ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures

Home

Download

Statistics

Examples

Help

Contact

	Protein Summary
	AS Summary
	Protein Functional Features
	Gene Isoform Structures and Expression Levels
	Protein Structures
	pLDDT Score Distribution
	Ramachandran Plot of Protein Structures
	Potential Active Site Information
	Protein Structure and Feature Comparision
	Protein-Protein Interaction
	Related Drugs
	Related Diseases
	Clinically Important Variants

Protein:HTR2C

Protein Summary

Gene summary

Gene name: HTR2C
ASpdb.0 ID: 3358
	Gene
Gene symbol	HTR2C
Gene ID	3358
Gene name	5-hydroxytryptamine receptor 2C
Synonyms	5-HT1C\|5-HT2C\|5-HTR2C\|5HTR2C\|HTR1C
Cytomap	Xq23
Type of gene	protein-coding
Description	5-hydroxytryptamine receptor 2C5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled5-hydroxytryptamine receptor 1Cserotonin 5-HT-1C receptorserotonin 5-HT-2C receptor
Modification date	20240411
UniProtAcc	P28335

Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Gene	HTR2C	GO:0001587	Gq/11-coupled serotonin receptor activity	18703043
Gene	HTR2C	GO:0004993	G protein-coupled serotonin receptor activity	7582481\|12970106
Gene	HTR2C	GO:0005886	plasma membrane	12970106\|18703043
Gene	HTR2C	GO:0006874	intracellular calcium ion homeostasis	19057895
Gene	HTR2C	GO:0007208	phospholipase C-activating serotonin receptor signaling pathway	12970106
Gene	HTR2C	GO:0010513	positive regulation of phosphatidylinositol biosynthetic process	19057895
Gene	HTR2C	GO:0019934	cGMP-mediated signaling	12970106
Gene	HTR2C	GO:0051378	serotonin binding	7582481\|12970106\|15831837\|18703043\|19057895
Gene	HTR2C	GO:0070374	positive regulation of ERK1 and ERK2 cascade	19057895
Gene	HTR2C	GO:0071886	1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding	19057895
Gene	HTR2C	GO:0098664	G protein-coupled serotonin receptor signaling pathway	18703043
Gene	HTR2C	GO:0098666	G protein-coupled serotonin receptor complex	12970106\|18703043

AS Summary

Information of the canonical protein with experimentally identified structure from PDB (2023).

UniProt Acc	File name	PDB ID	Method	Resolution	Chain	Start	End
P28335-1	P28335-1_6bqh_A.pdb	6BQH	X-ray	2.7	A	301	387

ASpdb's canonical and alternatively spliced isoform information.

accession_id

gene_name

canonical_id

alternative_id

canonical_length

alternative_length

canonical_start

canonical_end

type

originalSEQ

variationSEQ

alternative_start

alternative_end

P28335

HTR2C

P28335-1

P28335-2

458

248

153

458

Substitution

YVAIRNPIEHSRFNSRTKAIMKIAIVWAISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDFLKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVCSGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVENLELPVNPSSVVSERISSV

CISSYPCDWTEGRRKGVREQHDVRAQRPKFRSYWVLRSFLHTADDYGDYVLPDHLRSAPTSFDVTARPHRGTAWTKSGFPEVLQEEYGRGRELCKP

153

248

Multiple sequence alignment of our canonical and alternatively spliced HTR2C

Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HTR2C

UniProt-id	ENSG	ENST	ENSP
P28335-1	ENSG00000147246.10	ENST00000276198.6	ENSP00000276198.1
P28335-1	ENSG00000147246.10	ENST00000371951.5	ENSP00000361019.1
P28335-2	ENSG00000147246.10	ENST00000371950.3	ENSP00000361018.3

UniProt-id	NM ID	NP ID
P28335-1	NM_000868.3	NP_000859.1
P28335-1	NM_001256760.2	NP_001243689.1
P28335-2	NM_001256761.2	NP_001243690.1

Amino acid sequences of our canonical and alternatively spliced HTR2C

accession_id	Protein sequence
P28335-1	MVNLRNAVHSFLVHLIGLLVWQCDISVSPVAAIVTDIFNTSDGGRFKFPDGVQNWPALSIVIIIIMTIGGNILVIMAVSMEKKLHNATNY FLMSLAIADMLVGLLVMPLSLLAILYDYVWPLPRYLCPVWISLDVLFSTASIMHLCAISLDRYVAIRNPIEHSRFNSRTKAIMKIAIVWA ISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDFLKCCKRN TAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVC SGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVENLELPVNPSSV
P28335-2	MVNLRNAVHSFLVHLIGLLVWQCDISVSPVAAIVTDIFNTSDGGRFKFPDGVQNWPALSIVIIIIMTIGGNILVIMAVSMEKKLHNATNY FLMSLAIADMLVGLLVMPLSLLAILYDYVWPLPRYLCPVWISLDVLFSTASIMHLCAISLDRCISSYPCDWTEGRRKGVREQHDVRAQRP

Protein Functional Features

Main function of this protein. (from UniProt)

HTR2C (go to UniProt):P28335

Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained protein feature among the 13 regional features.

