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Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. Histamine receptor H2 belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and stimulates gastric acid secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
HRH2 (Histamine Receptor H2) is a Protein Coding gene. Diseases associated with HRH2 include Duodenal Ulcer and Peptic Ulcer Disease. Among its related pathways are Monoamine GPCRs and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and histamine receptor activity. An important paralog of this gene is HTR4.
Histamine H2 receptors are Galphas-protein-coupled receptors involved in the suppressive activities of histamine. H2 receptors exhibit a widespread distribution and are found in the gastrointestinal tract, the central nervous system, smooth muscle cells and endothelial cells.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH05J175657 | Promoter/Enhancer | 2 | EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER | 750.6 | +0.9 | 905 | 2.6 | SREBF1 ZNF133 POLR2A MTA3 SP7 PRDM1 ZNF547 GLIS2 ZIC2 ZBTB8A | HRH2 FAF2 RF00017-5128 LOC105377743 | |
GH05J175656 | Promoter/Enhancer | 0.5 | Ensembl dbSUPER | 750.6 | -0.9 | -895 | 0.2 | HRH2 RF00017-5128 | ||
GH05J175691 | Enhancer | 0.7 | FANTOM5 dbSUPER | 13.5 | +33.4 | 33412 | 0.2 | MYC L3MBTL2 MAX NRF1 CTCF POLR2A | HRH2 LOC105377743 RF00017-5128 | |
GH05J175670 | Enhancer | 0.5 | FANTOM5 dbSUPER | 14.3 | +13.4 | 13429 | 0.3 | POLR2A | HRH2 RF00017-5128 LOC105377743 | |
GH05J175689 | Enhancer | 0.8 | FANTOM5 ENCODE dbSUPER | 8.6 | +31.9 | 31905 | 0.5 | MAX POLR2A | HRH2 LOC105377743 RF00017-5128 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004930 | G protein-coupled receptor activity | IBA | 21873635 |
GO:0004969 | histamine receptor activity | TAS,IBA | 21873635 |
GO:0004993 | G protein-coupled serotonin receptor activity | IBA | 21873635 |
GO:0030594 | neurotransmitter receptor activity | IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | IBA,TAS | 21873635 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
GO:0030425 | dendrite | IBA | 21873635 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors | ||
2 | Monoamine GPCRs |
.75
|
|
3 | Signaling by GPCR | ||
4 | Development Ligand-independent activation of ESR1 and ESR2 | ||
5 | Calcium signaling pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001697 | histamine-induced gastric acid secretion | IEA | -- |
GO:0001698 | gastrin-induced gastric acid secretion | IEA | -- |
GO:0003382 | epithelial cell morphogenesis | IEA | -- |
GO:0006955 | immune response | TAS | 9725260 |
GO:0007165 | signal transduction | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Ranitidine | Approved | Pharma | Antagonist, Target, antagonist | Histamine H2-receptor antagonist | 96 | |
Cimetidine | Approved, Investigational | Pharma | Inhibition, Inhibitor, Target, antagonist | H2 receptor antagonist | 97 | |
Famotidine | Approved | Pharma | Target, antagonist | Histamine H2-receptor antagonist | 70 | |
Nizatidine | Approved | Pharma | Target, antagonist | 10 | ||
