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

Last modified January 19, 2010. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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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.11 Ref.12

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.

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Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processsynaptic transmission

Traceable author statement. Source: ProtInc

   Cellular componentintegral to plasma membrane

Traceable author statement. Source: ProtInc

   Molecular functionserotonin binding

Inferred from direct assay. Source: MGI

serotonin receptor activity

Inferred from direct assay. Source: MGI

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 4714715-hydroxytryptamine receptor 2A
PRO_0000068946

Regions

Topological domain1 – 7575Extracellular By similarity
Transmembrane76 – 99241 By similarity
Topological domain100 – 11011Cytoplasmic By similarity
Transmembrane111 – 132222 By similarity
Topological domain133 – 14715Extracellular By similarity
Transmembrane148 – 171243 By similarity
Topological domain172 – 19120Cytoplasmic By similarity
Transmembrane192 – 215244 By similarity
Topological domain216 – 23318Extracellular By similarity
Transmembrane234 – 254215 By similarity
Topological domain255 – 32470Cytoplasmic By similarity
Transmembrane325 – 346226 By similarity
Topological domain347 – 36216Extracellular By similarity
Transmembrane363 – 384227 By similarity
Topological domain385 – 47187Cytoplasmic By similarity
Motif469 – 4713PDZ-binding

Amino acid modifications

Glycosylation81N-linked (GlcNAc...) Potential
Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation441N-linked (GlcNAc...) Potential
Glycosylation511N-linked (GlcNAc...) Potential
Glycosylation541N-linked (GlcNAc...) Potential
Disulfide bond148 ↔ 227 By similarity

Natural variations

Natural variant251T → N: dbSNP rs1805055. Ref.13 Ref.14
VAR_003448
Natural variant1971I → V: dbSNP rs6304. Ref.15
VAR_013901
Natural variant4471A → V: dbSNP rs6308. Ref.15
VAR_013902
Natural variant4521H → Y: dbSNP rs6314. Ref.13 Ref.14 Ref.15
VAR_003449

Experimental info

Mutagenesis4631G → V: Loss of interaction with INADL. Ref.12
Mutagenesis4651N → S: No effect on interaction with INADL. Acquires the binding properties of HTR2C; when associated with S-470. Ref.12
Mutagenesis4701C → S: No effect on interaction with INADL. Acquires the binding properties of HTR2C; when associated with S-465. Ref.12
Mutagenesis4711V → A: Loss of interaction with INADL, CASK, APBA1, DLG1 and DLG4. Ref.12

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Sequences

Sequence LengthMass (Da)Tools
P28223-1 [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: EF8AAC0BC5379DA2

FASTA47152,603
        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

« Hide

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References

« Hide '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]"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. expand/collapse author list , 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].
Tissue: Thalamus.
[6]"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. expand/collapse author list , 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].
[7]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. expand/collapse author list , 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].
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]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.

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Web resources

SHMPD

The Singapore human mutation and polymorphism database

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X57830 mRNA. Translation: CAA40963.1.
S42168, S42165, S42167 Genomic DNA. Translation: AAB22791.2.
S71229 mRNA. Translation: AAB31320.1.
AF498982 mRNA. Translation: AAM21129.1.
AK314132 mRNA. Translation: BAG36822.1.
AL160397, AL136958 Genomic DNA. Translation: CAI16877.1.
AL136958, AL160397 Genomic DNA. Translation: CAI12227.1.
CH471075 Genomic DNA. Translation: EAX08770.1.
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.
IPIIPI00002185.
PIRA43956.
RefSeqNP_000612.1.
UniGeneHs.654586

3D structure databases

SMRP28223. Positions 78-399.
ModBaseSearch...

Protein-protein interaction databases

STRINGP28223.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP28223.

Proteomic databases

PRIDEP28223.

Genome annotation databases

EnsemblENST00000378688; ENSP00000367959; ENSG00000102468; Homo sapiens. [Genome view]
GeneID3356.
KEGGhsa:3356.
UCSCuc001vbq.2. human.

Organism-specific databases

CTD3356.
GeneCardsGC13M046305.
H-InvDBHIX0026550.
HGNCHGNC:5293. HTR2A.
HPAHPA014011.
MIM182135. gene.
PharmGKBPA193.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08127.
HOGENOMHBG445348.
HOVERGENP28223.
InParanoidP28223.
OMAMDILCEE.
OrthoDBEOG9ZSCNH.
PhylomeDBP28223.

Enzyme and pathway databases

ReactomeREACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpressP28223.
BgeeP28223.
CleanExHS_HTR2A.
GenevestigatorP28223.
GermOnlineENSG00000102468. Homo sapiens.

Family and domain databases

InterProIPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. 7TM_GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_supfam.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01238. 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.
NextBio13270.
SOURCESearch...

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Entry information

Entry name5HT2A_HUMAN
AccessionPrimary (citable) accession number: P28223
Secondary accession number(s): B2RAC5, Q5T8C0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: June 1, 1994
Last modified: January 19, 2010
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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List of 7-transmembrane G-linked receptor entries

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents