Suppressor of tumorigenicity 14 protein, also known as matriptase, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that in humans is encoded by the ST14

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. ST14

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...

have been identified in most

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fu ...

for which complete genome data are available.

Function

Matriptase is an epithelial-derived, integral membrane serine

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the form ...

. This protease forms a complex with the

Kunitz Kunitz is the surname of several people: * Chris Kunitz (born 1979), a Canadian professional ice hockey player * Jaana Kunitz (Yaana Kunitz; born 1972), an award-winning ballroom dancer and fitness program creator * Matt Kunitz (born 1968), a telev ...

-type serine protease inhibitor, HAI-1, and is found to be activated by

sphingosine-1-phosphate Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcoho ...

. This protease has been shown to cleave and activate hepatocyte growth factor/scatter factor, and

urokinase plasminogen activator Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...

, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors. Matriptase is a type II transmembrane serine protease expressed in most human epithelia, where it is coexpressed with its cognate transmembrane inhibitor,

hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on ...

activator inhibitor (HAI)-1. Activation of the matriptase zymogen requires sequential

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

cleavage, activation site autocleavage, and transient association with HAI-1. Matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the ...

, and is also critical for hair follicle growth. Matriptase is an 80- to 90-kDa cell surface glycoprotein with a complex modular structure that is common to all matriptases.

Clinical significance

The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis. Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models.

Function

Clinical significance

References

Further reading