Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

5-hydroxytryptamine receptor 2C

Gene

HTR2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-416476 G alpha (q) signalling events
SignaLinkiP28335
SIGNORiP28335

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:HTR1C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000147246.9
HGNCiHGNC:5295 HTR2C
MIMi312861 gene
neXtProtiNX_P28335

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 – 52ExtracellularBy similarityAdd BLAST20
Transmembranei53 – 78Helical; Name=1By similarityAdd BLAST26
Topological domaini79 – 89CytoplasmicBy similarityAdd BLAST11
Transmembranei90 – 110Helical; Name=2By similarityAdd BLAST21
Topological domaini111 – 127ExtracellularBy similarityAdd BLAST17
Transmembranei128 – 150Helical; Name=3By similarityAdd BLAST23
Topological domaini151 – 170CytoplasmicBy similarityAdd BLAST20
Transmembranei171 – 193Helical; Name=4By similarityAdd BLAST23
Topological domaini194 – 213ExtracellularBy similarityAdd BLAST20
Transmembranei214 – 235Helical; Name=5By similarityAdd BLAST22
Topological domaini236 – 311CytoplasmicBy similarityAdd BLAST76
Transmembranei312 – 333Helical; Name=6By similarityAdd BLAST22
Topological domaini334 – 348ExtracellularBy similarityAdd BLAST15
Transmembranei349 – 371Helical; Name=7By similarityAdd BLAST23
Topological domaini372 – 458CytoplasmicBy similarityAdd BLAST87

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi159P → A: Decreases interaction with ARRB2. 1 Publication1
Mutagenesisi456S → A: Loss of interaction with MPDZ. 1 Publication1
Mutagenesisi456S → T: No effect on interaction with MPDZ. 1 Publication1
Mutagenesisi457S → A: No effect on interaction with MPDZ. 1 Publication1
Mutagenesisi458V → A: Loss of interaction with MPDZ. 1 Publication1

Organism-specific databases

DisGeNETi3358
PharmGKBiPA194

Chemistry databases

ChEMBLiCHEMBL225
DrugBankiDB06594 Agomelatine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00714 Apomorphine
DB01238 Aripiprazole
DB06216 Asenapine
DB01200 Bromocriptine
DB00248 Cabergoline
DB09014 Captodiame
DB00477 Chlorpromazine
DB01239 Chlorprothixene
DB01242 Clomipramine
DB00363 Clozapine
DB00434 Cyproheptadine
DB04884 Dapoxetine
DB06512 Deramciclane
DB01151 Desipramine
DB01191 Dexfenfluramine
DB01142 Doxepin
DB05492 Epicept NP-1
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00574 Fenfluramine
DB00458 Imipramine
DB01221 Ketamine
DB00589 Lisuride
DB04871 Lorcaserin
DB00408 Loxapine
DB00934 Maprotiline
DB01403 Methotrimeprazine
DB00247 Methysergide
DB06148 Mianserin
DB00805 Minaprine
DB00370 Mirtazapine
DB01149 Nefazodone
DB00540 Nortriptyline
DB00334 Olanzapine
DB01267 Paliperidone
DB01186 Pergolide
DB00413 Pramipexole
DB00420 Promazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB06144 Sertindole
DB01079 Tegaserod
DB13025 Tiapride
DB00193 Tramadol
DB00656 Trazodone
DB00726 Trimipramine
DB01392 Yohimbine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi8

Polymorphism and mutation databases

BioMutaiHTR2C
DMDMi112816

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 321 PublicationAdd BLAST32
ChainiPRO_000006895833 – 4585-hydroxytryptamine receptor 2CAdd BLAST426

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi39N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi127 ↔ 207PROSITE-ProRule annotation
Disulfide bondi337 ↔ 341PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP28335
PeptideAtlasiP28335
PRIDEiP28335
ProteomicsDBi54476

PTM databases

iPTMnetiP28335
PhosphoSitePlusiP28335

Expressioni

Tissue specificityi

Detected in brain.1 Publication

Gene expression databases

BgeeiENSG00000147246 Expressed in 68 organ(s), highest expression level in choroid plexus epithelium
CleanExiHS_HTR2C
GenevisibleiP28335 HS

Interactioni

Subunit structurei

Interacts with MPDZ. Interacts with ARRB2.2 Publications

Protein-protein interaction databases

BioGridi109590, 100 interactors
IntActiP28335, 7 interactors
MINTiP28335
STRINGi9606.ENSP00000276198

Chemistry databases

BindingDBiP28335

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP28335
SMRiP28335
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni134 – 139Agonist bindingBy similarity6
Regioni324 – 328Agonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi151 – 153DRY motif; important for ligand-induced conformation changesBy similarity3
Motifi364 – 368NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity5
Motifi456 – 458PDZ-binding3

