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P25021 (HRH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histamine H2 receptor

Short name=H2R
Short name=HH2R
Alternative name(s):
Gastric receptor I
Gene names
Name:HRH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length359 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subcellular location

Cell membrane; Multi-pass membrane protein.

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement PubMed 9725260. Source: ProtInc

digestive tract development

Inferred from electronic annotation. Source: Ensembl

epithelial cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

gastrin-induced gastric acid secretion

Inferred from electronic annotation. Source: Ensembl

gland development

Inferred from electronic annotation. Source: Ensembl

histamine-induced gastric acid secretion

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement PubMed 9725260. Source: ProtInc

memory

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: InterPro

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionhistamine receptor activity

Traceable author statement PubMed 9725260. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P25021-1)

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.
Isoform 2 (identifier: P25021-2)

The sequence of this isoform differs from the canonical sequence as follows:
     359-359: R → RPWLCLPECWSVELTHSFIHLFIHSFANIHPIPTTCQEL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 359359Histamine H2 receptor
PRO_0000069684

Regions

Topological domain1 – 2222Extracellular Potential
Transmembrane23 – 4422Helical; Name=1; Potential
Topological domain45 – 5713Cytoplasmic Potential
Transmembrane58 – 8124Helical; Name=2; Potential
Topological domain82 – 9211Extracellular Potential
Transmembrane93 – 11422Helical; Name=3; Potential
Topological domain115 – 13420Cytoplasmic Potential
Transmembrane135 – 15925Helical; Name=4; Potential
Topological domain160 – 18021Extracellular Potential
Transmembrane181 – 20424Helical; Name=5; Potential
Topological domain205 – 23430Cytoplasmic Potential
Transmembrane235 – 25824Helical; Name=6; Potential
Topological domain259 – 2679Extracellular Potential
Transmembrane268 – 28922Helical; Name=7; Potential
Topological domain290 – 35970Cytoplasmic Potential

Sites

Site981Essential for histamine binding By similarity
Site1861Essential for tiotidine binding and implicated in H2 selectivity By similarity
Site1901Implicated in histamine binding By similarity

Amino acid modifications

Lipidation3051S-palmitoyl cysteine By similarity
Glycosylation41N-linked (GlcNAc...) Potential
Disulfide bond91 ↔ 174 By similarity

Natural variations

Alternative sequence3591R → RPWLCLPECWSVELTHSFIH LFIHSFANIHPIPTTCQEL in isoform 2.
VSP_043594
Natural variant2171N → D.
VAR_009958
Natural variant2311K → R.
VAR_009959
Natural variant2681V → M.
VAR_009960

Experimental info

Sequence conflict1331V → A in CAA66832. Ref.9
Sequence conflict1751K → N in CAA66832. Ref.9
Sequence conflict2071K → R in CAA66832. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1992. Version 1.
Checksum: 9835AE2BA60B9B0F

FASTA35940,098
        10         20         30         40         50         60 
MAPNGTASSF CLDSTACKIT ITVVLAVLIL ITVAGNVVVC LAVGLNRRLR NLTNCFIVSL 

        70         80         90        100        110        120 
AITDLLLGLL VLPFSAIYQL SCKWSFGKVF CNIYTSLDVM LCTASILNLF MISLDRYCAV 

       130        140        150        160        170        180 
MDPLRYPVLV TPVRVAISLV LIWVISITLS FLSIHLGWNS RNETSKGNHT TSKCKVQVNE 

       190        200        210        220        230        240 
VYGLVDGLVT FYLPLLIMCI TYYRIFKVAR DQAKRINHIS SWKAATIREH KATVTLAAVM 

       250        260        270        280        290        300 
GAFIICWFPY FTAFVYRGLR GDDAINEVLE AIVLWLGYAN SALNPILYAA LNRDFRTGYQ 

       310        320        330        340        350 
QLFCCRLANR NSHKTSLRSN ASQLSRTQSR EPRQQEEKPL KLQVWSGTEV TAPQGATDR 

« Hide

Isoform 2 [UniParc].

Checksum: BDEAD7C8FEC25480
Show »

FASTA39744,541

References

« Hide 'large scale' references
[1]"Molecular cloning of the human histamine H2 receptor."
Gantz I., Munzert G., Tashiro T., Schaeffer M., Wang L.-D., DelValle J., Yamada T.
Biochem. Biophys. Res. Commun. 178:1386-1392(1991) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Web resources

Wikipedia

H2 receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJH0449.
RefSeqNP_001124527.1. NM_001131055.1.
NP_071640.1. NM_022304.2.
XP_005265964.1. XM_005265907.1.
UniGeneHs.247885.

3D structure databases

ProteinModelPortalP25021.
SMRP25021. Positions 21-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000366506.

Chemistry

BindingDBP25021.
ChEMBLCHEMBL1941.
DrugBankDB00272. Betazole.
DB00501. Cimetidine.
DB01142. Doxepin.
DB00751. Epinastine.
DB00927. Famotidine.
DB00667. Histamine Phosphate.
DB00585. Nizatidine.
DB00863. Ranitidine.
GuidetoPHARMACOLOGY263.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP25021.

Polymorphism databases

DMDM123120.

Proteomic databases

PaxDbP25021.
PRIDEP25021.

Protocols and materials databases

DNASU3274.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231683; ENSP00000231683; ENSG00000113749. [P25021-1]
ENST00000377291; ENSP00000366506; ENSG00000113749. [P25021-2]
GeneID3274.
KEGGhsa:3274.
UCSCuc003mdc.4. human. [P25021-2]
uc003mdd.2. human. [P25021-1]

Organism-specific databases

CTD3274.
GeneCardsGC05P175085.
HGNCHGNC:5183. HRH2.
HPAHPA013770.
MIM142703. gene.
neXtProtNX_P25021.
PharmGKBPA29457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG283797.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidP25021.
KOK04150.
OMAQVWSGTE.
OrthoDBEOG7QC7W8.
PhylomeDBP25021.
TreeFamTF316350.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP25021.
CleanExHS_HRH2.
GenevestigatorP25021.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000503. Histamine_H2_rcpt.
[Graphical view]
PANTHERPTHR24249:SF29. PTHR24249:SF29. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00531. HISTAMINEH2R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHistamine_H2_receptor.
GenomeRNAi3274.
NextBio13003.
PROP25021.
SOURCESearch...

Entry information

Entry nameHRH2_HUMAN
AccessionPrimary (citable) accession number: P25021
Secondary accession number(s): B5BUP7, Q14464, Q7Z5R9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries