Ermelin, an endoplasmic reticulum transmembrane protein, contains the novel HELP domain conserved in eukaryotes.
We have cloned a cDNA encoding a novel protein referred to as ermelin from mouse C2 skeletal muscle cells. This protein contained six hydrophobic amino acid stretches corresponding to transmembrane domains, two histidine-rich sequences, and a sequence homologous to the fusion peptides of certain fusion proteins. Ermelin also contained a novel modular sequence, designated as HELP domain, which was highly conserved among eukaryotes, from yeast to higher plants and animals. All these HELP domain-containing proteins, including mouse KE4, Drosophila Catsup, and Arabidopsis IAR1, possessed multipass transmembrane domains and histidine-rich sequences. Ermelin was predominantly expressed in brain and testis, and induced during neuronal differentiation of N1E-115 neuroblastoma cells but downregulated during myogenic differentiation of C2 cells. The mRNA was accumulated in hippocampus and cerebellum of brain and central areas of seminiferous tubules in testis. Epitope-tagging experiments located ermelin and KE4 to a network structure throughout the cytoplasm. Staining with the fluorescent dye DiOC(6)(3) identified this structure as the endoplasmic reticulum. These results suggest that at least some, if not all, of the HELP domain-containing proteins are multipass endoplasmic reticulum membrane proteins with functions conserved among eukaryotes.
Suzuki
Akiko
A
Department of Biology, Faculty of Science, and Graduate School of Science and Technology, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan.
Endo
Takeshi
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism; D027682:Cation Transport Proteins; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; C454113:Slc39a6 protein, mouse