ID   5HT2A_RAT               Reviewed;         471 AA.
AC   P14842;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=5-hydroxytryptamine receptor 2A;
DE            Short=5-HT-2;
DE            Short=5-HT-2A;
DE   AltName: Full=Serotonin receptor 2A;
GN   Name=Htr2a; Synonyms=Htr2;
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=2300586; DOI=10.1073/pnas.87.3.928;
RA   Julius D., Huang K.N., Livelli T.J., Axel R., Jessell T.M.;
RT   "The 5HT2 receptor defines a family of structurally distinct but
RT   functionally conserved serotonin receptors.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:928-932(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=2854054; DOI=10.1002/j.1460-2075.1988.tb03308.x;
RA   Pritchett D.B., Bach A.W.J., Wozny M., Taleb O., Dal-Toso R., Shih J.C.,
RA   Seeburg P.H.;
RT   "Structure and functional expression of cloned rat serotonin 5HT-2
RT   receptor.";
RL   EMBO J. 7:4135-4140(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1765383; DOI=10.1016/0888-7543(91)90127-z;
RA   Liu J., Chen Y., Kozak C.A., Yu L.;
RT   "The 5-HT2 serotonin receptor gene Htr-2 is tightly linked to Es-10 on
RT   mouse chromosome 14.";
RL   Genomics 11:231-234(1991).
RN   [4]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=11960784; DOI=10.1152/ajpgi.00435.2001;
RA   Fiorica-Howells E., Hen R., Gingrich J., Li Z., Gershon M.D.;
RT   "5-HT(2A) receptors: location and functional analysis in intestines of
RT   wild-type and 5-HT(2A) knockout mice.";
RL   Am. J. Physiol. 282:G877-G893(2002).
CC   -!- FUNCTION: G-protein coupled receptor for 5-hydroxytryptamine
CC       (serotonin). Also functions as a receptor for various drugs and
CC       psychoactive substances, including mescaline, psilocybin, 1-(2,5-
CC       dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid
CC       diethylamide (LSD). Ligand binding causes a conformation change that
CC       triggers signaling via guanine nucleotide-binding proteins (G proteins)
CC       and modulates the activity of down-stream effectors. Beta-arrestin
CC       family members inhibit signaling via G proteins and mediate activation
CC       of alternative signaling pathways. Signaling activates phospholipase C
CC       and a phosphatidylinositol-calcium second messenger system that
CC       modulates the activity of phosphatidylinositol 3-kinase and promotes
CC       the release of Ca(2+) ions from intracellular stores. Affects neural
CC       activity, perception, cognition and mood. Plays a role in the
CC       regulation of behavior, including responses to anxiogenic situations
CC       and psychoactive substances. Plays a role in intestinal smooth muscle
CC       contraction, and may play a role in arterial vasoconstriction.
CC       {ECO:0000269|PubMed:2300586, ECO:0000269|PubMed:2854054}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with MPDZ and PATJ. May interact
CC       (via C-terminus) with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2.
CC       Interacts with GRM2 and DRD2; this may affect signaling.
CC       {ECO:0000250|UniProtKB:P28223}.
CC   -!- INTERACTION:
CC       P14842; P31421: Grm2; NbExp=3; IntAct=EBI-7090176, EBI-7090147;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11960784,
CC       ECO:0000269|PubMed:2300586, ECO:0000269|PubMed:2854054}; Multi-pass
CC       membrane protein {ECO:0000305}. Cell projection, axon
CC       {ECO:0000269|PubMed:11960784}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:11960784}. Membrane, caveola
CC       {ECO:0000269|PubMed:11960784}. Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:P35363}. Presynapse
CC       {ECO:0000269|PubMed:11960784}.
CC   -!- TISSUE SPECIFICITY: Detected in adult intestine, especially in mucosal
CC       epithelium, longitudinal and circular layers of muscularis externa and
CC       myenteric plexuses. Highly expressed in Paneth cells, and detected at
CC       lower levels in enterocytes (at protein level). Detected in brain
CC       cortex. {ECO:0000269|PubMed:11960784, ECO:0000269|PubMed:2300586}.
