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Protein

Histamine H2 receptor

Gene

HRH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei98 – 981Essential for histamine bindingBy similarity
Sitei186 – 1861Essential for tiotidine binding and implicated in H2 selectivityBy similarity
Sitei190 – 1901Implicated in histamine bindingBy similarity

GO - Molecular functioni

  • histamine receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16903. Histamine receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Histamine H2 receptor
Short name:
H2R
Short name:
HH2R
Alternative name(s):
Gastric receptor I
Gene namesi
Name:HRH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:5183. HRH2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222ExtracellularSequence AnalysisAdd
BLAST
Transmembranei23 – 4422Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini45 – 5713CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei58 – 8124Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini82 – 9211ExtracellularSequence AnalysisAdd
BLAST
Transmembranei93 – 11422Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini115 – 13420CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei135 – 15925Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini160 – 18021ExtracellularSequence AnalysisAdd
BLAST
Transmembranei181 – 20424Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini205 – 23430CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei235 – 25824Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini259 – 2679ExtracellularSequence Analysis
Transmembranei268 – 28922Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini290 – 35970CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29457.

Chemistry

DrugBankiDB00321. Amitriptyline.
DB06216. Asenapine.
DB00272. Betazole.
DB00501. Cimetidine.
DB01142. Doxepin.
DB00751. Epinastine.
DB00927. Famotidine.
DB00667. Histamine Phosphate.
DB00408. Loxapine.
DB00940. Methantheline.
DB00585. Nizatidine.
DB00334. Olanzapine.
DB00863. Ranitidine.
DB08806. Roxatidine acetate.
DB00797. Tolazoline.

Polymorphism and mutation databases

BioMutaiHRH2.
DMDMi123120.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 359359Histamine H2 receptorPRO_0000069684Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi4 – 41N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi91 ↔ 174PROSITE-ProRule annotation
Lipidationi305 – 3051S-palmitoyl cysteineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP25021.
PRIDEiP25021.

PTM databases

PhosphoSiteiP25021.

Expressioni

Gene expression databases

BgeeiP25021.
CleanExiHS_HRH2.
GenevestigatoriP25021.

Organism-specific databases

HPAiHPA013770.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000366506.

Structurei

3D structure databases

ProteinModelPortaliP25021.
SMRiP25021. Positions 21-325.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG283797.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP25021.
KOiK04150.
OMAiQVWSGTE.
OrthoDBiEOG7QC7W8.
PhylomeDBiP25021.
TreeFamiTF316350.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000503. Histamine_H2_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00531. HISTAMINEH2R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P25021-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPNGTASSF CLDSTACKIT ITVVLAVLIL ITVAGNVVVC LAVGLNRRLR
60 70 80 90 100
NLTNCFIVSL AITDLLLGLL VLPFSAIYQL SCKWSFGKVF CNIYTSLDVM
110 120 130 140 150
LCTASILNLF MISLDRYCAV MDPLRYPVLV TPVRVAISLV LIWVISITLS
160 170 180 190 200
FLSIHLGWNS RNETSKGNHT TSKCKVQVNE VYGLVDGLVT FYLPLLIMCI
210 220 230 240 250
TYYRIFKVAR DQAKRINHIS SWKAATIREH KATVTLAAVM GAFIICWFPY
260 270 280 290 300
FTAFVYRGLR GDDAINEVLE AIVLWLGYAN SALNPILYAA LNRDFRTGYQ
310 320 330 340 350
QLFCCRLANR NSHKTSLRSN ASQLSRTQSR EPRQQEEKPL KLQVWSGTEV

TAPQGATDR
Length:359
Mass (Da):40,098
Last modified:May 1, 1992 - v1
Checksum:i9835AE2BA60B9B0F
GO
Isoform 2 (identifier: P25021-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-359: R → RPWLCLPECWSVELTHSFIHLFIHSFANIHPIPTTCQEL

Note: No experimental confirmation available.

Show »
Length:397
Mass (Da):44,541
Checksum:iBDEAD7C8FEC25480
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti133 – 1331V → A in CAA66832 (PubMed:8817552).Curated
Sequence conflicti175 – 1751K → N in CAA66832 (PubMed:8817552).Curated
Sequence conflicti207 – 2071K → R in CAA66832 (PubMed:8817552).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti217 – 2171N → D.
VAR_009958
Natural varianti231 – 2311K → R.
VAR_009959
Natural varianti268 – 2681V → M.
VAR_009960

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei359 – 3591R → RPWLCLPECWSVELTHSFIH LFIHSFANIHPIPTTCQEL in isoform 2. 1 PublicationVSP_043594

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64799 Genomic DNA. Translation: AAA58647.1.
D49783 Genomic DNA. Translation: BAA08618.1.
AB023486 Genomic DNA. Translation: BAA84279.1.
AB041384 Genomic DNA. Translation: BAA94469.1.
AY136744 mRNA. Translation: AAN01270.1.
AB451483 mRNA. Translation: BAG70297.1.
CH471062 Genomic DNA. Translation: EAW61369.1.
BC054510 mRNA. Translation: AAH54510.1.
X98133 Genomic DNA. Translation: CAA66832.1.
CCDSiCCDS4395.1. [P25021-1]
CCDS47344.1. [P25021-2]
PIRiJH0449.
RefSeqiNP_001124527.1. NM_001131055.1. [P25021-2]
NP_071640.1. NM_022304.2. [P25021-1]
UniGeneiHs.247885.