Histamine | Approved, Investigational | Pharma | Full agonist, Agonist, Target, agonist | 1213 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
Compound | Action | Cas Number |
---|---|---|
Aminopotentidine | H2 antagonist | 140873-26-3 |
Amthamine dihydrobromide | Highly selective standard H2 agonist | 142457-00-9 |
Dimaprit dihydrochloride | Standard H2 selective agonist | 23256-33-9 |
ICI 162,846 | Potent H2 antagonist, active in vivo | 84545-30-2 |
Tiotidine | Potent, selective H2 antagonist | 69014-14-8 |
Compound | Action | Cas Number |
---|---|---|
(R)-(-)-α-Methylhistamine dihydrobromide | 868698-49-1 | |
(S)-(+)-α-Methylhistamine dihydrobromide | 75614-93-6 | |
2-Pyridylethylamine dihydrochloride | 3343-39-3 | |
Alcaftadine | 147084-10-4 | |
Aminopotentidine | 140873-26-3 | |
Amthamine dihydrobromide | 142457-00-9 | |
Astemizole | 68844-77-9 | |
Azatadine | 3964-81-6 | |
Azatadine dimaleate | 3978-86-7 | |
Azelastine HCl | 79307-93-0 | |
Benztropine mesylate | 132-17-2 | |
Bepotastine Besilate | 190786-44-8 | |
Betahistine 2HCl | 5579-84-0 | |
Bilastine | 202189-78-4 | |
Brompheniramine hydrogen maleate | 980-71-2 | |
Buclizine HCl | 129-74-8 | |
Carcinine ditrifluoroacetate | 56897-53-1 | |
Cetirizine | Antihistamine | 83881-51-0 |
Cetirizine DiHCl | H1 receptor inverse agonist | 83881-52-1 |
Chlorpheniramine Maleate | 113-92-8 | |
Cimetidine | H2 receptor antagonist | 51481-61-9 |
Ciproxifan | Histamine H3-receptor antagonist | 184025-18-1 |
Ciproxifan maleate | 184025-19-2 | |
Clemastine Fumarate | 14976-57-9 | |
Clemizole hydrochloride | H1 histamine receptor antagonist | 1163-36-6 |
Clobenpropit dihydrobromide | 145231-35-2 | |
Conessine | 546-06-5 | |
Cyclizine 2HCl | 5897-18-7 | |
Cyproheptadine hydrochloride | 969-33-5 | |
Decloxizine | 3733-63-9 | |
Decloxizine dihydrochloride | 13073-96-6 | |
Desloratadine | 100643-71-8 | |
Dimaprit dihydrochloride | 23256-33-9 | |
DPPE fumarate | 1185241-83-1 | |
Ebrotidine | H2-receptor antagonist,competitive | 100981-43-9 |
Epinastine HCl | 108929-04-0 | |
Famotidine | Histamine H2-receptor antagonist | 76824-35-6 |
Fexofenadine HCl | 153439-40-8 | |
GT 2016 | 152241-24-2 | |
Histamine 2HCl | 56-92-8 | |
Histamine Phosphate | 51-74-1 | |
HTMT dimaleate | 195867-54-0 | |
Hydroxyzine | 68-88-2 | |
Hydroxyzine 2HCl | 2192-20-3 | |
ICI 162,846 | 84545-30-2 | |
Imetit dihydrobromide | 32385-58-3 | |
Immepip dihydrobromide | 164391-47-3 | |
Immethridine dihydrobromide | 699020-93-4 | |
Impentamine dihydrobromide | 149629-70-9 | |
Iodophenpropit dihydrobromide | 145196-87-8 | |
JNJ 10181457 dihydrochloride | 544707-20-2 | |
JNJ 10191584 maleate | 869497-75-6 | |
JNJ 5207852 dihydrochloride | 398473-34-2 | |
JNJ-7777120 | Histamine H4 receptor antagonist | 459168-41-3 |
Ketotifen Fumarate | 34580-14-8 | |
Lafutidine | 118288-08-7 | |
LED209 | Highly selective for histidine sensor kinase QseC | 245342-14-7 |
Levodropropizine | Histamine receptor inhibitor,cough suppressant | 99291-25-5 |
Lidocaine | Anasthetic and class Ib antiarrhythmic agent | 137-58-6 |
