HRH2_HUMAN
ID HRH2_HUMAN Reviewed; 359 AA.
AC P25021; B5BUP7; Q14464; Q7Z5R9;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Histamine H2 receptor;
DE Short=H2R;
DE Short=HH2R;
DE AltName: Full=Gastric receptor I;
GN Name=HRH2;
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 [GENOMIC DNA].
RX PubMed=1714721; DOI=10.1016/0006-291x(91)91047-g;
RA Gantz I., Munzert G., Tashiro T., Schaeffer M., Wang L.-D., DelValle J.,
RA Yamada T.;
RT "Molecular cloning of the human histamine H2 receptor.";
RL Biochem. Biophys. Res. Commun. 178:1386-1392(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=7755641; DOI=10.1006/bbrc.1995.1703;
RA Nishi T., Koike T., Oka T., Maeda M., Futai M.;
RT "Identification of the promoter region of the human histamine H2-receptor
RT gene.";
RL Biochem. Biophys. Res. Commun. 210:616-623(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10371214; DOI=10.1016/s0014-5793(99)00618-3;
RA Murakami H., Sun-Wada G., Matsumoto M., Nishi T., Wada Y., Futai M.;
RT "Human histamine H2 receptor gene: multiple transcription initiation and
RT tissue-specific expression.";
RL FEBS Lett. 451:327-331(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Stomach;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-351, AND POLYMORPHISM.
RC TISSUE=Brain;
RX PubMed=8817552; DOI=10.1097/00001756-199605170-00015;
RA Orange P.R., Heath P.R., Wright S.R., Pearson R.C.A.;
RT "Allelic variations of the human histamine H2 receptor gene.";
RL NeuroReport 7:1293-1296(1996).
RN [10]
RP REVIEW.
RX PubMed=9374694; DOI=10.1152/ajpgi.1997.273.5.g987;
RA DelValle J., Gantz I.;
RT "Novel insights into histamine H2 receptor biology.";
RL Am. J. Physiol. 273:G987-G996(1997).
CC -!- FUNCTION: The H2 subclass of histamine receptors mediates gastric acid
CC secretion. Also appears to regulate gastrointestinal motility and
CC intestinal secretion. Possible role in regulating cell growth and
CC differentiation. The activity of this receptor is mediated by G
CC proteins which activate adenylyl cyclase and, through a separate G
CC protein-dependent mechanism, the phosphoinositide/protein kinase (PKC)
CC signaling pathway (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25021-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25021-2; Sequence=VSP_043594;
CC -!- MISCELLANEOUS: Antagonists for this receptor have proven to be
CC effective therapy for acid peptic disorders of the gastrointestinal
CC tract. Certain antagonists are used in the treatment of
CC neuropsychiatric and neurological diseases such as schizophrenia,
CC Alzheimer disease and Parkinson disease.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=H2 receptor entry;
CC URL="https://en.wikipedia.org/wiki/H2_receptor";
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DR EMBL; M64799; AAA58647.1; -; Genomic_DNA.
DR EMBL; D49783; BAA08618.1; -; Genomic_DNA.
DR EMBL; AB023486; BAA84279.1; -; Genomic_DNA.
DR EMBL; AB041384; BAA94469.1; -; Genomic_DNA.
DR EMBL; AY136744; AAN01270.1; -; mRNA.
DR EMBL; AB451483; BAG70297.1; -; mRNA.
DR EMBL; CH471062; EAW61369.1; -; Genomic_DNA.
DR EMBL; BC054510; AAH54510.1; -; mRNA.
DR EMBL; X98133; CAA66832.1; -; Genomic_DNA.
DR CCDS; CCDS47344.1; -. [P25021-2]
DR PIR; JH0449; JH0449.
DR RefSeq; NP_001124527.1; NM_001131055.1. [P25021-2]
DR RefSeq; NP_071640.1; NM_022304.2.
DR AlphaFoldDB; P25021; -.
DR SMR; P25021; -.
DR BioGRID; 109510; 1.
DR STRING; 9606.ENSP00000366506; -.
DR BindingDB; P25021; -.
DR ChEMBL; CHEMBL1941; -.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB06216; Asenapine.
DR DrugBank; DB00972; Azelastine.
DR DrugBank; DB00272; Betazole.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB00434; Cyproheptadine.
DR DrugBank; DB01142; Doxepin.
DR DrugBank; DB00751; Epinastine.
DR DrugBank; DB00927; Famotidine.
DR DrugBank; DB05381; Histamine.
DR DrugBank; DB05369; HZT-501.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB00940; Methantheline.
DR DrugBank; DB08805; Metiamide.
DR DrugBank; DB00585; Nizatidine.
