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Protein

5-hydroxytryptamine receptor 1A

Gene

HTR1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca2+ ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.4 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178394-MONOMER.
ReactomeiR-HSA-390666. Serotonin receptors.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP08908.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 1A
Short name:
5-HT-1A
Short name:
5-HT1A
Alternative name(s):
G-21
Serotonin receptor 1A
Gene namesi
Name:HTR1A
Synonyms:ADRB2RL1, ADRBRL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:5286. HTR1A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 36ExtracellularBy similarityAdd BLAST36
Transmembranei37 – 62Helical; Name=1By similarityAdd BLAST26
Topological domaini63 – 73CytoplasmicBy similarityAdd BLAST11
Transmembranei74 – 98Helical; Name=2By similarityAdd BLAST25
Topological domaini99 – 110ExtracellularBy similarityAdd BLAST12
Transmembranei111 – 132Helical; Name=3By similarityAdd BLAST22
Topological domaini133 – 152CytoplasmicBy similarityAdd BLAST20
Transmembranei153 – 178Helical; Name=4By similarityAdd BLAST26
Topological domaini179 – 191ExtracellularBy similarityAdd BLAST13
Transmembranei192 – 217Helical; Name=5By similarityAdd BLAST26
Topological domaini218 – 345CytoplasmicBy similarityAdd BLAST128
Transmembranei346 – 367Helical; Name=6By similarityAdd BLAST22
Topological domaini368 – 378ExtracellularBy similarityAdd BLAST11
Transmembranei379 – 403Helical; Name=7By similarityAdd BLAST25
Topological domaini404 – 422CytoplasmicBy similarityAdd BLAST19

GO - Cellular componenti

  • dendrite Source: GO_Central
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Periodic fever, menstrual cycle-dependent (PFMC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines.
See also OMIM:614674

Organism-specific databases

DisGeNETi3350.
MalaCardsiHTR1A.
MIMi614674. phenotype.
OpenTargetsiENSG00000178394.
PharmGKBiPA192.

Chemistry databases

ChEMBLiCHEMBL214.
DrugBankiDB01614. Acepromazine.
DB00866. Alprenolol.
DB01616. Alverine.
DB00321. Amitriptyline.
DB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB08807. Bopindolol.
DB09128. Brexpiprazole.
DB01200. Bromocriptine.
DB00490. Buspirone.
DB00248. Cabergoline.
DB06016. Cariprazine.
DB00477. Chlorpromazine.
DB08810. Cinitapride.
DB00363. Clozapine.
DB01151. Desipramine.
DB00988. Dopamine.
DB01142. Doxepin.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB04908. Flibanserin.
DB04946. Iloperidone.
DB00458. Imipramine.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB08815. Lurasidone.
DB00247. Methysergide.
DB06148. Mianserin.
DB01618. Molindone.
DB00952. Naratriptan.
DB01149. Nefazodone.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB01267. Paliperidone.
DB01359. Penbutolol.
DB01186. Pergolide.
DB00960. Pindolol.
DB01621. Pipotiazine.
DB00413. Pramipexole.
DB00571. Propranolol.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
DB00669. Sumatriptan.
DB01622. Thioproperazine.
DB00656. Trazodone.
DB00726. Trimipramine.
DB06684. Vilazodone.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGYi1.

Polymorphism and mutation databases

BioMutaiHTR1A.
DMDMi231454.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689031 – 4225-hydroxytryptamine receptor 1AAdd BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi10N-linked (GlcNAc...)Sequence analysis1
Glycosylationi11N-linked (GlcNAc...)Sequence analysis1
Glycosylationi24N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi109 ↔ 187PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP08908.
PeptideAtlasiP08908.
PRIDEiP08908.

PTM databases

iPTMnetiP08908.
PhosphoSitePlusiP08908.

Expressioni

Tissue specificityi

Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells.2 Publications

Gene expression databases

BgeeiENSG00000178394.
CleanExiHS_HTR1A.
ExpressionAtlasiP08908. baseline and differential.
GenevisibleiP08908. HS.

Organism-specific databases

HPAiHPA018073.

