P25021 (HRH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histamine H2 receptor
Short name=H2R
Short name=HH2R

Alternative name(s):
Gastric receptor I

Gene names

Name:

HRH2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cyclic nucleotide second messenger Traceable author statement. Source: ProtInc immune response Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	histamine receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	Histamine H2 receptor		PRO_0000069684
Regions
	Topological domain	1 – 22	22	Extracellular Potential
	Transmembrane	23 – 44	22	Helical; Name=1; Potential
	Topological domain	45 – 57	13	Cytoplasmic Potential
	Transmembrane	58 – 81	24	Helical; Name=2; Potential
	Topological domain	82 – 92	11	Extracellular Potential
	Transmembrane	93 – 114	22	Helical; Name=3; Potential
	Topological domain	115 – 134	20	Cytoplasmic Potential
	Transmembrane	135 – 159	25	Helical; Name=4; Potential
	Topological domain	160 – 180	21	Extracellular Potential
	Transmembrane	181 – 204	24	Helical; Name=5; Potential
	Topological domain	205 – 234	30	Cytoplasmic Potential
	Transmembrane	235 – 258	24	Helical; Name=6; Potential
	Topological domain	259 – 267	9	Extracellular Potential
	Transmembrane	268 – 289	22	Helical; Name=7; Potential
	Topological domain	290 – 359	70	Cytoplasmic Potential
Sites
	Site	98	1	Essential for histamine binding By similarity
	Site	186	1	Essential for tiotidine binding and implicated in H2 selectivity By similarity
	Site	190	1	Implicated in histamine binding By similarity
Amino acid modifications
	Lipidation	305	1	S-palmitoyl cysteine By similarity
	Glycosylation	4	1	N-linked (GlcNAc...) Potential
	Disulfide bond	91 ↔ 174		By similarity
Natural variations
	Natural variant	217	1	N → D.		VAR_009958
	Natural variant	231	1	K → R.		VAR_009959
	Natural variant	268	1	V → M.		VAR_009960
Experimental info
	Sequence conflict	133	1	V → A in CAA66832. Ref.8
	Sequence conflict	175	1	K → N in CAA66832. Ref.8
	Sequence conflict	207	1	K → R in CAA66832. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P25021 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 9835AE2BA60B9B0F	FASTA	359	40,098
	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

References

	« Hide 'large scale' referencesShow '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: 1714721] [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: 7755641] [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: 10371214] [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: 15014171] [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]. 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: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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. , 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]	"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: 8817552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-351, POLYMORPHISM. Tissue: Brain.
[9]	"Novel insights into histamine H2 receptor biology." DelValle J., Gantz I. Am. J. Physiol. 273:G987-G996(1997) [PubMed: 9374694] [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. X98133 Genomic DNA. Translation: CAA66832.1.
IPI	IPI00744547.
PIR	JH0449.
RefSeq	NP_071640.1. NM_022304.2.
UniGene	Hs.247885.
3D structure databases
ProteinModelPortal	P25021.
SMR	P25021. Positions 13-303.
ModBase	Search...
Protein-protein interaction databases
STRING	P25021.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P25021.
Polymorphism databases
DMDM	123120.
Proteomic databases
PRIDE	P25021.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000231683; ENSP00000231683; ENSG00000113749. ENST00000377291; ENSP00000366506; ENSG00000113749.
GeneID	3274.
KEGG	hsa:3274.
UCSC	uc003mdd.1. human.
Organism-specific databases
CTD	3274.
GeneCards	GC05P175085.
H-InvDB	HIX0024780.
HGNC	HGNC:5183. HRH2.
HPA	HPA013770.
MIM	142703. gene.
neXtProt	NX_P25021.
PharmGKB	PA29457.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05630.
GeneTree	ENSGT00600000084087.
HOVERGEN	HBG106962.
InParanoid	P25021.
OrthoDB	EOG418BP4.
PhylomeDB	P25021.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P25021.
Bgee	P25021.
CleanEx	HS_HRH2.
Genevestigator	P25021.
GermOnline	ENSG00000113749. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR000503. Histamine_H2_recept. [Graphical view]
KO	K04150.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR00531. HISTAMINEH2R.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00272. Betazole. DB00501. Cimetidine. DB01142. Doxepin. DB00751. Epinastine. DB00927. Famotidine. DB00667. Histamine Phosphate. DB00585. Nizatidine. DB00863. Ranitidine.
NextBio	13003.
SOURCE	Search...

Entry information

Entry name

HRH2_HUMAN

Accession

Primary (citable) accession number: P25021
Secondary accession number(s): B5BUP7, Q14464

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	May 1, 1992
Last modified:	January 25, 2012
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.