Accession_id	Subsection	Start	End	Funcitonal feature	Splicing information
P28335	Topological domain	151	170	Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Transmembrane	171	193	Note=Helical%3B Name%3D4;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Topological domain	194	213	Note=Extracellular;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Transmembrane	214	235	Note=Helical%3B Name%3D5;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Topological domain	236	311	Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Transmembrane	312	333	Note=Helical%3B Name%3D6;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Topological domain	334	348	Note=Extracellular;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Transmembrane	349	371	Note=Helical%3B Name%3D7;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Topological domain	372	458	Note=Cytoplasmic;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Region	274	301	Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256\|SAM:MobiDB-lite	Type=Substitution;Start=153;End=458
P28335	Motif	151	153	Note=DRY motif%3B important for ligand-induced conformation changes;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Motif	364	368	Note=NPxxY motif%3B important for ligand-induced conformation changes and signaling;Ontology_term=ECO:0000250;evidence=ECO:0000250	Type=Substitution;Start=153;End=458
P28335	Motif	456	458	Note=PDZ-binding	Type=Substitution;Start=153;End=458

Gene Isoform Structures and Expression Levels for HTR2C

Gene structures of our canonical and alternative spliced genes of HTR2C
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Expression levels of gene isoforms across GTEx.

Expression levels of gene isoforms across TCGA.

Protein Structures

PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

3D view using mol* of P28335-1

3D view using mol* of P28335-2

pLDDT Score Distribution

pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.

pLDDT distribution across the protein length of P28335-1

pLDDT distribution across the protein length of P28335-2

Ramachandran Plot of Protein Structures

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.

Ramachandran plot of P28335-1

Potential Active Site Information

The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.

UniProt-id	Site score	Size	D score	Volume	Exposure	Enclosure	Contact	Phobic	Philic	Balance	Don/Acc	Residues
P28335-1	1.231	155	1.35	420.175	0.438	0.811	1.038	3.086	0.234	13.176	35.75	8,11,12,15,16,19,20,23,25,27,30,31,34,68,72,75,76, 93,100,101,104,105,129,132,133,136,137,179,183,186 ,187,190,191,194
P28335-2	1.115	141	1.162	472.654	0.484	0.798	0.996	1.235	0.788	1.567	4.528	16,19,20,22,23,26,27,30,31,34,67,70,71,74,91,92,95 ,96,99,102,106,107,130,131,134,135,138,139

Protein Structure and Feature Comparision

Protein Structure Comparision Using Template Modeling Scores (TM-score).

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)

3D view using mol* of P28335-1_P28335-1_6bqh_A.pdb

Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P28335-1_6bqh_A_P28335-2.pdb

Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)

3D view using mol* of P28335-1_P28335-2.pdb

Protein Feature Comparison of the protein sequendary structures among the protiens.

./stats/secondary_structure/figure/P28335-1_vs_P28335-2.png

Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.

./stats/relative_asa/P28335-1_vs_P28335-2.png

Protein-Protein Interaction

Interactors from UniProt.

Accession_id

Subsection

Start

End

Funcitonal feature

Splicing information

Interactors from STRING.

Gene name

Interactors

Related Drugs to HTR2C

Drugs targeting this gene/protein.
(DrugBank)

