Molecular Cloning and Characterization of Human Tissue Inhibitor of Metalloproteinase 4

The tissue inhibitors of metalloproteinases (TIMPs) constitute a family of proteins, of which three members have so far been described. Using the expressed sequence tag sequencing approach, we have identified a novel TIMP-related cDNA fragment and subsequently cloned a fourth human TIMP (TIMP-4) fro...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-11, Vol.271 (48), p.30375-30380
Main Authors: Greene, John, Wang, Mingsheng, Liu, Yiliang E., Raymond, Lisa A., Rosen, Craig, Shi, Yuenian E.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Breast Neoplasms - enzymology
Cloning, Molecular
DNA, Complementary - genetics
Gene Expression
Glycoproteins - genetics
Humans
Metalloendopeptidases - antagonists & inhibitors
Molecular Sequence Data
Myocardium - enzymology
Protease Inhibitors
Proteins - genetics
RNA, Messenger - genetics
Sequence Alignment
Tissue Distribution
Tissue Inhibitor of Metalloproteinase-4
Tissue Inhibitor of Metalloproteinases
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Summary:The tissue inhibitors of metalloproteinases (TIMPs) constitute a family of proteins, of which three members have so far been described. Using the expressed sequence tag sequencing approach, we have identified a novel TIMP-related cDNA fragment and subsequently cloned a fourth human TIMP (TIMP-4) from a human heart cDNA library. The open reading frame encodes a 224-amino acid precursor including a 29-residue secretion signal. The predicted structure of the new protein shares 37% sequence identity with TIMP-1 and 51% identity with TIMP-2 and −3. The protein has a predicted isoelectric point of 7.34. The open reading frame-directed expression of TIMP-4 protein in MDA-MB-435 human breast cancer cells showed metalloproteinase inhibitory activity on reverse zymography. By Northern analysis, only the adult heart showed abundant TIMP-4 transcripts with a 1.4-kilobase predominant transcript band; very low levels of the transcripts were detected in the kidney, placenta, colon, and testes, and no transcripts were detected in the liver, brain, lung, thymus, and spleen. This unique expression pattern suggests that TIMP-4 may function in a tissue-specific fashion in extracellular matrix homeostasis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.271.48.30375