ID HRH3_HUMAN Reviewed; 445 AA.
AC Q9Y5N1; Q4QRI7; Q9GZX2; Q9H4K8;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2001, sequence version 2.
DT 27-MAR-2024, entry version 194.
DE RecName: Full=Histamine H3 receptor;
DE Short=H3R;
DE Short=HH3R;
DE AltName: Full=G-protein coupled receptor 97;
GN Name=HRH3; Synonyms=GPCR97;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thalamus;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHARACTERIZATION.
RX PubMed=11118334; DOI=10.1006/bbrc.2000.4008;
RA Nakamura T., Itadani H., Hidaka Y., Ohta M., Tanaka K.;
RT "Molecular cloning and characterization of a new human histamine receptor,
RT HH4R.";
RL Biochem. Biophys. Res. Commun. 279:615-620(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 3; 4; 5; 6 AND 7).
RC TISSUE=Thalamus;
RX PubMed=11284713; DOI=10.1042/0264-6021:3550279;
RA Coge F., Guenin S.-P., Audinot V., Renouard-Try A., Beauverger P.,
RA Macia C., Ouvry C., Nagel N., Rique H., Boutin J.A., Galizzi J.-P.;
RT "Genomic organization and characterization of splice variants of the human
RT histamine H3 receptor.";
RL Biochem. J. 355:279-288(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-280.
RC TISSUE=Blood;
RX PubMed=11956964; DOI=10.1007/s007020200036;
RA Wiedemann P., Boenisch H., Oerters F., Bruess M.;
RT "Structure of the human histamine H3 receptor gene (HRH3) and
RT identification of naturally occurring variations.";
RL J. Neural Transm. 109:443-453(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Ullmer C., Zirwes E., Lubbert H.;
RT "Cloning and functional expression of the human histamine H3S receptor.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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). Agonist
CC stimulation of isoform 3 neither modified adenylate cyclase activity
CC nor induced intracellular calcium mobilization.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9Y5N1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y5N1-2; Sequence=VSP_001886;
CC Name=3; Synonyms=H3S;
CC IsoId=Q9Y5N1-3; Sequence=VSP_001885;
CC Name=4;
CC IsoId=Q9Y5N1-4; Sequence=VSP_001881;
CC Name=5;
CC IsoId=Q9Y5N1-5; Sequence=VSP_001882;
CC Name=6;
CC IsoId=Q9Y5N1-6; Sequence=VSP_001883;
CC Name=7;
CC IsoId=Q9Y5N1-7; Sequence=VSP_001884;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the CNS, with the
CC greatest expression in the thalamus and caudate nucleus. The various
CC isoforms are mainly coexpressed in brain, but their relative expression
CC level varies in a region-specific manner. Isoform 3 and isoform 7 are
CC highly expressed in the thalamus, caudate nucleus and cerebellum while
CC isoform 5 and isoform 6 show a poor expression. Isoform 5 and isoform 6
CC show a high expression in the amygdala, substantia nigra, cerebral
CC cortex and hypothalamus. Isoform 7 is not found in hypothalamus or
CC substantia nigra.
CC -!- MISCELLANEOUS: Does not bind to cimetidine and tripolidine. Shows
CC modest affinity for thioperamide, imetit, N-alpha-methylhistamine and
CC R(-)-alpha-methylhistamine. Isoform 4 is unable to bind to iodoproxyfan
CC while isoforms 1 and 3 bind it with high affinity.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF140538; AAD38151.1; -; mRNA.
DR EMBL; AB045369; BAB20090.1; -; mRNA.
DR EMBL; AB019000; BAB17030.1; -; mRNA.
DR EMBL; AJ296652; CAC51025.1; -; Genomic_DNA.
DR EMBL; AJ278250; CAC39434.1; -; Genomic_DNA.
DR EMBL; AF363791; AAK50040.1; -; mRNA.
DR EMBL; AL078633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096840; AAH96840.1; -; mRNA.
DR CCDS; CCDS13493.1; -. [Q9Y5N1-1]
DR RefSeq; NP_009163.2; NM_007232.2. [Q9Y5N1-1]
DR RefSeq; XP_005260323.1; XM_005260266.3. [Q9Y5N1-2]
DR PDB; 7F61; X-ray; 2.60 A; A=27-433.
DR PDBsum; 7F61; -.
DR AlphaFoldDB; Q9Y5N1; -.
DR SMR; Q9Y5N1; -.
DR BioGRID; 116416; 4.
DR DIP; DIP-61456N; -.
DR IntAct; Q9Y5N1; 2.
DR STRING; 9606.ENSP00000342560; -.
DR BindingDB; Q9Y5N1; -.
DR ChEMBL; CHEMBL264; -.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB06698; Betahistine.
DR DrugBank; DB05381; Histamine.
DR DrugBank; DB17087; JNJ-17216498.
DR DrugBank; DB05080; OBE101.
DR DrugBank; DB00768; Olopatadine.
DR DrugBank; DB11642; Pitolisant.
DR DrugCentral; Q9Y5N1; -.
DR GuidetoPHARMACOLOGY; 264; -.
