Alternative titles; symbols
HGNC Approved Gene Symbol: SERPINA4
Cytogenetic location: 14q32.13 Genomic coordinates (GRCh38) : 14:94,561,442-94,569,906 (from NCBI)
Zhou et al. (1992) purified and characterized a human tissue kallikrein inhibitor from plasma which rapidly bound to tissue kallikrein and inhibited its activity. Designated kallistatin, this tissue kallikrein inhibitor is a member of the serpin superfamily and represents a major inhibitor of human tissue kallikrein in the circulation.
Chai et al. (1993) cloned a full-length SERPINA4 cDNA encoding kallistatin from human liver RNA by PCR. The 1,284-bp cDNA encodes 427 amino acid residues, including a 26-residue signal peptide and a 401-residue mature peptide. The translated amino acid sequence of kallistatin matches the protein sequence and shares 44 to 46% sequence identity with other serpin family members including, human alpha-1-antichymotrypsin (AACT; 107280), alpha-1-antitrypsin (PI; 107400), corticosteroid-binding globulin (CBG; 122500), thyroxine-binding globulin of serum (TBG; 314200), and protein C inhibitor (PCI; 601841).
By screening a chromosome 14-specific genomic DNA library, Chai et al. (1993) localized the SERPINA4 gene to chromosome 14. By FISH analysis, Chai et al. (1994) localized the SERPINA4 gene to chromosome 14q31-q32.1, close to the serpin genes AACT, PCI, PI, and CBG.
Kallistatin is a serine proteinase inhibitor (serpin) and a heparin-binding protein. It is localized in vascular smooth muscle cells and endothelial cells of blood vessels, suggesting that it may be involved in the regulation of vascular function. Miao et al. (2000) showed that kallistatin plays a role in neointima hyperplasia. Miao et al. (2002) investigated the potential role of kallistatin in angiogenesis in vitro and in vivo, and presented results demonstrating a novel role of the protein in the inhibition of angiogenesis and tumor growth.
Chai, K. X., Chen, L.-M., Chao, J., Chao, L. Kallistatin: a novel human serine proteinase inhibitor: molecular cloning, tissue distribution, and expression in Escherichia coli. J. Biol. Chem. 268: 24498-24505, 1993. [PubMed: 8227002]
Chai, K. X., Ward, D. C., Chao, J., Chao, L. Molecular cloning, sequence analysis, and chromosomal localization of the human protease inhibitor 4 (kallistatin) gene (PI4). Genomics 23: 370-378, 1994. [PubMed: 7835886] [Full Text: https://doi.org/10.1006/geno.1994.1513]
Miao, R. Q., Agata, J., Chao, L., Chao, J. Kallistatin is a new inhibitor of angiogenesis and tumor growth. Blood 100: 3245-3252, 2002. [PubMed: 12384424] [Full Text: https://doi.org/10.1182/blood-2002-01-0185]
Miao, R. Q., Murakami, H., Song, Q., Chao, L., Chao, J. Kallistatin stimulates vascular smooth muscle cell proliferation and migration in vitro and neointima formation in balloon-injured rat artery. Circ. Res. 86: 418-424, 2000. [PubMed: 10700446] [Full Text: https://doi.org/10.1161/01.res.86.4.418]
Zhou, G. X., Chao, L., Chao, J. Kallistatin: a novel human tissue kallikrein inhibitor; purification, characterization, and reactive center sequence. J. Biol. Chem. 267: 25873-25880, 1992. [PubMed: 1334488]