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{{Infobox_gene}}
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'''Kallikrein-related peptidase 7''' ('''KLK7''') is a [[serine protease]] that in humans is encoded by the ''KLK7'' [[gene]].<ref name="pmid8034709" /><ref name="pmid16800724" /><ref name="pmid16800723" /><ref name="entrez" /> KLK7 was initially purified from the [[epidermis (skin)|epidermis]] and characterised as stratum corneum chymotryptic enzyme (SCCE).<ref name="pmid1685827" /> It was later identified as the seventh member of the human [[kallikrein]] family, which includes fifteen homologous serine proteases located on [[chromosome 19]] (19q13).<ref name="pmid10974542" />
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== Gene ==
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Alternative splicing of the ''KLK7'' gene results in two transcript variants encoding the same protein.<ref name="entrez" />
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| update_citations = yes
== Function ==
}}
KLK7 is secreted as an inactive [[zymogen]] in the [[stratum granulosum]] layer of the [[Epidermis (skin)|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.<ref name="sales" /><ref name="cascade" />
 
Once active, KLK7 is able to cleave [[desmocollin]] and [[corneodesmosin]].<ref name="klksubstrates" /> These proteins constitute the extracellular component of [[desmosome|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.<ref name="klksubstrates" /> KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.<ref name="cascade" />
 
KLK7 activity is regulated by a number of endogenous protein [[Protease inhibitor (biology)|inhibitors]] including [[LEKTI]],<ref name="lekti1" /><ref name="lekti2" /> [[SPINK6]],<ref name="spink6" /> [[elafin]]<ref name="franzke" /> and [[alpha-2-Macroglobulin-like 1]].<ref name="a2mg1" /> Both [[zinc|Zn<sup>2+</sup>]] and [[copper|Cu<sup>2+</sup>]] ions are also able to inhibit KLK7.<ref name="franzke" />
 
KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues [[tyrosine]], [[phenylalanine]] or [[leucine]].<ref name="skytt" /> Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.<ref name="psscl" />
 
== Clinical significance ==
 
===Skin disease===
Dysregulation of KLK7 has been linked to several skin disorders including [[atopic dermatitis]],<ref name="pmid17518992" /><ref name="ad2" /> [[psoriasis]]<ref name="pmid10335915" /> and [[Netherton syndrome]].<ref name="pmid15619623" /><ref name="ns2" /> 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 cancer|ovarian]],<ref name="pmid12738725" /> [[breast cancer|breast]],<ref name="pmid14691584" /> [[pancreatic cancer|pancreatic]],<ref name="pmid17354228" /> [[cervical cancer|cervix]],<ref name="pmid15297163" /> and [[melanoma]]<ref name="pmid21193224" /> [[cancers]] by excessive cleavage of cell junction proteins. It may also be underexpressed in [[lung cancer]].<ref name="lung" />
 
==References==
{{Reflist|refs=
<ref name="pmid8034709">{{cite journal |vauthors=Hansson L, Stromqvist M, Backman A, Wallbrandt P, Carlstein A, Egelrud T | title = Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase | journal = J Biol Chem | volume = 269 | issue = 30 | pages = 19420–6 |date=Aug 1994 | pmid = 8034709 | pmc =  | doi =  }}</ref>
 
<ref name="pmid16800724">{{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 }}</ref>
 
<ref name="pmid16800723">{{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 }}</ref>
 
<ref name="entrez">{{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 = }}</ref>
 
<ref name="pmid1685827">{{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 =  }}</ref>
 
<ref name="pmid10974542">{{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  }}</ref>
 
<ref name="pmid17518992">{{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}}</ref>
 
<ref name="pmid10335915">{{cite journal |vauthors=Ekholm E, Egelrud T | title = Stratum corneum chymotryptic enzyme in psoriasis | journal = Arch of Dermatol Res | volume = 291 | issue = 4 | pages = 195–200 |date=Apr 1999 | pmid = 10335915 | pmc =  | doi =  10.1007/s004030050393}}</ref>
 
<ref name="pmid15619623">{{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}}</ref>
 
<ref name="pmid12738725">{{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=  }}</ref>
 
<ref name="pmid14691584">{{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=  10.1267/THRO04010180}}</ref>
 
<ref name="pmid17354228">{{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}}
</ref>
 
<ref name="pmid15297163">{{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 }}</ref>
 
<ref name="pmid21193224">{{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}}</ref>
 
<ref name="sales">{{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}}</ref>
 
