P28335 (5HT2C_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 139.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: 5-hydroxytryptamine receptor 2C Short name=5-HT-2C Short name=5-HT2C Short name=5-HTR2C Alternative name(s): 5-hydroxytryptamine receptor 1C Short name=5-HT-1C Short name=5-HT1C Serotonin receptor 2C | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference 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 further processed into a mature form. |
| 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 | |
| Subcellular location | |
| Domain | The PDZ domain-binding motif is involved in the interaction with MPDZ. Ref.9 |
| Post-translational modification | N-glycosylated. Ref.9 |
| 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. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P28335-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P28335-2) The sequence of this isoform differs from the canonical sequence as follows: 153-458: YVAIRNPIEH...SVVSERISSV → CISSYPCDWT...YGRGRELCKP |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 32 | 32 | |||||||||
| Chain | 33 – 458 | 426 | 5-hydroxytryptamine receptor 2C | PRO_0000068958 | |||||||
Regions | |||||||||||
| Topological domain | 33 – 52 | 20 | Extracellular By similarity | ||||||||
| Transmembrane | 53 – 78 | 26 | Helical; Name=1; By similarity | ||||||||
| Topological domain | 79 – 89 | 11 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 90 – 110 | 21 | Helical; Name=2; By similarity | ||||||||
| Topological domain | 111 – 127 | 17 | Extracellular By similarity | ||||||||
| Transmembrane | 128 – 150 | 23 | Helical; Name=3; By similarity | ||||||||
| Topological domain | 151 – 170 | 20 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 171 – 193 | 23 | Helical; Name=4; By similarity | ||||||||
| Topological domain | 194 – 213 | 20 | Extracellular By similarity | ||||||||
| Transmembrane | 214 – 235 | 22 | Helical; Name=5; By similarity | ||||||||
| Topological domain | 236 – 311 | 76 | Cytoplasmic By similarity | ||||||||
| Transmembrane | 312 – 333 | 22 | Helical; Name=6; By similarity | ||||||||
| Topological domain | 334 – 348 | 15 | Extracellular By similarity | ||||||||
| Transmembrane | 349 – 371 | 23 | Helical; Name=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 | |||||||||||
| Alternative sequence | 153 – 458 | 306 | YVAIR…RISSV → CISSYPCDWTEGRRKGVREQ HDVRAQRPKFRSYWVLRSFL HTADDYGDYVLPDHLRSAPT SFDVTARPHRGTAWTKSGFP EVLQEEYGRGRELCKP in isoform 2. | VSP_045171 | |||||||
| Natural variant | 23 | 1 | C → S. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Corresponds to variant rs6318 [ dbSNP | Ensembl ]. | 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 | 159 | 1 | P → A: Decreases interaction with ARRB2. Ref.10 | ||||||||
| Mutagenesis | 456 | 1 | S → A: Loss of interaction with MPDZ. Ref.9 | ||||||||
| Mutagenesis | 456 | 1 | S → T: No effect on interaction with MPDZ. Ref.9 | ||||||||
| Mutagenesis | 457 | 1 | S → A: No effect on interaction with MPDZ. Ref.9 | ||||||||
| Mutagenesis | 458 | 1 | V → A: Loss of interaction with MPDZ. Ref.9 | ||||||||
Sequences
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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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] (ISOFORM 1). Tissue: Brain. |
| [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Hippocampus. |
| [7] | "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. Bentley D.R.Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MPDZ, DOMAIN, MUTAGENESIS OF SER-456; SER-457 AND VAL-458, GLYCOSYLATION. |
| [10] | "A beta-arrestin binding determinant common to the second intracellular loops of rhodopsin family G protein-coupled receptors." Marion S., Oakley R.H., Kim K.-M., Caron M.G., Barak L.S. J. Biol. Chem. 281:2932-2938(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2, MUTAGENESIS OF PRO-159. |
| [11] | "The N-terminal region of the human 5-HT(2)C receptor has as a cleavable signal peptide." Jahnsen J.A., Uhlen S. Eur. J. Pharmacol. 684:44-50(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SIGNAL PEPTIDE, VARIANT SER-23. |
| [12] | "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] [Europe PMC] [Abstract] Cited for: VARIANT SER-23. |
| [13] | "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] [Europe PMC] [Abstract] Cited for: VARIANT SER-23. |
| [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] [Europe PMC] [Abstract] Cited for: VARIANT SER-23. |
| [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] [Europe PMC] [Abstract] Cited for: VARIANT SER-23. |
| [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. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. AK295753 mRNA. Translation: BAG58583.1. AC007022 Genomic DNA. No translation available. AC007025 Genomic DNA. No translation available. AL591402 Genomic DNA. No translation available. AL355812, AC004822, AL590097 Genomic DNA. Translation: CAI41334.1. 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. NM_000868.2. NP_001243689.1. NM_001256760.1. NP_001243690.1. NM_001256761.1. |
| UniGene | Hs.149037. |
3D structure databases | |
| ProteinModelPortal | P28335. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P28335. 1 interaction. |
| MINT | MINT-443944. |
| STRING | 9606.ENSP00000276198. |
Protein family/group databases | |
| GPCRDB | Search... |
PTM databases | |
| PhosphoSite | P28335. |
Polymorphism databases | |
| DMDM | 112816. |
Proteomic databases | |
| PaxDb | P28335. |
| PRIDE | P28335. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000276198; ENSP00000276198; ENSG00000147246. ENST00000371950; ENSP00000361018; ENSG00000147246. ENST00000371951; ENSP00000361019; ENSG00000147246. |
| GeneID | 3358. |
| KEGG | hsa:3358. |
| UCSC | uc004epu.1. human. |
Organism-specific databases | |
| CTD | 3358. |
| GeneCards | GC0XP113818. |
| HGNC | HGNC:5295. HTR2C. |
| HPA | CAB006857. HPA003133. |
| MIM | 312861. gene. |
| neXtProt | NX_P28335. |
| PharmGKB | PA194. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG247243. |
| HOGENOM | HOG000240378. |
| HOVERGEN | HBG107487. |
| InParanoid | P28335. |
| KO | K04157. |
| OMA | VFLIMWC. |
| OrthoDB | EOG4M0F2D. |
| PhylomeDB | P28335. |
Enzyme and pathway databases | |
| Reactome | REACT_111102. Signal Transduction. |
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. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [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 | |
| BindingDB | P28335. |
| ChEMBL | CHEMBL225. |
| 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. |
| GenomeRNAi | 3358. |
| NextBio | 13278. |
| SOURCE | Search... |
Entry information
| Entry name | 5HT2C_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P28335 Secondary accession number(s): B1AMW4, Q5VUF8, Q9NP28 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| 7-transmembrane G-linked receptors List of 7-transmembrane G-linked receptor entries |
| Human chromosome X Human chromosome X: 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 |

Clusters with
