Mucin
Encyclopedia
Mucins are a family of high molecular weight, heavily glycosylated
proteins (glycoconjugates) produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. They often take an inhibitory role. Some mucins are associated with controlling mineralization, including nacre formation in molluscs, calcification in echinoderms and bone formation in vertebrates. They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especially MUC1
is associated with many types of cancer.
Although some mucins are membrane
-bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, most mucins are secreted
onto mucosal surfaces or secreted to become a component of saliva
.
, MUC2
, MUC3A
, MUC3B, MUC4
, MUC5AC
, MUC5B
, MUC6
, MUC7
, MUC8, MUC12, MUC13, MUC15, MUC16, MUC17
, MUC19, and MUC20
.
The major secreted airway mucins are MUC5AC
and MUC5B
, while MUC2
is secreted mostly in the intestine but also in the airway.
s encode mucin monomers that are synthesized as rod-shape apomucin cores that are post-translationally modified by exceptionally abundant glycosylation
.
The dense "sugar coating" of mucins gives them considerable water-holding capacity and also makes them resistant to proteolysis
, which may be important in maintaining mucosal
barriers.
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 million Da. Within these aggregates, monomer
s are linked to one another mostly by non-covalent interactions, although intermolecular disulfide
bonds may also play a role in this process.
within the specialized epithelial cells. Fusion of the vesicles to the plasma membrane causes release of the mucin, which as it exchanges Ca2+
for Na+
expands up to 600 fold. The result is a viscoelastic product of interwoven molecules which, combined with other secretions (e.g., from the airway epithelium
and the submucosal glands
in the respiratory system
), is called mucus
.
s, including cancers of the pancreas, lung, breast, ovary, colon and other tissues. Mucins are also overexpressed in lung diseases such as asthma
, bronchitis
, COPD
or cystic fibrosis
. Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process. Mucins are under investigation as possible diagnostic markers for malignancies and other disease processes in which they are most commonly over- or mis-expressed.
Abnormal deposits of mucin are responsible for the non-pitting facial edema seen in untreated hypothryoidism. This edema is seen in the pretibial area as well.
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
proteins (glycoconjugates) produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. They often take an inhibitory role. Some mucins are associated with controlling mineralization, including nacre formation in molluscs, calcification in echinoderms and bone formation in vertebrates. They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especially MUC1
MUC1
Mucin 1, cell surface associated or polymorphic epithelial mucin is a mucin encoded by the MUC1 gene in humans. MUC1 is a proteoglycan with extensive O-linked glycosylation of its extracellular domain. Mucins line the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and...
is associated with many types of cancer.
Although some mucins are membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
-bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, most mucins are secreted
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
onto mucosal surfaces or secreted to become a component of saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
.
Genes
At least 19 human mucin genes have been distinguished by cDNA cloning — MUC1MUC1
Mucin 1, cell surface associated or polymorphic epithelial mucin is a mucin encoded by the MUC1 gene in humans. MUC1 is a proteoglycan with extensive O-linked glycosylation of its extracellular domain. Mucins line the apical surface of epithelial cells in the lungs, stomach, intestines, eyes and...
, MUC2
MUC2
Mucin 2, oligomeric mucus/gel-forming, also known as MUC2, is a protein that in humans is encoded by the MUC2 gene.-Function:This gene encodes a member of the mucin protein family...
, MUC3A
MUC3A
Mucin-3A is a protein that in humans is encoded by the MUC3A gene.-Further reading:...
, MUC3B, MUC4
MUC4
Mucin-4 is a protein that in humans is encoded by the MUC4 gene.-Further reading:...
, MUC5AC
MUC5AC
Mucin-5AC is a protein that in humans is encoded by the MUC5AC gene.-Further reading:...
, MUC5B
MUC5B
Mucin-5B is a protein that in humans is encoded by the MUC5B gene.-Further reading:...
, MUC6
MUC6
Mucin 6, oligomeric mucus/gel-forming, also known as MUC6, is a human gene.-Further reading:...
, MUC7
MUC7
Mucin-7 is a protein that in humans is encoded by the MUC7 gene.-Further reading:...
, MUC8, MUC12, MUC13, MUC15, MUC16, MUC17
MUC17
Mucin-17 is a protein that in humans is encoded by the MUC17 gene.-Further reading:...
, MUC19, and MUC20
MUC20
Mucin-20 is a protein that in humans is encoded by the MUC20 gene.-Further reading:...
.
The major secreted airway mucins are MUC5AC
MUC5AC
Mucin-5AC is a protein that in humans is encoded by the MUC5AC gene.-Further reading:...
and MUC5B
MUC5B
Mucin-5B is a protein that in humans is encoded by the MUC5B gene.-Further reading:...
, while MUC2
MUC2
Mucin 2, oligomeric mucus/gel-forming, also known as MUC2, is a protein that in humans is encoded by the MUC2 gene.-Function:This gene encodes a member of the mucin protein family...
is secreted mostly in the intestine but also in the airway.
Protein structure
Mature mucins are composed of two distinct regions:- The amino- and carboxy-terminal regions are very lightly glycosylated, but rich in cysteineCysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s. The cysteine residues participate in establishing disulfideDisulfideIn chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....
linkages within and among mucin monomers.
- A large central region formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of the amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s are serineSerineSerine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
or threonineThreonineThreonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
. This area becomes saturated with hundreds of O-linked oligosaccharides. N-linked oligosaccharides are also found on mucins, but in less abundance than O-linked sugars.
Glycosylation and aggregation
Mucin geneGene
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...
s encode mucin monomers that are synthesized as rod-shape apomucin cores that are post-translationally modified by exceptionally abundant glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
.
The dense "sugar coating" of mucins gives them considerable water-holding capacity and also makes them resistant to proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
, which may be important in maintaining mucosal
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
barriers.
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 million Da. Within these aggregates, monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s are linked to one another mostly by non-covalent interactions, although intermolecular disulfide
Disulfide
In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....
bonds may also play a role in this process.
Secretion
Upon stimulation, MARCKS (myristylated alanine-rich C kinase substrate) protein coordinates the secretion of mucin from mucin filled vesiclesVesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
within the specialized epithelial cells. Fusion of the vesicles to the plasma membrane causes release of the mucin, which as it exchanges Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
for Na+
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
expands up to 600 fold. The result is a viscoelastic product of interwoven molecules which, combined with other secretions (e.g., from the airway epithelium
Respiratory epithelium
Respiratory epithelium is a type of epithelium found lining the respiratory tract, where it serves to moisten and protect the airways. It also functions as a barrier to potential pathogens and foreign particles, preventing infection and tissue injury by action of the mucociliary escalator.-...
and the submucosal glands
Submucosal glands
Submucosal glands can refer to:*Esophageal glands, the submucosal glands of the esophagus.*Brunner's glands, the submucosal glands of the duodenum.*Submucosal glands in the upper airways of mammals....
in the respiratory system
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
), is called mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
.
Clinical significance
Increased mucin production occurs in many adenocarcinomaAdenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
s, including cancers of the pancreas, lung, breast, ovary, colon and other tissues. Mucins are also overexpressed in lung diseases such as asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, bronchitis
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
, COPD
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
or cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
. Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process. Mucins are under investigation as possible diagnostic markers for malignancies and other disease processes in which they are most commonly over- or mis-expressed.
Abnormal deposits of mucin are responsible for the non-pitting facial edema seen in untreated hypothryoidism. This edema is seen in the pretibial area as well.