Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. 2013

Adam P Siebert, and Zhongming Ma, and Jeremy D Grevet, and Angelo Demuro, and Ian Parker, and J Kevin Foskett
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA.

CALHM1 (calcium homeostasis modulator 1) forms a plasma membrane ion channel that mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration. Six human CALHM homologs exist with no homology to other proteins, although CALHM1 is conserved across >20 species. Here we demonstrate that CALHM1 shares functional and quaternary and secondary structural similarities with connexins and evolutionarily distinct innexins and their vertebrate pannexin homologs. A CALHM1 channel is a hexamer, comprised of six monomers, each of which possesses four transmembrane domains, cytoplasmic amino and carboxyl termini, an amino-terminal helix, and conserved extracellular cysteines. The estimated pore diameter of the CALHM1 channel is ∼14 Å, enabling permeation of large charged molecules. Thus, CALHMs, connexins, and pannexins and innexins are structurally related protein families with shared and distinct functional properties.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D017630 Connexins A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. Connexin,Connexin Complex Proteins,Gap Junction Proteins,Gap Junction Channel Proteins,Gap Junction Protein,Junction Protein, Gap,Junction Proteins, Gap
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D040681 Structural Homology, Protein The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN. Protein Structural Homology,3-D Homologs, Protein,3-D Homology, Protein,3-Dimensional Homologs, Protein,3-Dimensional Homology, Protein,Homologs, 3-D, Protein,Homologs, 3-Dimensional, Protein,Homologs, Sturctural, Protein,Protein Structural Homologs,Structural Homologs, Protein,3 D Homologs, Protein,3 D Homology, Protein,3 Dimensional Homologs, Protein,3 Dimensional Homology, Protein,3-D Homolog, Protein,3-D Homologies, Protein,3-Dimensional Homolog, Protein,3-Dimensional Homologies, Protein,Homolog, Protein 3-D,Homolog, Protein 3-Dimensional,Homolog, Protein Structural,Homologies, Protein 3-D,Homologies, Protein 3-Dimensional,Homologies, Protein Structural,Homologs, Protein 3-D,Homologs, Protein 3-Dimensional,Homologs, Protein Structural,Homology, Protein 3-D,Homology, Protein 3-Dimensional,Homology, Protein Structural,Protein 3-D Homolog,Protein 3-D Homologies,Protein 3-D Homologs,Protein 3-D Homology,Protein 3-Dimensional Homolog,Protein 3-Dimensional Homologies,Protein 3-Dimensional Homologs,Protein 3-Dimensional Homology,Protein Structural Homolog,Protein Structural Homologies,Structural Homolog, Protein,Structural Homologies, Protein

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