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Q64264

- 5HT1A_MOUSE

UniProt

Q64264 - 5HT1A_MOUSE

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Protein

5-hydroxytryptamine receptor 1A

Gene

Htr1a

Organism
Mus musculus (Mouse)
Status
Reviewed - 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. 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.6 Publications

GO - Molecular functioni

  1. serotonin receptor activity Source: UniProtKB

GO - Biological processi

  1. adenylate cyclase-inhibiting serotonin receptor signaling pathway Source: UniProtKB
  2. behavioral fear response Source: UniProtKB
  3. cell proliferation Source: InterPro
  4. exploration behavior Source: UniProtKB
  5. regulation of behavior Source: InterPro
  6. regulation of dopamine metabolic process Source: UniProtKB
  7. regulation of hormone secretion Source: InterPro
  8. regulation of serotonin secretion Source: UniProtKB
  9. serotonin metabolic process Source: UniProtKB
  10. serotonin receptor signaling pathway Source: UniProtKB
  11. vasoconstriction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Enzyme and pathway databases

ReactomeiREACT_232980. Serotonin receptors.
REACT_250376. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 1A
Short name:
5-HT-1A
Short name:
5-HT1A
Alternative name(s):
Serotonin receptor 1A
Gene namesi
Name:Htr1a
Synonyms:Gpcr18
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:96273. Htr1a.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3636ExtracellularBy similarityAdd
BLAST
Transmembranei37 – 6226Helical; Name=1By similarityAdd
BLAST
Topological domaini63 – 7311CytoplasmicBy similarityAdd
BLAST
Transmembranei74 – 9825Helical; Name=2By similarityAdd
BLAST
Topological domaini99 – 11012ExtracellularBy similarityAdd
BLAST
Transmembranei111 – 13222Helical; Name=3By similarityAdd
BLAST
Topological domaini133 – 15220CytoplasmicBy similarityAdd
BLAST
Transmembranei153 – 17826Helical; Name=4By similarityAdd
BLAST
Topological domaini179 – 19113ExtracellularBy similarityAdd
BLAST
Transmembranei192 – 21726Helical; Name=5By similarityAdd
BLAST
Topological domaini218 – 345128CytoplasmicBy similarityAdd
BLAST
Transmembranei346 – 36722Helical; Name=6By similarityAdd
BLAST
Topological domaini368 – 37811ExtracellularBy similarityAdd
BLAST
Transmembranei379 – 40325Helical; Name=7By similarityAdd
BLAST
Topological domaini404 – 42118CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice display decreased exploratory behavior and increased fear-related behavior in anxiogenic environments. Mutant mice display altered monoamine metabolism in specific parts of the brain, especially in dorsal and medial raphe nuclei, thalamus and hypothalamus, leading to altered levels of 5-hydroxytryptamine, dopamine and their metabolites, as well as altered noradrenaline levels.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4214215-hydroxytryptamine receptor 1APRO_0000068904Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi10 – 101N-linked (GlcNAc...)Sequence Analysis
Glycosylationi11 – 111N-linked (GlcNAc...)Sequence Analysis
Glycosylationi24 – 241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi30 – 301N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi109 ↔ 187PROSITE-ProRule annotation
Cross-linki334 – 334Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiQ64264.

PTM databases

PhosphoSiteiQ64264.

Expressioni

Tissue specificityi

Most abundantly expressed in midbrain, in dorsal raphe and hippocampus. Detected at lower levels in amygdala and brain cortex.1 Publication

Gene expression databases

BgeeiQ64264.
CleanExiMM_HTR1A.
GenevestigatoriQ64264.

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with GPER1.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000022235.

Structurei

3D structure databases

ProteinModelPortaliQ64264.
SMRiQ64264. Positions 30-418.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni112 – 12110Agonist bindingBy similarity
Regioni358 – 3625Agonist bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi133 – 1353DRY motif; important for ligand-induced conformation changesBy similarity
Motifi396 – 4005NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity

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

eggNOGiNOG249628.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiQ64264.
KOiK04153.
OMAiREWRQGV.
OrthoDBiEOG7NCV3Q.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF20. PTHR24247:SF20. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00512. 5HT1ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q64264-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDMFSLGQGN NTTTSLEPFG TGGNDTGLSN VTFSYQVITS 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 RSNPNECTIS KDHGYTIYST
210 220 230 240 250
FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKKGAGT SFGTSSAPPP
260 270 280 290 300
KKSLNGQPGS GDCRRSAENR AVGTPCANGA VRQGEDDATL EVIEVHRVGN
310 320 330 340 350
SKGHLPLPSE SGATSYVPAC LERKNERTAE AKRKMALARE RKTVKTLGII
360 370 380 390 400
MGTFILCWLP FFIVALVLPF CESSCHMPEL LGAIINWLGY SNSLLNPVIY
410 420
AYFNKDFQNA FKKIIKCKFC R
Length:421
Mass (Da):46,176
Last modified:July 27, 2011 - v2
Checksum:i74F519DF7CC0C7AA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti177 – 1771T → A in AAA81519. (PubMed:8254366)Curated
Sequence conflicti242 – 2421F → L in AAA16850. (PubMed:8288218)Curated
Sequence conflicti247 – 2471A → V in AAA16850. (PubMed:8288218)Curated
Sequence conflicti263 – 2631C → W in AAA16850. (PubMed:8288218)Curated
Sequence conflicti304 – 3041H → D in AAA81519. (PubMed:8254366)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti17 – 193EPF → DHL in strain: C3H/An.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39391 mRNA. Translation: AAA81519.1.
AK043668 mRNA. Translation: BAC31611.1.
AK049814 mRNA. Translation: BAC33931.1.
AK049884 mRNA. Translation: BAC33970.1.
AK140194 mRNA. Translation: BAE24273.1.
CH466568 Genomic DNA. Translation: EDL18479.1.
BC138669 mRNA. Translation: AAI38670.1.
BC138681 mRNA. Translation: AAI38682.1.
U33820 Genomic DNA. Translation: AAC52572.1.
L20339 mRNA. Translation: AAA16850.1.
CCDSiCCDS26756.1.
PIRiI49375.
RefSeqiNP_032334.2. NM_008308.4.
UniGeneiMm.4716.

