5HT1A_MOUSE
ID 5HT1A_MOUSE Reviewed; 421 AA.
AC Q64264; Q60956; Q61617; Q8BGS4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=5-hydroxytryptamine receptor 1A;
DE Short=5-HT-1A;
DE Short=5-HT1A;
DE AltName: Full=Serotonin receptor 1A;
GN Name=Htr1a; Synonyms=Gpcr18;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=NIH Swiss; TISSUE=Brain;
RX PubMed=8254366; DOI=10.1523/jneurosci.13-12-05164.1993;
RA Charest A., Wainer B.H., Albert P.R.;
RT "Cloning and differentiation-induced expression of a murine serotonin 1A
RT receptor in a septal cell line.";
RL J. Neurosci. 13:5164-5171(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Brain cortex, Corpora quadrigemina, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
RC STRAIN=C3H/An;
RX PubMed=8626793; DOI=10.1074/jbc.271.8.4417;
RA Parks C.L., Shenk T.;
RT "The serotonin 1a receptor gene contains a TATA-less promoter that responds
RT to MAZ and Sp1.";
RL J. Biol. Chem. 271:4417-4430(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 136-353.
RC TISSUE=Testis;
RX PubMed=8288218; DOI=10.1006/geno.1993.1452;
RA Wilkie T.M., Chen Y., Gilbert D.J., Moore K.J., Yu L., Simon M.I.,
RA Copeland N.G., Jenkins N.A.;
RT "Identification, chromosomal location, and genome organization of mammalian
RT G-protein-coupled receptors.";
RL Genomics 18:175-184(1993).
RN [7]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=9826725; DOI=10.1073/pnas.95.24.14476;
RA Ramboz S., Oosting R., Amara D.A., Kung H.F., Blier P., Mendelsohn M.,
RA Mann J.J., Brunner D., Hen R.;
RT "Serotonin receptor 1A knockout: an animal model of anxiety-related
RT disorder.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14476-14481(1998).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11080193; DOI=10.1046/j.1471-4159.2000.0752415.x;
RA Ase A.R., Reader T.A., Hen R., Riad M., Descarries L.;
RT "Altered serotonin and dopamine metabolism in the CNS of serotonin 5-HT(1A)
RT or 5-HT(1B) receptor knockout mice.";
RL J. Neurochem. 75:2415-2426(2000).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17543467; DOI=10.1016/j.neuroscience.2007.04.004;
RA Deng D.R., Djalali S., Holtje M., Grosse G., Stroh T., Voigt I.,
RA Kusserow H., Theuring F., Ahnert-Hilger G., Hortnagl H.;
RT "Embryonic and postnatal development of the serotonergic raphe system and
RT its target regions in 5-HT1A receptor deletion or overexpressing mouse
RT mutants.";
RL Neuroscience 147:388-402(2007).
RN [10]
RP FUNCTION.
RX PubMed=18599790; DOI=10.1126/science.1157871;
RA Audero E., Coppi E., Mlinar B., Rossetti T., Caprioli A.,
RA Banchaabouchi M.A., Corradetti R., Gross C.;
RT "Sporadic autonomic dysregulation and death associated with excessive
RT serotonin autoinhibition.";
RL Science 321:130-133(2008).
RN [11]
RP FUNCTION.
RX PubMed=21508226; DOI=10.1523/jneurosci.5836-10.2011;
RA Richardson-Jones J.W., Craige C.P., Nguyen T.H., Kung H.F., Gardier A.M.,
RA Dranovsky A., David D.J., Guiard B.P., Beck S.G., Hen R., Leonardo E.D.;
RT "Serotonin-1A autoreceptors are necessary and sufficient for the normal
RT formation of circuits underlying innate anxiety.";
RL J. Neurosci. 31:6008-6018(2011).
CC -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine
CC (serotonin). Also functions as a receptor for various drugs and
CC psychoactive substances. Ligand binding causes a conformation change
CC that triggers signaling via guanine nucleotide-binding proteins (G
CC proteins) and modulates the activity of down-stream effectors, such as
CC adenylate cyclase. Beta-arrestin family members inhibit signaling via G
CC proteins and mediate activation of alternative signaling pathways.
