Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known asserine protease inhibitor Kazal-type 5 (SPINK5) is aprotein that in humans is encoded by theSPINK5gene.[5][6]
LEKTI is a large multidomainserine proteaseinhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the proteasefurin. Only two of these domains (2 and 15) contain 6 evenly spacedcysteines responsible for 3 intramoleculardisulfide bonds characteristic ofKazal-type related inhibitors. The remaining domains contain 4 cysteines.[7] These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extendedbeta-sheet. All domains (excepting 1, 2 and 15) contain anarginine at P1, indicating trypsin-like proteases are the likely targets.[7]
SPINK5 is a member of a gene family cluster located onchromosome 5q32,[10] which encode inhibitors of serine proteases. This includes other epidermal proteinsSPINK6 andLEKTI-2 (SPINK9). TheSPINK5 gene is 61 kb in length and contains 33 exons.[7] Alternative processing ofSPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.[11]
^Mitsudo K, Jayakumar A, Henderson Y, Frederick MJ, Kang Y, Wang M, El-Naggar AK, Clayman GL (April 2003). "Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis".Biochemistry.42 (13):3874–81.doi:10.1021/bi027029v.PMID12667078.
Mägert HJ, Kreutzmann P, Ständker L, et al. (2002). "LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance".Int. J. Biochem. Cell Biol.34 (6):573–6.doi:10.1016/S1357-2725(01)00179-0.PMID11943586.
Walden M, Kreutzmann P, Drögemüller K, et al. (2003). "Biochemical features, molecular biology and clinical relevance of the human 15-domain serine proteinase inhibitor LEKTI".Biol. Chem.383 (7–8):1139–41.doi:10.1515/BC.2002.124.PMID12437098.S2CID26084613.
Chavanas S, Bodemer C, Rochat A, et al. (2000). "Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome".Nat. Genet.25 (2):141–2.doi:10.1038/75977.PMID10835624.S2CID40421711.
Walley AJ, Chavanas S, Moffatt MF, et al. (2001). "Gene polymorphism in Netherton and common atopic disease".Nat. Genet.29 (2):175–8.doi:10.1038/ng728.PMID11544479.S2CID20292050.
Ahmed A, Kandola P, Ziada G, Parenteau N (2002). "Purification and partial amino acid sequence of proteins from human epidermal keratinocyte conditioned medium".J. Protein Chem.20 (4):273–8.doi:10.1023/A:1010902815953.PMID11594460.S2CID11877191.
