title: Histaminylation of glutamine residues is a novel posttranslational modification implicated in G-protein signaling.
abstract: Posttranslational modifications (PTM) have been shown to be essential for protein function and signaling. Here we report the identification of a novel modification, protein transfer of histamine, and provide evidence for its function in G protein signaling. Histamine, known as neurotransmitter and mediator of the inflammatory response, was found incorporated into mastocytoma proteins. Histaminylation was dependent on transglutaminase II. Mass spectrometry confirmed histamine modification of the small and heterotrimeric G proteins Cdc42, Gαo1 and Gαq. The modification was specific for glutamine residues in the catalytic core, and triggered their constitutive activation. TGM2-mediated histaminylation is thus a novel PTM that functions in G protein signaling. Protein αmonoaminylations, thus including histaminylation, serotonylation, dopaminylation and norepinephrinylation, hence emerge as a novel class of regulatory PTMs.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany. jv330@cam.ac.uk
authors.forename: Jakob
authors.initials: J
authors.lastname: Vowinckel
authors.forename: Silke
authors.initials: S
authors.lastname: Stahlberg
authors.forename: Nils
authors.initials: N
authors.lastname: Paulmann
authors.forename: Katharina
authors.initials: K
authors.lastname: Bluemlein
authors.forename: Maik
authors.initials: M
authors.lastname: Grohmann
authors.forename: Markus
authors.initials: M
authors.lastname: Ralser
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Walther
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000235:genetics; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006632:Histamine / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D034801:Mastocytoma / Q000201:enzymology / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020543:Proteome; D011993:Recombinant Fusion Proteins; D005973:Glutamine; D006632:Histamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020764:cdc42 GTP-Binding Protein