Apte S S, Mattei M G, Olsen B R
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Genomics. 1994 Jan 1;19(1):86-90. doi: 10.1006/geno.1994.1016.
The tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of the matrix metalloproteinases, a group of zinc-binding endopeptidases involved in the degradation of the extracellular matrix. We have isolated overlapping cDNAs encoding a novel human TIMP, TIMP-3. The cDNAs contain a 591-bp-long open reading frame encoding 9 amino acid residues of the signal peptide and 188 residues of the mature TIMP-3 polypeptide. Both the nucleotide sequence and the conceptual translation product of the human TIMP3 cDNA have a high degree of similarity to ChIMP-3, a recently cloned metalloproteinase inhibitor in the chicken, and to the TIMP1 and TIMP2 gene products, including 12 conserved cysteinyl residues at the same relative positions. The TIMP3 gene is expressed in many tissues, with highest expression in the placenta. Upon hybridization with a panel of human-hamster somatic cell hybrid DNAs, the TIMP3 gene segregated with clones containing chromosome 22. Using in situ hybridization to human metaphase chromosomes, we have assigned the locus for the TIMP3 gene to the q12.1-q13.2 region of human chromosome 22.
金属蛋白酶组织抑制剂（TIMPs）是基质金属蛋白酶的天然抑制剂，基质金属蛋白酶是一组参与细胞外基质降解的锌结合内肽酶。我们已分离出编码一种新型人类TIMPs即TIMP - 3的重叠cDNA。这些cDNA包含一个591bp长的开放阅读框，编码信号肽的9个氨基酸残基和成熟TIMP - 3多肽的188个残基。人类TIMP3 cDNA的核苷酸序列和概念翻译产物与ChIMP - 3（鸡中最近克隆的一种金属蛋白酶抑制剂）以及TIMP1和TIMP2基因产物具有高度相似性，包括在相同相对位置的12个保守半胱氨酸残基。TIMP3基因在许多组织中表达，在胎盘中表达最高。在用一组人 - 仓鼠体细胞杂交DNA进行杂交时，TIMP3基因与包含22号染色体的克隆分离。通过对人类中期染色体进行原位杂交，我们已将TIMP3基因的基因座定位到人类22号染色体的q12.1 - q13.2区域。
