HGNC Approved Gene Symbol: SERPINB12
Cytogenetic location: 18q21.33 Genomic coordinates (GRCh38): 18:63,519,110-63,569,329 (from NCBI)
Serpins inhibit serine or cysteine proteases via a 'suicide substrate' mechanism. Upon proteolytic cleavage of their pseudosubstrate bait sequence, serpins undergo a conformational change and form an inactivating covalent bond with the protease. SERPINB12 is a clade B serpin that shares sequence similarity with chicken ovalbumin. Clade B serpins lack an N-terminal signal sequence and N- and C-terminal extensions, and they localize predominantly to the cytoplasm (summary by Askew et al., 2001).
By searching a genomic database for clade B serpin sequences, followed by PCR of a testis cDNA library, Askew et al. (2001) cloned SERPINB12. The deduced 405-amino acid protein has a calculated molecular mass of 46.3 kD. SERPINB12 has a transmembrane domain near the N terminus and an alanine-rich hinge region and reactive-site loop near the C terminus. The reactive-site loop has an arg-ser pseudosubstrate bait sequence. SERPINB12 also has 6 putative N-glycosylation sites. Hemi-nested PCR detected SERPINB12 expression in approximately half of the 26 adult and fetal human tissues examined, including brain, lymphoid tissues, heart, lung, liver, pancreas, kidney, ovary, testis, and intestine.
Askew et al. (2001) showed that recombinant human SERPINB12 completely inhibited the enzymatic activities of trypsin (see 276000)-like serine proteinases, including human and bovine trypsin and plasmin (173350), but not other serine or cysteine proteinases examined. SDS-PAGE analysis revealed that SERPINB12 formed a covalent complex with plasmin. Mass spectroscopy of the complex confirmed that SERPINB12 was cleaved at the arg-ser bond.
Askew et al. (2001) determined that the SERPINB12 gene contains 8 exons and spans over 10.8 kb. Exon 2 contains the translational start site.
By genomic sequence analysis, Askew et al. (2001) mapped the SERPINB12 gene to an approximately 800-kb serpin gene cluster on chromosome 18q21.3.
Askew, Y. S., Pak, S. C., Luke, C. J., Askew, D. J., Cataltepe, S., Mills, D. R., Kato, H., Lehoczky, J., Dewar, K., Birren, B., Silverman, G. A. SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases. J. Biol. Chem. 276: 49320-49330, 2001. [PubMed: 11604408] [Full Text: https://doi.org/10.1074/jbc.M108879200]