5HT2A_MOUSE
ID 5HT2A_MOUSE Reviewed; 471 AA.
AC P35363;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 171.
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 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].
RC TISSUE=Brain;
RX PubMed=1333538; DOI=10.1002/jnr.490330203;
RA Yang W., Chen K., Lan N.C., Gallaher T.K., Shih J.C.;
RT "Gene structure and expression of the mouse 5-HT2 receptor.";
RL J. Neurosci. Res. 33:196-204(1992).
RN [2]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP 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).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=14988405; DOI=10.1074/jbc.m312106200;
RA Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A.,
RA Bockaert J., Marin P.;
RT "The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of
RT PDZ proteins.";
RL J. Biol. Chem. 279:20257-20266(2004).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16873667; DOI=10.1126/science.1123432;
RA Weisstaub N.V., Zhou M., Lira A., Lambe E., Gonzalez-Maeso J.,
RA Hornung J.P., Sibille E., Underwood M., Itohara S., Dauer W.T.,
RA Ansorge M.S., Morelli E., Mann J.J., Toth M., Aghajanian G., Sealfon S.C.,
RA Hen R., Gingrich J.A.;
RT "Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in
RT mice.";
RL Science 313:536-540(2006).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17270739; DOI=10.1016/j.neuron.2007.01.008;
RA Gonzalez-Maeso J., Weisstaub N.V., Zhou M., Chan P., Ivic L., Ang R.,
RA Lira A., Bradley-Moore M., Ge Y., Zhou Q., Sealfon S.C., Gingrich J.A.;
RT "Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated
RT signaling pathways to affect behavior.";
RL Neuron 53:439-452(2007).
RN [6]
RP INTERACTION WITH GRM2, FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18297054; DOI=10.1038/nature06612;
RA Gonzalez-Maeso J., Ang R.L., Yuen T., Chan P., Weisstaub N.V.,
RA Lopez-Gimenez J.F., Zhou M., Okawa Y., Callado L.F., Milligan G.,
RA Gingrich J.A., Filizola M., Meana J.J., Sealfon S.C.;
RT "Identification of a serotonin/glutamate receptor complex implicated in
RT psychosis.";
RL Nature 452:93-97(2008).
RN [7]
RP INTERACTION WITH DRD2, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21645528; DOI=10.1016/j.neuropharm.2011.05.023;
RA Albizu L., Holloway T., Gonzalez-Maeso J., Sealfon S.C.;
RT "Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine
RT D2 receptors.";
RL Neuropharmacology 61:770-777(2011).
RN [8]
RP FUNCTION.
RX PubMed=23346101; DOI=10.1155/2012/398406;
RA Nelson P.M., Harrod J.S., Lamping K.G.;
RT "5HT(2A) and 5HT(2B) receptors contribute to serotonin-induced vascular
RT dysfunction in diabetes.";
RL Exp. Diabetes Res. 2012:398406-398406(2012).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23129762; DOI=10.1074/jbc.m112.413161;
RA Moreno J.L., Muguruza C., Umali A., Mortillo S., Holloway T.,
RA Pilar-Cuellar F., Mocci G., Seto J., Callado L.F., Neve R.L., Milligan G.,
RA Sealfon S.C., Lopez-Gimenez J.F., Meana J.J., Benson D.L.,
RA Gonzalez-Maeso J.;
RT "Identification of three residues essential for 5-hydroxytryptamine 2A-
RT metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its
RT psychoactive behavioral function.";
RL J. Biol. Chem. 287:44301-44319(2012).
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:11960784, ECO:0000269|PubMed:16873667,
CC ECO:0000269|PubMed:17270739, ECO:0000269|PubMed:18297054,
CC ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:23129762,
CC ECO:0000269|PubMed:23346101}.
CC -!- SUBUNIT: Interacts with MPDZ and PATJ. May interact with MPP3, PRDX6,
CC DLG4, DLG1, CASK, APBA1 and MAGI2 (By similarity). Interacts with GRM2
CC and DRD2; this may affect signaling. {ECO:0000250|UniProtKB:P28223,
CC ECO:0000269|PubMed:18297054, ECO:0000269|PubMed:21645528}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21645528};
CC Multi-pass membrane protein {ECO:0000305}. Cell projection, dendrite
CC {ECO:0000269|PubMed:11960784}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P14842}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:11960784}. Membrane, caveola
CC {ECO:0000250|UniProtKB:P14842}. Presynapse
CC {ECO:0000250|UniProtKB:P14842}.
CC -!- TISSUE SPECIFICITY: Detected in neurons in brain cortex. Detected in
CC adult intestine, especially in mucosal epithelium, longitudinal and
CC circular layers of muscularis externa and myenteric plexuses. Highly
CC expressed in Paneth cells, and detected at lower levels in enterocytes
CC (at protein level). Detected in neurons in the brain cortex.
CC {ECO:0000269|PubMed:11960784, ECO:0000269|PubMed:18297054,
CC ECO:0000269|PubMed:23129762}.