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with GPER1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FGFR1P1136211EBI-6570214,EBI-1028277

Protein-protein interaction databases

BioGridi109582. 5 interactors.
IntActiP08908. 4 interactors.
STRINGi9606.ENSP00000316244.

Chemistry databases

BindingDBiP08908.

Structurei

3D structure databases

ProteinModelPortaliP08908.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni112 – 121Agonist bindingBy similarity10
Regioni358 – 362Agonist bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 135DRY motif; important for ligand-induced conformation changesBy similarity3
Motifi396 – 400NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity5

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP08908.
KOiK04153.
OMAiGPTPCAP.
OrthoDBiEOG091G06VI.
PhylomeDBiP08908.
TreeFamiTF316350.

Family and domain databases

InterProiIPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF20. PTHR24247:SF20. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00512. 5HT1ARECEPTR.
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.

P08908-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVLSPGQGN NTTSPPAPFE TGGNTTGISD VTVSYQVITS LLLGTLIFCA
60 70 80 90 100
VLGNACVVAA IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN
110 120 130 140 150
KWTLGQVTCD LFIALDVLCC TSSILHLCAI ALDRYWAITD PIDYVNKRTP
160 170 180 190 200
RRAAALISLT WLIGFLISIP PMLGWRTPED RSDPDACTIS KDHGYTIYST
210 220 230 240 250
FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKTGADT RHGASPAPQP
260 270 280 290 300
KKSVNGESGS RNWRLGVESK AGGALCANGA VRQGDDGAAL EVIEVHRVGN
310 320 330 340 350
SKEHLPLPSE AGPTPCAPAS FERKNERNAE AKRKMALARE RKTVKTLGII
360 370 380 390 400
MGTFILCWLP FFIVALVLPF CESSCHMPTL LGAIINWLGY SNSLLNPVIY
410 420
AYFNKDFQNA FKKIIKCKFC RQ
Length:422
Mass (Da):46,107
Last modified:April 1, 1993 - v3
Checksum:i762664FCF62CFD8F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti152 – 154RAA → PR in AAA36440 (PubMed:3041227).Curated3
Sequence conflicti152 – 154RAA → PR in CAA31908 (PubMed:3041227).Curated3
Sequence conflicti172M → I in AAA36440 (PubMed:3041227).Curated1
Sequence conflicti172M → I in CAA31908 (PubMed:3041227).Curated1
Sequence conflicti200 – 202TFG → RPR no nucleotide entry (PubMed:8393041).Curated3
Sequence conflicti228K → R no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti244A → AA no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti355I → T no nucleotide entry (PubMed:8393041).Curated1
Sequence conflicti363 – 365IVA → MRP no nucleotide entry (PubMed:8393041).Curated3
Sequence conflicti418K → N in AAA36440 (PubMed:3041227).Curated1
Sequence conflicti418K → N in CAA31908 (PubMed:3041227).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00344616P → L.1 PublicationCorresponds to variant rs1800041dbSNPEnsembl.1
Natural variantiVAR_01182622G → S.1 PublicationCorresponds to variant rs1799920dbSNPEnsembl.1
Natural variantiVAR_01182728I → V.1 PublicationCorresponds to variant rs1799921dbSNPEnsembl.1
Natural variantiVAR_011828184P → L.Corresponds to variant rs1800043dbSNPEnsembl.1
Natural variantiVAR_011829220R → L.Corresponds to variant rs1800044dbSNPEnsembl.1
Natural variantiVAR_011830273G → D.1 PublicationCorresponds to variant rs1800042dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28269 Genomic DNA. Translation: AAA36440.1.
X13556 Genomic DNA. Translation: CAA31908.1.
X57829 Genomic DNA. Translation: CAA40962.1.
M83181 Genomic DNA. Translation: AAA66493.1.
AB041403 Genomic DNA. Translation: BAA94488.1.
AF498978 mRNA. Translation: AAM21125.1.
BC069159 mRNA. Translation: AAH69159.1.
Z11168 Genomic DNA. Translation: CAA77560.1.
CCDSiCCDS34168.1.
PIRiI38209.
RefSeqiNP_000515.2. NM_000524.3.
UniGeneiHs.247940.