DR GlyCosmos; Q9Y5N1; 1 site, No reported glycans.
DR GlyGen; Q9Y5N1; 1 site.
DR PhosphoSitePlus; Q9Y5N1; -.
DR BioMuta; HRH3; -.
DR DMDM; 17367264; -.
DR MassIVE; Q9Y5N1; -.
DR PaxDb; 9606-ENSP00000342560; -.
DR PeptideAtlas; Q9Y5N1; -.
DR Antibodypedia; 14714; 561 antibodies from 36 providers.
DR DNASU; 11255; -.
DR Ensembl; ENST00000340177.10; ENSP00000342560.5; ENSG00000101180.17. [Q9Y5N1-1]
DR GeneID; 11255; -.
DR KEGG; hsa:11255; -.
DR MANE-Select; ENST00000340177.10; ENSP00000342560.5; NM_007232.3; NP_009163.2.
DR UCSC; uc002ycf.3; human. [Q9Y5N1-1]
DR AGR; HGNC:5184; -.
DR CTD; 11255; -.
DR DisGeNET; 11255; -.
DR GeneCards; HRH3; -.
DR HGNC; HGNC:5184; HRH3.
DR HPA; ENSG00000101180; Tissue enriched (brain).
DR MIM; 604525; gene.
DR neXtProt; NX_Q9Y5N1; -.
DR OpenTargets; ENSG00000101180; -.
DR PharmGKB; PA29458; -.
DR VEuPathDB; HostDB:ENSG00000101180; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161502; -.
DR InParanoid; Q9Y5N1; -.
DR OMA; DIFHEVH; -.
DR OrthoDB; 5405331at2759; -.
DR PhylomeDB; Q9Y5N1; -.
DR TreeFam; TF351747; -.
DR PathwayCommons; Q9Y5N1; -.
DR Reactome; R-HSA-390650; Histamine receptors.
DR SignaLink; Q9Y5N1; -.
DR SIGNOR; Q9Y5N1; -.
DR BioGRID-ORCS; 11255; 13 hits in 1158 CRISPR screens.
DR ChiTaRS; HRH3; human.
DR GeneWiki; Histamine_H3_receptor; -.
DR GenomeRNAi; 11255; -.
DR Pharos; Q9Y5N1; Tclin.
DR PRO; PR:Q9Y5N1; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9Y5N1; Protein.
DR Bgee; ENSG00000101180; Expressed in putamen and 68 other cell types or tissues.
DR ExpressionAtlas; Q9Y5N1; baseline and differential.
DR Genevisible; Q9Y5N1; HS.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
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:0004969; F:histamine receptor activity; TAS:ProtInc.
DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; IBA:GO_Central.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0014050; P:negative regulation of glutamate secretion; IBA:GO_Central.
DR GO; GO:0014063; P:negative regulation of serotonin secretion; IBA:GO_Central.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:ProtInc.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IBA:GO_Central.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003980; Histamine_H3_rcpt.
DR PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1.
DR PANTHER; PTHR24247:SF194; HISTAMINE H3 RECEPTOR; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01471; HISTAMINEH3R.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 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; Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..445
FT /note="Histamine H3 receptor"
FT /id="PRO_0000069690"
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..395
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 237..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 288..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..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 DISULFID 107..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 85..98
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_001881"
FT VAR_SEQ 197..315
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_001882"
FT VAR_SEQ 227..342
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_001883"
FT VAR_SEQ 234..263
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_001884"
FT VAR_SEQ 274..353
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_001885"
FT VAR_SEQ 445
FT /note="K -> KKMKKKTCL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11118334"
FT /id="VSP_001886"
FT VARIANT 280
FT /note="A -> V (in a Shy-Drager syndrome patient; uncertain
FT significance; dbSNP:rs752380770)"
FT /evidence="ECO:0000269|PubMed:11956964"
FT /id="VAR_012235"
FT CONFLICT 19
FT /note="E -> D (in Ref. 1 and 5)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 48671 MW; 2ACF7440FBE95B6C CRC64;
MERAPPDGPL NASGALAGEA AAAGGARGFS AAWTAVLAAL MALLIVATVL GNALVMLAFV
ADSSLRTQNN FFLLNLAISD FLVGAFCIPL YVPYVLTGRW TFGRGLCKLW LVVDYLLCTS
SAFNIVLISY DRFLSVTRAV SYRAQQGDTR RAVRKMLLVW VLAFLLYGPA ILSWEYLSGG
SSIPEGHCYA EFFYNWYFLI TASTLEFFTP FLSVTFFNLS IYLNIQRRTR LRLDGAREAA
GPEPPPEAQP SPPPPPGCWG CWQKGHGEAM PLHRYGVGEA AVGAEAGEAT LGGGGGGGSV
ASPTSSSGSS SRGTERPRSL KRGSKPSASS ASLEKRMKMV SQSFTQRFRL SRDRKVAKSL
AVIVSIFGLC WAPYTLLMII RAACHGHCVP DYWYETSFWL LWANSAVNPV LYPLCHHSFR
RAFTKLLCPQ KLKIQPHSSL EHCWK
//
