LEKTI

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Serine peptidase inhibitor, Kazal type 5

PDB rendering based on 1h0z.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SPINK5 ; LEKTI; LETKI; NETS; NS; VAKTI
External IDs OMIM605010 MGI1919682 HomoloGene4987 GeneCards: SPINK5 Gene
RNA expression pattern
PBB GE SPINK5 205185 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 11005 72432
Ensembl ENSG00000133710 ENSMUSG00000055561
UniProt Q9NQ38 Q148R4
RefSeq (mRNA) NM_001127698 NM_001081180
RefSeq (protein) NP_001121170 NP_001074649
Location (UCSC) Chr 5:
147.41 – 147.52 Mb
Chr 18:
43.96 – 44.02 Mb
PubMed search [1] [2]

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the SPINK5 gene.[1][2]

Structure and function[edit]

LEKTI is a large multidomain serine protease inhibitor expressed in stratified epithelial tissue. It consists of 15 domains that are cleaved into smaller, functional fragments by the protease furin. Only two of these domains (2 and 15) contain 6 evenly spaced cysteines responsible for 3 intramolecular disulfide bonds characteristic of Kazal-type related inhibitors. The remaining domains contain 4 cysteines.[3] These disulfide bonds force the molecule into a rigid conformation that enables the protein to interact with a target protease via an extended beta-sheet. All domains (excepting 1, 2 and 15) contain an arginine at P1, indicating trypsin-like proteases are the likely targets.[3]

In the epidermis, LEKTI is implicated in the regulation of desquamation via its ability to selectively inhibit KLK5, KLK7 and KLK14.[4] Recombinant full length LEKTI inhibits the exogenous serine proteases trypsin, plasmin, subtilisin A, cathepsin G and human neutrophil elastase.[5]

LEKTI may play a role in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia.[2]

Gene[edit]

SPINK5 is a member of a gene family cluster located on chromosome 5q33.1, which encode inhibitors of serine proteases. This includes other epidermal proteins SPINK6 and LEKTI-2 (SPINK9). The SPINK5 gene is 61 kb in length and contains 33 exons.[3] Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.[6]

Clinical significance[edit]

Mutations in the SPINK5 gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy.[2]

See also[edit]

References[edit]

  1. ^ Magert HJ, Standker L, Kreutzmann P, Zucht HD, Reinecke M, Sommerhoff CP, Fritz H, Forssmann WG (Aug 1999). "LEKTI, a novel 15-domain type of human serine proteinase inhibitor". J Biol Chem 274 (31): 21499–502. doi:10.1074/jbc.274.31.21499. PMID 10419450. 
  2. ^ a b c "Entrez Gene: SPINK5 serine peptidase inhibitor, Kazal type 5". 
  3. ^ a b c Furio L, Hovnanian A. (November 2011). "When Activity Requires Breaking Up: LEKTI Proteolytic Activation Cascade for Specific Proteinase Inhibition.". J Invest Dermatol. 131 (11): 2169–73. doi:10.1038/jid.2011.295. PMID 21997416. 
  4. ^ Deraison C, Bonnart C, Lopez F, Besson C, Robinson R, Jayakumar A, Wagberg F, Brattsand M, Hachem JP, Leonardsson G, Hovnanian A (September 2007). "LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction". Mol. Biol. Cell 18 (9): 3607–19. doi:10.1091/mbc.E07-02-0124. PMC 1951746. PMID 17596512. 
  5. ^ 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. PMID 12667078. 
  6. ^ Tartaglia-Polcini A, Bonnart C, Micheloni A, Cianfarani F, Andrè A, Zambruno G, Hovnanian A, D'Alessio M. (February 2006). "SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing.". J Invest Dermatol. 126 (2): 315–24. doi:10.1038/sj.jid.5700015. PMID 16374478. 

Further reading[edit]