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P34968

- 5HT2C_MOUSE

UniProt

P34968 - 5HT2C_MOUSE

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Protein

5-hydroxytryptamine receptor 2C

Gene

Htr2c

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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.8 Publications

GO - Molecular functioni

  1. 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: Ensembl
  2. drug binding Source: Ensembl
  3. Gq/11-coupled serotonin receptor activity Source: UniProtKB
  4. serotonin binding Source: MGI
  5. serotonin receptor activity Source: UniProtKB

GO - Biological processi

  1. behavioral fear response Source: UniProtKB
  2. cGMP biosynthetic process Source: Ensembl
  3. feeding behavior Source: UniProtKB
  4. locomotory behavior Source: InterPro
  5. phospholipase C-activating serotonin receptor signaling pathway Source: UniProtKB
  6. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
  7. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  8. positive regulation of fat cell differentiation Source: MGI
  9. positive regulation of phosphatidylinositol biosynthetic process Source: Ensembl
  10. regulation of appetite Source: UniProtKB
  11. regulation of corticotropin-releasing hormone secretion Source: UniProtKB
  12. regulation of neurological system process Source: UniProtKB
  13. release of sequestered calcium ion into cytosol Source: Ensembl
  14. response to drug Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

ReactomeiREACT_207651. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Htr2c
Synonyms:5ht1c, Htr1c
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:96281. Htr2c.

Subcellular locationi

GO - Cellular componenti

  1. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

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.9 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232By similarityAdd
BLAST
Chaini33 – 4594275-hydroxytryptamine receptor 2CPRO_0000068959Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi39 – 391N-linked (GlcNAc...)By similarity
Disulfide bondi128 ↔ 208PROSITE-ProRule annotation
Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi338 ↔ 342PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP34968.

PTM databases

PhosphoSiteiP34968.

Expressioni

Tissue specificityi

Detected in brain cortex, hypothalamus, brainstem and arcuate nucleus. Detected in the paraventricular nucleus of the hypothalamus.3 Publications

Gene expression databases

BgeeiP34968.
CleanExiMM_HTR2C.
ExpressionAtlasiP34968. baseline.
GenevestigatoriP34968.

Interactioni

Subunit structurei

Interacts with MPDZ. Interacts with ARRB2 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP34968.
SMRiP34968. Positions 55-389.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 5321ExtracellularBy similarityAdd
BLAST
Topological domaini80 – 9011CytoplasmicBy similarityAdd
BLAST
Topological domaini112 – 12817ExtracellularBy similarityAdd
BLAST
Topological domaini152 – 17120CytoplasmicBy similarityAdd
BLAST
Topological domaini195 – 21420ExtracellularBy similarityAdd
BLAST
Topological domaini237 – 31276CytoplasmicBy similarityAdd
BLAST
Topological domaini335 – 34915ExtracellularBy similarityAdd
BLAST
Topological domaini373 – 45987CytoplasmicBy similarityAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei54 – 7926Helical; Name=1By similarityAdd
BLAST
Transmembranei91 – 11121Helical; Name=2By similarityAdd
BLAST
Transmembranei129 – 15123Helical; Name=3By similarityAdd
BLAST
Transmembranei172 – 19423Helical; Name=4By similarityAdd
BLAST
Transmembranei215 – 23622Helical; Name=5By similarityAdd
BLAST
Transmembranei313 – 33422Helical; Name=6By similarityAdd
BLAST
Transmembranei350 – 37223Helical; Name=7By similarityAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni135 – 1406Agonist bindingBy similarity
Regioni325 – 3295Agonist bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi152 – 1543DRY motif; important for ligand-induced conformation changesBy similarity
Motifi365 – 3695NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity
Motifi457 – 4593PDZ-binding

