SPINK5

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/14 14:36:48」(JST)

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Serine peptidase inhibitor, Kazal type 5
PDB rendering based on 1h0z.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1H0Z, 1HDL, 1UUC, 1UVF, 1UVG
Identifiers
Symbols	SPINK5 ; LEKTI; LETKI; NETS; NS; VAKTI
External IDs	OMIM: 605010 MGI: 1919682 HomoloGene: 4987 GeneCards: SPINK5 Gene
Gene ontology Molecular function • serine-type endopeptidase inhibitor activity Cellular component • extracellular region • cytoplasm • endoplasmic reticulum • endoplasmic reticulum membrane • cytosol • cell cortex • perinuclear region of cytoplasm • extracellular vesicular exosome • epidermal lamellar body Biological process • epidermal cell differentiation • negative regulation of endopeptidase activity • negative regulation of angiogenesis • regulation of cell adhesion • extracellular matrix organization • epithelial cell differentiation • hair cell differentiation • anagen • regulation of T cell differentiation • negative regulation of proteolysis • negative regulation of immune response Sources: Amigo / QuickGO
RNA expression pattern
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.

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. 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.

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

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

Gene

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. Alternative processing of SPINK5 results in the formation of three different gene products, which have been identified in differentiated keratinocytes.

Clinical significance

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

See also

• Kazal-type serine protease inhibitor domain

References

Further reading

• Norgett EE, Kelsell DP (2002). "SPINK5: both rare and common skin disease.". Trends in molecular medicine 8 (1): 7. doi:10.1016/S1471-4914(01)02228-6. 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. doi:10.1016/S1357-2725(01)00179-0. PMID 11943586.  CS1 maint: Explicit use of et al. (link)
• 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. PMID 12437098.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1086/302824. PMC 1288172. PMID 10712206.  CS1 maint: Explicit use of et al. (link)
• 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. PMID 10835624.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1046/j.1523-1747.2001.01389.x. PMID 11511292.  CS1 maint: Explicit use of et al. (link)
• 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. PMID 11544479.  CS1 maint: Explicit use of et al. (link)
• 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. PMID 11594460. 
• 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. doi:10.1046/j.1523-1747.2002.01603.x. PMID 11841556.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1046/j.0022-202x.2001.01663.x. PMID 11874482.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1093/hmg/ddg247. PMID 12915442.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1038/sj.gene.6363889. PMID 14551605.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1111/j.0022-202X.2004.23220.x. PMID 15304086.  CS1 maint: Explicit use of et al. (link)
• Tidow H, Lauber T, Vitzithum K et al. (2004). "The solution structure of a chimeric LEKTI domain reveals a chameleon sequence.". Biochemistry 43 (35): 11238–47. doi:10.1021/bi0492399. PMID 15366933.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1101/gad.1232104. PMC 522985. PMID 15466487.  CS1 maint: Explicit use of et al. (link)
• 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. doi:10.1111/j.0022-202X.2004.23583.x. PMID 15675955.  CS1 maint: Explicit use of et al. (link)

UpToDate Contents

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• 1. アトピー性皮膚炎（湿疹）の病因、臨床症状、および診断 pathogenesis clinical manifestations and diagnosis of atopic dermatitis eczema

English Journal

• The Co-Expression of Kallikrein 5 and Kallikrein 7 Associates with Poor Survival in Non-HPV Oral Squamous-Cell Carcinoma.

• Leusink FK1, van Diest PJ, Frank MH, Broekhuizen R, Braunius W, van Hooff SR, Willems SM, Koole R.
• Pathobiology : journal of immunopathology, molecular and cellular biology.Pathobiology.2015 May 28;82(2):58-67. [Epub ahead of print]
• OBJECTIVE: Oral squamous-cell carcinoma (OSCC) still has a poor prognosis. Lymph node metastasis (LNM) is a major determinant of treatment decisions and prognosis. Serine protease inhibitor Kazal-type 5 (SPINK5) is the inhibitor of kallikrein 5 (KLK5) and KLK7. SPINK5, KLK5 and KLK7 are three of the
• PMID 26022646

• Exon-Specific U1s Correct SPINK5 Exon 11 Skipping Caused by a Synonymous Substitution that Affects a Bifunctional Splicing Regulatory Element.

• Dal Mas A1, Fortugno P, Donadon I, Levati L, Castiglia D, Pagani F.
• Human mutation.Hum Mutat.2015 May;36(5):504-12. doi: 10.1002/humu.22762. Epub 2015 Mar 19.
• The c.891C>T synonymous transition in SPINK5 induces exon 11 (E11) skipping and causes Netherton syndrome (NS). Using a specific RNA-protein interaction assay followed by mass spectrometry analysis along with silencing and overexpression of splicing factors, we showed that this mutation affects a
• PMID 25665175

• Betapapillomavirus in multiple non-melanoma skin cancers of Netherton syndrome: Case report and published work review.

• Guerra L1, Fortugno P, Sinistro A, Proto V, Zambruno G, Didona B, Castiglia D.
• The Journal of dermatology.J Dermatol.2015 Apr 28. doi: 10.1111/1346-8138.12913. [Epub ahead of print]
• Netherton syndrome (NS) is a rare genetic disease presenting with ichthyosiform erythroderma, hair alterations and atopy. NS is due to SPINK5 gene mutations, which cause absent or decreased expression of the encoded protein lymphoepithelial Kazal-type-related inhibitor (LEKTI) in all stratified epit
• PMID 25917539

Japanese Journal

• 多彩な合併症を呈した Netherton 症候群の1剖検例

• 近藤 武史,北澤 理子,榎木 英介,森 清,長野 徹,竹島 泰弘,北澤 荘平
• 診断病理 : Japanese journal of diagnostic pathology 26(3), 186-190, 2009-07-31
• NAID 10025621693

Related Links

• SPINK5 - serine peptidase inhibitor, Kazal type 5 - Genetics ...

Netherton syndrome - caused by mutations in the SPINK5 gene At least 70 SPINK5 gene mutations have been identified in people with Netherton syndrome, a disorder involving skin and hair abnormalities and a high risk ...

• SPINK5 Gene - GeneCards | ISK5 Protein | ISK5 Antibody

Complete information for SPINK5 gene (Protein Coding), Serine Peptidase Inhibitor, Kazal Type 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... A ...

Related Pictures

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★リンクテーブル★

リンク元	「ネザートン症候群」

「ネザートン症候群」

　　[★]

英

Netherton syndrome、Netherton's syndrome

同

Netherton症候群

関

SPINK5、アトピー性皮膚炎、魚鱗癬、角化症

• 常染色体遺伝性の魚鱗癬紅皮症