Genome annotation databases

EnsembliENSMUST00000022235; ENSMUSP00000022235; ENSMUSG00000021721.
GeneIDi15550.
KEGGimmu:15550.
UCSCiuc007rtu.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39391 mRNA. Translation: AAA81519.1 .
AK043668 mRNA. Translation: BAC31611.1 .
AK049814 mRNA. Translation: BAC33931.1 .
AK049884 mRNA. Translation: BAC33970.1 .
AK140194 mRNA. Translation: BAE24273.1 .
CH466568 Genomic DNA. Translation: EDL18479.1 .
BC138669 mRNA. Translation: AAI38670.1 .
BC138681 mRNA. Translation: AAI38682.1 .
U33820 Genomic DNA. Translation: AAC52572.1 .
L20339 mRNA. Translation: AAA16850.1 .
CCDSi CCDS26756.1.
PIRi I49375.
RefSeqi NP_032334.2. NM_008308.4.
UniGenei Mm.4716.

3D structure databases

ProteinModelPortali Q64264.
SMRi Q64264. Positions 30-418.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000022235.

Chemistry

BindingDBi Q64264.
ChEMBLi CHEMBL3737.
GuidetoPHARMACOLOGYi 1.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei Q64264.

Proteomic databases

PRIDEi Q64264.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000022235 ; ENSMUSP00000022235 ; ENSMUSG00000021721 .
GeneIDi 15550.
KEGGi mmu:15550.
UCSCi uc007rtu.2. mouse.

Organism-specific databases

CTDi 3350.
MGIi MGI:96273. Htr1a.

Phylogenomic databases

eggNOGi NOG249628.
GeneTreei ENSGT00760000118795.
HOGENOMi HOG000239242.
HOVERGENi HBG106962.
InParanoidi Q64264.
KOi K04153.
OMAi REWRQGV.
OrthoDBi EOG7NCV3Q.
TreeFami TF316350.

Enzyme and pathway databases

Reactomei REACT_232980. Serotonin receptors.
REACT_250376. G alpha (i) signalling events.

Miscellaneous databases

NextBioi 288480.
PROi Q64264.
SOURCEi Search...

Gene expression databases

Bgeei Q64264.
CleanExi MM_HTR1A.
Genevestigatori Q64264.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR000610. 5HT1A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24247:SF20. PTHR24247:SF20. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00512. 5HT1ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and differentiation-induced expression of a murine serotonin 1A receptor in a septal cell line."
    Charest A., Wainer B.H., Albert P.R.
    J. Neurosci. 13:5164-5171(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Strain: NIH Swiss.
    Tissue: Brain.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain cortex, Corpora quadrigemina and Hippocampus.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1."
    Parks C.L., Shenk T.
    J. Biol. Chem. 271:4417-4430(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
    Strain: C3H/An.
  6. "Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors."
    Wilkie T.M., Chen Y., Gilbert D.J., Moore K.J., Yu L., Simon M.I., Copeland N.G., Jenkins N.A.
    Genomics 18:175-184(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 136-353.
    Tissue: Testis.
  7. Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION.
  8. "Altered serotonin and dopamine metabolism in the CNS of serotonin 5-HT(1A) or 5-HT(1B) receptor knockout mice."
    Ase A.R., Reader T.A., Hen R., Riad M., Descarries L.
    J. Neurochem. 75:2415-2426(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  9. "Embryonic and postnatal development of the serotonergic raphe system and its target regions in 5-HT1A receptor deletion or overexpressing mouse mutants."
    Deng D.R., Djalali S., Holtje M., Grosse G., Stroh T., Voigt I., Kusserow H., Theuring F., Ahnert-Hilger G., Hortnagl H.
    Neuroscience 147:388-402(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  10. "Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition."
    Audero E., Coppi E., Mlinar B., Rossetti T., Caprioli A., Banchaabouchi M.A., Corradetti R., Gross C.
    Science 321:130-133(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Serotonin-1A autoreceptors are necessary and sufficient for the normal formation of circuits underlying innate anxiety."
    Richardson-Jones J.W., Craige C.P., Nguyen T.H., Kung H.F., Gardier A.M., Dranovsky A., David D.J., Guiard B.P., Beck S.G., Hen R., Leonardo E.D.
    J. Neurosci. 31:6008-6018(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry namei5HT1A_MOUSE
AccessioniPrimary (citable) accession number: Q64264
Secondary accession number(s): Q60956, Q61617, Q8BGS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 130 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

External Data

Dasty 3