5HT2A_RAT
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 03-AUG-2022, entry version 179.
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 GlyGen; P14842; 5 sites.
DR iPTMnet; P14842; -.
DR PhosphoSitePlus; P14842; -.
DR PaxDb; P14842; -.
DR Ensembl; ENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063.
DR GeneID; 29595; -.
DR KEGG; rno:29595; -.
DR UCSC; RGD:61800; rat.
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; RLYNNDF; -.
DR OrthoDB; 962038at2759; -.
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 tissues.
DR Genevisible; P14842; RN.
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; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0051378; F:serotonin binding; ISO:RGD.
DR GO; GO:0007202; P:activation of phospholipase C activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP: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:0008219; P:cell death; IMP:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO: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; IEA:Ensembl.
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:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; 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:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; 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:0044380; P:protein localization to cytoskeleton; ISO:RGD.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
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:0019233; P:sensory perception of pain; IMP:RGD.
DR GO; GO:0030431; P:sleep; IMP:RGD.
DR GO; GO:0001659; P:temperature homeostasis; IMP:RGD.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; IMP:RGD.
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 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