UniProt accession	Gene name	DrugBank ID	Drug name	Drug group	Actions
P28335	HTR2C	DB00320	Dihydroergotamine	approved, investigational	agonist
P28335	HTR2C	DB00714	Apomorphine	approved, investigational	agonist
P28335	HTR2C	DB00472	Fluoxetine	approved, vet_approved	antagonist
P28335	HTR2C	DB00696	Ergotamine	approved	agonist
P28335	HTR2C	DB00540	Nortriptyline	approved	antagonist, downregulator
P28335	HTR2C	DB01238	Aripiprazole	approved, investigational	antagonist, partial agonist
P28335	HTR2C	DB00875	Flupentixol	approved, investigational, withdrawn	antagonist
P28335	HTR2C	DB05316	Pimavanserin	approved, investigational	inverse agonist
P28335	HTR2C	DB00543	Amoxapine	approved	antagonist
P28335	HTR2C	DB00363	Clozapine	approved	antagonist
P28335	HTR2C	DB06446	Dotarizine	investigational
P28335	HTR2C	DB05492	Epicept NP-1	investigational
P28335	HTR2C	DB01175	Escitalopram	approved	inhibitor
P28335	HTR2C	DB01454	Midomafetamine	experimental, illicit, investigational	agonist
P28335	HTR2C	DB01200	Bromocriptine	approved, investigational, withdrawn	agonist
P28335	HTR2C	DB00246	Ziprasidone	approved	antagonist
P28335	HTR2C	DB00458	Imipramine	approved	antagonist, binder
P28335	HTR2C	DB12110	m-Chlorophenylpiperazine	investigational	agonist
P28335	HTR2C	DB00777	Propiomazine	approved	antagonist
P28335	HTR2C	DB00589	Lisuride	approved, investigational	agonist
P28335	HTR2C	DB00334	Olanzapine	approved, investigational	antagonist
P28335	HTR2C	DB00193	Tramadol	approved, investigational	antagonist
P28335	HTR2C	DB09014	Captodiame	experimental	antagonist
P28335	HTR2C	DB00734	Risperidone	approved, investigational	antagonist
P28335	HTR2C	DB01224	Quetiapine	approved	ligand
P28335	HTR2C	DB04884	Dapoxetine	investigational
P28335	HTR2C	DB00726	Trimipramine	approved	antagonist
P28335	HTR2C	DB01403	Methotrimeprazine	approved, investigational	antagonist
P28335	HTR2C	DB12163	Sarpogrelate	investigational
P28335	HTR2C	DB01191	Dexfenfluramine	approved, illicit, investigational, withdrawn	agonist
P28335	HTR2C	DB00805	Minaprine	approved	antagonist
P28335	HTR2C	DB01186	Pergolide	approved, investigational, vet_approved, withdrawn	agonist
P28335	HTR2C	DB00248	Cabergoline	approved	agonist
P28335	HTR2C	DB01392	Yohimbine	approved, investigational, vet_approved	antagonist
P28335	HTR2C	DB06229	Ocaperidone	investigational
P28335	HTR2C	DB00247	Methysergide	approved	antagonist
P28335	HTR2C	DB00477	Chlorpromazine	approved, investigational, vet_approved	binder
P28335	HTR2C	DB06016	Cariprazine	approved, investigational	antagonist
P28335	HTR2C	DB06216	Asenapine	approved	antagonist
P28335	HTR2C	DB09185	Viloxazine	approved, investigational, withdrawn	agonist
P28335	HTR2C	DB06148	Mianserin	approved, investigational	antagonist
P28335	HTR2C	DB09194	Etoperidone	withdrawn	agonist
P28335	HTR2C	DB13940	2,5-Dimethoxy-4-ethylthioamphetamine	experimental	agonist
P28335	HTR2C	DB01537	4-Bromo-2,5-dimethoxyphenethylamine	experimental, illicit	partial agonist
P28335	HTR2C	DB09195	Lorpiprazole	approved	antagonist
P28335	HTR2C	DB00934	Maprotiline	approved, investigational	binder
P28335	HTR2C	DB00370	Mirtazapine	approved	antagonist
P28335	HTR2C	DB01149	Nefazodone	approved, withdrawn	antagonist
P28335	HTR2C	DB04948	Lofexidine	approved, investigational	agonist
P28335	HTR2C	DB00574	Fenfluramine	approved, illicit, investigational, withdrawn	agonist
P28335	HTR2C	DB12177	Eplivanserin	investigational
P28335	HTR2C	DB00408	Loxapine	approved	antagonist
P28335	HTR2C	DB01079	Tegaserod	approved, investigational, withdrawn	antagonist
P28335	HTR2C	DB00623	Fluphenazine	approved
P28335	HTR2C	DB06153	Pizotifen	approved	antagonist
P28335	HTR2C	DB06594	Agomelatine	approved, investigational	antagonist
P28335	HTR2C	DB01151	Desipramine	approved, investigational	binder
P28335	HTR2C	DB14185	Aripiprazole lauroxil	approved, investigational
P28335	HTR2C	DB01267	Paliperidone	approved	antagonist
P28335	HTR2C	DB00321	Amitriptyline	approved	antagonist
P28335	HTR2C	DB01242	Clomipramine	approved, investigational, vet_approved	antagonist
P28335	HTR2C	DB00502	Haloperidol	approved
P28335	HTR2C	DB00420	Promazine	approved, vet_approved	antagonist
P28335	HTR2C	DB06144	Sertindole	approved, investigational, withdrawn	antagonist
P28335	HTR2C	DB04871	Lorcaserin	approved, withdrawn
P28335	HTR2C	DB06512	Deramciclane	investigational	inverse agonist
P28335	HTR2C	DB01142	Doxepin	approved, investigational	antagonist
P28335	HTR2C	DB00924	Cyclobenzaprine	approved	antagonist
P28335	HTR2C	DB00656	Trazodone	approved, investigational	agonist
P28335	HTR2C	DB00434	Cyproheptadine	approved	antagonist

