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词条 KLK7
释义

  1. Gene

  2. Function

  3. Clinical significance

     Skin disease  Cancer 

  4. References

  5. Further reading

  6. External links

{{Infobox_gene}}Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene.[2][3][4] KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE).[5] It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).[6]

Gene

Alternative splicing of the KLK7 gene results in two transcript variants encoding the same protein.[4]

Function

KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are in vitro activators of KLK7.[8][9]

Once active, KLK7 is able to cleave desmocollin and corneodesmosin.[10] These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum. Proteolysis of corneodesmosomes is required for desquamation, the shedding of corneocytes from the outer layer of the epidermis. This indicates a role for KLK7 in maintaining skin homeostasis.

Both KLK5 and KLK14, other skin-expressed proteases, also cleave corneodesmosomal proteins.[10] KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.[9]

KLK7 activity is regulated by a number of endogenous protein inhibitors including LEKTI,[13][14] SPINK6,[15] elafin[16] and alpha-2-Macroglobulin-like 1.[17] Both Zn2+ and Cu2+ ions are also able to inhibit KLK7.[16]

KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues tyrosine, phenylalanine or leucine.[19] Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.[20]

Clinical significance

Skin disease

Dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis,[21][22] psoriasis[23] and Netherton syndrome.[24][25] These diseases are characterised by excessively dry, scaly and inflamed skin, due to a disruption of skin homeostasis and correct barrier function.

Cancer

Overexpression of KLK7 may provide a route for metastasis in ovarian,[26] breast,[27] pancreatic,[28] cervix,[29] and melanoma[30] cancers by excessive cleavage of cell junction proteins. It may also be underexpressed in lung cancer.[31]

