Kallikrein-14 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''KLK14''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (encoded by ''KLKB1 gene'') has no known paralogue, while tissue kallikrein-related peptidases (''KLKs'') encode a f ...
s are a subgroup of
serine protease
Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site.
They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...
s having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in
carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...
and some have potential as novel cancer,
skin disorders and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Apart from its common transcript, an additional transcript variant has been described but its difference in function and full length nature has not been determined.
KLK14 displays optimal
trypsin
Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...
-like activity at an alkaline pH of 8.0 and remains active in the pH ranges of 5.0 - 9.0 and is produced as a
zymogen
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the activ ...
, but can function also in a
chymotrypsin
Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenu ...
-like fashion. Activation of KLK14 is mediated by
KLK5
Kallikrein-5, formerly known as stratum corneum tryptic enzyme (SCTE), 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 clust ...
and after KLK14 activation, it further amplifies the activity of KLK proteases by a
positive feedback loop
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop where the outcome of a process reinforces the inciting process to build momentum. As such, these forces can exacerbate the effects ...
via cleavage of pro-KLK5, which is a central player in KLK cascade. KLK14 function has not yet been fully elucidated, but its most notable substrate is
PAR2. Its activity is inhibited by a wide variety of proteins, like
macroglobulin
Macroglobulins are large globular proteins and are found in the blood and other body fluids. Various physiological processes, including immunity, coagulation, and chemical transport, rely on these proteins. A macroglobulin is a plasma globulin ...
s,
serpin
Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be ...
s, and the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (
LEKTI
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 prot ...
) and also micro-environmental pH; and single-metal-ion inhibitors of KLKs among others.
References
Further reading
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External links
* The
MEROPS
MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibito ...
online database for peptidases and their inhibitors
S01.029
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