Genome annotation databases

EnsembliENST00000323865; ENSP00000316244; ENSG00000178394.
GeneIDi3350.
KEGGihsa:3350.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M28269 Genomic DNA. Translation: AAA36440.1.
X13556 Genomic DNA. Translation: CAA31908.1.
X57829 Genomic DNA. Translation: CAA40962.1.
M83181 Genomic DNA. Translation: AAA66493.1.
AB041403 Genomic DNA. Translation: BAA94488.1.
AF498978 mRNA. Translation: AAM21125.1.
BC069159 mRNA. Translation: AAH69159.1.
Z11168 Genomic DNA. Translation: CAA77560.1.
CCDSiCCDS34168.1.
PIRiI38209.
RefSeqiNP_000515.2. NM_000524.3.
UniGeneiHs.247940.

3D structure databases

ProteinModelPortaliP08908.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109582. 5 interactors.
IntActiP08908. 4 interactors.
STRINGi9606.ENSP00000316244.

Chemistry databases

BindingDBiP08908.
ChEMBLiCHEMBL214.
DrugBankiDB01614. Acepromazine.
DB00866. Alprenolol.
DB01616. Alverine.
DB00321. Amitriptyline.
DB00543. Amoxapine.
DB00714. Apomorphine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB08807. Bopindolol.
DB09128. Brexpiprazole.
DB01200. Bromocriptine.
DB00490. Buspirone.
DB00248. Cabergoline.
DB06016. Cariprazine.
DB00477. Chlorpromazine.
DB08810. Cinitapride.
DB00363. Clozapine.
DB01151. Desipramine.
DB00988. Dopamine.
DB01142. Doxepin.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB04908. Flibanserin.
DB04946. Iloperidone.
DB00458. Imipramine.
DB01221. Ketamine.
DB00589. Lisuride.
DB00408. Loxapine.
DB08815. Lurasidone.
DB00247. Methysergide.
DB06148. Mianserin.
DB01618. Molindone.
DB00952. Naratriptan.
DB01149. Nefazodone.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB01267. Paliperidone.
DB01359. Penbutolol.
DB01186. Pergolide.
DB00960. Pindolol.
DB01621. Pipotiazine.
DB00413. Pramipexole.
DB00571. Propranolol.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
DB00669. Sumatriptan.
DB01622. Thioproperazine.
DB00656. Trazodone.
DB00726. Trimipramine.
DB06684. Vilazodone.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00246. Ziprasidone.
DB00315. Zolmitriptan.
GuidetoPHARMACOLOGYi1.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP08908.
PhosphoSitePlusiP08908.

Polymorphism and mutation databases

BioMutaiHTR1A.
DMDMi231454.

Proteomic databases

PaxDbiP08908.
PeptideAtlasiP08908.
PRIDEiP08908.

Protocols and materials databases

DNASUi3350.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323865; ENSP00000316244; ENSG00000178394.
GeneIDi3350.
KEGGihsa:3350.

Organism-specific databases

CTDi3350.
DisGeNETi3350.
GeneCardsiHTR1A.
HGNCiHGNC:5286. HTR1A.
HPAiHPA018073.
MalaCardsiHTR1A.
MIMi109760. gene.
614674. phenotype.
neXtProtiNX_P08908.
OpenTargetsiENSG00000178394.
PharmGKBiPA192.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP08908.
KOiK04153.
OMAiGPTPCAP.
OrthoDBiEOG091G06VI.
PhylomeDBiP08908.
TreeFamiTF316350.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000178394-MONOMER.
ReactomeiR-HSA-390666. Serotonin receptors.
R-HSA-418594. G alpha (i) signalling events.
SIGNORiP08908.

Miscellaneous databases

GenomeRNAii3350.
PROiP08908.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178394.
CleanExiHS_HTR1A.
ExpressionAtlasiP08908. baseline and differential.
GenevisibleiP08908. HS.

Family and domain databases

InterProiIPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF20. PTHR24247:SF20. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00512. 5HT1ARECEPTR.
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 namei5HT1A_HUMAN
AccessioniPrimary (citable) accession number: P08908
Secondary accession number(s): Q6LAE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: April 1, 1993
Last modified: November 30, 2016
This is version 167 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.