Cathepsin Z, a novel human cysteine proteinase with a short propeptide domain and a unique chromosomal location.
We have identified and characterized a novel human cysteine proteinase of the papain family. A full-length cDNA for this enzyme was cloned from a human brain cDNA library. Nucleotide sequence analysis revealed that the isolated cDNA codes for a polypeptide of 303 amino acids, tentatively called cathepsin Z, that exhibits structural features characteristic of cysteine proteinases. Fluorescent in situ hybridization experiments revealed that the human cathepsin Z gene maps to chromosome 20q13, a location that differs from all cysteine proteinase genes mapped to date. The cDNA encoding cathepsin Z was expressed in Escherichia coli as a fusion protein with glutathione S-transferase, and after purification, the recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin, used as a substrate for cysteine proteinases. Northern blot analysis demonstrated that cathepsin Z is widely expressed in human tissues, suggesting that this enzyme could be involved in the normal intracellular protein degradation taking place in all cell types. Cathepsin Z is also ubiquitously distributed in cancer cell lines and in primary tumors from different sources, suggesting that this enzyme may participate in tumor progression as reported for other cathepsins. Finally, on the basis of a series of distinctive structural features, including diverse peptide insertions and an unusual short propeptide, together with its unique chromosomal location among cysteine proteinases, we propose that cathepsin Z may be the first representative of a novel subfamily of this class of proteolytic enzymes.
Santamaría
I
I
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, 33006-Oviedo, Spain.
Velasco
G
G
Pendás
A M
AM
Fueyo
A
A
López-Otín
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D056657:Cathepsin K; D056663:Cathepsin Z; D002403:Cathepsins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D018076:DNA, Complementary; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011994:Recombinant Proteins; D002403:Cathepsins; C534182:CTSZ protein, human; D056663:Cathepsin Z; C534130:CTSK protein, human; D056657:Cathepsin K