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 -!- DISRUPTION PHENOTYPE: Mutant mice display increased exploratory
CC behavior in open spaces and reduced anxiety-like behavior
CC (PubMed:16873667). Mutant mice fail to show behavorial responses to
CC psychoactive substances and hallucinogens, such as mescaline,
CC psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 1-
CC (2,5-dimethoxy-4-bromophenyl)-2-aminopropane and lysergic acid
CC diethylamide (LSD) (PubMed:17270739). Besides, the colon from mutant
CC mice does not contract in response to 5-hydroxytryptamine
CC (PubMed:11960784). {ECO:0000269|PubMed:11960784,
CC ECO:0000269|PubMed:16873667, ECO:0000269|PubMed:17270739}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; S49542; AAB24369.1; -; mRNA.
DR CCDS; CCDS27275.1; -.
DR PIR; S40689; S40689.
DR RefSeq; NP_766400.1; NM_172812.2.
DR AlphaFoldDB; P35363; -.
DR SMR; P35363; -.
DR IntAct; P35363; 1.
DR STRING; 10090.ENSMUSP00000047774; -.
DR BindingDB; P35363; -.
DR ChEMBL; CHEMBL5377; -.
DR DrugCentral; P35363; -.
DR GlyGen; P35363; 5 sites.
DR iPTMnet; P35363; -.
DR PhosphoSitePlus; P35363; -.
DR SwissPalm; P35363; -.
DR PaxDb; P35363; -.
DR PRIDE; P35363; -.
DR ProteomicsDB; 285689; -.
DR Antibodypedia; 2927; 378 antibodies from 34 providers.
DR DNASU; 15558; -.
DR Ensembl; ENSMUST00000036653; ENSMUSP00000047774; ENSMUSG00000034997.
DR GeneID; 15558; -.
DR KEGG; mmu:15558; -.
DR UCSC; uc007uqc.1; mouse.
DR CTD; 3356; -.
DR MGI; MGI:109521; Htr2a.
DR VEuPathDB; HostDB:ENSMUSG00000034997; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244937; -.
DR HOGENOM; CLU_009579_11_3_1; -.
DR InParanoid; P35363; -.
DR OMA; RLYNNDF; -.
DR OrthoDB; 962038at2759; -.
DR PhylomeDB; P35363; -.
DR TreeFam; TF316350; -.
DR Reactome; R-MMU-390666; Serotonin receptors.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 15558; 1 hit in 74 CRISPR screens.
DR PRO; PR:P35363; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P35363; protein.
DR Bgee; ENSMUSG00000034997; Expressed in superior frontal gyrus and 33 other tissues.
DR ExpressionAtlas; P35363; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0098666; C:G protein-coupled serotonin receptor complex; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
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:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0071886; F:1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding; ISO:MGI.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; ISO:MGI.
DR GO; GO:0001587; F:Gq/11-coupled serotonin receptor activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0051378; F:serotonin binding; ISO:MGI.
DR GO; GO:0007202; P:activation of phospholipase C activity; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0014824; P:artery smooth muscle contraction; ISO:MGI.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:MGI.
DR GO; GO:0008219; P:cell death; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; 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:0098664; P:G protein-coupled serotonin receptor signaling pathway; ISO:MGI.
DR GO; GO:0006096; P:glycolytic process; IMP:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:MGI.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:MGI.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IMP:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IMP:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0010513; P:positive regulation of phosphatidylinositol biosynthetic process; ISO:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0044380; P:protein localization to cytoskeleton; IDA:MGI.
DR GO; GO:0014059; P:regulation of dopamine secretion; ISO:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0030431; P:sleep; ISO:MGI.
DR GO; GO:0001659; P:temperature homeostasis; ISO:MGI.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; ISO:MGI.
DR InterPro; IPR000455; 5HT2A_rcpt.
DR InterPro; IPR002231; 5HT_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24247:SF30; PTHR24247:SF30; 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 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; Cytoplasmic vesicle;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Synapse; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..471
FT /note="5-hydroxytryptamine receptor 2A"
FT /id="PRO_0000068948"
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"
SQ SEQUENCE 471 AA; 52842 MW; DE763E5617EE8435 CRC64;
MEILCEDNIS LSSIPNSLMQ LGDDSRLYPN DFNSRDANTS EASNWTIDAE NRTNLSCEGY
LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS LEKKLQNATN YFLMSLAIAD
MLLGFLVMPV SMLTILYGYR WPLPSKLCAV WIYLDVLFST ASIMHLCAIS LDRYVAIQNP
IHHSRFNSRT KAFLKIIAVW TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF
VAFFIPLTIM VITYFLTIKS LQKEATLCVS DLSTRAKLSS FSFLPQSSLS SEKLFQRSIH
REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK ESCNENVIGA
LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK ENRKPLQLIL VNTIPTLAYK
SSQLQVGQKK NSQEDAEPTA NDCSMVTLGN QHSEEMCTDN IETVNEKVSC V