Domaini

The PDZ domain-binding motif is involved in the interaction with MPDZ.1 Publication

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
HOGENOMiHOG000240378
HOVERGENiHBG107487
InParanoidiP28335
KOiK04157
OrthoDBiEOG091G06VI
PhylomeDBiP28335
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P28335-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVNLRNAVHS FLVHLIGLLV WQCDISVSPV AAIVTDIFNT SDGGRFKFPD
60 70 80 90 100
GVQNWPALSI VIIIIMTIGG NILVIMAVSM EKKLHNATNY FLMSLAIADM
110 120 130 140 150
LVGLLVMPLS LLAILYDYVW PLPRYLCPVW ISLDVLFSTA SIMHLCAISL
160 170 180 190 200
DRYVAIRNPI EHSRFNSRTK AIMKIAIVWA ISIGVSVPIP VIGLRDEEKV
210 220 230 240 250
FVNNTTCVLN DPNFVLIGSF VAFFIPLTIM VITYCLTIYV LRRQALMLLH
260 270 280 290 300
GHTEEPPGLS LDFLKCCKRN TAEEENSANP NQDQNARRRK KKERRPRGTM
310 320 330 340 350
QAINNERKAS KVLGIVFFVF LIMWCPFFIT NILSVLCEKS CNQKLMEKLL
360 370 380 390 400
NVFVWIGYVC SGINPLVYTL FNKIYRRAFS NYLRCNYKVE KKPPVRQIPR
410 420 430 440 450
VAATALSGRE LNVNIYRHTN EPVIEKASDN EPGIEMQVEN LELPVNPSSV

VSERISSV
Length:458
Mass (Da):51,821
Last modified:December 1, 1992 - v1
Checksum:i9E76B3FFD3E09C93
GO
Isoform 2 (identifier: P28335-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-458: YVAIRNPIEH...SVVSERISSV → CISSYPCDWT...YGRGRELCKP

Show »
Length:248
Mass (Da):28,055
Checksum:i8A8C81B80DA6B59E
GO

RNA editingi

Edited at positions 156, 158 and 160.1 Publication
Partially edited. RNA editing generates receptor isoforms that differ in their ability to interact with the phospholipase C signaling cascade in a transfected cell line, suggesting that this RNA processing event may contribute to the modulation of serotonergic neurotransmission in the central nervous system.

Polymorphismi

Position 23 is polymorphic; the frequencies in unrelated Caucasians are 0.87 for Cys and 0.13 for Ser.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00345023C → S5 PublicationsCorresponds to variant dbSNP:rs6318EnsemblClinVar.1
Natural variantiVAR_010166156I → V in RNA edited version. 1
Natural variantiVAR_010167158N → S in RNA edited version. 1
Natural variantiVAR_010168160I → V in RNA edited version. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045171153 – 458YVAIR…RISSV → CISSYPCDWTEGRRKGVREQ HDVRAQRPKFRSYWVLRSFL HTADDYGDYVLPDHLRSAPT SFDVTARPHRGTAWTKSGFP EVLQEEYGRGRELCKP in isoform 2. 1 PublicationAdd BLAST306

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81778 mRNA Translation: AAA60317.1
X80763 Genomic DNA Translation: CAB59978.1
U49516 mRNA Translation: AAB40898.1
AF208053 mRNA Translation: AAF35842.1
AF498983 mRNA Translation: AAM21130.1
AK295753 mRNA Translation: BAG58583.1
AC007022 Genomic DNA No translation available.
AC007025 Genomic DNA No translation available.
AL591402 Genomic DNA No translation available.
AL355812, AC004822, AL590097 Genomic DNA Translation: CAI41334.1
AC004822 Genomic DNA Translation: AAC71658.1
AL355812, AL590097, AC004822 Genomic DNA Translation: CAI41335.1
AL590097, AC004822, AL355812 Genomic DNA Translation: CAH70193.1
BC095543 mRNA Translation: AAH95543.1
CCDSiCCDS14564.1 [P28335-1]
CCDS59174.1 [P28335-2]
PIRiJS0616
RefSeqiNP_000859.1, NM_000868.3 [P28335-1]
NP_001243689.1, NM_001256760.2 [P28335-1]
NP_001243690.1, NM_001256761.2 [P28335-2]
UniGeneiHs.149037

