5HT2A_PONPY
ID 5HT2A_PONPY Reviewed; 471 AA.
AC Q5R4Q6; Q9N2F2;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 84.
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;
OS Pongo pygmaeus (Bornean orangutan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9600;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 216-460.
RC STRAIN=Isolate oran-U1;
RX PubMed=15014171; DOI=10.1093/molbev/msh100;
RA Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT "Human-specific amino acid changes found in 103 protein-coding genes.";
RL Mol. Biol. Evol. 21:936-944(2004).
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 (By
CC similarity). {ECO:0000250|UniProtKB:P28223}.
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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P14842};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P14842}. Cell
CC projection, axon {ECO:0000250|UniProtKB:P14842}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:P14842}. Membrane, caveola
CC {ECO:0000250|UniProtKB:P14842}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P35363}. Presynapse
CC {ECO:0000250|UniProtKB:P14842}.
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}.
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DR EMBL; CR861189; CAH93260.1; -; mRNA.
DR EMBL; AB037516; BAA90436.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5R4Q6; -.
DR SMR; Q5R4Q6; -.
DR PRIDE; Q5R4Q6; -.
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:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IEA:InterPro.
DR GO; GO:0007610; P:behavior; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Behavior; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Synapse; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..471
FT /note="5-hydroxytryptamine receptor 2A"
FT /id="PRO_0000068950"
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 REGION 450..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 38
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 CONFLICT 330
FT /note="S -> F (in Ref. 2; BAA90436)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 471 AA; 52529 MW; EFE1DC10C48C9D02 CRC64;
MDILCEENTS LSSTTNSLMQ LNDDTRLYSN DFNSGEANTS DAFNWTVDSE NRTNLSCEGC
LSPSCLSLLH LQEKNWSALL TAVVIILTIA GNILVIMAVS LEKKLQNATN YFLMSLAIAD
MLLGFLVMPV SMLTILYGYR WPLPSKLCAV WIYLDVLFST ASIMHLCAIS LDRYVAIQNP
IHHSRFNSRT KAFLKIIAVW TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF
VSFFIPLTIM VITYFLTIKS LQKEATLCVS DLGTRAKLAS FSFLPQSSLS SEKLFQRSIH
REPGSYTGRR TMQSISNEQK ACKVLGIVFS LFVVMWCPFF ITNIMAVICK ESCNEDVIGA
LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK ENKKPLQLIL VNTIPALAYK
SSQLQMGQKK NSKQDAKTTD NDCSMVALGK QHSEDASKDN SDGVNEKVSC V
