LEKTI

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)
End	148,137,382 bp
Gene location (Mouse)
Chr.	Chromosome 18 (mouse)
End	44,155,568 bp
RNA expression pattern
	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
	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
	11005
	72432
	ENSG00000133710
	ENSMUSG00000055561
	Q9NQ38
	Q148R4
	NM_001127698; NM_001127699; NM_006846
	NM_001081180
	NP_001121170; NP_001121171; NP_006837
	NP_001074649
	Wikidata
View/Edit Human	View/Edit Mouse

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 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]

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.
^ 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.
^ ^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. doi:10.1038/jid.2011.295. PMID 21997416.
^ 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.
^ 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.
^ "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. doi:10.1038/sj.jid.5700015. PMID 16374478.

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.

This article on a gene on human chromosome 5 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000133710 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000055561 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10419450-5] 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.

[entrez-6] "Entrez Gene: SPINK5 serine peptidase inhibitor, Kazal type 5".

[furio-7] 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.

[pmid17596512-8] 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.

[pmid12667078-9] 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.

[10] "SPINK5 serine peptidase inhibitor, Kazal type 5 [Homo sapiens (human)] - Gene - NCBI".

[tartaglia-11] 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.

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