Lysyl oxidase homolog 2 is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''LOXL2''

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 ...

Function

This gene encodes a member of the

lysyl oxidase Lysyl oxidase (LOX), also known as protein-lysine 6-oxidase, is an enzyme that, in humans, is encoded by the ''LOX'' gene. It catalyzes the conversion of lysine residues into its aldehyde derivative allysine. Allysine form cross-links in extr ...

gene family. The prototypic member of the family is essential to the

biogenesis Spontaneous generation is a Superseded scientific theories, superseded scientific theory that held that living creatures could arise from abiotic component, non-living matter and that such processes were commonplace and regular. It was Hypoth ...

of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

s and

elastin Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...

. A highly conserved amino acid sequence at the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The

N-terminus 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 ...

is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and

chemotaxis Chemotaxis (from ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct thei ...

to each member of the family. LOXL2 can also crosslink

collagen type IV Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, ...

and hence influence the sprouting of new

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

vessels.

Clinical significance

LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis. LOXL2 changes the structure of

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...

s (proteins that are attached to DNA) and thus changes the shape of the cells, making it easier for the cancer cells to

metastasize Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

. An antibody that inhibits the activity of LOXL2, simtuzumab, is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as

liver fibrosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

Function

Clinical significance

See also

References

External links

Further reading