., Sahagan B.G., Horlick R.A. Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-464. Tissue: Brain.
[8]	"Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes." Stam N.J., van Huizen F., van Alebeek C., Brands J., Dijkema R., Tonnaer J.A., Olijve W. Eur. J. Pharmacol. 227:153-162(1992) [PubMed: 1330647] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 105-218.
[9]	"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.
[10]	"The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins." Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A., Bockaert J., Marin P. J. Biol. Chem. 279:20257-20266(2004) [PubMed: 14988405] [Abstract] Cited for: INTERACTION WITH INADL; MPP3; PRDX6; DLG4; DLG1; CASK; APBA1 AND MAGI2, MUTAGENESIS OF GLY-463; ASN-465; CYS-470 AND VAL-471.
[11]	"Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia." Erdmann J., Shimron-Abarbanell D., Rietschel M., Albus M., Maier W., Koerner J., Bondy B., Chen K., Shih J.C., Knapp M., Propping P., Noethen M.M. Hum. Genet. 97:614-619(1996) [PubMed: 8655141] [Abstract] Cited for: VARIANTS ASN-25 AND TYR-452.
[12]	"Unified approach to the analysis of genetic variation in serotonergic pathways." Marshall S.E., Bird T.G., Hart K., Welsh K.I. Am. J. Med. Genet. 88:621-627(1999) [PubMed: 10581480] [Abstract] Cited for: VARIANTS ASN-25 AND TYR-452.
[13]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS VAL-197; VAL-447 AND TYR-452.
[14]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases
EMBLGenBankDDBJ	X57830 mRNA. Translation: CAA40963.1. S42168, S42165, S42167 Genomic DNA. Translation: AAB22791.2. S71229 mRNA. Translation: AAB31320.1. AF498982 mRNA. Translation: AAM21129.1. AL160397, AL136958 Genomic DNA. Translation: CAI16877.1. AL136958, AL160397 Genomic DNA. Translation: CAI12227.1. BC069356 mRNA. Translation: AAH69356.1. BC069576 mRNA. Translation: AAH69576.1. BC074848 mRNA. Translation: AAH74848.1. BC074849 mRNA. Translation: AAH74849.1. BC096839 mRNA. Translation: AAH96839.1. M86841 mRNA. Translation: AAA58354.1. S50130, S49737, S50113 Genomic DNA. Translation: AAB24166.2.
IPI	IPI00002185.
PIR	A43956.
RefSeq	NP_000612.1.
UniGene	Hs.654586
3D structure databases
HSSP	HSSP built from PDB template 1HLL based on UniProtKB P08913.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P28223.
Proteomic databases
PRIDE	P28223.
Genome annotation databases
Ensembl	ENSG00000102468. Homo sapiens. [Contig view]
GeneID	3356.
KEGG	hsa:3356.
Organism-specific databases
GeneCards	GC13M046305.
H-InvDB	HIX0026550.
HGNC	HGNC:5293. HTR2A.
HPA	HPA014011.
MIM	182135. gene.
PharmGKB	PA193.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P28223.
HOVERGEN	P28223.
OMA	P28223. LMQLNDD.
Gene expression databases
ArrayExpress	P28223.
Bgee	P28223.
CleanEx	HS_HTR2A.
GermOnline	ENSG00000102468. Homo sapiens.
Family and domain databases
InterPro	IPR000455. 5HT2A_rcpt. IPR002231. 5HT_rcpt. IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00516. 5HT2ARECEPTR. 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 Resources
DrugBank	DB01238. Aripiprazole. DB00477. Chlorpromazine. DB01239. Chlorprothixene. DB00604. Cisapride. DB01242. Clomipramine. DB00363. Clozapine. DB00924. Cyclobenzaprine. DB00434. Cyproheptadine. DB00320. Dihydroergotamine. DB00843. Donepezil. DB00751. Epinastine. DB00696. Ergotamine. DB00176. Fluvoxamine. DB00933. Mesoridazine. DB00247. Methysergide. DB06148. Mianserin. DB00805. Minaprine. DB00370. Mirtazapine. DB01149. Nefazodone. DB00334. Olanzapine. DB01267. Paliperidone. DB00715. Paroxetine. DB00433. Prochlorperazine. DB00420. Promazine. DB01069. Promethazine. DB00777. Propiomazine. DB01224. Quetiapine. DB00734. Risperidone. DB06144. Sertindole. DB00372. Thiethylperazine. DB00679. Thioridazine. DB00752. Tranylcypromine. DB00656. Trazodone. DB00285. Venlafaxine. DB00246. Ziprasidone.
NextBio	13270.
SOURCE	Search...

Entry information

Entry name

5HT2A_HUMAN

Accession

Primary (citable) accession number: P28223
Secondary accession number(s): Q5T8C0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	June 1, 1994
Last modified:	June 16, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)