Genome annotation databases

EnsembliENST00000276198; ENSP00000276198; ENSG00000147246
ENST00000371950; ENSP00000361018; ENSG00000147246
ENST00000371951; ENSP00000361019; ENSG00000147246
GeneIDi3358
KEGGihsa:3358
UCSCiuc004epu.1 human [P28335-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism, RNA editing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81778 mRNA Translation: AAA60317.1
X80763 Genomic DNA Translation: CAB59978.1
U49516 mRNA Translation: AAB40898.1
AF208053 mRNA Translation: AAF35842.1
AF498983 mRNA Translation: AAM21130.1
AK295753 mRNA Translation: BAG58583.1
AC007022 Genomic DNA No translation available.
AC007025 Genomic DNA No translation available.
AL591402 Genomic DNA No translation available.
AL355812, AC004822, AL590097 Genomic DNA Translation: CAI41334.1
AC004822 Genomic DNA Translation: AAC71658.1
AL355812, AL590097, AC004822 Genomic DNA Translation: CAI41335.1
AL590097, AC004822, AL355812 Genomic DNA Translation: CAH70193.1
BC095543 mRNA Translation: AAH95543.1
CCDSiCCDS14564.1 [P28335-1]
CCDS59174.1 [P28335-2]
PIRiJS0616
RefSeqiNP_000859.1, NM_000868.3 [P28335-1]
NP_001243689.1, NM_001256760.2 [P28335-1]
NP_001243690.1, NM_001256761.2 [P28335-2]
UniGeneiHs.149037

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6BQGX-ray3.00A40-245[»]
A301-393[»]
6BQHX-ray2.70A40-245[»]
A301-393[»]
ProteinModelPortaliP28335
SMRiP28335
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109590, 100 interactors
IntActiP28335, 7 interactors
MINTiP28335
STRINGi9606.ENSP00000276198

Chemistry databases

BindingDBiP28335
ChEMBLiCHEMBL225
DrugBankiDB06594 Agomelatine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00714 Apomorphine
DB01238 Aripiprazole
DB06216 Asenapine
DB01200 Bromocriptine
DB00248 Cabergoline
DB09014 Captodiame
DB00477 Chlorpromazine
DB01239 Chlorprothixene
DB01242 Clomipramine
DB00363 Clozapine
DB00434 Cyproheptadine
DB04884 Dapoxetine
DB06512 Deramciclane
DB01151 Desipramine
DB01191 Dexfenfluramine
DB01142 Doxepin
DB05492 Epicept NP-1
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB06678 Esmirtazapine
DB00574 Fenfluramine
DB00458 Imipramine
DB01221 Ketamine
DB00589 Lisuride
DB04871 Lorcaserin
DB00408 Loxapine
DB00934 Maprotiline
DB01403 Methotrimeprazine
DB00247 Methysergide
DB06148 Mianserin
DB00805 Minaprine
DB00370 Mirtazapine
DB01149 Nefazodone
DB00540 Nortriptyline
DB00334 Olanzapine
DB01267 Paliperidone
DB01186 Pergolide
DB00413 Pramipexole
DB00420 Promazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00734 Risperidone
DB00268 Ropinirole
DB06144 Sertindole
DB01079 Tegaserod
DB13025 Tiapride
DB00193 Tramadol
DB00656 Trazodone
DB00726 Trimipramine
DB01392 Yohimbine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi8

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP28335
PhosphoSitePlusiP28335

Polymorphism and mutation databases

BioMutaiHTR2C
DMDMi112816

Proteomic databases

PaxDbiP28335
PeptideAtlasiP28335
PRIDEiP28335
ProteomicsDBi54476

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276198; ENSP00000276198; ENSG00000147246
ENST00000371950; ENSP00000361018; ENSG00000147246
ENST00000371951; ENSP00000361019; ENSG00000147246
GeneIDi3358
KEGGihsa:3358
UCSCiuc004epu.1 human [P28335-1]

Organism-specific databases

CTDi3358
DisGeNETi3358
EuPathDBiHostDB:ENSG00000147246.9
GeneCardsiHTR2C
HGNCiHGNC:5295 HTR2C
MIMi312861 gene
neXtProtiNX_P28335
PharmGKBiPA194
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
HOGENOMiHOG000240378
HOVERGENiHBG107487
InParanoidiP28335
KOiK04157
OrthoDBiEOG091G06VI
PhylomeDBiP28335
TreeFamiTF316350

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-416476 G alpha (q) signalling events
SignaLinkiP28335
SIGNORiP28335

Miscellaneous databases

ChiTaRSiHTR2C human
GeneWikii5-HT2C_receptor
GenomeRNAii3358
PROiPR:P28335
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147246 Expressed in 68 organ(s), highest expression level in choroid plexus epithelium
CleanExiHS_HTR2C
GenevisibleiP28335 HS

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
ProtoNetiSearch...

Entry informationi

Entry namei5HT2C_HUMAN
AccessioniPrimary (citable) accession number: P28335
Secondary accession number(s): B1AMW4, Q5VUF8, Q9NP28
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: November 7, 2018
This is version 194 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again