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P25021

- HRH2_HUMAN

UniProt

P25021 - HRH2_HUMAN

Protein

Histamine H2 receptor

Gene

HRH2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 May 1992)
      Previous versions | rss
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    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

    1. histamine receptor activity Source: ProtInc

    GO - Biological processi

    1. digestive tract development Source: Ensembl
    2. epithelial cell morphogenesis Source: Ensembl
    3. gastrin-induced gastric acid secretion Source: Ensembl
    4. gland development Source: Ensembl
    5. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
    6. histamine-induced gastric acid secretion Source: Ensembl
    7. immune response Source: ProtInc
    8. memory Source: Ensembl
    9. positive regulation of vasoconstriction Source: InterPro
    10. regulation of synaptic plasticity Source: Ensembl
    11. visual learning Source: Ensembl

    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: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:5183. HRH2.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29457.

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2222ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini45 – 5713CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini82 – 9211ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini115 – 13420CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini160 – 18021ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini205 – 23430CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini259 – 2679ExtracellularSequence Analysis
    Topological domaini290 – 35970CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei23 – 4422Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei58 – 8124Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei93 – 11422Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei135 – 15925Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei181 – 20424Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei235 – 25824Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei268 – 28922Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

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

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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. Align

    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

    MAPNGTASSF CLDSTACKIT ITVVLAVLIL ITVAGNVVVC LAVGLNRRLR    50
    NLTNCFIVSL AITDLLLGLL VLPFSAIYQL SCKWSFGKVF CNIYTSLDVM 100
    LCTASILNLF MISLDRYCAV MDPLRYPVLV TPVRVAISLV LIWVISITLS 150
    FLSIHLGWNS RNETSKGNHT TSKCKVQVNE VYGLVDGLVT FYLPLLIMCI 200
    TYYRIFKVAR DQAKRINHIS SWKAATIREH KATVTLAAVM GAFIICWFPY 250
    FTAFVYRGLR GDDAINEVLE AIVLWLGYAN SALNPILYAA LNRDFRTGYQ 300
    QLFCCRLANR NSHKTSLRSN ASQLSRTQSR EPRQQEEKPL KLQVWSGTEV 350
    TAPQGATDR 359
    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:
    EMBL
    GenBank
    DDBJ
    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]
    XP_005265964.1. XM_005265907.1. [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]

    Polymorphism databases

    DMDMi123120.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    H2 receptor entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4395.1. [P25021-1 ]
    CCDS47344.1. [P25021-2 ]
    PIRi JH0449.
    RefSeqi NP_001124527.1. NM_001131055.1. [P25021-2 ]
    NP_071640.1. NM_022304.2. [P25021-1 ]
    XP_005265964.1. XM_005265907.1. [P25021-1 ]
    UniGenei Hs.247885.

    3D structure databases

    ProteinModelPortali P25021.
    SMRi P25021. Positions 21-325.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000366506.

    Chemistry

    BindingDBi P25021.
    ChEMBLi CHEMBL1941.
    DrugBanki DB00272. Betazole.
    DB00501. Cimetidine.
    DB01142. Doxepin.
    DB00751. Epinastine.
    DB00927. Famotidine.
    DB00667. Histamine Phosphate.
    DB00585. Nizatidine.
    DB00863. Ranitidine.
    GuidetoPHARMACOLOGYi 263.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P25021.

    Polymorphism databases

    DMDMi 123120.

    Proteomic databases

    PaxDbi P25021.
    PRIDEi P25021.

    Protocols and materials databases

    DNASUi 3274.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000231683 ; ENSP00000231683 ; ENSG00000113749 . [P25021-1 ]
    ENST00000377291 ; ENSP00000366506 ; ENSG00000113749 . [P25021-2 ]
    GeneIDi 3274.
    KEGGi hsa:3274.
    UCSCi uc003mdc.4. human. [P25021-2 ]
    uc003mdd.2. human. [P25021-1 ]

    Organism-specific databases

    CTDi 3274.
    GeneCardsi GC05P175085.
    HGNCi HGNC:5183. HRH2.
    HPAi HPA013770.
    MIMi 142703. gene.
    neXtProti NX_P25021.
    PharmGKBi PA29457.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG283797.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi P25021.
    KOi K04150.
    OMAi QVWSGTE.
    OrthoDBi EOG7QC7W8.
    PhylomeDBi P25021.
    TreeFami TF316350.

    Enzyme and pathway databases

    Reactomei REACT_16903. Histamine receptors.
    REACT_19327. G alpha (s) signalling events.

    Miscellaneous databases

    GeneWikii Histamine_H2_receptor.
    GenomeRNAii 3274.
    NextBioi 13003.
    PROi P25021.
    SOURCEi Search...

    Gene expression databases

    Bgeei P25021.
    CleanExi HS_HRH2.
    Genevestigatori P25021.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR000503. Histamine_H2_rcpt.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR00531. HISTAMINEH2R.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 135 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