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Protein

5-hydroxytryptamine receptor 2C

Gene

Htr2c

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

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: GO_Central
  • behavioral fear response Source: UniProtKB
  • cellular calcium ion homeostasis Source: MGI
  • cGMP biosynthetic process Source: MGI
  • chemical synaptic transmission Source: GO_Central
  • feeding behavior Source: UniProtKB
  • inositol phosphate-mediated signaling Source: MGI
  • locomotory behavior Source: InterPro
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: MGI
  • phospholipase C-activating serotonin receptor signaling pathway Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of fat cell differentiation Source: MGI
  • positive regulation of phosphatidylinositol biosynthetic process Source: MGI
  • regulation of appetite Source: UniProtKB
  • regulation of corticotropin-releasing hormone secretion Source: UniProtKB
  • regulation of neurological system process Source: UniProtKB
  • release of sequestered calcium ion into cytosol Source: MGI
  • response to drug Source: MGI
  • serotonin receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:96281. Htr2c.

Subcellular locationi

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

GO - Cellular componenti

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

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...)By similarity1
Disulfide bondi128 ↔ 208PROSITE-ProRule annotation
Glycosylationi204N-linked (GlcNAc...)Sequence analysis1
Glycosylationi205N-linked (GlcNAc...)Sequence 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.

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.
GeneTreeiENSGT00780000121897.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP34968.
KOiK04157.
OMAiLCGKACN.
OrthoDBiEOG091G06VI.
TreeFamiTF316350.

Family and domain databases

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
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

« 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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP34968.
SMRiP34968.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043936.

Chemistry databases

ChEMBLiCHEMBL3006.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP34968.
PhosphoSitePlusiP34968.

Proteomic databases

PaxDbiP34968.
PRIDEiP34968.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3358.
MGIiMGI:96281. Htr2c.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00780000121897.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP34968.
KOiK04157.
OMAiLCGKACN.
OrthoDBiEOG091G06VI.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiR-MMU-390666. Serotonin receptors.
R-MMU-416476. G alpha (q) signalling events.

Miscellaneous databases

ChiTaRSiHtr2c. mouse.
PROiP34968.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000041380.
CleanExiMM_HTR2C.
ExpressionAtlasiP34968. baseline and differential.
GenevisibleiP34968. MM.

Family and domain databases

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 136 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.