ID   HRH2_PONPY              Reviewed;         359 AA.
AC   P61752;
DT   07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2004, sequence version 1.
DT   25-MAY-2022, entry version 83.
DE   RecName: Full=Histamine H2 receptor;
DE            Short=H2R;
DE            Short=HH2R;
DE   AltName: Full=Gastric receptor I;
GN   Name=HRH2;
OS   Pongo pygmaeus (Bornean orangutan).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9600;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Isolate oran-Po13;
RX   PubMed=15014171; DOI=10.1093/molbev/msh100;
RA   Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT   "Human-specific amino acid changes found in 103 protein-coding genes.";
RL   Mol. Biol. Evol. 21:936-944(2004).
CC   -!- FUNCTION: The H2 subclass of histamine receptors mediates gastric acid
CC       secretion. Also appears to regulate gastrointestinal motility and
CC       intestinal secretion. Possible role in regulating cell growth and
CC       differentiation. The activity of this receptor is mediated by G
CC       proteins which activate adenylyl cyclase and, through a separate G
CC       protein-dependent mechanism, the phosphoinositide/protein kinase (PKC)
CC       signaling pathway (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB041387; BAA94472.1; -; Genomic_DNA.
DR   AlphaFoldDB; P61752; -.
DR   SMR; P61752; -.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004969; F:histamine receptor activity; IEA:InterPro.
DR   GO; GO:0001696; P:gastric acid secretion; IEA:InterPro.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:InterPro.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR000503; Histamine_H2_rcpt.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00531; HISTAMINEH2R.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE   3: Inferred from homology;
KW   Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW   Lipoprotein; Membrane; Palmitate; Receptor; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..359
FT                   /note="Histamine H2 receptor"
FT                   /id="PRO_0000069687"
FT   TOPO_DOM        1..22
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        23..44
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        45..57
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        58..81
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        82..92
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        93..114
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        115..134
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        135..159
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        160..180
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        181..204
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        205..234
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        235..258
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        259..267
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        268..289
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        290..359
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          316..340
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            98
FT                   /note="Essential for histamine binding"
FT                   /evidence="ECO:0000250"
FT   SITE            186
FT                   /note="Essential for tiotidine binding and implicated in H2
FT                   selectivity"
FT                   /evidence="ECO:0000250"
FT   SITE            190
FT                   /note="Implicated in histamine binding"
FT                   /evidence="ECO:0000250"
FT   LIPID           305
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        4
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        91..174
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ   SEQUENCE   359 AA;  40098 MW;  9835AE2BA60B9B0F CRC64;
     MAPNGTASSF CLDSTACKIT ITVVLAVLIL ITVAGNVVVC LAVGLNRRLR NLTNCFIVSL
     AITDLLLGLL VLPFSAIYQL SCKWSFGKVF CNIYTSLDVM LCTASILNLF MISLDRYCAV
     MDPLRYPVLV TPVRVAISLV LIWVISITLS FLSIHLGWNS RNETSKGNHT TSKCKVQVNE
     VYGLVDGLVT FYLPLLIMCI TYYRIFKVAR DQAKRINHIS SWKAATIREH KATVTLAAVM
     GAFIICWFPY FTAFVYRGLR GDDAINEVLE AIVLWLGYAN SALNPILYAA LNRDFRTGYQ
     QLFCCRLANR NSHKTSLRSN ASQLSRTQSR EPRQQEEKPL KLQVWSGTEV TAPQGATDR