Mucins (/ˈmjuːsɪn/) are a family of highmolecular weight, heavilyglycosylated proteins (glycoconjugates) produced byepithelial tissues in mostanimals.[1] Mucins' key characteristic is their ability to formgels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers.[1] They often take an inhibitory role.[1] Some mucins are associated with controllingmineralization, includingnacre formation inmollusks,[2]calcification inechinoderms[3] and bone formation in vertebrates.[4] They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especiallyMUC1, is associated with many types of cancer.[5][6]
Human mucins include genes with theHUGO symbol MUC 1 through 22. Of these mucins, the following classes have been defined by localization:[7][8][9][10]
Secreted mucins in humans, with their chromosomal location, repeat size in amino acids (aa), whether they are gel-forming (Y) or not (N), and their tissue expression.[11]
The major secreted airway mucins areMUC5AC andMUC5B, whileMUC2 is secreted mostly in the intestine but also in the airway. MUC7 is the major salivary protein.[10]
Mature mammalian mucins are composed of two distinct regions:[7]
Theamino- andcarboxy-terminal regions are very lightly glycosylated, but rich incysteines. The cysteine residues participate in establishingdisulfide linkages within and among mucinmonomers.
A large central region ("PTS domain") formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of theamino acids areserine orthreonine. This area becomes saturated with hundreds ofO-linkedoligosaccharides.N-linkedoligosaccharides are also found on mucins, but in less abundance than O-linked sugars.
The functional classification does not correspond to an exact evolutionary relationship, which is still incomplete and ongoing.[10] Known-related groups include:
The gel-forming mucins (2, 5AC, 5B, 6, 19) are related both to each other and tootogelin andvon Willebrand Factor (PTHR11339).[14] Four of these occur in a well-conserved gene cluster (at 11p.15.5 in humans).[15]
TheEGF-like domain containing mucins. These include MUC3(A,B), MUC4, MUC12, MUC13, and MUC17.[16]
Some EGF-like mucins, plus MUC1 and MUC16, carrySEA domains, a vertebrate invention. It is unclear whether this points to a common origin among these transmembrane mucins.[14]
MUC21 and MUC22 are related to each other by sharing a C-terminal domain (PF14654). They also occur in a human gene cluster on 6p21.33.
Mucins have been found to have important functions in defense against bacterial and fungal infections. MUC5B, the predominant mucin in the mouth and female genital tract, has been shown to significantly reduce attachment andbiofilm formation ofStreptococcus mutans, a bacterium with the potential to form cavities.[18] Unusually, MUC5B does not kill the bacteria but rather maintains it in the planktonic (non-biofilm) phase, thus maintaining a diverse and healthy oral microbiome.[18] Similar effects of MUC5B and other mucins have been demonstrated with other pathogens, such asCandida albicans,Helicobacter pylori, and evenHIV.[19][20] In the mouth, mucins can also recruit anti-microbial proteins such asstatherins andhistatine 1, which further reduces risk of infection.[20]
Eleven mucins are expressed by theeye surface epithelia,goblet cells and associated glands, even though most of them are expressed at very low levels. They maintain wetness, lubricate the blink, stabilize thetear film, and create a physical barrier to the outside world.[12]
Mucingenes encode mucin monomers that are synthesized as rod-shapedapomucin cores that are post-translationally modified by exceptionally abundantglycosylation.
The dense "sugar coating" of mucins gives them considerablewater-holding capacity and also makes them resistant toproteolysis, which may be important in maintainingmucosal barriers.
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 millionDa. Within these aggregates, monomers are linked to one another mostly by non-covalent interactions, although intermoleculardisulfide bonds may also play a role in this process.
Upon stimulation,MARCKS (myristylated alanine-rich C kinase substrate) protein coordinates the secretion of mucin from mucin-filledvesicles within the specialized epithelial cells.[21] Fusion of the vesicles to theplasma membrane causes release of the mucin, which as it exchangesCa2+ forNa+ expands up to 600 fold. The result is aviscoelastic product of interwoven molecules which, combined with other secretions (e.g., from theairway epithelium and thesubmucosal glands in therespiratory system), is calledmucus.[22][23]
Increased mucin production occurs in manyadenocarcinomas, including cancers of the pancreas, lung, breast, ovary, colon and other tissues. Mucins are also overexpressed in lung diseases such asasthma,bronchitis,chronic obstructive pulmonary disease (COPD) orcystic fibrosis.[24] Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process.[25][26][27] 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 facialedema seen in untreatedhypothyroidism. This edema is seen in thepretibial area as well.[28]
Misuse of skincare products containing snail secretions of mucin have resulted in pain, swelling, and oozing.[31][32] Counterfeit versions of a Korean snail mucin product called COSRX have been selling online, putting users at risk.[33] It’s important to follow manufacturer guidelines on their use and buy skin products from authorized vendors.
^Perez-Vilar J, Hill RL (2004). Lennarz WJ, Lane MD (eds.). "Mucin Family of Glycoproteins".Encyclopedia of Biological Chemistry.2. Oxford: Academic Press/Elsevier:758–764.doi:10.1016/B0-12-443710-9/00411-7.ISBN9780124437104.
^Liberelle M, Jonckheere N, Melnyk P, Van Seuningen I, Lebègue N (May 2020). "EGF-Containing Membrane-Bound Mucins: A Hidden ErbB2 Targeting Pathway?".Journal of Medicinal Chemistry.63 (10):5074–5088.doi:10.1021/acs.jmedchem.9b02001.PMID32027502.S2CID211044898.
^Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N, et al. (March 2006). "Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas".The Prostate.66 (4):421–429.doi:10.1002/pros.20372.PMID16302265.S2CID21904013.
Ali MS, Hutton DA, Wilson JA, Pearson JP (September 2005). "Major secretory mucin expression in chronic sinusitis".Otolaryngology–Head and Neck Surgery.133 (3):423–428.doi:10.1016/j.otohns.2005.06.005.PMID16143194.S2CID42482788.