CC Signaling inhibits adenylate cyclase activity and activates a
CC phosphatidylinositol-calcium second messenger system that regulates the
CC release of Ca(2+) ions from intracellular stores. Plays a role in the
CC regulation of 5-hydroxytryptamine release and in the regulation of
CC dopamine and 5-hydroxytryptamine metabolism. Plays a role in the
CC regulation of dopamine and 5-hydroxytryptamine levels in the brain, and
CC thereby affects neural activity, mood and behavior. Plays a role in the
CC response to anxiogenic stimuli. {ECO:0000269|PubMed:11080193,
CC ECO:0000269|PubMed:17543467, ECO:0000269|PubMed:18599790,
CC ECO:0000269|PubMed:21508226, ECO:0000269|PubMed:8254366,
CC ECO:0000269|PubMed:9826725}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with GPER1 (By similarity).
CC Interacts with YIF1B (By similarity). {ECO:0000250|UniProtKB:P08908,
CC ECO:0000250|UniProtKB:P19327}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8254366};
CC Multi-pass membrane protein {ECO:0000269|PubMed:8254366}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:P19327}.
CC -!- TISSUE SPECIFICITY: Most abundantly expressed in midbrain, in dorsal
CC raphe and hippocampus. Detected at lower levels in amygdala and brain
CC cortex. {ECO:0000269|PubMed:9826725}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice display decreased exploratory
CC behavior and increased fear-related behavior in anxiogenic
CC environments. Mutant mice display altered monoamine metabolism in
CC specific parts of the brain, especially in dorsal and medial raphe
CC nuclei, thalamus and hypothalamus, leading to altered levels of 5-
CC hydroxytryptamine, dopamine and their metabolites, as well as altered
CC noradrenaline levels. {ECO:0000269|PubMed:11080193,
CC ECO:0000269|PubMed:17543467, ECO:0000269|PubMed:9826725}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. 5-
CC hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U39391; AAA81519.1; -; mRNA.
DR EMBL; AK043668; BAC31611.1; -; mRNA.
DR EMBL; AK049814; BAC33931.1; -; mRNA.
DR EMBL; AK049884; BAC33970.1; -; mRNA.
DR EMBL; AK140194; BAE24273.1; -; mRNA.
DR EMBL; CH466568; EDL18479.1; -; Genomic_DNA.
DR EMBL; BC138669; AAI38670.1; -; mRNA.
DR EMBL; BC138681; AAI38682.1; -; mRNA.
DR EMBL; U33820; AAC52572.1; -; Genomic_DNA.
DR EMBL; L20339; AAA16850.1; -; mRNA.
DR CCDS; CCDS26756.1; -.
DR PIR; I49375; I49375.
DR RefSeq; NP_032334.2; NM_008308.4.
DR AlphaFoldDB; Q64264; -.
DR SMR; Q64264; -.
DR STRING; 10090.ENSMUSP00000022235; -.
DR BindingDB; Q64264; -.
DR ChEMBL; CHEMBL3737; -.
DR DrugCentral; Q64264; -.
DR GlyGen; Q64264; 4 sites.
DR iPTMnet; Q64264; -.
DR PhosphoSitePlus; Q64264; -.
DR SwissPalm; Q64264; -.
DR MaxQB; Q64264; -.
DR PaxDb; Q64264; -.
DR PRIDE; Q64264; -.
DR ProteomicsDB; 285688; -.
DR Antibodypedia; 2959; 333 antibodies from 39 providers.
DR DNASU; 15550; -.
DR Ensembl; ENSMUST00000022235; ENSMUSP00000022235; ENSMUSG00000021721.
DR GeneID; 15550; -.
DR KEGG; mmu:15550; -.
DR UCSC; uc007rtu.2; mouse.
DR CTD; 3350; -.
DR MGI; MGI:96273; Htr1a.
DR VEuPathDB; HostDB:ENSMUSG00000021721; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000154484; -.
DR HOGENOM; CLU_009579_11_1_1; -.
DR InParanoid; Q64264; -.