Loratadine | Peripheral HH1R antagonist | 79794-75-5 |
Mepyramine maleate | 59-33-6 | |
Methimepip dihydrobromide | 817636-54-7 | |
Metiamide | Histamine H2-receptor antagonist | 34839-70-8 |
Mianserin | 24219-97-4 | |
Mianserin HCl | 5-HT2 receptor antagonist | 21535-47-7 |
Mizolastine | 108612-45-9 | |
Nizatidine | 76963-41-2 | |
Nα-Methylhistamine dihydrochloride | 16503-22-3 | |
Olopatadine HCl | Histamine blocker | 140462-76-6 |
Pemirolast potassium | 100299-08-9 | |
Pitolisant | Nonimidazole inverse agonist | 362665-56-3 |
Pitolisant hydrochloride | Nonimidazole inverse agonist | 903576-44-3 |
Pitolisant oxalate | Nonimidazole inverse agonist | 362665-57-4 |
Proxyfan oxalate | 177708-09-7 | |
Ranitidine | Histamine H2-receptor antagonist | 66357-59-3 |
ROS 234 dioxalate | 184576-87-2 | |
Roxatidine Acetate HCl | 93793-83-0 | |
Rupatadine Fumarate | 182349-12-8 | |
Serotonin HCl | 153-98-0 | |
Thioperamide | 106243-16-7 | |
Tiotidine | 69014-14-8 | |
trans-Triprolidine hydrochloride | 550-70-9 | |
Tripelennamine HCl | H1-receptor antagonist | 154-69-8 |
VUF 10460 | 1028327-66-3 | |
VUF 5681 dihydrobromide | 639089-06-8 | |
VUF 8430 dihydrobromide | 100130-32-3 | |
Zaltidine | H2-receptor antagonist | 85604-00-8 |
Zolantidine dimaleate | 104076-39-3 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
chimpanzee (Pan troglodytes) |
Mammalia | HRH2 33 32 |
|
OneToOne | |
dog (Canis familiaris) |
Mammalia | HRH2 33 32 |
|
OneToOne | |
rat (Rattus norvegicus) |
Mammalia | Hrh2 32 |
|
||
mouse (Mus musculus) |
Mammalia | Hrh2 17 33 32 |
|
||
cow (Bos Taurus) |
Mammalia | LOC521257 32 |
|
||
HRH2 33 |
|
OneToOne | |||
oppossum (Monodelphis domestica) |
Mammalia | HRH2 33 |
|
OneToOne | |
platypus (Ornithorhynchus anatinus) |
Mammalia | HRH2 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | HRH2 33 32 |
|
OneToOne | |
lizard (Anolis carolinensis) |
Reptilia | HRH2 33 |
|
OneToOne | |
tropical clawed frog (Silurana tropicalis) |
Amphibia | hrh2 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | hrh2 32 |
|
||
HRH2 33 |
|
OneToOne | |||
fruit fly (Drosophila melanogaster) |
Insecta | Octbeta3R 32 |
|
||
CG6919 34 |
|
|
|||
African malaria mosquito (Anopheles gambiae) |
Insecta | GPRNNA3 32 |
|
||
worm (Caenorhabditis elegans) |
Secernentea | M03F4.3 34 |
|
|
|
ser-6 33 |
|
ManyToMany | |||
ser-5 33 |
|
ManyToMany |
SNP ID | Clin | Chr 05 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs1000044005 | -- | 175,676,118(+) | C/T | intron_variant | |
rs1000142021 | -- | 175,686,391(+) | A/G | downstream_transcript_variant, genic_downstream_transcript_variant, intron_variant | |
rs1000146634 | -- | 175,708,112(+) | GGGG/GGG | 3_prime_UTR_variant, genic_downstream_transcript_variant, non_coding_transcript_variant | |
rs1000230301 | -- | 175,665,840(+) | A/G | intron_variant | |
rs1000237198 | -- | 175,691,886(+) | A/G | genic_downstream_transcript_variant, intron_variant |
Disorder | Aliases | PubMed IDs |
---|---|---|
duodenal ulcer |
|
|
peptic ulcer disease |
|
|
gastric ulcer |
|
|
zollinger-ellison syndrome |
|
|
esophagitis |
|