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P14842

- 5HT2A_RAT

UniProt

P14842 - 5HT2A_RAT

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Protein

5-hydroxytryptamine receptor 2A

Gene

Htr2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca2+ ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.2 Publications

GO - Molecular functioni

  1. 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding Source: Ensembl
  2. drug binding Source: Ensembl
  3. G-protein alpha-subunit binding Source: RGD
  4. protein complex binding Source: RGD
  5. serotonin binding Source: RGD
  6. serotonin receptor activity Source: RGD

GO - Biological processi

  1. activation of phospholipase C activity Source: Ensembl
  2. aging Source: RGD
  3. artery smooth muscle contraction Source: RGD
  4. behavioral response to cocaine Source: RGD
  5. cell death Source: RGD
  6. detection of mechanical stimulus involved in sensory perception of pain Source: RGD
  7. detection of temperature stimulus involved in sensory perception of pain Source: RGD
  8. G-protein coupled receptor signaling pathway Source: RGD
  9. memory Source: RGD
  10. negative regulation of potassium ion transport Source: RGD
  11. negative regulation of synaptic transmission, glutamatergic Source: RGD
  12. phosphatidylinositol 3-kinase signaling Source: Ensembl
  13. phospholipase C-activating serotonin receptor signaling pathway Source: RGD
  14. positive regulation of cell proliferation Source: RGD
  15. positive regulation of cytosolic calcium ion concentration Source: RGD
  16. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  17. positive regulation of glycolytic process Source: Ensembl
  18. positive regulation of MAP kinase activity Source: RGD
  19. positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  20. positive regulation of phosphatidylinositol biosynthetic process Source: Ensembl
  21. positive regulation of vasoconstriction Source: RGD
  22. protein localization to cytoskeleton Source: Ensembl
  23. regulation of behavior Source: InterPro
  24. regulation of dopamine secretion Source: RGD
  25. regulation of hormone secretion Source: InterPro
  26. release of sequestered calcium ion into cytosol Source: Ensembl
  27. response to drug Source: RGD
  28. sensory perception of pain Source: RGD
  29. sleep Source: RGD
  30. temperature homeostasis Source: RGD
  31. urinary bladder smooth muscle contraction Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Behavior

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 2A
Short name:
5-HT-2
Short name:
5-HT-2A
Alternative name(s):
Serotonin receptor 2A
Gene namesi
Name:Htr2a
Synonyms:Htr2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 15

Organism-specific databases

RGDi61800. Htr2a.

Subcellular locationi

Cell membrane; Multi-pass membrane protein. Cell projectionaxon. Cytoplasmic vesicle. Membranecaveola. Cell projectiondendrite By similarity
Note: Localizes to the postsynaptic thickening of axo-dendritic synapses.By similarity

GO - Cellular componenti

  1. cell body fiber Source: RGD
  2. cytoplasm Source: RGD
  3. cytoplasmic vesicle Source: UniProtKB-KW
  4. cytosol Source: RGD
  5. dendrite Source: RGD
  6. dendritic shaft Source: RGD
  7. integral component of plasma membrane Source: InterPro
  8. membrane Source: RGD
  9. neuronal cell body Source: RGD
  10. plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4714715-hydroxytryptamine receptor 2APRO_0000068951Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi8 – 81N-linked (GlcNAc...)Sequence Analysis
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi44 – 441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi51 – 511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi54 – 541N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi148 ↔ 227PROSITE-ProRule annotation
Modified residuei280 – 2801PhosphoserineBy similarity
Disulfide bondi349 ↔ 353PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP14842.
PRIDEiP14842.

PTM databases

PhosphoSiteiP14842.

Expressioni

Tissue specificityi

Detected in adult intestine, especially in mucosal epithelium, longitudinal and circular layers of muscularis externa and myenteric plexuses. Highly expressed in Paneth cells, and detected at lower levels in enterocytes (at protein level). Detected in brain cortex.2 Publications

Gene expression databases

GenevestigatoriP14842.

Interactioni

Subunit structurei

Interacts with MPDZ and INADL. May interact with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2. Interacts with GRM2 and DRD2; this may affect signaling (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Grm2P314213EBI-7090176,EBI-7090147

Protein-protein interaction databases

BioGridi248227. 1 interaction.
IntActiP14842. 1 interaction.
STRINGi10116.ENSRNOP00000013408.

Structurei

Secondary structure

1
471
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi469 – 4713

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4OAJX-ray2.30B465-471[»]
ProteinModelPortaliP14842.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 7575ExtracellularBy similarityAdd
BLAST
Topological domaini100 – 11011CytoplasmicBy similarityAdd
BLAST
Topological domaini133 – 14816ExtracellularBy similarityAdd
BLAST
Topological domaini172 – 19120CytoplasmicBy similarityAdd
BLAST
Topological domaini216 – 23318ExtracellularBy similarityAdd
BLAST
Topological domaini255 – 32470CytoplasmicBy similarityAdd
BLAST
Topological domaini347 – 36216ExtracellularBy similarityAdd
BLAST
Topological domaini385 – 47187CytoplasmicBy similarityAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei76 – 9924Helical; Name=1By similarityAdd
BLAST
Transmembranei111 – 13222Helical; Name=2By similarityAdd
BLAST
Transmembranei149 – 17123Helical; Name=3By similarityAdd
BLAST
Transmembranei192 – 21524Helical; Name=4By similarityAdd
BLAST
Transmembranei234 – 25421Helical; Name=5By similarityAdd
BLAST
Transmembranei325 – 34622Helical; Name=6By similarityAdd
BLAST
Transmembranei363 – 38422Helical; Name=7By similarityAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni155 – 1606Agonist bindingBy similarity
Regioni336 – 3405Agonist bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi172 – 1743DRY motif; important for ligand-induced conformation changesBy similarity
Motifi376 – 3805NPxxY motif; important for ligand-induced conformation changes and signalingBy similarity
Motifi469 – 4713PDZ-binding

Domaini

The PDZ domain-binding motif is involved in the interaction with INADL, CASK, APBA1, DLG1 and DLG4.By similarity

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG247243.
GeneTreeiENSGT00760000119257.
HOGENOMiHOG000240378.
HOVERGENiHBG107487.
InParanoidiP14842.
KOiK04157.
OMAiCTMVALG.
OrthoDBiEOG70ZZN5.
PhylomeDBiP14842.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24247:SF30. PTHR24247:SF30. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P14842-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEILCEDNIS LSSIPNSLMQ LGDGPRLYHN DFNSRDANTS EASNWTIDAE
60 70 80 90 100
NRTNLSCEGY LPPTCLSILH LQEKNWSALL TTVVIILTIA GNILVIMAVS
110 120 130 140 150
LEKKLQNATN YFLMSLAIAD MLLGFLVMPV SMLTILYGYR WPLPSKLCAI
160 170 180 190 200
WIYLDVLFST ASIMHLCAIS LDRYVAIQNP IHHSRFNSRT KAFLKIIAVW
210 220 230 240 250
TISVGISMPI PVFGLQDDSK VFKEGSCLLA DDNFVLIGSF VAFFIPLTIM
260 270 280 290 300
VITYFLTIKS LQKEATLCVS DLSTRAKLAS FSFLPQSSLS SEKLFQRSIH
310 320 330 340 350
REPGSYAGRR TMQSISNEQK ACKVLGIVFF LFVVMWCPFF ITNIMAVICK
360 370 380 390 400
ESCNENVIGA LLNVFVWIGY LSSAVNPLVY TLFNKTYRSA FSRYIQCQYK
410 420 430 440 450
ENRKPLQLIL VNTIPALAYK SSQLQVGQKK NSQEDAEQTV DDCSMVTLGK
460 470
QQSEENCTDN IETVNEKVSC V
Length:471
Mass (Da):52,850
Last modified:April 1, 1990 - v1
Checksum:i3626DACE5F6C7FF4
GO

Sequence cautioni

The sequence CAA32150.1 differs from that shown. Reason: Frameshift at position 37.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M30705 mRNA. Translation: AAA42178.1.
X13971 mRNA. Translation: CAA32150.1. Frameshift.
M64867 mRNA. No translation available.
PIRiA34863.
S02011.
RefSeqiNP_058950.1. NM_017254.1.
UniGeneiRn.10294.
Rn.146756.

Genome annotation databases

EnsembliENSRNOT00000013408; ENSRNOP00000013408; ENSRNOG00000010063.
GeneIDi29595.
KEGGirno:29595.
UCSCiRGD:61800. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M30705 mRNA. Translation: AAA42178.1 .
X13971 mRNA. Translation: CAA32150.1 . Frameshift.
M64867 mRNA. No translation available.
PIRi A34863.
S02011.
RefSeqi NP_058950.1. NM_017254.1.
UniGenei Rn.10294.
Rn.146756.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4OAJ X-ray 2.30 B 465-471 [» ]
ProteinModelPortali P14842.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 248227. 1 interaction.
IntActi P14842. 1 interaction.
STRINGi 10116.ENSRNOP00000013408.

Chemistry

BindingDBi P14842.
ChEMBLi CHEMBL2093870.
GuidetoPHARMACOLOGYi 6.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P14842.

Proteomic databases

PaxDbi P14842.
PRIDEi P14842.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000013408 ; ENSRNOP00000013408 ; ENSRNOG00000010063 .
GeneIDi 29595.
KEGGi rno:29595.
UCSCi RGD:61800. rat.

Organism-specific databases

CTDi 3356.
RGDi 61800. Htr2a.

Phylogenomic databases

eggNOGi NOG247243.
GeneTreei ENSGT00760000119257.
HOGENOMi HOG000240378.
HOVERGENi HBG107487.
InParanoidi P14842.
KOi K04157.
OMAi CTMVALG.
OrthoDBi EOG70ZZN5.
PhylomeDBi P14842.
TreeFami TF316350.

Miscellaneous databases

NextBioi 609738.
PROi P14842.

Gene expression databases

Genevestigatori P14842.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000455. 5HT2A_rcpt.
IPR002231. 5HT_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24247:SF30. PTHR24247:SF30. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00516. 5HT2ARECEPTR.
PR01101. 5HTRECEPTOR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors."
    Julius D., Huang K.N., Livelli T.J., Axel R., Jessell T.M.
    Proc. Natl. Acad. Sci. U.S.A. 87:928-932(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. "Structure and functional expression of cloned rat serotonin 5HT-2 receptor."
    Pritchett D.B., Bach A.W.J., Wozny M., Taleb O., Dal-Toso R., Shih J.C., Seeburg P.H.
    EMBO J. 7:4135-4140(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
  3. "The 5-HT2 serotonin receptor gene Htr-2 is tightly linked to Es-10 on mouse chromosome 14."
    Liu J., Chen Y., Kozak C.A., Yu L.
    Genomics 11:231-234(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "5-HT(2A) receptors: location and functional analysis in intestines of wild-type and 5-HT(2A) knockout mice."
    Fiorica-Howells E., Hen R., Gingrich J., Li Z., Gershon M.D.
    Am. J. Physiol. 282:G877-G893(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry namei5HT2A_RAT
AccessioniPrimary (citable) accession number: P14842
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: October 29, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3