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P34968

- 5HT2C_MOUSE

UniProt

P34968 - 5HT2C_MOUSE

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Protein
5-hydroxytryptamine receptor 2C
Gene
Htr2c, 5ht1c, Htr1c
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. Gq/11-coupled serotonin receptor activity Source: UniProtKB
  3. drug binding Source: Ensembl
  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 ERK1 and ERK2 cascade Source: Ensembl
  7. positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
  8. positive regulation of phosphatidylinositol biosynthetic process Source: Ensembl
  9. regulation of appetite Source: UniProtKB
  10. regulation of corticotropin-releasing hormone secretion Source: UniProtKB
  11. regulation of neurological system process Source: UniProtKB
  12. release of sequestered calcium ion into cytosol Source: Ensembl
  13. 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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 5321Extracellular By similarity
Add
BLAST
Transmembranei54 – 7926Helical; Name=1; By similarity
Add
BLAST
Topological domaini80 – 9011Cytoplasmic By similarity
Add
BLAST
Transmembranei91 – 11121Helical; Name=2; By similarity
Add
BLAST
Topological domaini112 – 12817Extracellular By similarity
Add
BLAST
Transmembranei129 – 15123Helical; Name=3; By similarity
Add
BLAST
Topological domaini152 – 17120Cytoplasmic By similarity
Add
BLAST
Transmembranei172 – 19423Helical; Name=4; By similarity
Add
BLAST
Topological domaini195 – 21420Extracellular By similarity
Add
BLAST
Transmembranei215 – 23622Helical; Name=5; By similarity
Add
BLAST
Topological domaini237 – 31276Cytoplasmic By similarity
Add
BLAST
Transmembranei313 – 33422Helical; Name=6; By similarity
Add
BLAST
Topological domaini335 – 34915Extracellular By similarity
Add
BLAST
Transmembranei350 – 37223Helical; Name=7; By similarity
Add
BLAST
Topological domaini373 – 45987Cytoplasmic By similarity
Add
BLAST

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 – 3232 By similarity
Add
BLAST
Chaini33 – 4594275-hydroxytryptamine receptor 2C
PRO_0000068959Add
BLAST

Amino acid modifications

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

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.
GenevestigatoriP34968.

Interactioni

Subunit structurei

Interacts with MPDZ. Interacts with ARRB2 By similarity.

Structurei

3D structure databases

ProteinModelPortaliP34968.
SMRiP34968. Positions 55-389.

Family & Domainsi

Region

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

Motif

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

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG247243.
GeneTreeiENSGT00750000117240.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiB1ATN5.
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.

P34968-1 [UniParc]FASTAAdd to Basket

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MVNLGTAVRS LLVHLIGLLV WQFDISISPV AAIVTDTFNS SDGGRLFQFP    50
DGVQNWPALS IVVIIIMTIG GNILVIMAVS MEKKLHNATN YFLMSLAIAD 100
MLVGLLVMPL SLLAILYDYV WPLPRYLCPV WISLDVLFST ASIMHLCAIS 150
LDRYVAIRNP IEHSRFNSRT KAIMKIAIVW AISIGVSVPI PVIGLRDESK 200
VFVNNTTCVL NDPNFVLIGS FVAFFIPLTI MVITYFLTIY VLRRQTLMLL 250
RGHTEEELRN ISLNFLKCCC KKGDEEENAP NPNPDQKPRR KKKEKRPRGT 300
MQAINNEKKA SKVLGIVFFV FLIMWCPFFI TNILSVLCGK ACNQKLMEKL 350
LNVFVWIGYV CSGINPLVYT LFNKIYRRAF SKYLRCDYKP DKKPPVRQIP 400
RVAATALSGR ELNVNIYRHT NERVVRKAND TEPGIEMQVE NLELPVNPSN 450
VVSERISSV 459
Length:459
Mass (Da):51,929
Last modified:July 27, 2011 - v2
Checksum:iAA3C537B2ADCB0C9
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti157 – 1615IRNPI → VRSPV in CAA51031. 1 Publication
Sequence conflicti157 – 1615IRNPI → VRSPV in AAA10521. 1 Publication

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 CHEMBL2109245.
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 ENSGT00750000117240.
HOGENOMi HOG000240378.
HOVERGENi HBG107487.
InParanoidi B1ATN5.
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.
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: September 3, 2014
This is version 116 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

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