ID   5HT1A_RAT               Reviewed;         422 AA.
AC   P19327;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=5-hydroxytryptamine receptor 1A {ECO:0000305};
DE            Short=5-HT-1A;
DE            Short=5-HT1A;
DE   AltName: Full=Serotonin receptor 1A;
GN   Name=Htr1a {ECO:0000312|RGD:2845}; Synonyms=5ht1a;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=2156831; DOI=10.1016/s0021-9258(19)39437-2;
RA   Albert P.R., Zhou Q.-Y., van Tol H.H.M., Bunzow J.R., Civelli O.;
RT   "Cloning, functional expression, and mRNA tissue distribution of the rat 5-
RT   hydroxytryptamine1A receptor gene.";
RL   J. Biol. Chem. 265:5825-5832(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2167416; DOI=10.1016/0024-3205(90)90225-g;
RA   Fujiwara Y., Nelson D.L., Kashihara K., Varga E., Roeske W.R.,
RA   Yamamura H.I.;
RT   "Role of cytochrome P450 in the control of the production of
RT   erythropoietin.";
RL   Life Sci. 47:127-134(1990).
RN   [3]
RP   FUNCTION.
RX   PubMed=2140514; DOI=10.1016/0896-6273(90)90201-p;
RA   Penington N.J., Kelly J.S.;
RT   "Serotonin receptor activation reduces calcium current in an acutely
RT   dissociated adult central neuron.";
RL   Neuron 4:751-758(1990).
RN   [4]
RP   TISSUE SPECIFICITY, INTERACTION WITH YIF1B, AND SUBCELLULAR LOCATION.
RX   PubMed=18685031; DOI=10.1523/jneurosci.4487-07.2008;
RA   Carrel D., Masson J., Al Awabdh S., Capra C.B., Lenkei Z., Hamon M.,
RA   Emerit M.B., Darmon M.;
RT   "Targeting of the 5-HT1A serotonin receptor to neuronal dendrites is
RT   mediated by Yif1B.";
RL   J. Neurosci. 28:8063-8073(2008).
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:2140514,
CC       ECO:0000269|PubMed:2156831}.
CC   -!- SUBUNIT: Heterodimer; heterodimerizes with GPER1. Interacts with YIF1B
CC       (PubMed:18685031). Interacts with GPR39 and GALR1 (By similarity).
CC       {ECO:0000250|UniProtKB:P08908, ECO:0000269|PubMed:18685031}.
CC   -!- INTERACTION:
CC       P19327; Q04589: Fgfr1; NbExp=5; IntAct=EBI-6570156, EBI-2480918;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2156831};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:2156831}. Cell
CC       projection, dendrite {ECO:0000269|PubMed:18685031}.
CC   -!- TISSUE SPECIFICITY: Detected in hypothalamus, mesencephalon, amygdala,
CC       medulla, thalamus, septum and hippocampus.
CC       {ECO:0000269|PubMed:18685031, ECO:0000269|PubMed:2156831}.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J05276; AAA40612.1; -; Genomic_DNA.
DR   PIR; JH0315; JH0315.
DR   RefSeq; NP_036717.1; NM_012585.1.
DR   AlphaFoldDB; P19327; -.
DR   SMR; P19327; -.
DR   IntAct; P19327; 2.
DR   STRING; 10116.ENSRNOP00000013618; -.
DR   BindingDB; P19327; -.
DR   ChEMBL; CHEMBL273; -.
DR   DrugCentral; P19327; -.
DR   GuidetoPHARMACOLOGY; 1; -.
DR   GlyCosmos; P19327; 3 sites, No reported glycans.
DR   GlyGen; P19327; 3 sites.
DR   iPTMnet; P19327; -.
DR   PhosphoSitePlus; P19327; -.
DR   PaxDb; 10116-ENSRNOP00000013618; -.
DR   GeneID; 24473; -.
DR   KEGG; rno:24473; -.
DR   UCSC; RGD:2845; rat.
DR   AGR; RGD:2845; -.
DR   CTD; 3350; -.
DR   RGD; 2845; Htr1a.
DR   eggNOG; KOG3656; Eukaryota.
DR   InParanoid; P19327; -.
DR   OrthoDB; 2999405at2759; -.
DR   PhylomeDB; P19327; -.
DR   Reactome; R-RNO-390666; Serotonin receptors.
DR   PRO; PR:P19327; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0043203; C:axon hillock; IDA:RGD.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR   GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:RGD.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:RGD.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0090722; F:receptor-receptor interaction; ISO:RGD.
DR   GO; GO:0051378; F:serotonin binding; IDA:RGD.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR   GO; GO:0007198; P:adenylate cyclase-inhibiting serotonin receptor signaling pathway; IMP:RGD.
DR   GO; GO:0001662; P:behavioral fear response; ISS:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0035640; P:exploration behavior; ISS:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR   GO; GO:0098664; P:G protein-coupled serotonin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISO:RGD.
DR   GO; GO:0014053; P:negative regulation of gamma-aminobutyric acid secretion; IMP:CACAO.
DR   GO; GO:0097114; P:NMDA glutamate receptor clustering; IDA:RGD.
DR   GO; GO:0031117; P:positive regulation of microtubule depolymerization; IDA:RGD.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR   GO; GO:0042053; P:regulation of dopamine metabolic process; ISS:UniProtKB.
DR   GO; GO:0060259; P:regulation of feeding behavior; IDA:RGD.
DR   GO; GO:0046883; P:regulation of hormone secretion; IEA:InterPro.
DR   GO; GO:0014062; P:regulation of serotonin secretion; ISS:UniProtKB.
DR   GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR   GO; GO:0042428; P:serotonin metabolic process; ISS:UniProtKB.
DR   GO; GO:0007210; P:serotonin receptor signaling pathway; IMP:RGD.
DR   CDD; cd15330; 7tmA_5-HT1A_vertebrates; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000610; 5HT1A_rcpt.
DR   InterPro; IPR002231; 5HT_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR24248:SF191; G-PROTEIN COUPLED RECEPTORS FAMILY 1 PROFILE DOMAIN-CONTAINING PROTEIN; 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   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE   1: Evidence at protein 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..422
FT                   /note="5-hydroxytryptamine receptor 1A"
FT                   /id="PRO_0000068907"
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..422
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          235..261
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   DISULFID        109..187
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   CONFLICT        373
FT                   /note="S -> N (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   422 AA;  46429 MW;  19C2731834C4BBC9 CRC64;
     MDVFSFGQGN NTTASQEPFG TGGNVTSISD VTFSYQVITS LLLGTLIFCA VLGNACVVAA
     IALERSLQNV ANYLIGSLAV TDLMVSVLVL PMAALYQVLN KWTLGQVTCD LFIALDVLCC
     TSSILHLCAI ALDRYWAITD PIDYVNKRTP RRAAALISLT WLIGFLISIP PMLGWRTPED
     RSDPDACTIS KDHGYTIYST FGAFYIPLLL MLVLYGRIFR AARFRIRKTV RKVEKKGAGT
     SLGTSSAPPP KKSLNGQPGS GDWRRCAENR AVGTPCTNGA VRQGDDEATL EVIEVHRVGN
     SKEHLPLPSE SGSNSYAPAC LERKNERNAE AKRKMALARE RKTVKTLGII MGTFILCWLP
     FFIVALVLPF CESSCHMPAL LGAIINWLGY SNSLLNPVIY AYFNKDFQNA FKKIIKCKFC
     RR
//