title: The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER CA²⁺-filling state.
abstract: Bax inhibitor-1 (BI-1) is an evolutionarily conserved pH-dependent Ca²⁺ leak channel in the endoplasmic reticulum and the founding member of a family of six highly hydrophobic mammalian proteins named transmembrane BAX inhibitor motif containing (TMBIM) 1-6 with BI-1 being TMBIM6. Here we compared the structure, subcellular localization, tissue expression and the effect on the cellular Ca²⁺ homeostasis of all family members side by side. We found that all TMBIM proteins possess the di-aspartyl pH sensor responsible for pH sensing identified in TMBIM6 and its bacterial homologue BsYetJ. TMBIM1-3 and TMBIM4-6 represent two phylogenetically distinct groups that are localized in the Golgi apparatus (TMBIM1-3), endoplasmic reticulum (TMBIM4-6) or mitochondria (TMBIM5) but share a common structure of at least seven transmembrane domains with the last domain being semi-hydrophobic. TMBIM1 is mainly expressed in muscle, TMBIM2 and 3 in the nervous system, TMBIM4 and 5 are ubiquitously expressed and TMBIM6 in skeletal muscle, kidney, liver and spleen. All TMBIM proteins reduce the Ca²⁺ content of the endoplasmic reticulum, and all but TMBIM5 also reduce the cytosolic resting Ca²⁺ concentration. These results suggest that the TMBIM family has comparable functions in the maintenance of intracellular Ca²⁺ homeostasis in a wide variety of tissues. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Dmitrij A
authors.initials: DA
authors.lastname: Lisak
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Schacht
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Vitalij
authors.initials: V
authors.lastname: Enders
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Habicht
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, Leuven BE-3000, Belgium.
authors.forename: Santeri
authors.initials: S
authors.lastname: Kiviluoto
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Henke
authors.affiliation: Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Campus Gasthuisberg O/N-I bus 802, Herestraat 49, Leuven BE-3000, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
authors.affiliation: Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn(2)), Department of Neurology, Johannes Gutenberg University Medical Center Mainz, Langenbeckstr. 1, Mainz D-55131, Germany. Electronic address: axel.methner@gmail.com.
authors.forename: Axel
authors.initials: A
authors.lastname: Methner
mesh_terms: D020816:Amino Acid Motifs; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D002118:Calcium
keywords: FAIM2; GAAP; GHITM; GRINA; MICS1; RECS1