Genome annotation databases

EnsembliENST00000231683; ENSP00000231683; ENSG00000113749. [P25021-1]
ENST00000377291; ENSP00000366506; ENSG00000113749. [P25021-2]
GeneIDi3274.
KEGGihsa:3274.
UCSCiuc003mdc.4. human. [P25021-2]
uc003mdd.2. human. [P25021-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

H2 receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64799 Genomic DNA. Translation: AAA58647.1.
D49783 Genomic DNA. Translation: BAA08618.1.
AB023486 Genomic DNA. Translation: BAA84279.1.
AB041384 Genomic DNA. Translation: BAA94469.1.
AY136744 mRNA. Translation: AAN01270.1.
AB451483 mRNA. Translation: BAG70297.1.
CH471062 Genomic DNA. Translation: EAW61369.1.
BC054510 mRNA. Translation: AAH54510.1.
X98133 Genomic DNA. Translation: CAA66832.1.
CCDSiCCDS4395.1. [P25021-1]
CCDS47344.1. [P25021-2]
PIRiJH0449.
RefSeqiNP_001124527.1. NM_001131055.1. [P25021-2]
NP_071640.1. NM_022304.2. [P25021-1]
UniGeneiHs.247885.

3D structure databases

ProteinModelPortaliP25021.
SMRiP25021. Positions 21-325.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000366506.

Chemistry

BindingDBiP25021.
ChEMBLiCHEMBL1941.
DrugBankiDB00321. Amitriptyline.
DB06216. Asenapine.
DB00272. Betazole.
DB00501. Cimetidine.
DB01142. Doxepin.
DB00751. Epinastine.
DB00927. Famotidine.
DB00667. Histamine Phosphate.
DB00408. Loxapine.
DB00940. Methantheline.
DB00585. Nizatidine.
DB00334. Olanzapine.
DB00863. Ranitidine.
DB08806. Roxatidine acetate.
DB00797. Tolazoline.
GuidetoPHARMACOLOGYi263.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP25021.

Polymorphism and mutation databases

BioMutaiHRH2.
DMDMi123120.

Proteomic databases

PaxDbiP25021.
PRIDEiP25021.

Protocols and materials databases

DNASUi3274.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000231683; ENSP00000231683; ENSG00000113749. [P25021-1]
ENST00000377291; ENSP00000366506; ENSG00000113749. [P25021-2]
GeneIDi3274.
KEGGihsa:3274.
UCSCiuc003mdc.4. human. [P25021-2]
uc003mdd.2. human. [P25021-1]

Organism-specific databases

CTDi3274.
GeneCardsiGC05P175085.
HGNCiHGNC:5183. HRH2.
HPAiHPA013770.
MIMi142703. gene.
neXtProtiNX_P25021.
PharmGKBiPA29457.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG283797.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP25021.
KOiK04150.
OMAiQVWSGTE.
OrthoDBiEOG7QC7W8.
PhylomeDBiP25021.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiREACT_16903. Histamine receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiHistamine_H2_receptor.
GenomeRNAii3274.
NextBioi13003.
PROiP25021.
SOURCEiSearch...

Gene expression databases

BgeeiP25021.
CleanExiHS_HRH2.
GenevestigatoriP25021.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000503. Histamine_H2_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00531. HISTAMINEH2R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Identification of the promoter region of the human histamine H2-receptor gene."
    Nishi T., Koike T., Oka T., Maeda M., Futai M.
    Biochem. Biophys. Res. Commun. 210:616-623(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Liver.
  3. "Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression."
    Murakami H., Sun-Wada G., Matsumoto M., Nishi T., Wada Y., Futai M.
    FEBS Lett. 451:327-331(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Human-specific amino acid changes found in 103 protein-coding genes."
    Kitano T., Liu Y.-H., Ueda S., Saitou N.
    Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Stomach.
  6. "Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
    Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.
    , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
    Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Skin.
  9. "Allelic variations of the human histamine H2 receptor gene."
    Orange P.R., Heath P.R., Wright S.R., Pearson R.C.A.
    NeuroReport 7:1293-1296(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-351, POLYMORPHISM.
    Tissue: Brain.
  10. "Novel insights into histamine H2 receptor biology."
    DelValle J., Gantz I.
    Am. J. Physiol. 273:G987-G996(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiHRH2_HUMAN
AccessioniPrimary (citable) accession number: P25021
Secondary accession number(s): B5BUP7, Q14464, Q7Z5R9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: April 29, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Antagonists for this receptor have proven to be effective therapy for acid peptic disorders of the gastrointestinal tract. Certain antagonists are used in the treatment of neuropsychiatric and neurological diseases such as schizophrenia, Alzheimer disease and Parkinson disease.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.