<ref name="cascade">{{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 }}</ref>
 
<ref name="klksubstrates">{{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 }}</ref>
 
<ref name="lekti1">{{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}}</ref>
 
<ref name="lekti2">{{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= |doi= 10.1111/j.1365-2133.2005.06834.x}}</ref>
 
<ref name="spink6">{{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 }}</ref>
 
<ref name="franzke">{{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 =  | pmc =  | doi =  10.1074/jbc.271.36.21886}}</ref>
 
<ref name="a2mg1">{{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}}</ref>
 
<ref name="ad2">{{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 }}</ref>
 
<ref name="ns2">{{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 }}</ref>
 
<ref name="skytt">{{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 }}</ref>
 
<ref name="psscl">{{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 }}</ref>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
<ref name="lung">{{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 }}</ref>
{{GNF_Protein_box
| image =
| image_source = 
| PDB =
| Name = Kallikrein-related peptidase 7
| HGNCid = 6368
| Symbol = KLK7
| AltSymbols =; PRSS6; SCCE
| OMIM = 604438
| ECnumber = 
| Homologene = 37998
| MGIid = 1346336
| GeneAtlas_image1 = PBB_GE_KLK7_205778_at_tn.png
| Function = {{GNF_GO|id=GO:0004252 |text = serine-type endopeptidase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}} {{GNF_GO|id=GO:0008544 |text = epidermis development}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5650
    | Hs_Ensembl = ENSG00000169035
    | Hs_RefseqProtein = NP_005037
    | Hs_RefseqmRNA = NM_005046
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 56171541
    | Hs_GenLoc_end = 56178962
    | Hs_Uniprot = P49862
    | Mm_EntrezGene = 23993
    | Mm_Ensembl = ENSMUSG00000030713
    | Mm_RefseqmRNA = XM_001001759
    | Mm_RefseqProtein = XP_001001759
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 43679486
    | Mm_GenLoc_end = 43684401
    | Mm_Uniprot = Q91VE3
  }}
}}
'''Kallikrein-related peptidase 7''', also known as '''KLK7''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KLK7 kallikrein-related peptidase 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5650| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its encoded enzyme is thought to be involved in the proteolysis of intercellular cohesive structures preceding desquamation, which is the shedding of the outermost layer of the epidermis. Alternative splicing of this gene results in two transcript variants encoding the same protein.<ref name="entrez">{{cite web | title = Entrez Gene: KLK7 kallikrein-related peptidase 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5650| accessdate = }}</ref>
}}
}}


==References==
{{reflist|2}}
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading
*{{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 }}
| citations =
*{{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  | author=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 }}
*{{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  | author=Hansson L, Strömqvist M, Bäckman A, ''et al.'' |title=Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase. |journal=J. Biol. Chem. |volume=269 |issue= 30 |pages= 19420-6 |year= 1994 |pmid= 8034709 |doi=  }}
*{{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 | author=Yousef GM, Scorilas A, Magklara A, ''et al.'' |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=  }}
*{{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  | author=Gan L, Lee I, Smith R, ''et al.'' |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=  }}
*{{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 | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
*{{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 }}
*{{cite journal | author=Dong Y, Kaushal A, Brattsand M, ''et al.'' |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=  }}
{{Refend}}
*{{cite journal  | author=Talieri M, Diamandis EP, Gourgiotis D, ''et al.'' |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= 180-6 |year= 2004 |pmid= 14691584 |doi= 10.1267/THRO04010180 }}
 
*{{cite journal | author=Diamandis EP, Scorilas A, Kishi T, ''et al.'' |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 }}
==External links==
*{{cite journal | author=Caubet C, Jonca N, Brattsand M, ''et al.'' |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 }}
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=S01.017 S01.017]
*{{cite journal  | author=Vasilopoulos Y, Cork MJ, Murphy R, ''et al.'' |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 }}
 
