Biomedical subjects

K Matena

Publications and source records attributed to K Matena.

3 recordsLinked to original sources

PubMed1998

Genomic organization of mouse Capn5 and Capn6 genes confirms that they are a distinct calpain subfamily.

CAPN5 and CAPN6 are recently identified human and mouse genes lacking a calmodulin-like domain with homology to the calpain family of proteases. To clarify their relationship to the known calpains, we have compared their genomic organization and chromosome location with other human calpain gene family members. In the mouse, both genes have 11 introns of identical location, with 6 of these being similar in location to those of the known vertebrate members. Surprisingly, there were no splice junctions in common with the nematode gene tra-3, the calpain with highest homology to CAPN5 and CAPN6. CAPN5 is localized on human chromosome 11, closely linked to the mu-calpain gene CAPN1. CAPN6, which is expressed only in the placenta, is localized on the X chromosome, to which no other calpain has yet been mapped.

Animals↗

PubMed1997

A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution.

Calpains are calcium-dependent intracellular nonlysosomal proteases that are believed to participate in signal transduction. In vertebrates, five different calpains have so far been identified, of which three, mu-, m-, and mu/m-calpain, are ubiquitously expressed while the other two, nCL-1 (p94) and nCL-2, exhibit a restricted tissue distribution. We have identified two new vertebrate calpain genes, Capn5 and Capn6. The human and mouse amino acid sequences of these new calpains are the most divergent of the vertebrate calpains identified. They possess most of the residues conserved in calpain family members but the C-terminal region lacks any homology to the calmodulin-like domain of other vertebrate calpains. They both exhibit significant homology over the entire coding region to the protein encoded by the gene tra-3, involved in nematode sex determination, and Capn5 may represent its vertebrate orthologue. The predicted Capn6 protein lacks critical active site residues and may not be proteolytically active. Both genes are differentially expressed in human tissues with highest RNA levels for Capn5 occurring in the testis, liver, trachea, colon, and kidney, while Capn6 is highly expressed only in the placenta sample of the 50 tissues examined. Phylogenetic analysis suggests that the vertebrate calpains arose through a series of gene duplication events that began before the initial divergence of the vertebrate and invertebrate lineages. The discovery of these two new calpains highlights a hitherto unknown complexity of the calpain family with subclasses perhaps possessing different modes of regulation.

Amino Acid Sequence↗

PubMed1997

Identification of interaction partners for the basic-helix-loop-helix protein E47.

Helix-loop-helix proteins constitute a family of transcription factors with the potential to form homo- and hetero-dimers mediated by the helix-loop-helix domain. Oncogenic mutations in such genes can disrupt the equilibrium of protein-protein interactions in the affected cell. In order to assess the biological consequences of such mutations, the full complement of interacting proteins must be known. To identify proteins interacting with the basic-helix-loop-helix domain of the ubiquitously expressed E47 protein, a 'sandwich'-screening procedure was developed which distinguishes between homo- and hetero-oligomers, and specifically excludes the detection of complexes which cannot bind DNA. Nine distinct cDNAs were identified which encode proteins with apparent basic-helix-loop-helix domains, including a novel clone termed eip1 which is distantly related in the basic-helix-loop-helix domain to the Drosophila enhancer-of-split m7 protein. Using epitope-tagging, interaction of E47 basic-helix-loop-helix protein with the eip1 protein encoded by this novel cDNA was confirmed by immunoprecipitation experiments in COS7 cells. Interaction was also observed in the yeast two-hybrid system. Three cDNAs encoding proteins without basic-helix-loop-helix domains were also found to interact in the sandwich-expression screen. Interactions with human PARP and mouse replication factor 1a were confirmed using glutathione transferase-tagged cDNAs. A cDNA encoding part of the nucleolin protein sequence interacted with the E47 basic-helix-loop-helix only when fused to a beta-galactosidase tag.

Amino Acid Sequence↗