Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P34968 (5HT2C_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length459 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12

Subunit structure

Interacts with MPDZ. Interacts with ARRB2 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Detected in brain cortex, hypothalamus, brainstem and arcuate nucleus. Detected in the paraventricular nucleus of the hypothalamus. Ref.4 Ref.7 Ref.8

Domain

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

Post-translational modification

N-glycosylated By similarity.

Disruption phenotype

No obvious phenotype at birth, but mutant mice are prone to sudden death from seizures. When fed ad libitum, adult mice display higher body weight and increased adiposity compared to wild-type littermates. No difference in body weight is found when they receive the same amount of food as their wild-type littermates, indicating that the increased body weight is due to altered feeding behavior. Overweight older mice develop insulin resistance and impaired glucose tolerance. Young mice exibit insulin resistance, but normal glucose tolerance, due to increased insulin levels in the blood. Insulin resistance is reversed when Htr2c expression is restored in pro-opiomelacortin neurons. Mutant mice display impaired activation of pro-opiomelacortin neurons in the paraventricular nucleus of the hypothalamus, leading to decreased release of CRH and corticosterone. Likewise, they exhibit blunted behavorial responses to anxiogenic environments and stress. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

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_processbehavioral fear response

Inferred from mutant phenotype Ref.6. Source: UniProtKB

cGMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

feeding behavior

Inferred from mutant phenotype Ref.4. Source: UniProtKB

locomotory behavior

Inferred from electronic annotation. Source: InterPro

phospholipase C-activating serotonin receptor signaling pathway

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

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

Inferred from mutant phenotype Ref.12. Source: UniProtKB

positive regulation of phosphatidylinositol biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of appetite

Inferred from mutant phenotype Ref.10. Source: UniProtKB

regulation of corticotropin-releasing hormone secretion

Inferred from mutant phenotype Ref.6Ref.7. Source: UniProtKB

regulation of neurological system process

Inferred from mutant phenotype Ref.7Ref.10. Source: UniProtKB

release of sequestered calcium ion into cytosol

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_function1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding

Inferred from electronic annotation. Source: Ensembl

Gq/11-coupled serotonin receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

drug binding

Inferred from electronic annotation. Source: Ensembl

serotonin binding

Inferred from sequence orthology PubMed 7582481. Source: MGI

serotonin receptor activity

Inferred from mutant phenotype Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 By similarity
Chain33 – 4594275-hydroxytryptamine receptor 2C
PRO_0000068959

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 – 31276Cytoplasmic By similarity
Transmembrane313 – 33422Helical; Name=6; By similarity
Topological domain335 – 34915Extracellular By similarity
Transmembrane350 – 37223Helical; Name=7; By similarity
Topological domain373 – 45987Cytoplasmic By similarity
Region135 – 1406Agonist binding By similarity
Region325 – 3295Agonist binding By similarity
Motif152 – 1543DRY motif; important for ligand-induced conformation changes By similarity
Motif365 – 3695NPxxY motif; important for ligand-induced conformation changes and signaling By similarity
Motif457 – 4593PDZ-binding

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) By similarity
Glycosylation2041N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Disulfide bond128 ↔ 208 By similarity
Disulfide bond338 ↔ 342 By similarity

Experimental info

Sequence conflict157 – 1615IRNPI → VRSPV in CAA51031. Ref.1
Sequence conflict157 – 1615IRNPI → VRSPV in AAA10521. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P34968 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: AA3C537B2ADCB0C9

FASTA45951,929
        10         20         30         40         50         60 
MVNLGTAVRS LLVHLIGLLV 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 RGHTEEELRN ISLNFLKCCC KKGDEEENAP NPNPDQKPRR KKKEKRPRGT 

       310        320        330        340        350        360 
MQAINNEKKA SKVLGIVFFV FLIMWCPFFI TNILSVLCGK ACNQKLMEKL LNVFVWIGYV 

       370        380        390        400        410        420 
CSGINPLVYT LFNKIYRRAF SKYLRCDYKP DKKPPVRQIP RVAATALSGR ELNVNIYRHT 

