LEKTI
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SPINK5
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| Location (UCSC) | Chr 5: 148.03 – 148.14 Mb | Chr 18: 44.1 – 44.16 Mb | |||||||
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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]
Structure and function
LEKTI is a large multidomain
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
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
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000133710 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055561 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10419450.
- ^ a b c "Entrez Gene: SPINK5 serine peptidase inhibitor, Kazal type 5".
- ^ 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. PMID 21997416.
- PMID 17596512.
- PMID 12667078.
- ^ "SPINK5 serine peptidase inhibitor, Kazal type 5 [Homo sapiens (human)] - Gene - NCBI".
- ^
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. PMID 16374478.
Further reading
- Norgett EE, Kelsell DP (2002). "SPINK5: both rare and common skin disease". Trends in Molecular Medicine. 8 (1): 7. PMID 11796258.
- 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. PMID 11943586.
- 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. S2CID 26084613.
- Chavanas S, Garner C, Bodemer C, et al. (2000). "Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping". Am. J. Hum. Genet. 66 (3): 914–21. PMID 10712206.
- 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. S2CID 40421711.
- Sprecher E, Chavanas S, DiGiovanna JJ, et al. (2001). "The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis". J. Invest. Dermatol. 117 (2): 179–87. PMID 11511292.
- Walley AJ, Chavanas S, Moffatt MF, et al. (2001). "Gene polymorphism in Netherton and common atopic disease". Nat. Genet. 29 (2): 175–8. S2CID 20292050.
- 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. S2CID 11877191.
- Bitoun E, Chavanas S, Irvine AD, et al. (2002). "Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families". J. Invest. Dermatol. 118 (2): 352–61. PMID 11841556.
- Komatsu N, Takata M, Otsuki N, et al. (2002). "Elevated stratum corneum hydrolytic activity in Netherton syndrome suggests an inhibitory regulation of desquamation by SPINK5-derived peptides". J. Invest. Dermatol. 118 (3): 436–43. PMID 11874482.
- Bitoun E, Micheloni A, Lamant L, et al. (2004). "LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome". Hum. Mol. Genet. 12 (19): 2417–30. PMID 12915442.
- Nishio Y, Noguchi E, Shibasaki M, et al. (2004). "Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese". Genes Immun. 4 (7): 515–7. PMID 14551605.
- Raghunath M, Tontsidou L, Oji V, et al. (2004). "SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases". J. Invest. Dermatol. 123 (3): 474–83. PMID 15304086.
- Tidow H, Lauber T, Vitzithum K, et al. (2004). "The solution structure of a chimeric LEKTI domain reveals a chameleon sequence" (PDF). Biochemistry. 43 (35): 11238–47. PMID 15366933.
- Yang T, Liang D, Koch PJ, et al. (2004). "Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice". Genes Dev. 18 (19): 2354–8. PMID 15466487.
- Ishida-Yamamoto A, Deraison C, Bonnart C, et al. (2005). "LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum". J. Invest. Dermatol. 124 (2): 360–6. PMID 15675955.
External links
- Overview of all the structural information available in the PDB for UniProt: Q9NQ38 (Serine protease inhibitor Kazal-type 5) at the PDBe-KB.
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