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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)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

  • histamine receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113749-MONOMER.
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

HGNCiHGNC:5183. HRH2.

Subcellular locationi

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

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

DisGeNETi3274.
OpenTargetsiENSG00000113749.
PharmGKBiPA29457.

Chemistry databases

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.

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...)Sequence analysis1
Disulfide bondi91 ↔ 174PROSITE-ProRule annotation
Lipidationi305S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP25021.
PRIDEiP25021.

PTM databases

PhosphoSitePlusiP25021.

Expressioni

Gene expression databases

BgeeiENSG00000113749.
CleanExiHS_HRH2.
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.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP25021.
KOiK04150.
OMAiCKVQVNL.
OrthoDBiEOG091G06VI.
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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
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)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.
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.5. 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.
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.
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

PhosphoSitePlusiP25021.

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.5. human. [P25021-1]

Organism-specific databases

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

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP25021.
KOiK04150.
OMAiCKVQVNL.
OrthoDBiEOG091G06VI.
PhylomeDBiP25021.
TreeFamiTF316350.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113749-MONOMER.
ReactomeiR-HSA-390650. Histamine receptors.
R-HSA-418555. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiHistamine_H2_receptor.
GenomeRNAii3274.
PROiP25021.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113749.
CleanExiHS_HRH2.
GenevisibleiP25021. HS.

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 152 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

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 one 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.