Domaini

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

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG247243.
GeneTreeiENSGT00760000119257.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP34968.
KOiK04157.
OMAiSSYIRCQ.
OrthoDBiEOG70ZZN5.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR000377. 5HT2C_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF32. PTHR24247:SF32. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00517. 5HT2CRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P34968 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVNLGTAVRS LLVHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP
60 70 80 90 100
DGVQNWPALS IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD
110 120 130 140 150
MLVGLLVMPL SLLAILYDYV WPLPRYLCPV WISLDVLFST ASIMHLCAIS
160 170 180 190 200
LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW AISIGVSVPI PVIGLRDESK
210 220 230 240 250
VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY VLRRQTLMLL
260 270 280 290 300
RGHTEEELRN ISLNFLKCCC KKGDEEENAP NPNPDQKPRR KKKEKRPRGT
310 320 330 340 350
MQAINNEKKA SKVLGIVFFV FLIMWCPFFI TNILSVLCGK ACNQKLMEKL
360 370 380 390 400
LNVFVWIGYV CSGINPLVYT LFNKIYRRAF SKYLRCDYKP DKKPPVRQIP
410 420 430 440 450
RVAATALSGR ELNVNIYRHT NERVVRKAND TEPGIEMQVE NLELPVNPSN

VVSERISSV
Length:459
Mass (Da):51,929
Last modified:July 27, 2011 - v2
Checksum:iAA3C537B2ADCB0C9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1615IRNPI → VRSPV in CAA51031. (PubMed:1661811)Curated
Sequence conflicti157 – 1615IRNPI → VRSPV in AAA10521. (PubMed:1381232)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X72230 mRNA. Translation: CAA51031.1.
S44559
, S44556, S44557, S44558 Genomic DNA. Translation: AAA10521.1.
AL808014, AL662932 Genomic DNA. Translation: CAM15060.1.
AL662932, AL808014 Genomic DNA. Translation: CAM15766.1.
CCDSiCCDS30459.1.
PIRiA43951.
RefSeqiNP_032338.3. NM_008312.4.
UniGeneiMm.439670.

Genome annotation databases

EnsembliENSMUST00000036303; ENSMUSP00000043936; ENSMUSG00000041380.
ENSMUST00000096299; ENSMUSP00000094021; ENSMUSG00000041380.
GeneIDi15560.
KEGGimmu:15560.
UCSCiuc009und.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X72230 mRNA. Translation: CAA51031.1 .
S44559
, S44556 , S44557 , S44558 Genomic DNA. Translation: AAA10521.1 .
AL808014 , AL662932 Genomic DNA. Translation: CAM15060.1 .
AL662932 , AL808014 Genomic DNA. Translation: CAM15766.1 .
CCDSi CCDS30459.1.
PIRi A43951.
RefSeqi NP_032338.3. NM_008312.4.
UniGenei Mm.439670.

3D structure databases

ProteinModelPortali P34968.
SMRi P34968. Positions 55-389.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P34968.
ChEMBLi CHEMBL3006.
GuidetoPHARMACOLOGYi 8.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P34968.

Proteomic databases

PRIDEi P34968.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000036303 ; ENSMUSP00000043936 ; ENSMUSG00000041380 .
ENSMUST00000096299 ; ENSMUSP00000094021 ; ENSMUSG00000041380 .
GeneIDi 15560.
KEGGi mmu:15560.
UCSCi uc009und.2. mouse.

Organism-specific databases

CTDi 3358.
MGIi MGI:96281. Htr2c.

Phylogenomic databases

eggNOGi NOG247243.
GeneTreei ENSGT00760000119257.
HOGENOMi HOG000240378.
HOVERGENi HBG107487.
InParanoidi P34968.
KOi K04157.
OMAi SSYIRCQ.
OrthoDBi EOG70ZZN5.
TreeFami TF316350.

Enzyme and pathway databases

Reactomei REACT_207651. G alpha (q) signalling events.

Miscellaneous databases

ChiTaRSi HTR2C. mouse.
NextBioi 288508.
PROi P34968.
SOURCEi Search...

Gene expression databases

Bgeei P34968.
CleanExi MM_HTR2C.
ExpressionAtlasi P34968. baseline.
Genevestigatori P34968.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR000377. 5HT2C_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24247:SF32. PTHR24247:SF32. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00517. 5HT2CRECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  11. 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.

Entry informationi

Entry namei5HT2C_MOUSE
AccessioniPrimary (citable) accession number: P34968
Secondary accession number(s): B1ATN5, Q5WRU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3