HRH3_RAT
ID HRH3_RAT Reviewed; 445 AA.
AC Q9QYN8; Q9QYN6; Q9QYN7; Q9QYN9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Histamine H3 receptor;
DE Short=H3R;
DE Short=HH3R;
GN Name=Hrh3;
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] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=10869375;
RA Lovenberg T.W., Pyati J., Chang H., Wilson S.J., Erlander M.G.;
RT "Cloning of rat histamine H3 receptor reveals distinct species
RT pharmacological profiles.";
RL J. Pharmacol. Exp. Ther. 293:771-778(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Corpus striatum;
RX PubMed=11130725; DOI=10.1038/35048583;
RA Morisset S., Rouleau A., Ligneau X., Gbahou F., Tardivel-Lacombe J.,
RA Stark H., Schunack W., Ganellin C.R., Schwartz J.-C., Arrang J.-M.;
RT "High constitutive activity of native H3 receptors regulates histamine
RT neurons in brain.";
RL Nature 408:860-864(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RA Itadani H., Takimura T., Nakamura T., Ohta M.;
RT "Cloning of a novel G protein-coupled receptor.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10347254; DOI=10.1124/mol.55.6.1101;
RA Lovenberg T.W., Roland B.L., Wilson S.J., Jiang X., Pyati J., Huvar A.,
RA Jackson M.R., Erlander M.G.;
RT "Cloning and functional expression of the human histamine H3 receptor.";
RL Mol. Pharmacol. 55:1101-1107(1999).
CC -!- FUNCTION: The H3 subclass of histamine receptors could mediate the
CC histamine signals in CNS and peripheral nervous system. Signals through
CC the inhibition of adenylate cyclase and displays high constitutive
CC activity (spontaneous activity in the absence of agonist).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=H3L;
CC IsoId=Q9QYN8-1; Sequence=Displayed;
CC Name=2; Synonyms=H3S;
CC IsoId=Q9QYN8-2; Sequence=VSP_001887;
CC Name=3;
CC IsoId=Q9QYN8-3; Sequence=VSP_001888;
CC Name=4;
CC IsoId=Q9QYN8-4; Sequence=VSP_001888, VSP_001889;
CC -!- TISSUE SPECIFICITY: Expressed abundantly in brain, most notably
CC throughout the thalamus, the ventromedial hypothalamus and the caudate
CC nucleus. Isoform 1 is largely predominant in all tissues.
CC {ECO:0000269|PubMed:10347254}.
CC -!- MISCELLANEOUS: Proxyfan acts as a potent neutral antagonist while
CC thioperamide, ciproxifan and FUB465 act as potent inverse agonists.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF237919; AAF82086.1; -; mRNA.
DR EMBL; AY009370; AAK02069.1; -; mRNA.
DR EMBL; AB015646; BAA88765.1; -; mRNA.
DR EMBL; AB015646; BAA88766.1; -; mRNA.
DR EMBL; AB015646; BAA88767.1; -; mRNA.
DR EMBL; AB015646; BAA88768.1; -; mRNA.
DR RefSeq; NP_001257493.1; NM_001270564.1. [Q9QYN8-2]
DR RefSeq; NP_001257494.1; NM_001270565.1. [Q9QYN8-3]
DR RefSeq; NP_001257497.1; NM_001270568.1. [Q9QYN8-4]
DR RefSeq; NP_445958.1; NM_053506.2. [Q9QYN8-1]
DR AlphaFoldDB; Q9QYN8; -.
DR SMR; Q9QYN8; -.
DR BioGRID; 250072; 1.
DR BindingDB; Q9QYN8; -.
DR ChEMBL; CHEMBL4124; -.
DR DrugCentral; Q9QYN8; -.
DR GuidetoPHARMACOLOGY; 264; -.
DR GlyGen; Q9QYN8; 1 site.
DR PhosphoSitePlus; Q9QYN8; -.
DR PRIDE; Q9QYN8; -.
DR Ensembl; ENSRNOT00000086761; ENSRNOP00000069003; ENSRNOG00000061153. [Q9QYN8-1]
DR Ensembl; ENSRNOT00000116829; ENSRNOP00000090011; ENSRNOG00000061153. [Q9QYN8-2]
DR GeneID; 85268; -.
DR KEGG; rno:85268; -.
DR CTD; 11255; -.
DR RGD; 620630; Hrh3.
DR GeneTree; ENSGT00940000161502; -.
DR InParanoid; Q9QYN8; -.
DR PhylomeDB; Q9QYN8; -.
DR Reactome; R-RNO-390650; Histamine receptors.
DR PRO; PR:Q9QYN8; -.
DR Proteomes; UP000002494; Chromosome 3.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043209; C:myelin sheath; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0043176; F:amine binding; IPI:RGD.
DR GO; GO:0016907; F:G protein-coupled acetylcholine receptor activity; IBA:GO_Central.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR GO; GO:1901363; F:heterocyclic compound binding; IPI:RGD.
DR GO; GO:0004969; F:histamine receptor activity; IEA:InterPro.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; IMP:RGD.
DR GO; GO:0042756; P:drinking behavior; IMP:RGD.
DR GO; GO:0042755; P:eating behavior; 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:0007612; P:learning; IMP:RGD.
DR GO; GO:0007613; P:memory; IMP:RGD.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; IDA:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR GO; GO:0014053; P:negative regulation of gamma-aminobutyric acid secretion; IMP:RGD.
DR GO; GO:0014050; P:negative regulation of glutamate secretion; IMP:RGD.
DR GO; GO:0014063; P:negative regulation of serotonin secretion; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0001505; P:regulation of neurotransmitter levels; IEA:InterPro.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IMP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:RGD.
DR CDD; cd15296; 7tmA_Histamine_H3R; 1.
DR InterPro; IPR041998; 7tmA_HRH3.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003980; Histamine_H3_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01471; HISTAMINEH3R.
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 Alternative splicing; Cell membrane; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..445
FT /note="Histamine H3 receptor"
FT /id="PRO_0000069692"
FT TOPO_DOM 1..39
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 40..60
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..108
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..129
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..196
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 218..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 381..396
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 397..417
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 418..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 234..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..259
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58406"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 274..321
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_001888"
FT VAR_SEQ 274..305
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11130725, ECO:0000303|Ref.3"
FT /id="VSP_001887"
FT VAR_SEQ 393..445
FT /note="WYETSFWLLWANSAVNPVLYPLCHYSFRRAFTKLLCPQKLKVQPHGSLEQCW
FT K -> CVERLGKLEASLLLPLWMFSGRWRRRKHVCELDVPWMFNQERQNCRGARGWIGR
FT CGLPRPPPSVLQLPAEPRQLLLPAPPPGLGRWPCPACPVCTIRIWGWVVMG (in
FT isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_001889"
SQ SEQUENCE 445 AA; 48588 MW; 63DFEFC21758FE5B CRC64;
MERAPPDGLM NASGTLAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV
ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCAS
SVFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMALVW VLAFLLYGPA ILSWEYLSGG
SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGGREAG
PEPPPDAQPS PPPAPPSCWG CWPKGHGEAM PLHRYGVGEA GPGVEAGEAA LGGGSGGGAA
ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSITQRFRL SRDKKVAKSL
AIIVSIFGLC WAPYTLLMII RAACHGRCIP DYWYETSFWL LWANSAVNPV LYPLCHYSFR
RAFTKLLCPQ KLKVQPHGSL EQCWK
