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UniProtKB - P08908 (5HT1A_HUMAN)

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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

  • G-protein coupled serotonin receptor activity Source: UniProtKB
  • neurotransmitter receptor activity Source: GO_Central
  • receptor-receptor interaction Source: ParkinsonsUK-UCL
  • serotonin binding Source: GO_Central
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

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

Enzyme and pathway databases

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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

  • 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.
DB04888. Bifeprunox.
DB08807. Bopindolol.
DB09128. Brexpiprazole.
DB01200. Bromocriptine.
DB00490. Buspirone.
DB00248. Cabergoline.
DB06016. Cariprazine.
DB00477. Chlorpromazine.
DB08810. Cinitapride.
DB00363. Clozapine.
DB04884. Dapoxetine.
DB01151. Desipramine.
DB00988. Dopamine.
DB01142. Doxepin.
DB00216. Eletriptan.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB04908. Flibanserin.
DB04946. Iloperidone.
DB00458. Imipramine.
DB01221. Ketamine.
DB04970. Lesopitron.
DB05509. LI-301.
DB00589. Lisuride.
DB00408. Loxapine.
DB08815. Lurasidone.
DB04829. Lysergic Acid Diethylamide.
DB00247. Methysergide.
DB06148. Mianserin.
DB05339. MN-305.
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.
DB05280. SLV 308.
DB00669. Sumatriptan.
DB01622. Thioproperazine.
DB13025. Tiapride.
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...) asparagineSequence analysis1
Glycosylationi11N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi24N-linked (GlcNAc...) asparagineSequence 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

GO - Molecular functioni

  • receptor-receptor interaction Source: ParkinsonsUK-UCL
Complete GO annotation...

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.
OMAiYQVLNKW.
OrthoDBiEOG091G06VI.
PhylomeDBiP08908.
TreeFamiTF316350.

Family and domain databases

InterProiView protein in InterPro
IPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PANTHERiPTHR24247:SF126. PTHR24247:SF126. 1 hit.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00512. 5HT1ARECEPTR.
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.

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 → L1 PublicationCorresponds to variant dbSNP:rs1800041Ensembl.1
Natural variantiVAR_01182622G → S1 PublicationCorresponds to variant dbSNP:rs1799920Ensembl.1
Natural variantiVAR_01182728I → V1 PublicationCorresponds to variant dbSNP:rs1799921Ensembl.1
Natural variantiVAR_011828184P → L. Corresponds to variant dbSNP:rs1800043Ensembl.1
Natural variantiVAR_011829220R → L. Corresponds to variant dbSNP:rs1800044Ensembl.1
Natural variantiVAR_011830273G → D1 PublicationCorresponds to variant dbSNP:rs1800042Ensembl.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

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.

Entry informationi

Entry namei5HT1A_HUMAN
AccessioniPrimary (citable) accession number: P08908
Secondary accession number(s): Q6LAE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: April 1, 1993
Last modified: June 7, 2017
This is version 171 of the entry and version 3 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

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