       430        440        450 
NERVVRKAND TEPGIEMQVE NLELPVNPSN VVSERISSV 

« Hide

References

« Hide 'large scale' references
[1]"The mouse 5-HT1C receptor contains eight hydrophobic domains and is X-linked."
Yu L., Nguyen H., Le H., Bloem L.J., Kozak C.A., Hoffman B.J., Snutch T.P., Lester H.A., Davidson N., Luebbert H.
Brain Res. Mol. Brain Res. 11:143-149(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the mouse 5-HT1C, 5-HT2 and stomach fundus serotonin receptor genes."
Foguet M., Nguyen H., Le H., Luebbert H.
NeuroReport 3:345-348(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors."
Tecott L.H., Sun L.M., Akana S.F., Strack A.M., Lowenstein D.H., Dallman M.F., Julius D.
Nature 374:542-546(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
[5]"Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene."
Nonogaki K., Strack A.M., Dallman M.F., Tecott L.H.
Nat. Med. 4:1152-1156(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]"Serotonin 5-HT(2C) receptors regulate anxiety-like behavior."
Heisler L.K., Zhou L., Bajwa P., Hsu J., Tecott L.H.
Genes Brain Behav. 6:491-496(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[7]"Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation."
Heisler L.K., Pronchuk N., Nonogaki K., Zhou L., Raber J., Tung L., Yeo G.S., O'Rahilly S., Colmers W.F., Elmquist J.K., Tecott L.H.
J. Neurosci. 27:6956-6964(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
[8]"5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis."
Xu Y., Jones J.E., Kohno D., Williams K.W., Lee C.E., Choi M.J., Anderson J.G., Heisler L.K., Zigman J.M., Lowell B.B., Elmquist J.K.
Neuron 60:582-589(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
[9]"Characterizing the effects of 5-HT(2C) receptor ligands on motor activity and feeding behaviour in 5-HT(2C) receptor knockout mice."
Fletcher P.J., Tampakeras M., Sinyard J., Slassi A., Isaac M., Higgins G.A.
Neuropharmacology 57:259-267(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[10]"A serotonin and melanocortin circuit mediates D-fenfluramine anorexia."
Xu Y., Jones J.E., Lauzon D.A., Anderson J.G., Balthasar N., Heisler L.K., Zinn A.R., Lowell B.B., Elmquist J.K.
J. Neurosci. 30:14630-14634(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[11]"5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver."
Xu Y., Berglund E.D., Sohn J.W., Holland W.L., Chuang J.C., Fukuda M., Rossi J., Williams K.W., Jones J.E., Zigman J.M., Lowell B.B., Scherer P.E., Elmquist J.K.
Nat. Neurosci. 13:1457-1459(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[12]"Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels."
Sohn J.W., Xu Y., Jones J.E., Wickman K., Williams K.W., Elmquist J.K.
Neuron 71:488-497(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X72230 mRNA. Translation: CAA51031.1.
S44559 expand/collapse EMBL AC list , S44556, S44557, S44558 Genomic DNA. Translation: AAA10521.1.
AL808014, AL662932 Genomic DNA. Translation: CAM15060.1.
AL662932, AL808014 Genomic DNA. Translation: CAM15766.1.
CCDSCCDS30459.1.
PIRA43951.
RefSeqNP_032338.3. NM_008312.4.
UniGeneMm.439670.

3D structure databases

ProteinModelPortalP34968.
SMRP34968. Positions 55-389.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP34968.
ChEMBLCHEMBL2109245.
GuidetoPHARMACOLOGY8.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP34968.

Proteomic databases

PRIDEP34968.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000036303; ENSMUSP00000043936; ENSMUSG00000041380.
ENSMUST00000096299; ENSMUSP00000094021; ENSMUSG00000041380.
GeneID15560.
KEGGmmu:15560.
UCSCuc009und.2. mouse.

Organism-specific databases

CTD3358.
MGIMGI:96281. Htr2c.

Phylogenomic databases

eggNOGNOG247243.
GeneTreeENSGT00750000117240.
HOGENOMHOG000240378.
HOVERGENHBG107487.
InParanoidB1ATN5.
KOK04157.
OMASSYIRCQ.
OrthoDBEOG70ZZN5.
TreeFamTF316350.

Gene expression databases

BgeeP34968.
CleanExMM_HTR2C.
GenevestigatorP34968.

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

ChiTaRSHTR2C. mouse.
NextBio288508.
PROP34968.
SOURCESearch...

Entry information

Entry name5HT2C_MOUSE
AccessionPrimary (citable) accession number: P34968
Secondary accession number(s): B1ATN5, Q5WRU6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 115 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries