Reviewed, UniProtKB/Swiss-Prot P28335 (5HT2C_HUMAN)

Names and origin

Protein names

Recommended name:
    5-hydroxytryptamine receptor 2C
      Short name=5-HTR2C
      Short name=5-HT-2C
      Short name=5-HT2C
Alternative name(s):
    5HT-1C
    Serotonin receptor 2C

Gene names

Name:	HTR2C
Synonyms:	HTR1C

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	458 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. Ref.2
Subunit structure	Interacts with MPDZ. Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein.
Domain	The PDZ domain-binding motif is involved in the interaction with MPDZ. Ref.8
Post-translational modification	N-glycosylated. Ref.8
Polymorphism	Position 23 is polymorphic; the frequencies in unrelated Caucasians are 0.87 for Cys and 0.13 for Ser.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
RNA editing	Edited at positions 156, 158 and 160. Partially edited. RNA editing generates receptor isoforms that differ in their ability to interact with the phospholipase C signaling cascade in a transfected cell line, suggesting that this RNA processing event may contribute to the modulation of serotonergic neurotransmission in the central nervous system. Ref.4

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism RNA editing
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from Experiment. Source: Reactome feeding behavior Traceable author statement. Source: ProtInc synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: IntAct serotonin binding Inferred from direct assay. Source: MGI serotonin receptor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arrb2	Q91YI4	1	EBI-994141,EBI-994161	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 458	458	5-hydroxytryptamine receptor 2C		PRO_0000068958
Regions
	Topological domain	1 – 52	52	Extracellular By similarity
	Transmembrane	53 – 78	26	1 By similarity
	Topological domain	79 – 89	11	Cytoplasmic By similarity
	Transmembrane	90 – 110	21	2 By similarity
	Topological domain	111 – 127	17	Extracellular By similarity
	Transmembrane	128 – 150	23	3 By similarity
	Topological domain	151 – 170	20	Cytoplasmic By similarity
	Transmembrane	171 – 193	23	4 By similarity
	Topological domain	194 – 213	20	Extracellular By similarity
	Transmembrane	214 – 235	22	5 By similarity
	Topological domain	236 – 311	76	Cytoplasmic By similarity
	Transmembrane	312 – 333	22	6 By similarity
	Topological domain	334 – 348	15	Extracellular By similarity
	Transmembrane	349 – 371	23	7 By similarity
	Topological domain	372 – 458	87	Cytoplasmic By similarity
	Motif	456 – 458	3	PDZ-binding
Amino acid modifications
	Glycosylation	39	1	N-linked (GlcNAc...) Probable
	Disulfide bond	127 ↔ 207		By similarity
Natural variations
	Natural variant	23	1	C → S: dbSNP rs6318. Ref.9 Ref.10 Ref.11 Ref.12		VAR_003450
	Natural variant	156	1	I → V in RNA edited version.		VAR_010166
	Natural variant	158	1	N → S in RNA edited version.		VAR_010167
	Natural variant	160	1	I → V in RNA edited version.		VAR_010168
Experimental info
	Mutagenesis	456	1	S → A: Loss of interaction with MPDZ. Ref.8
	Mutagenesis	456	1	S → T: No effect on interaction with MPDZ. Ref.8
	Mutagenesis	457	1	S → A: No effect on interaction with MPDZ. Ref.8
	Mutagenesis	458	1	V → A: Loss of interaction with MPDZ. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P28335-1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 9E76B3FFD3E09C93	FASTA	458	51,821
	10 20 30 40 50 60 MVNLRNAVHS FLVHLIGLLV WQCDISVSPV AAIVTDIFNT SDGGRFKFPD GVQNWPALSI 70 80 90 100 110 120 VIIIIMTIGG NILVIMAVSM EKKLHNATNY FLMSLAIADM LVGLLVMPLS LLAILYDYVW 130 140 150 160 170 180 PLPRYLCPVW ISLDVLFSTA SIMHLCAISL DRYVAIRNPI EHSRFNSRTK AIMKIAIVWA 190 200 210 220 230 240 ISIGVSVPIP VIGLRDEEKV FVNNTTCVLN DPNFVLIGSF VAFFIPLTIM VITYCLTIYV 250 260 270 280 290 300 LRRQALMLLH GHTEEPPGLS LDFLKCCKRN TAEEENSANP NQDQNARRRK KKERRPRGTM 310 320 330 340 350 360 QAINNERKAS KVLGIVFFVF LIMWCPFFIT NILSVLCEKS CNQKLMEKLL NVFVWIGYVC 370 380 390 400 410 420 SGINPLVYTL FNKIYRRAFS NYLRCNYKVE KKPPVRQIPR VAATALSGRE LNVNIYRHTN 430 440 450 EPVIEKASDN EPGIEMQVEN LELPVNPSSV VSERISSV

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.
[2]	"Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor." Stam N.J., Vanderheyden P., Van Alebeek C., Klomp J., De Boer T., Van Delft A.M.L., Olijve W. Eur. J. Pharmacol. 269:339-348(1994) [PubMed: 7895773] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION. Tissue: Hippocampus and Placenta.
[3]	"The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant." Xie E., Zhao L., Levine A.J., Shenk T., Chang L.-S. Genomics 35:551-561(1996) [PubMed: 8812491] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Identification and characterization of RNA editing events within the 5-HT2C receptor." Niswender C.M., Sanders-Bush E., Emeson R.B. Ann. N. Y. Acad. Sci. 861:38-48(1998) [PubMed: 9928237] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], RNA EDITING OF POSITIONS 156; 158 AND 160. Tissue: Brain.
[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 (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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].
[8]	"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, DOMAIN, MUTAGENESIS OF SER-456; SER-457 AND VAL-458, GLYCOSYLATION.
[9]	"Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C)." Lappalainen J., Zhang L., Dean M., Oz M., Ozaki N., Yu D., Virkkunen M., Weight F., Linnoila M., Goldman D. Genomics 27:274-279(1995) [PubMed: 7557992] [Abstract] Cited for: VARIANT SER-23.
[10]	"Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability." Samochowiec J., Smolka M., Winterer G., Rommelspacher H., Schmidt L.G., Sander T. Am. J. Med. Genet. 88:126-130(1999) [PubMed: 10206230] [Abstract] Cited for: VARIANT SER-23.
[11]	"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: VARIANT SER-23.
[12]	"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: VARIANT SER-23.
[13]	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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M81778 mRNA. Translation: AAA60317.1. X80763 Genomic DNA. Translation: CAB59978.1. U49516 mRNA. Translation: AAB40898.1. AF208053 mRNA. Translation: AAF35842.1. AF498983 mRNA. Translation: AAM21130.1. AC004822 Genomic DNA. Translation: AAC71658.1. AL355812, AL590097, AC004822 Genomic DNA. Translation: CAI41335.1. AL590097, AC004822, AL355812 Genomic DNA. Translation: CAH70193.1. BC095543 mRNA. Translation: AAH95543.1.
IPI	IPI00002876.
PIR	JS0616.
RefSeq	NP_000859.1.
UniGene	Hs.149037
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P28335. 1 interaction.
STRING	P28335.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P28335.
Proteomic databases
PRIDE	P28335.
Genome annotation databases
Ensembl	ENST00000276198; ENSP00000276198; ENSG00000147246; Homo sapiens. [Genome view] ENST00000371951; ENSP00000361019; ENSG00000147246; Homo sapiens. [Genome view]
GeneID	3358.
KEGG	hsa:3358.
UCSC	uc004epu.1. human.
Organism-specific databases
CTD	3358.
GeneCards	GC0XP113641.
H-InvDB	HIX0028341.
HGNC	HGNC:5295. HTR2C.
HPA	CAB006857. HPA003133.
MIM	312861. gene.
PharmGKB	PA194.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P28335.
HOVERGEN	P28335.
OMA	NPSNVVS
OrthoDB	EOG9ZSCNH
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P28335.
Bgee	P28335.
CleanEx	HS_HTR2C.
Genevestigator	P28335.
GermOnline	ENSG00000147246. Homo sapiens.
Family and domain databases
InterPro	IPR000377. 5HT2C_rcpt. IPR002231. 5HT_rcpt. IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00517. 5HT2CRECEPTR. 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	DB01239. Chlorprothixene. DB00363. Clozapine. DB01191. Dexfenfluramine. DB00574. Fenfluramine. DB00247. Methysergide. DB06148. Mianserin. DB00805. Minaprine. DB00370. Mirtazapine. DB00334. Olanzapine. DB00420. Promazine. DB00777. Propiomazine. DB01224. Quetiapine. DB06144. Sertindole. DB00372. Thiethylperazine. DB00193. Tramadol. DB00246. Ziprasidone.
NextBio	13278.
SOURCE	Search...

Entry information

Entry name

5HT2C_HUMAN

Accession

Primary (citable) accession number: P28335
Secondary accession number(s): Q5VUF8, Q9NP28

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	November 24, 2009
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.