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SERINE PROTEASE INHIBITOR, KAZAL-TYPE, 9; SPINK9

SERINE PROTEASE INHIBITOR, KAZAL-TYPE, 9; SPINK9

Alternative titles; symbolsLYMPHOEPITHELIAL KAZAL-TYPE-RELATED INHIBITOR 2; LEKTI2HGNC Approved Gene Symbol: SPINK9Cytogenetic location: 5q32 Genomic coordin...

Alternative titles; symbols

  • LYMPHOEPITHELIAL KAZAL-TYPE-RELATED INHIBITOR 2; LEKTI2

HGNC Approved Gene Symbol: SPINK9

Cytogenetic location: 5q32 Genomic coordinates (GRCh38): 5:148,323,218-148,341,973 (from NCBI)

▼ TEXT
The SPINK9 gene encodes a Kazal-type serine protease inhibitor expressed in human skin (Brattsand et al., 2009, Meyer-Hoffert et al., 2009).

▼ Cloning and Expression
Using mass spectrometry and peptide sequencing to identify protease inhibitors isolated from extracts of plantar stratum corneum, followed by database analysis and RT-PCR of HaCaT keratinocyte mRNA, Brattsand et al. (2009) cloned SPINK9. The deduced 86-amino acid protein has a signal cleavage site between amino acids 19 and 20. RT-PCR detected highest SPINK9 expression in palmar epidermis, with much lower expression in most other tissues examined, except leukocytes and ovary. Immunohistochemical analysis and Western blot analysis revealed that SPINK9 protein expression appeared limited to palmoplantar stratum corneum.

Meyer-Hoffert et al. (2009) independently cloned SPINK9, which they called LEKTI2, from normal human skin. The deduced 86-amino acid protein contains 3 Kazal domains that include a conserved tyrosine residue and conserved number and spacing of cysteines and disulfide bonds. RT-PCR and real-time PCR detected SPINK9 in foreskin and cultured primary keratinocytes, and in thymus, tonsils, testis, placenta, and brain, but not in other tissues examined. The expression of SPINK9 mRNA increased with differentiation in cultured primary keratinocytes. Immunohistochemical analysis detected SPINK9 in palmoplantar stratum granulosum and stratum corneum, with no immunoreactivity detected at other sites of normal human skin. SPINK9 was also highly expressed at sites of hyperkeratosis.

▼ Gene Function
Brattsand et al. (2009) found that recombinant human SPINK9 bound KLK5 (605643) with high affinity and inhibited its serine protease activity. SPINK9 also bound KLK8 (605644), but with lower affinity and showed much weaker inhibition of KLK8 activity. SPINK9 did not bind or inhibit any other serine protease tested.

Meyer-Hoffert et al. (2009) independently showed that SPINK9 inhibited the serine protease activity of KLK5, but not other serine proteases tested. Meyer-Hoffert et al. (2009) concluded that inhibition of KLK5 by SPINK9 may be important in desquamation at palmar and plantar sites.

▼ Gene Structure
Meyer-Hoffert et al. (2009) determined that the SPINK9 gene contains 4 exons and spans 4.3 kb.

▼ Mapping
By genomic sequence analysis, Brattsand et al. (2009) and Meyer-Hoffert et al. (2009) mapped the SPINK9 gene to chromosome 5q33.1.

Tags: 5q32