Evidence for potential functionality of nuclearly-encoded humanin isoforms.
Humanin (HN) is a recently identified neuroprotective and antiapoptotic peptide derived from a portion of the mitochondrial MT-RNR2 gene. We provide bioinformatic and expression data suggesting the existence of 13 MT-RNR2-like nuclear loci predicted to maintain the open reading frames of 15 distinct full-length HN-like peptides. At least ten of these nuclear genes are expressed in human tissues, and respond to staurosporine (STS) and beta-carotene. Sequence comparisons of the nuclear HN isoforms and their homologues in other species reveal two consensus motifs, encompassing residues 5-11 (GFS/NCLLL), and 14-19 (SEIDLP/S). Proline vs serine in position 19 may determine whether the peptide is secreted or not, while threonine in position 13 may be important for cell surface receptor binding. Cytoprotection against the STS-induced apoptosis conferred by the polymorphic HN5 variant, in which threonine in position 13 is replaced with isoleucine, is reduced compared to the wild type HN5 peptide.
Bodzioch
Marek
M
Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Kopernika 15a, 31-501 Krakow, Poland. mb22@mp.pl
Lapicka-Bodzioch
Katarzyna
K
Zapala
Barbara
B
Kamysz
Wojciech
W
Kiec-Wilk
Beata
B
Dembinska-Kiec
Aldona
A
D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D002877:Chromosomes, Human; D033481:Chromosomes, Mammalian; D019295:Computational Biology / Q000379:methods; D016384:Consensus Sequence; D018076:DNA, Complementary; D004305:Dose-Response Relationship, Drug; D015894:Genome, Human; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007532:Isoleucine / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016366:Open Reading Frames / Q000235:genetics; D002679:Pan troglodytes; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010449:Peptide Mapping; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D019207:beta Carotene / Q000494:pharmacology
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D020033:Protein Isoforms; D012235:Rhodamines; C427211:humanin; C401833:tetramethylrhodamine methyl ester; D019207:beta Carotene; D007532:Isoleucine; D019311:Staurosporine