References

1. ^1 {{cite journal |vauthors=Lundwall A, Band V, Blaber M, Clements JA, Courty Y, Diamandis EP, Fritz H, Lilja H, Malm J, Maltais LJ, Olsson AY, Petraki C, Scorilas A, Sotiropoulou G, Stenman UH, Stephan C, Talieri M, Yousef GM | title = A comprehensive nomenclature for serine proteases with homology to tissue kallikreins | journal = Biol Chem | volume = 387 | issue = 6 | pages = 637–41 |date=Jun 2006 | pmid = 16800724 | pmc = | doi = 10.1515/BC.2006.082 }}
2. ^1 {{cite journal | title = Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005 | journal = Biol Chem | volume = 387 | issue = 6 | pages = 635–824 |date=Jun 2006 | pmid = 16800723 | pmc = | doi = 10.1515/BC.2006.081 | last1 = Diamandis | first1 = Eleftherios P. | last2 = Deperthes | first2 = David | last3 = Lundwall | first3 = Åke }}
3. ^1 2 {{cite web | title = Entrez Gene: KLK7 kallikrein-related peptidase 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5650| accessdate = }}
4. ^1 {{cite journal |vauthors=Lundstrom A, Egelrud T | title = Stratum-Corneum Chymotryptic Enzyme: a Proteinase Which May Be Generally Present in the Stratum-Corneum and with a Possible Involvement in Desquamation | journal = Acta Dermato-Venereologica | volume = 71 | issue = 6 | pages = 471–474 | year = 1991 | month = | pmid = 1685827 | pmc = | doi = }}
5. ^1 {{cite journal |vauthors=Yousef GM, Scorilas A, Magklara A, etal |title=The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family - genomic characterization, mapping, tissue expression and hormonal regulation. |journal=Gene |volume=254 |issue= 1–2 |pages= 119–28 |year= 2000 |pmid= 10974542 |doi=10.1016/S0378-1119(00)00280-8 }}
6. ^1 {{cite journal |vauthors=Komatsu N, Saijoh K, Kuk C, Liu AC, Khan S, Shirasaki F, Takehara K, Diamandis EP | title = Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients | journal = Exp Dermatol | volume = 16 | issue = 6 | pages = 513–519 |date=Jun 2007 | pmid = 17518992 | pmc = | doi = 10.1111/j.1600-0625.2007.00562.x}}
7. ^1 {{cite journal |vauthors=Ekholm E, Egelrud T | title = Stratum corneum chymotryptic enzyme in psoriasis | journal = Arch Dermatol Res | volume = 291 | issue = 4 | pages = 195–200 |date=Apr 1999 | pmid = 10335915 | pmc = | doi = 10.1007/s004030050393}}
8. ^1 {{cite journal |vauthors=Descargues P, Deraison C, Bonnart C, Kreft M, Kishibe M, Ishida-Yamamoto A, Elias P, Barrandon Y, Zambruno G, Sonnenberg A, Hovnanian A | title = Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity | journal = Nat Genet | volume = 37 | issue = 1 | pages = 56–65 |date=Jan 2005 | pmid = 15619623 | pmc = | doi = 10.1038/ng1493}}
9. ^1 {{cite journal |vauthors=Dong Y, Kaushal A, Brattsand M, etal |title=Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers |journal=Clin. Cancer Res. |volume=9 |issue= 5 |pages= 1710–20 |year= 2004 |pmid= 12738725 |doi= }}
10. ^1 {{cite journal |vauthors=Talieri M, Diamandis EP, Gourgiotis D, Mathioudaki K, Scorilas A |title=Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma |journal=Thromb Haemost |volume=91 |issue= 1 |pages= 180–186 |year= 2004 |pmid= 14691584 |doi= 10.1160/TH03-05-0261}}
11. ^1 {{cite journal |vauthors=Johnson SK, Rarnani VC, Hennings L, Haun RS |title=Kallikrein 7 enhances pancreatic cancer cell invasion by shedding E-cadherin |journal=Cancer |volume=109 |issue= 9 |pages= 1811–1820 |year= 2007 |pmid=17354228 |doi= 10.1002/cncr.22606}}
12. ^1 {{cite journal |vauthors=Santin AD, Cane' S, Bellone S, etal |title=The serine protease stratum corneum chymotryptic enzyme (kallikrein 7) is highly overexpressed in squamous cervical cancer cells |journal=Gynecol. Oncol. |volume=94 |issue= 2 |pages= 283–8 |year= 2004 |pmid= 15297163 |doi= 10.1016/j.ygyno.2004.05.023 }}
13. ^1 {{cite journal |author1=Rezze GG |author2=Fregnani JHTG |author3=Duprat J |author4=Landman G |title=Cell adhesion and communication proteins are differentially expressed in melanoma progression model |journal=Hum Pathol |volume=42 |issue= 3 |pages= 409–418 |year= 2011 |pmid=21193224 |doi= 10.1016/j.humpath.2010.09.004}}
14. ^1 {{cite journal |author1=Katiuchia Uzzun Sales |author2=Andrius Masedunskas |author3=Alexandra L. Bey |author4=Amber Rasmussen |author5=Roberto Weigert |author6=Karin List |author7=Roman Szabo |author8=Paul A. Overbeek |author9=Thomas H. Bugge |title=Matriptase initiates epidermal prokallikrein activation and disease onset in a mouse model of Netherton syndrome |journal=Nat. Genet. |volume=42 |issue=8 |pages= 676–683 |year= 2010 |pmid= 20657595|doi=10.1038/ng.629 |pmc=3081165}}
15. ^1 2 {{cite journal | author=Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., & Egelrud, T. |title=A proteolytic cascade of kallikreins in the stratum corneum. |journal=Journal of Investigative Dermatology |volume=124 |issue=1 |pages=198–203 |year=2005 |pmid= 15654974|doi=10.1111/j.0022-202X.2004.23547.x }}
16. ^1 2 {{cite journal |vauthors=Caubet C, Jonca N, Brattsand M, etal |title=Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. |journal=J. Invest. Dermatol. |volume=122 |issue= 5 |pages= 1235–44 |year= 2004 |pmid= 15140227 |doi= 10.1111/j.0022-202X.2004.22512.x }}
17. ^1 {{cite journal | author=Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., Wagberg, F., Brattsand, M., Hachem, J. P., Leonardsson, G., & Hovnanian, A. |title=LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction. |journal=Molecular Biology of the Cell |volume=18 |issue=9 |pages=3607–3619 |year=2007 |pmid= 17596512|doi= 10.1091/mbc.e07-02-0124 |pmc=1951746}}
18. ^1 {{cite journal |vauthors=Egelrud T, Brattsand M, Kreutzmann P, Walden M, Vitzithum K, Marx UC, Forssmann WG, Mägert HJ |title=hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6. |journal=Br J Dermatol |volume=153 |issue=6 |pages=1200–1203 |year=2005 |pmid= 16307658|doi= 10.1111/j.1365-2133.2005.06834.x}}
19. ^1 {{cite journal |vauthors=Meyer-Hoffert U, Wu Z, Kantyka T, Fischer J, Latendorf T, Hansmann B, Bartels J, He Y, Gläser R, Schröder JM | title = Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. | journal = J Biol Chem | volume = 285 | issue = 42 | pages = 32174–81 |date=October 2010 | pmid = 20667819 | pmc = 2952218| doi = 10.1074/jbc.M109.091850 }}
20. ^1 2 {{cite journal |vauthors=Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O | title = Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation. | journal = J Biol Chem | volume = 271 | issue = 36 | pages = 21886–90 |date=September 1996 | pmid = 8702990| pmc = | doi = 10.1074/jbc.271.36.21886}}
21. ^1 {{cite journal |vauthors=Galliano MF, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M | title = A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis. | journal = J Biol Chem | volume = 281 | issue = 9 | pages = 5780–5789 |date=November 2005 | pmid = 16298998| pmc = | doi = 10.1074/jbc.m508017200}}
22. ^1 {{cite journal |vauthors=Vasilopoulos Y, Cork MJ, Murphy R, etal |title=Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. |journal=J. Invest. Dermatol. |volume=123 |issue= 1 |pages= 62–6 |year= 2004 |pmid= 15191543 |doi= 10.1111/j.0022-202X.2004.22708.x }}
23. ^1 {{cite journal |vauthors=Descargues P, Deraison C, Prost C, etal |title=Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. |journal=J. Invest. Dermatol. |volume=126 |issue= 7 |pages= 1622–32 |year= 2006 |pmid= 16628198 |doi= 10.1038/sj.jid.5700284 }}
24. ^1 {{cite journal |vauthors=Skytt A, Strömqvist M, Egelrud T |title=Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme. |journal=Biochem. Biophys. Res. Commun. |volume=211 |issue= 2 |pages= 586–9 |year= 1995 |pmid= 7794273 |doi= 10.1006/bbrc.1995.1853 }}
25. ^1 {{cite journal |vauthors=Debela M, Magdolen V, Schechter N, Valachova M, Lottspeich F, Craik CS, Choe Y, Bode W, Goettig P |title=Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences. |journal= J Biol Chem |volume= 281 |issue= 35 |pages= 25678–88 |year= 2006 |pmid= 16740631 |doi= 10.1074/jbc.M602372200 }}
26. ^1 {{cite journal |vauthors=Planque C, de Monte M, Guyetant S, etal |title=KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer. |journal=Biochem. Biophys. Res. Commun. |volume=329 |issue= 4 |pages= 1260–6 |year= 2005 |pmid= 15766562 |doi= 10.1016/j.bbrc.2005.02.100 }}
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Further reading

