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Protein

Histamine H2 receptor

Gene

HRH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei98Essential for histamine bindingBy similarity1
Sitei186Essential for tiotidine binding and implicated in H2 selectivityBy similarity1
Sitei190Implicated in histamine bindingBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390650 Histamine receptors
R-HSA-418555 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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113749.6
HGNCiHGNC:5183 HRH2
MIMi142703 gene
neXtProtiNX_P25021

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22ExtracellularSequence analysisAdd BLAST22
Transmembranei23 – 44Helical; Name=1Sequence analysisAdd BLAST22
Topological domaini45 – 57CytoplasmicSequence analysisAdd BLAST13
Transmembranei58 – 81Helical; Name=2Sequence analysisAdd BLAST24
Topological domaini82 – 92ExtracellularSequence analysisAdd BLAST11
Transmembranei93 – 114Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini115 – 134CytoplasmicSequence analysisAdd BLAST20
Transmembranei135 – 159Helical; Name=4Sequence analysisAdd BLAST25
Topological domaini160 – 180ExtracellularSequence analysisAdd BLAST21
Transmembranei181 – 204Helical; Name=5Sequence analysisAdd BLAST24
Topological domaini205 – 234CytoplasmicSequence analysisAdd BLAST30
Transmembranei235 – 258Helical; Name=6Sequence analysisAdd BLAST24
Topological domaini259 – 267ExtracellularSequence analysis9
Transmembranei268 – 289Helical; Name=7Sequence analysisAdd BLAST22
Topological domaini290 – 359CytoplasmicSequence analysisAdd BLAST70

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3274
OpenTargetsiENSG00000113749
PharmGKBiPA29457

Chemistry databases

ChEMBLiCHEMBL1941
DrugBankiDB00321 Amitriptyline
DB06216 Asenapine
DB00272 Betazole
DB00501 Cimetidine
DB01142 Doxepin
DB00751 Epinastine
DB00927 Famotidine
DB05381 Histamine
DB05369 HZT-501
DB00408 Loxapine
DB00940 Methantheline
DB08805 Metiamide
DB00585 Nizatidine
DB00334 Olanzapine
DB00863 Ranitidine
DB08806 Roxatidine acetate
DB00797 Tolazoline
GuidetoPHARMACOLOGYi263

Polymorphism and mutation databases

BioMutaiHRH2
DMDMi123120

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000696841 – 359Histamine H2 receptorAdd BLAST359

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi4N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi91 ↔ 174PROSITE-ProRule annotation
Lipidationi305S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP25021
PRIDEiP25021
ProteomicsDBi54243
54244 [P25021-2]

PTM databases

PhosphoSitePlusiP25021

Expressioni

Gene expression databases

BgeeiENSG00000113749 Expressed in 91 organ(s), highest expression level in blood
CleanExiHS_HRH2
ExpressionAtlasiP25021 baseline and differential
GenevisibleiP25021 HS

Organism-specific databases

HPAiHPA013770

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000366506

Chemistry databases

BindingDBiP25021

Structurei

3D structure databases

ProteinModelPortaliP25021
SMRiP25021
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

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00890000139331
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP25021
KOiK04150
OrthoDBiEOG091G06VI
PhylomeDBiP25021
TreeFamiTF316350

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000503 Histamine_H2_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR00531 HISTAMINEH2R
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1B0GTK7A0A1B0GTK7_HUMAN
Histamine H2 receptor
HRH2
422Annotation score:
A0A1B0GVZ0A0A1B0GVZ0_HUMAN
Histamine H2 receptor
HRH2
363Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133V → A in CAA66832 (PubMed:8817552).Curated1
Sequence conflicti175K → N in CAA66832 (PubMed:8817552).Curated1
Sequence conflicti207K → R in CAA66832 (PubMed:8817552).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_009958217N → D. 1
Natural variantiVAR_009959231K → R. 1
Natural variantiVAR_009960268V → M. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043594359R → RPWLCLPECWSVELTHSFIH LFIHSFANIHPIPTTCQEL in isoform 2. 1 Publication1

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
CCDSiCCDS47344.1 [P25021-2]
PIRiJH0449
RefSeqiNP_001124527.1, NM_001131055.1 [P25021-2]
NP_071640.1, NM_022304.2
UniGeneiHs.247885

Genome annotation databases

EnsembliENST00000231683; ENSP00000231683; ENSG00000113749 [P25021-1]
ENST00000377291; ENSP00000366506; ENSG00000113749 [P25021-2]
GeneIDi3274
KEGGihsa:3274
UCSCiuc003mdc.5 human [P25021-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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
CCDSiCCDS47344.1 [P25021-2]
PIRiJH0449
RefSeqiNP_001124527.1, NM_001131055.1 [P25021-2]
NP_071640.1, NM_022304.2
UniGeneiHs.247885

3D structure databases

ProteinModelPortaliP25021
SMRiP25021
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000366506

Chemistry databases

BindingDBiP25021
ChEMBLiCHEMBL1941
DrugBankiDB00321 Amitriptyline
DB06216 Asenapine
DB00272 Betazole
DB00501 Cimetidine
DB01142 Doxepin
DB00751 Epinastine
DB00927 Famotidine
DB05381 Histamine
DB05369 HZT-501
DB00408 Loxapine
DB00940 Methantheline
DB08805 Metiamide
DB00585 Nizatidine
DB00334 Olanzapine
DB00863 Ranitidine
DB08806 Roxatidine acetate
DB00797 Tolazoline
GuidetoPHARMACOLOGYi263

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiP25021

Polymorphism and mutation databases

BioMutaiHRH2
DMDMi123120

Proteomic databases

PaxDbiP25021
PRIDEiP25021
ProteomicsDBi54243
54244 [P25021-2]

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.5 human [P25021-1]

Organism-specific databases

CTDi3274
DisGeNETi3274
EuPathDBiHostDB:ENSG00000113749.6
GeneCardsiHRH2
HGNCiHGNC:5183 HRH2
HPAiHPA013770
MIMi142703 gene
neXtProtiNX_P25021
OpenTargetsiENSG00000113749
PharmGKBiPA29457
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00890000139331
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP25021
KOiK04150
OrthoDBiEOG091G06VI
PhylomeDBiP25021
TreeFamiTF316350

Enzyme and pathway databases

ReactomeiR-HSA-390650 Histamine receptors
R-HSA-418555 G alpha (s) signalling events

Miscellaneous databases

GeneWikiiHistamine_H2_receptor
GenomeRNAii3274
PROiPR:P25021
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113749 Expressed in 91 organ(s), highest expression level in blood
CleanExiHS_HRH2
ExpressionAtlasiP25021 baseline and differential
GenevisibleiP25021 HS

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000503 Histamine_H2_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR00531 HISTAMINEH2R
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHRH2_HUMAN
AccessioniPrimary (citable) accession number: P25021
Secondary accession number(s): B5BUP7, Q14464, Q7Z5R9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: November 7, 2018
This is version 164 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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