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P08909 (5HT2C_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Name:Htr2c
Synonyms:5ht1c, Htr1c
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length460 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca2+ ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and feeding behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis. Ref.1

Subunit structure

Interacts with MPDZ. Interacts with ARRB2 By similarity. Ref.2

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1.

Domain

The PDZ domain-binding motif is involved in the interaction with MPDZ.

Post-translational modification

N-glycosylated By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Biological processBehavior
   Cellular componentCell membrane
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement PubMed 9153397. Source: RGD

behavioral fear response

Inferred from sequence or structural similarity. Source: UniProtKB

behavioral response to nicotine

Inferred from mutant phenotype PubMed 17473916. Source: RGD

feeding behavior

Inferred from mutant phenotype PubMed 15705738. Source: RGD

inositol phosphate-mediated signaling

Inferred from direct assay PubMed 8626447. Source: MGI

locomotory behavior

Inferred from electronic annotation. Source: InterPro

negative regulation of dopamine metabolic process

Inferred from mutant phenotype PubMed 17018023. Source: RGD

negative regulation of locomotion

Inferred from mutant phenotype PubMed 15896731. Source: RGD

organ regeneration

Inferred from expression pattern PubMed 17258772. Source: RGD

phospholipase C-activating serotonin receptor signaling pathway

Inferred from direct assay PubMed 12435801. Source: RGD

phospholipase D-activating G-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 12435801. Source: RGD

positive regulation of acetylcholine secretion, neurotransmission

Inferred from mutant phenotype PubMed 15266551. Source: RGD

positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gamma-aminobutyric acid secretion

Inferred from mutant phenotype PubMed 17043669. Source: RGD

positive regulation of vasoconstriction

Inferred from mutant phenotype PubMed 15118345. Source: RGD

regulation of appetite

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of corticotropin-releasing hormone secretion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neurological system process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of sensory perception of pain

Inferred from mutant phenotype PubMed 17451674. Source: RGD

response to drug

Inferred from mutant phenotype PubMed 16807362. Source: RGD

   Cellular_componentcell surface

Inferred from direct assay PubMed 15663485. Source: RGD

external side of plasma membrane

Inferred from direct assay PubMed 1373499. Source: MGI

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionGq/11-coupled serotonin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

serotonin receptor activity

Inferred from direct assay PubMed 8626447. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 By similarity
Chain33 – 4604285-hydroxytryptamine receptor 2C
PRO_0000068961

Regions

Topological domain33 – 5321Extracellular By similarity
Transmembrane54 – 7926Helical; Name=1; By similarity
Topological domain80 – 9011Cytoplasmic By similarity
Transmembrane91 – 11121Helical; Name=2; By similarity
Topological domain112 – 12817Extracellular By similarity
Transmembrane129 – 15123Helical; Name=3; By similarity
Topological domain152 – 17120Cytoplasmic By similarity
Transmembrane172 – 19423Helical; Name=4; By similarity
Topological domain195 – 21420Extracellular By similarity
Transmembrane215 – 23622Helical; Name=5; By similarity
Topological domain237 – 31377Cytoplasmic By similarity
Transmembrane314 – 33522Helical; Name=6; By similarity
Topological domain336 – 35015Extracellular By similarity
Transmembrane351 – 37323Helical; Name=7; By similarity
Topological domain374 – 46087Cytoplasmic By similarity
Region135 – 1406Agonist binding By similarity
Region326 – 3305Agonist binding By similarity
Motif152 – 1543DRY motif; important for ligand-induced conformation changes By similarity
Motif366 – 3705NPxxY motif; important for ligand-induced conformation changes and signaling By similarity
Motif458 – 4603PDZ-binding

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) By similarity
Glycosylation2041N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Disulfide bond128 ↔ 208 By similarity
Disulfide bond339 ↔ 343 By similarity

Experimental info

Mutagenesis4581S → A or D: Loss of interaction with MPDZ. Ref.2
Mutagenesis4591S → D: No effect on interaction with MPDZ. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P08909 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: D44E977D8F80047E

FASTA46051,917
        10         20         30         40         50         60 
MVNLGNAVRS LLMHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP DGVQNWPALS 

        70         80         90        100        110        120 
IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD MLVGLLVMPL SLLAILYDYV 

       130        140        150        160        170        180 
WPLPRYLCPV WISLDVLFST ASIMHLCAIS LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW 

       190        200        210        220        230        240 
AISIGVSVPI PVIGLRDESK VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY 

       250        260        270        280        290        300 
VLRRQTLMLL RGHTEEELAN MSLNFLNCCC KKNGGEEENA PNPNPDQKPR RKKKEKRPRG 

       310        320        330        340        350        360 
TMQAINNEKK ASKVLGIVFF VFLIMWCPFF ITNILSVLCG KACNQKLMEK LLNVFVWIGY 

       370        380        390        400        410        420 
VCSGINPLVY TLFNKIYRRA FSKYLRCDYK PDKKPPVRQI PRVAATALSG RELNVNIYRH 

       430        440        450        460 
TNERVARKAN DPEPGIEMQV ENLELPVNPS NVVSERISSV 

« Hide

References

[1]"Molecular characterization of a functional cDNA encoding the serotonin 1c receptor."
Julius D., McDermott A.B., Axel R., Jessell T.M.
Science 241:558-564(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION.
[2]"Agonist-induced phosphorylation of the serotonin 5-HT2C receptor regulates its interaction with multiple PDZ protein 1."
Parker L.L., Backstrom J.R., Sanders-Bush E., Shieh B.H.
J. Biol. Chem. 278:21576-21583(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPDZ, MUTAGENESIS OF SER-458 AND SER-459.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M21410 Genomic DNA. Translation: AAA42177.1.
PIRA32605.
RefSeqNP_036897.2. NM_012765.3.
UniGeneRn.9935.

3D structure databases

ProteinModelPortalP08909.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-443850.
STRING10116.ENSRNOP00000062375.

Chemistry

BindingDBP08909.
ChEMBLCHEMBL2094123.
GuidetoPHARMACOLOGY8.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP08909.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25187.
KEGGrno:25187.

Organism-specific databases

CTD3358.
RGD2848. Htr2c.

Phylogenomic databases

eggNOGNOG247243.
HOGENOMHOG000240378.
HOVERGENHBG107487.
InParanoidP08909.
KOK04157.
PhylomeDBP08909.

Gene expression databases

GenevestigatorP08909.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000377. 5HT2C_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24247:SF32. PTHR24247:SF32. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00517. 5HT2CRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio605689.

Entry information

Entry name5HT2C_RAT
AccessionPrimary (citable) accession number: P08909
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries