LEKTI

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.^[5][6]

SPINK5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H0Z, 1HDL, 1UUC, 1UVF, 1UVG
Identifiers
Aliases	SPINK5, LEKTI, LETKI, NETS, NS, VAKTI, serine peptidase inhibitor, Kazal type 5, serine peptidase inhibitor Kazal type 5
External IDs	OMIM: 605010; MGI: 1919682; HomoloGene: 4987; GeneCards: SPINK5; OMA:SPINK5 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q32 Start 148,025,683 bp[1] End 148,137,382 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 B3|18 23.74 cM Start 44,096,302 bp[2] End 44,155,568 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vulva gums skin of thigh gingival epithelium oral cavity mucosa of pharynx human penis skin of hip skin of arm body of tongue Top expressed in skin of abdomen esophagus skin of external ear lip skin of back prostate lobe of prostate umbilical cord left lung lobe stomach More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity serine-type endopeptidase inhibitor activity Cellular component cytoplasm cytosol endoplasmic reticulum membrane cell cortex endoplasmic reticulum perinuclear region of cytoplasm epidermal lamellar body extracellular region intracellular membrane-bounded organelle Biological process epidermal cell differentiation negative regulation of proteolysis negative regulation of serine-type peptidase activity negative regulation of peptidase activity epithelial cell differentiation hair cell differentiation extracellular matrix organization negative regulation of antibacterial peptide production negative regulation of immune response regulation of cell adhesion negative regulation of angiogenesis negative regulation of serine-type endopeptidase activity regulation of T cell differentiation cornification regulation of timing of anagen Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11005 72432 Ensembl ENSG00000133710 ENSMUSG00000055561 UniProt Q9NQ38 Q148R4 RefSeq (mRNA) NM_001127698 NM_001127699 NM_006846 NM_001081180 RefSeq (protein) NP_001121170 NP_001121171 NP_006837 NP_001074649 Location (UCSC) Chr 5: 148.03 – 148.14 Mb Chr 18: 44.1 – 44.16 Mb PubMed search [3] [4]
Wikidata
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Structure and function

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.^[7] 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.^[7]

In the epidermis, LEKTI is implicated in the regulation of desquamation via its ability to selectively inhibit KLK5, KLK7 and KLK14.^[8] Recombinant full length LEKTI inhibits the exogenous serine proteases trypsin, plasmin, subtilisin A, cathepsin G and human neutrophil elastase.^[9]

LEKTI may play a role in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia.^[6]

Gene

SPINK5 is a member of a gene family cluster located on chromosome 5q32,^[10] 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.^[7] Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.^[11]

Clinical significance

Mutations in the SPINK5 gene result in Netherton syndrome, a disorder characterized by ichthyosis and specific immune system defects.^[6]

See also

• Kazal-type serine protease inhibitor domain