Kallikrein-related peptidase 7 (KLK7) is a serine protease

Serine protease

Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...

 that in humans is encoded by the KLK7 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein

Kallikrein

Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...

 family, which includes fifteen homologous serine proteases located on chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 19q13.

Gene

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

Function

KLK7 is secreted as an inactive zymogen

Zymogen

A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...

 in the stratum granulosum

Stratum granulosum

The stratum granulosum is a thin layer of cells in the epidermis. Keratinocytes migrating from the underlying stratum spinosum become known as granular cells in this layer...

 layer of the epidermis

Epidermis

Epidermis may refer to:* Epidermis , in plants, the outermost layer of cells covering the leaves and young parts of a plant* Epidermis , the outermost layer of the skin of a human...

, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5

KLK5

Kallikrein-related peptidase 5 , formerly known as stratum corneum tryptic enzyme , is a serine protease expressed in the epidermis. In humans it is encoded by the KLK5 gene. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its expression is...

 or matriptase, which are in vitro activators of KLK7.

Once active, KLK7 is able to cleave desmocollin

Desmocollin

Desmocollin is a type of cadherin.Specifically, it can refer to one of the following human genes :* DSC1* DSC2* DSC3...

 and corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes

Desmosome

A desmosome , also known as macula adherens , is a cell structure specialized for cell-to-cell adhesion...

, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum

Stratum corneum

The stratum corneum is the outermost layer of the epidermis, consisting of dead cells that lack nuclei and organelles. The purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress...

. Proteolysis of corneodesmosomes is required for desquamation

Desquamation

Desquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...

, the shedding of corneocytes from the outer layer of the epidermis. This indicates a role for KLK7 in maintaining skin homeostasis

Homeostasis

Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

.

Both KLK5 and KLK14

KLK14

Kallikrein-14 is a protein that in humans is encoded by the KLK14 gene.-External Links:* The MEROPS online database for peptidases and their inhibitors:...

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

KLK7 activity is regulated by a number of endogenous protein inhibitors

Protease inhibitor

Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...

 including LEKTI, SPINK6

SPINK6

Serine protease inhibitor Kazal-type 6 is a protein encoded by the SPINK6 gene in humans. It is a potent inhibitor of epidermal proteases involved in maintaining skin homeostasis, including KLK5, KLK7 and KLK14. SPINK6 is a member of a gene family cluster located on chromosome 5q33.1, which...

, elafin and alpha-2-Macroglobulin-like 1

Alpha-2-Macroglobulin-like 1

alpha-2-macroglobulin-like 1, also known as α2-macroglobulin-like 1 and abbreviated as α2ML1 is a large, 180 kDa protein found in the epidermis. It is able to the inhibit the chymotryptic activity of KLK7....

. Both Zn²⁺

Zinc

Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

 and Cu²⁺

Copper

Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...

 ions are also able to inhibit KLK7.

KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues tyrosine

Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

, phenylalanine

Phenylalanine

Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

 or leucine

Leucine

Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...

. Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.

Skin disease

Dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis

Atopic dermatitis

Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...

, psoriasis

Psoriasis

Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

 and Netherton syndrome

Netherton syndrome

Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is named after E.W. Netherton.- Characteristics :...

. These diseases are characterised by excessively dry, scaly and inflammed skin, due to a disruption of skin homeostasis and correct barrier function.

Cancer

Overexpression of KLK7 may provide a route for metastasis

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 in ovarian

Ovarian cancer

Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....

, breast

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, pancreatic

Pancreatic cancer

Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...

, cervix

Cervical cancer

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...

, and melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

 cancers by excessive cleavage of cell junction proteins. It may also be underexpressed in lung cancer

Lung cancer

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

.

External Links

• The MEROPS
  Merops
  Merops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
  
  online database for peptidases and their inhibitors: S01.017