CC   -!- DOMAIN: The PDZ domain-binding motif is involved in the interaction
CC       with PATJ, CASK, APBA1, DLG1 and DLG4. {ECO:0000250|UniProtKB:P28223}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA32150.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; M30705; AAA42178.1; -; mRNA.
DR   EMBL; X13971; CAA32150.1; ALT_FRAME; mRNA.
DR   EMBL; M64867; -; NOT_ANNOTATED_CDS; mRNA.
DR   PIR; A34863; A34863.
DR   PIR; S02011; S02011.
DR   RefSeq; NP_058950.1; NM_017254.1.
DR   PDB; 4OAJ; X-ray; 2.30 A; B=465-471.
DR   PDBsum; 4OAJ; -.
DR   AlphaFoldDB; P14842; -.
DR   SMR; P14842; -.
DR   BioGRID; 248227; 2.
DR   DIP; DIP-57661N; -.
DR   IntAct; P14842; 4.
DR   MINT; P14842; -.
DR   STRING; 10116.ENSRNOP00000013408; -.
DR   BindingDB; P14842; -.
DR   ChEMBL; CHEMBL322; -.
DR   DrugCentral; P14842; -.
DR   GuidetoPHARMACOLOGY; 6; -.
DR   GlyCosmos; P14842; 5 sites, No reported glycans.
DR   GlyGen; P14842; 5 sites.
DR   iPTMnet; P14842; -.
DR   PhosphoSitePlus; P14842; -.
DR   PaxDb; 10116-ENSRNOP00000013408; -.
DR   Ensembl; ENSRNOT00000013408.7; ENSRNOP00000013408.4; ENSRNOG00000010063.7.
DR   Ensembl; ENSRNOT00055025574; ENSRNOP00055020859; ENSRNOG00055014961.
DR   Ensembl; ENSRNOT00060029001; ENSRNOP00060023352; ENSRNOG00060016970.
DR   Ensembl; ENSRNOT00065014166; ENSRNOP00065010601; ENSRNOG00065008875.
DR   GeneID; 29595; -.
DR   KEGG; rno:29595; -.
DR   UCSC; RGD:61800; rat.
DR   AGR; RGD:61800; -.
DR   CTD; 3356; -.
DR   RGD; 61800; Htr2a.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01050000244937; -.
DR   HOGENOM; CLU_009579_11_3_1; -.
DR   InParanoid; P14842; -.
DR   OMA; VTIGIHH; -.
DR   OrthoDB; 2880253at2759; -.
DR   PhylomeDB; P14842; -.
DR   TreeFam; TF316350; -.
DR   Reactome; R-RNO-390666; Serotonin receptors.
DR   Reactome; R-RNO-416476; G alpha (q) signalling events.
DR   PRO; PR:P14842; -.
DR   Proteomes; UP000002494; Chromosome 15.
DR   Bgee; ENSRNOG00000010063; Expressed in frontal cortex and 5 other cell types or tissues.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR   GO; GO:0070852; C:cell body fiber; IDA:RGD.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0043198; C:dendritic shaft; IDA:RGD.
DR   GO; GO:0098666; C:G protein-coupled serotonin receptor complex; ISO:RGD.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR   GO; GO:0071886; F:1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding; ISO:RGD.
DR   GO; GO:0004993; F:G protein-coupled serotonin receptor activity; ISO:RGD.
DR   GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0030296; F:protein tyrosine kinase activator activity; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0051378; F:serotonin binding; ISO:RGD.
DR   GO; GO:0014824; P:artery smooth muscle contraction; IMP:RGD.
DR   GO; GO:0048148; P:behavioral response to cocaine; IDA:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:RGD.
DR   GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP: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:0006096; P:glycolytic process; ISO:RGD.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD.
DR   GO; GO:0007613; P:memory; IMP:RGD.
DR   GO; GO:0043267; P:negative regulation of potassium ion transport; IMP:RGD.
DR   GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; IMP:RGD.