DR OMA; CAESCYM; -.
DR OrthoDB; 703991at2759; -.
DR PhylomeDB; Q64264; -.
DR TreeFam; TF316350; -.
DR Reactome; R-MMU-390666; Serotonin receptors.
DR BioGRID-ORCS; 15550; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q64264; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q64264; protein.
DR Bgee; ENSMUSG00000021721; Expressed in ventral nuclear group and 73 other tissues.
DR Genevisible; Q64264; MM.
DR GO; GO:0043203; C:axon hillock; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:MGI.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0090722; F:receptor-receptor interaction; ISO:MGI.
DR GO; GO:0051378; F:serotonin binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0007198; P:adenylate cyclase-inhibiting serotonin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; IMP:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0035640; P:exploration behavior; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IMP:MGI.
DR GO; GO:0014053; P:negative regulation of gamma-aminobutyric acid secretion; ISO:MGI.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; ISO:MGI.
DR GO; GO:0031117; P:positive regulation of microtubule depolymerization; ISO:MGI.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; IMP:UniProtKB.
DR GO; GO:0060259; P:regulation of feeding behavior; ISO:MGI.
DR GO; GO:0046883; P:regulation of hormone secretion; IEA:InterPro.
DR GO; GO:0014062; P:regulation of serotonin secretion; IMP:UniProtKB.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:MGI.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0042428; P:serotonin metabolic process; IMP:UniProtKB.
DR GO; GO:0007210; P:serotonin receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR000610; 5HT1A_rcpt.
DR InterPro; IPR002231; 5HT_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24247:SF20; PTHR24247:SF20; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00512; 5HT1ARECEPTR.
DR PRINTS; PR01101; 5HTRECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Behavior; Cell membrane; Cell projection; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..421
FT /note="5-hydroxytryptamine receptor 1A"
FT /id="PRO_0000068904"
FT TOPO_DOM 1..36
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 37..62
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 63..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 74..98
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 99..110
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 111..132
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 133..152
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 153..178
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 179..191
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 192..217
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 218..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 346..367
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 368..378
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 379..403
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 404..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 237..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 133..135
FT /note="DRY motif; important for ligand-induced conformation
FT changes"
FT /evidence="ECO:0000250"
FT MOTIF 396..400
FT /note="NPxxY motif; important for ligand-induced
FT conformation changes and signaling"
FT /evidence="ECO:0000250"
FT COMPBIAS 239..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 116
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT BINDING 121
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT BINDING 189
FT /ligand="ergotamine"
FT /ligand_id="ChEBI:CHEBI:190463"
FT /ligand_note="agonist"
FT /evidence="ECO:0000250|UniProtKB:P28222"
FT CARBOHYD 10
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 109..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 17..19
FT /note="EPF -> DHL (in strain: C3H/An)"
FT CONFLICT 177
FT /note="T -> A (in Ref. 1; AAA81519)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="F -> L (in Ref. 6; AAA16850)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="A -> V (in Ref. 6; AAA16850)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="C -> W (in Ref. 6; AAA16850)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="H -> D (in Ref. 1; AAA81519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 421 AA; 46176 MW; 74F519DF7CC0C7AA CRC64;
MDMFSLGQGN NTTTSLEPFG TGGNDTGLSN VTFSYQVITS LLLGTLIFCA VLGNACVVAA
IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN KWTLGQVTCD LFIALDVLCC
TSSILHLCAI ALDRYWAITD PIDYVNKRTP RRAAALISLT WLIGFLISIP PMLGWRTPED
RSNPNECTIS KDHGYTIYST FGAFYIPLLL MLVLYGRIFR AARFRIRKTV KKVEKKGAGT
SFGTSSAPPP KKSLNGQPGS GDCRRSAENR AVGTPCANGA VRQGEDDATL EVIEVHRVGN
SKGHLPLPSE SGATSYVPAC LERKNERTAE AKRKMALARE RKTVKTLGII MGTFILCWLP
FFIVALVLPF CESSCHMPEL LGAIINWLGY SNSLLNPVIY AYFNKDFQNA FKKIIKCKFC
R
