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Protein

5-hydroxytryptamine receptor 2C

Gene

Htr2c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBehavior

Enzyme and pathway databases

ReactomeiR-MMU-390666 Serotonin receptors
R-MMU-416476 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:96281 Htr2c

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 53ExtracellularBy similarityAdd BLAST21
Transmembranei54 – 79Helical; Name=1By similarityAdd BLAST26
Topological domaini80 – 90CytoplasmicBy similarityAdd BLAST11
Transmembranei91 – 111Helical; Name=2By similarityAdd BLAST21
Topological domaini112 – 128ExtracellularBy similarityAdd BLAST17
Transmembranei129 – 151Helical; Name=3By similarityAdd BLAST23
Topological domaini152 – 171CytoplasmicBy similarityAdd BLAST20
Transmembranei172 – 194Helical; Name=4By similarityAdd BLAST23
Topological domaini195 – 214ExtracellularBy similarityAdd BLAST20
Transmembranei215 – 236Helical; Name=5By similarityAdd BLAST22
Topological domaini237 – 312CytoplasmicBy similarityAdd BLAST76
Transmembranei313 – 334Helical; Name=6By similarityAdd BLAST22
Topological domaini335 – 349ExtracellularBy similarityAdd BLAST15
Transmembranei350 – 372Helical; Name=7By similarityAdd BLAST23
Topological domaini373 – 459CytoplasmicBy similarityAdd BLAST87

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

Chemistry databases

ChEMBLiCHEMBL3006

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32By similarityAdd BLAST32
ChainiPRO_000006895933 – 4595-hydroxytryptamine receptor 2CAdd BLAST427

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi128 ↔ 208PROSITE-ProRule annotation
Glycosylationi204N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi205N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi338 ↔ 342PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP34968
PRIDEiP34968

PTM databases

iPTMnetiP34968
PhosphoSitePlusiP34968

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

BgeeiENSMUSG00000041380
CleanExiMM_HTR2C
ExpressionAtlasiP34968 baseline and differential
GenevisibleiP34968 MM

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043936

Chemistry databases

BindingDBiP34968

Structurei

3D structure databases

ProteinModelPortaliP34968
SMRiP34968
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 140Agonist bindingBy similarity6
Regioni325 – 329Agonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi152 – 154DRY motif; important for ligand-induced conformation changesBy similarity3
Motifi365 – 369NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity5
Motifi457 – 459PDZ-binding3

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

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00890000139331
HOGENOMiHOG000240378
HOVERGENiHBG107487
InParanoidiP34968
KOiK04157
OMAiLCGKACN
OrthoDBiEOG091G06VI
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR000377 5HT2C_rcpt
IPR002231 5HT_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24247:SF32 PTHR24247:SF32, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00517 5HT2CRECEPTR
PR01101 5HTRECEPTOR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

P34968-1 [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)DescriptionActionsGraphical viewLength
Sequence conflicti157 – 161IRNPI → VRSPV in CAA51031 (PubMed:1661811).Curated5
Sequence conflicti157 – 161IRNPI → VRSPV in AAA10521 (PubMed:1381232).Curated5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Entry informationi

Entry namei5HT2C_MOUSE
AccessioniPrimary (citable) accession number: P34968
Secondary accession number(s): B1ATN5, Q5WRU6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 143 of the entry and version 2 of the sequence. See 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

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