DR   GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007208; P:phospholipase C-activating serotonin receptor signaling pathway; IDA:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR   GO; GO:0045821; P:positive regulation of glycolytic process; ISO:RGD.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR   GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; ISO:RGD.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO.
DR   GO; GO:0044380; P:protein localization to cytoskeleton; ISO:RGD.
DR   GO; GO:0014059; P:regulation of dopamine secretion; IMP:RGD.
DR   GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR   GO; GO:0001659; P:temperature homeostasis; IMP:RGD.
DR   GO; GO:0014832; P:urinary bladder smooth muscle contraction; IMP:RGD.
DR   CDD; cd15304; 7tmA_5-HT2A; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000455; 5HT2A_rcpt.
DR   InterPro; IPR002231; 5HT_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1.
DR   PANTHER; PTHR24247:SF30; 5-HYDROXYTRYPTAMINE RECEPTOR 2A; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00516; 5HT2ARECEPTR.
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.
DR   Genevisible; P14842; RN.
PE   1: Evidence at protein level;
KW   3D-structure; Behavior; Cell membrane; Cell projection;
KW   Cytoplasmic vesicle; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW   Synapse; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..471
FT                   /note="5-hydroxytryptamine receptor 2A"
FT                   /id="PRO_0000068951"
FT   TOPO_DOM        1..75
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        76..99
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        100..110
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        111..132
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        133..148
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        149..171
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        172..191
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        192..215
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        216..233
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        234..254
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        255..324
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        325..346
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        347..362
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        363..384
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        385..471
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   MOTIF           172..174
FT                   /note="DRY motif; important for ligand-induced conformation
FT                   changes"
FT                   /evidence="ECO:0000250|UniProtKB:P41595"
FT   MOTIF           376..380
FT                   /note="NPxxY motif; important for ligand-induced
FT                   conformation changes and signaling"
FT                   /evidence="ECO:0000250|UniProtKB:P41595"
FT   MOTIF           469..471
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P28223"
FT   BINDING         155
FT                   /ligand="ergotamine"
FT                   /ligand_id="ChEBI:CHEBI:190463"
FT                   /ligand_note="agonist"
FT                   /evidence="ECO:0000250|UniProtKB:P41595"
FT   BINDING         160
FT                   /ligand="ergotamine"
FT                   /ligand_id="ChEBI:CHEBI:190463"
FT                   /ligand_note="agonist"
FT                   /evidence="ECO:0000250|UniProtKB:P41595"
FT   BINDING         229
FT                   /ligand="ergotamine"
FT                   /ligand_id="ChEBI:CHEBI:190463"
FT                   /ligand_note="agonist"
FT                   /evidence="ECO:0000250|UniProtKB:P41595"
FT   SITE            229
FT                   /note="Hydrophobic barrier that decreases the speed of
FT                   ligand binding and dissociation"
FT                   /evidence="ECO:0000250|UniProtKB:P28223"
FT   MOD_RES         280
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P28223"
FT   CARBOHYD        8
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        38
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        44
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        51
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        54
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        148..227
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   DISULFID        349..353
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   STRAND          469..471
FT                   /evidence="ECO:0007829|PDB:4OAJ"
SQ   SEQUENCE   471 AA;  52850 MW;  3626DACE5F6C7FF4 CRC64;
     MEILCEDNIS LSSIPNSLMQ LGDGPRLYHN DFNSRDANTS EASNWTIDAE NRTNLSCEGY
     LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS LEKKLQNATN YFLMSLAIAD
     MLLGFLVMPV SMLTILYGYR WPLPSKLCAI WIYLDVLFST ASIMHLCAIS LDRYVAIQNP
     IHHSRFNSRT KAFLKIIAVW TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF
     VAFFIPLTIM VITYFLTIKS LQKEATLCVS DLSTRAKLAS FSFLPQSSLS SEKLFQRSIH
     REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK ESCNENVIGA
     LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK ENRKPLQLIL VNTIPALAYK
     SSQLQVGQKK NSQEDAEQTV DDCSMVTLGK QQSEENCTDN IETVNEKVSC V
//