DR DrugBank; DB00768; Olopatadine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB00863; Ranitidine.
DR DrugBank; DB08806; Roxatidine acetate.
DR DrugBank; DB00797; Tolazoline.
DR DrugCentral; P25021; -.
DR GuidetoPHARMACOLOGY; 263; -.
DR GlyGen; P25021; 1 site.
DR PhosphoSitePlus; P25021; -.
DR BioMuta; HRH2; -.
DR DMDM; 123120; -.
DR PaxDb; P25021; -.
DR PeptideAtlas; P25021; -.
DR PRIDE; P25021; -.
DR ProteomicsDB; 54243; -. [P25021-1]
DR ProteomicsDB; 54244; -. [P25021-2]
DR Antibodypedia; 2931; 343 antibodies from 39 providers.
DR DNASU; 3274; -.
DR Ensembl; ENST00000377291.2; ENSP00000366506.2; ENSG00000113749.8. [P25021-2]
DR GeneID; 3274; -.
DR KEGG; hsa:3274; -.
DR UCSC; uc003mdc.5; human. [P25021-1]
DR CTD; 3274; -.
DR DisGeNET; 3274; -.
DR GeneCards; HRH2; -.
DR HGNC; HGNC:5183; HRH2.
DR HPA; ENSG00000113749; Tissue enhanced (bone).
DR MIM; 142703; gene.
DR neXtProt; NX_P25021; -.
DR OpenTargets; ENSG00000113749; -.
DR PharmGKB; PA29457; -.
DR VEuPathDB; HostDB:ENSG00000113749; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000158761; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P25021; -.
DR OMA; ITYYRIL; -.
DR PhylomeDB; P25021; -.
DR TreeFam; TF316350; -.
DR PathwayCommons; P25021; -.
DR Reactome; R-HSA-390650; Histamine receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P25021; -.
DR SIGNOR; P25021; -.
DR BioGRID-ORCS; 3274; 13 hits in 1070 CRISPR screens.
DR GeneWiki; Histamine_H2_receptor; -.
DR GenomeRNAi; 3274; -.
DR Pharos; P25021; Tclin.
DR PRO; PR:P25021; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P25021; protein.
DR Bgee; ENSG00000113749; Expressed in monocyte and 116 other tissues.
DR ExpressionAtlas; P25021; baseline and differential.
DR Genevisible; P25021; HS.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:GOC.
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:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; 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:0001696; P:gastric acid secretion; IEA:InterPro.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:InterPro.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000503; Histamine_H2_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00531; HISTAMINEH2R.
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; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..359
FT /note="Histamine H2 receptor"
FT /id="PRO_0000069684"
FT TOPO_DOM 1..22
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..44
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..81
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..92
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..114
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 115..134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..159
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..204
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..258
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..267
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..289
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 316..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 98
FT /note="Essential for histamine binding"
FT /evidence="ECO:0000250"
FT SITE 186
FT /note="Essential for tiotidine binding and implicated in H2
FT selectivity"
FT /evidence="ECO:0000250"
FT SITE 190
FT /note="Implicated in histamine binding"
FT /evidence="ECO:0000250"
FT LIPID 305
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 91..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 359
FT /note="R -> RPWLCLPECWSVELTHSFIHLFIHSFANIHPIPTTCQEL (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043594"
FT VARIANT 217
FT /note="N -> D"
FT /id="VAR_009958"
FT VARIANT 231
FT /note="K -> R"
FT /id="VAR_009959"
FT VARIANT 268
FT /note="V -> M"
FT /id="VAR_009960"
FT CONFLICT 133
FT /note="V -> A (in Ref. 9; CAA66832)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="K -> N (in Ref. 9; CAA66832)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="K -> R (in Ref. 9; CAA66832)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 40098 MW; 9835AE2BA60B9B0F CRC64;
MAPNGTASSF CLDSTACKIT ITVVLAVLIL ITVAGNVVVC LAVGLNRRLR NLTNCFIVSL
AITDLLLGLL VLPFSAIYQL SCKWSFGKVF CNIYTSLDVM LCTASILNLF MISLDRYCAV
MDPLRYPVLV TPVRVAISLV LIWVISITLS FLSIHLGWNS RNETSKGNHT TSKCKVQVNE
VYGLVDGLVT FYLPLLIMCI TYYRIFKVAR DQAKRINHIS SWKAATIREH KATVTLAAVM
GAFIICWFPY FTAFVYRGLR GDDAINEVLE AIVLWLGYAN SALNPILYAA LNRDFRTGYQ
QLFCCRLANR NSHKTSLRSN ASQLSRTQSR EPRQQEEKPL KLQVWSGTEV TAPQGATDR