*{{cite journal  | author=Santin AD, Cane' S, Bellone S, ''et al.'' |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 }}
{{Serine endopeptidases}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |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 }}
{{Enzymes}}
*{{cite journal | author=Ishida-Yamamoto A, Deraison C, Bonnart C, ''et al.'' |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 }}
{{Portal bar|Molecular and Cellular Biology|border=no}}
*{{cite journal | author=Planque C, de Monte M, Guyetant S, ''et al.'' |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 }}
*{{cite journal  | author=Descargues P, Deraison C, Prost C, ''et al.'' |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 }}
*{{cite journal  | author= |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 |year= 2006 |pmid= 16800723 |doi= 10.1515/BC.2006.081 }}
*{{cite journal  | author=Lundwall A, Band V, Blaber M, ''et al.'' |title=A comprehensive nomenclature for serine proteases with homology to tissue kallikreins. |journal=Biol. Chem. |volume=387 |issue= 6 |pages= 637-41 |year= 2006 |pmid= 16800724 |doi= 10.1515/BC.2006.082 }}
*{{cite journal  | author=Yamasaki K, Schauber J, Coda A, ''et al.'' |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 | author=Debela M, Hess P, Magdolen V, ''et al.'' |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 }}
}}
{{refend}}


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[[Category:EC 3.4.21]]
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Revision as of 23:40, 14 November 2017

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Orthologs
SpeciesHumanMouse
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Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene.[1][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.[7][8]

Once active, KLK7 is able to cleave desmocollin and corneodesmosin.[9] 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.[9] KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.[8]

KLK7 activity is regulated by a number of endogenous protein inhibitors including LEKTI,[10][11] SPINK6,[12] elafin[13] and alpha-2-Macroglobulin-like 1.[14] Both Zn2+ and Cu2+ ions are also able to inhibit KLK7.[13]

KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues tyrosine, phenylalanine or leucine.[15] Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.[16]

Clinical significance

Skin disease

Dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis,[17][18] psoriasis[19] and Netherton syndrome.[20][21] 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,[22] breast,[23] pancreatic,[24] cervix,[25] and melanoma[26] cancers by excessive cleavage of cell junction proteins. It may also be underexpressed in lung cancer.[27]