Related Diseases to HTR2C

Previous studies relating to the alternative splicing of HTR2C and disease information from the MeSH term (PubMed)

Gene	PMID	Title	Abstract	MeSH ID	MeSH term
HTR2C	16357227	The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C.	The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15. This region contains a small nucleolar RNA (snoRNA), HBII-52, that exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin receptor 5-HT(2C)R. We found that HBII-52 regulates alternative splicing of 5-HT(2C)R by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different 5-HT(2C)R messenger RNA (mRNA) isoforms than healthy individuals. Our results show that a snoRNA regulates the processing of an mRNA expressed from a gene located on a different chromosome, and the results indicate that a defect in pre-mRNA processing contributes to the Prader-Willi syndrome.	D011218	Prader-Willi Syndrome
HTR2C	19304781	Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour.	The Prader-Willi syndrome (PWS) genetic interval contains several brain-expressed small nucleolar (sno)RNA species that are subject to genomic imprinting. In vitro studies have shown that one of these snoRNA molecules, h/mbii-52, negatively regulates editing and alternative splicing of the serotonin 2C receptor (5htr2c) pre-RNA. However, the functional consequences of loss of h/mbii-52 and subsequent increased post-transcriptional modification of 5htr2c are unknown. 5HT2CRs are important in controlling aspects of cognition and the cessation of feeding, and disruption of their function may underlie some of the psychiatric and feeding abnormalities seen in PWS. In a mouse model for PWS lacking expression of mbii-52 (PWS-IC+/-), we show an increase in editing, but not alternative splicing, of the 5htr2c pre-RNA. This change in post-transcriptional modification is associated with alterations in a number of 5HT2CR-related behaviours, including impulsive responding, locomotor activity and reactivity to palatable foodstuffs. In a non-5HT2CR-related behaviour, marble burying, loss of mbii-52 was without effect. The specificity of the behavioural effects to changes in 5HT2CR function was further confirmed using drug challenges. These data illustrate, for the first time, the physiological consequences of altered RNA editing of 5htr2c linked to mbii-52 loss that may underlie specific aspects of the complex PWS phenotype and point to an important functional role for this imprinted snoRNA.	D004195	Disease Models, Animal
HTR2C	19304781	Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour.	The Prader-Willi syndrome (PWS) genetic interval contains several brain-expressed small nucleolar (sno)RNA species that are subject to genomic imprinting. In vitro studies have shown that one of these snoRNA molecules, h/mbii-52, negatively regulates editing and alternative splicing of the serotonin 2C receptor (5htr2c) pre-RNA. However, the functional consequences of loss of h/mbii-52 and subsequent increased post-transcriptional modification of 5htr2c are unknown. 5HT2CRs are important in controlling aspects of cognition and the cessation of feeding, and disruption of their function may underlie some of the psychiatric and feeding abnormalities seen in PWS. In a mouse model for PWS lacking expression of mbii-52 (PWS-IC+/-), we show an increase in editing, but not alternative splicing, of the 5htr2c pre-RNA. This change in post-transcriptional modification is associated with alterations in a number of 5HT2CR-related behaviours, including impulsive responding, locomotor activity and reactivity to palatable foodstuffs. In a non-5HT2CR-related behaviour, marble burying, loss of mbii-52 was without effect. The specificity of the behavioural effects to changes in 5HT2CR function was further confirmed using drug challenges. These data illustrate, for the first time, the physiological consequences of altered RNA editing of 5htr2c linked to mbii-52 loss that may underlie specific aspects of the complex PWS phenotype and point to an important functional role for this imprinted snoRNA.	D011218	Prader-Willi Syndrome

Clinically important variants in HTR2C

(ClinVar, 04/20/2024)

accession_id

uniprot_id

gene_name

Type

Variant

Clinical_significance