{{Refbegin | 2}}
  • {{cite journal |vauthors=Gan L, Lee I, Smith R, etal |title=Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. |journal=Gene |volume=257 |issue= 1 |pages= 119–30 |year= 2001 |pmid= 11054574 |doi=10.1016/S0378-1119(00)00382-6 }}
  • {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
  • {{cite journal |vauthors=Diamandis EP, Scorilas A, Kishi T, etal |title=Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. |journal=Clin. Biochem. |volume=37 |issue= 3 |pages= 230–7 |year= 2004 |pmid= 14972646 |doi= 10.1016/j.clinbiochem.2003.11.012 }}
  • {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
  • {{cite journal |vauthors=Ishida-Yamamoto A, Deraison C, Bonnart C, etal |title=LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. |journal=J. Invest. Dermatol. |volume=124 |issue= 2 |pages= 360–6 |year= 2005 |pmid= 15675955 |doi= 10.1111/j.0022-202X.2004.23583.x }}
  • {{cite journal |vauthors=Yamasaki K, Schauber J, Coda A, etal |title=Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. |journal=FASEB J. |volume=20 |issue= 12 |pages= 2068–80 |year= 2006 |pmid= 17012259 |doi= 10.1096/fj.06-6075com }}
  • {{cite journal |vauthors=Debela M, Hess P, Magdolen V, etal |title=Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue= 41 |pages= 16086–91 |year= 2007 |pmid= 17909180 |doi= 10.1073/pnas.0707811104 | pmc=2042166 }}
{{Refend}}

External links

  • The MEROPS online database for peptidases and their inhibitors: S01.017
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1 : EC 3.4.21
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