References

  1. ↑ Hansson L, Stromqvist M, Backman A, Wallbrandt P, Carlstein A, Egelrud T (Aug 1994). "Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase". J Biol Chem. 269 (30): 19420–6. PMID 8034709.
  2. ↑ 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 (Jun 2006). "A comprehensive nomenclature for serine proteases with homology to tissue kallikreins". Biol Chem. 387 (6): 637–41. doi:10.1515/BC.2006.082. PMID 16800724.
  3. ↑ Diamandis, Eleftherios P.; Deperthes, David; Lundwall, Åke (Jun 2006). "Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005". Biol Chem. 387 (6): 635–824. doi:10.1515/BC.2006.081. PMID 16800723.
  4. ↑ 4.0 4.1 "Entrez Gene: KLK7 kallikrein-related peptidase 7".
  5. ↑ Lundstrom A, Egelrud T (1991). "Stratum-Corneum Chymotryptic Enzyme: a Proteinase Which May Be Generally Present in the Stratum-Corneum and with a Possible Involvement in Desquamation". Acta Dermato-Venereologica. 71 (6): 471–474. PMID 1685827.
  6. ↑ Yousef GM, Scorilas A, Magklara A, et al. (2000). "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". Gene. 254 (1–2): 119–28. doi:10.1016/S0378-1119(00)00280-8. PMID 10974542.
  7. ↑ Katiuchia Uzzun Sales; Andrius Masedunskas; Alexandra L. Bey; Amber Rasmussen; Roberto Weigert; Karin List; Roman Szabo; Paul A. Overbeek; Thomas H. Bugge (2010). "Matriptase initiates epidermal prokallikrein activation and disease onset in a mouse model of Netherton syndrome". Nat. Genet. 42 (8): 676–683. doi:10.1038/ng.629. PMC 3081165. PMID 20657595.
  8. ↑ 8.0 8.1 Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., & Egelrud, T. (2005). "A proteolytic cascade of kallikreins in the stratum corneum". Journal of Investigative Dermatology. 124 (1): 198–203. doi:10.1111/j.0022-202X.2004.23547.x. PMID 15654974.
  9. ↑ 9.0 9.1 Caubet C, Jonca N, Brattsand M, et al. (2004). "Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7". J. Invest. Dermatol. 122 (5): 1235–44. doi:10.1111/j.0022-202X.2004.22512.x. PMID 15140227.
  10. ↑ Deraison, C., Bonnart, C., Lopez, F., Besson, C., Robinson, R., Jayakumar, A., Wagberg, F., Brattsand, M., Hachem, J. P., Leonardsson, G., & Hovnanian, A. (2007). "LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction". Molecular Biology of the Cell. 18 (9): 3607–3619. doi:10.1091/mbc.e07-02-0124. PMC 1951746. PMID 17596512.
  11. ↑ Egelrud T, Brattsand M, Kreutzmann P, Walden M, Vitzithum K, Marx UC, Forssmann WG, Mägert HJ (2005). "hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6". Br J Dermatol. 153 (6): 1200–1203. doi:10.1111/j.1365-2133.2005.06834.x.
  12. ↑ Meyer-Hoffert U, Wu Z, Kantyka T, Fischer J, Latendorf T, Hansmann B, Bartels J, He Y, Gläser R, Schröder JM (October 2010). "Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases". J Biol Chem. 285 (42): 32174–81. doi:10.1074/jbc.M109.091850. PMC 2952218. PMID 20667819.
  13. ↑ 13.0 13.1 Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O (September 1996). "Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation". J Biol Chem. 271 (36): 21886–90. doi:10.1074/jbc.271.36.21886.
  14. ↑ Galliano MF, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M (November 2005). "A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis". J Biol Chem. 281 (9): 5780–5789. doi:10.1074/jbc.m508017200. PMID 16298998.
  15. ↑ Skytt A, Strömqvist M, Egelrud T (1995). "Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme". Biochem. Biophys. Res. Commun. 211 (2): 586–9. doi:10.1006/bbrc.1995.1853. PMID 7794273.
  16. ↑ Debela M, Magdolen V, Schechter N, Valachova M, Lottspeich F, Craik CS, Choe Y, Bode W, Goettig P (2006). "Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences". J Biol Chem. 281 (35): 25678–88. doi:10.1074/jbc.M602372200. PMID 16740631.
  17. ↑ Komatsu N, Saijoh K, Kuk C, Liu AC, Khan S, Shirasaki F, Takehara K, Diamandis EP (Jun 2007). "Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients". Exp Dermatol. 16 (6): 513–519. doi:10.1111/j.1600-0625.2007.00562.x. PMID 17518992.
  18. ↑ Vasilopoulos Y, Cork MJ, Murphy R, et al. (2004). "Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis". J. Invest. Dermatol. 123 (1): 62–6. doi:10.1111/j.0022-202X.2004.22708.x. PMID 15191543.
  19. ↑ Ekholm E, Egelrud T (Apr 1999). "Stratum corneum chymotryptic enzyme in psoriasis". Arch of Dermatol Res. 291 (4): 195–200. doi:10.1007/s004030050393. PMID 10335915.
  20. ↑ Descargues P, Deraison C, Bonnart C, Kreft M, Kishibe M, Ishida-Yamamoto A, Elias P, Barrandon Y, Zambruno G, Sonnenberg A, Hovnanian A (Jan 2005). "Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity". Nat Genet. 37 (1): 56–65. doi:10.1038/ng1493. PMID 15619623.
  21. ↑ Descargues P, Deraison C, Prost C, et al. (2006). "Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome". J. Invest. Dermatol. 126 (7): 1622–32. doi:10.1038/sj.jid.5700284. PMID 16628198.
  22. ↑ Dong Y, Kaushal A, Brattsand M, et al. (2004). "Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers". Clin. Cancer Res. 9 (5): 1710–20. PMID 12738725.
  23. ↑ Talieri M, Diamandis EP, Gourgiotis D, Mathioudaki K, Scorilas A (2004). "Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma". Thromb Haemost. 91 (1): 180–186. doi:10.1267/THRO04010180. PMID 14691584.
  24. ↑ Johnson SK, Rarnani VC, Hennings L, Haun RS (2007). "Kallikrein 7 enhances pancreatic cancer cell invasion by shedding E-cadherin". Cancer. 109 (9): 1811–1820. doi:10.1002/cncr.22606. PMID 17354228.
  25. ↑ Santin AD, Cane' S, Bellone S, et al. (2004). "The serine protease stratum corneum chymotryptic enzyme (kallikrein 7) is highly overexpressed in squamous cervical cancer cells". Gynecol. Oncol. 94 (2): 283–8. doi:10.1016/j.ygyno.2004.05.023. PMID 15297163.
  26. ↑ Rezze GG; Fregnani JHTG; Duprat J; Landman G (2011). "Cell adhesion and communication proteins are differentially expressed in melanoma progression model". Hum Pathol. 42 (3): 409–418. doi:10.1016/j.humpath.2010.09.004. PMID 21193224.
  27. ↑ Planque C, de Monte M, Guyetant S, et al. (2005). "KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer". Biochem. Biophys. Res. Commun. 329 (4): 1260–6. doi:10.1016/j.bbrc.2005.02.100. PMID 15766562.

Further reading

External links

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