mucin

Human mucins include genes with the HUGO symbol MUC 1 through 22. Of these mucins, the following classes have been defined by localization:{{cite journal | vauthors = Perez-Vilar J, Hill RL | title = Mucin Family of Glycoproteins | journal = Encyclopedia of Biological Chemistry |editor-last1=Lennarz |editor-first1=William J. |editor-last2=Lane |editor-first2=M. Daniel | volume = 2 | pages = 758–764 | publisher = Academic Press/Elsevier | location = Oxford | year = 2004 | doi = 10.1016/B0-12-443710-9/00411-7 | isbn = 9780124437104 }}{{cite journal | vauthors = Hoorens PR, Rinaldi M, Li RW, Goddeeris B, Claerebout E, Vercruysse J, Geldhof P | title = Genome wide analysis of the bovine mucin genes and their gastrointestinal transcription profile | journal = BMC Genomics | volume = 12 | pages = 140 | date = March 2011 | pmid = 21385362 | doi = 10.1186/1471-2164-12-140 | pmc = 3056801 | doi-access = free }}{{cite journal | vauthors = Kasprzak A, Adamek A | title = Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis | journal = International Journal of Molecular Sciences | volume = 20 | issue = 6 | date = March 2019 | page = 1288 | pmid = 30875782 | doi = 10.3390/ijms20061288 | pmc = 6471604 | doi-access = free }}

• 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.{{Cite journal |last=Corfield |first=Anthony P. |date=2015-01-01 |title=Mucins: A biologically relevant glycan barrier in mucosal protection |url=https://www.sciencedirect.com/science/article/pii/S0304416514001603 |journal=Biochimica et Biophysica Acta (BBA) - General Subjects |language=en |volume=1850 |issue=1 |pages=236–252 |doi=10.1016/j.bbagen.2014.05.003 |pmid=24821013 |issn=0304-4165|url-access=subscription }}

• Membrane-bound (transmembrane) mucins: MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, MUC15, MUC16, MUC17, MUC21 (formerly C6orf205), MUC22 (highly polymorphic{{cite journal | vauthors = Norman PJ, Norberg SJ, Guethlein LA, Nemat-Gorgani N, Royce T, Wroblewski EE, Dunn T, Mann T, Alicata C, Hollenbach JA, Chang W, Shults Won M, Gunderson KL, Abi-Rached L, Ronaghi M, Parham P | display-authors = 6 | title = Sequences of 95 human MHC haplotypes reveal extreme coding variation in genes other than highly polymorphic HLA class I and II | journal = Genome Research | volume = 27 | issue = 5 | pages = 813–823 | date = May 2017 | pmid = 28360230 | pmc = 5411776 | doi = 10.1101/gr.213538.116 }})

The major secreted airway mucins are MUC5AC and MUC5B, while MUC2 is secreted mostly in the intestine but also in the airway. MUC7 is the major salivary protein.

Mature mammalian mucins are composed of two distinct regions:{{cite journal | vauthors = Moniaux N, Escande F, Porchet N, Aubert JP, Batra SK | title = Structural organization and classification of the human mucin genes | journal = Frontiers in Bioscience| volume = 6 | pages = D1192–D1206 | date = October 2001 | pmid = 11578969 | doi = 10.2741/moniaux | doi-access = free }}

• The amino- and carboxy-terminal regions are very lightly glycosylated, but rich in cysteines. The cysteine residues participate in establishing disulfide linkages within and among mucin monomers.
• A large central region ("PTS domain") formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of the amino acids are serine or threonine. 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.

The functional classification does not correspond to an exact evolutionary relationship, which is still incomplete and ongoing. Known-related groups include:

• The gel-forming mucins (2, 5AC, 5B, 6, 19) are related both to each other and to otogelin and von Willebrand Factor (PTHR11339).{{cite journal | vauthors = Lang T, Hansson GC, Samuelsson T | title = Gel-forming mucins appeared early in metazoan evolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 41 | pages = 16209–16214 | date = October 2007 | pmid = 17911254 | doi = 10.1073/pnas.0705984104 | pmc = 2042186 | bibcode = 2007PNAS..10416209L | doi-access = free }} Four of these occur in a well-conserved gene cluster (at 11p.15.5 in humans).{{cite journal | vauthors = Lang T, Klasson S, Larsson E, Johansson ME, Hansson GC, Samuelsson T | title = Searching the Evolutionary Origin of Epithelial Mucus Protein Components-Mucins and FCGBP | journal = Molecular Biology and Evolution | volume = 33 | issue = 8 | pages = 1921–1936 | date = August 2016 | pmid = 27189557 | doi = 10.1093/molbev/msw066 | pmc = 4948705 }}
• The EGF-like domain containing mucins. These include MUC3(A,B), MUC4, MUC12, MUC13, and MUC17.{{cite journal | vauthors = Liberelle M, Jonckheere N, Melnyk P, Van Seuningen I, Lebègue N | title = EGF-Containing Membrane-Bound Mucins: A Hidden ErbB2 Targeting Pathway? | journal = Journal of Medicinal Chemistry | volume = 63 | issue = 10 | pages = 5074–5088 | date = May 2020 | pmid = 32027502 | doi = 10.1021/acs.jmedchem.9b02001 | s2cid = 211044898 }}
• Some EGF-like mucins, plus MUC1 and MUC16, carry SEA domains, a vertebrate invention. It is unclear whether this points to a common origin among these transmembrane mucins.
• 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.
• MUC7 is a recent invention in placental mammals. It started as a copy in the secretory calcium-binding phosphoprotein (SCPP) gene cluster and rapidly gained PTS repeats.{{cite journal | vauthors = Xu D, Pavlidis P, Thamadilok S, Redwood E, Fox S, Blekhman R, Ruhl S, Gokcumen O | display-authors = 6 | title = Recent evolution of the salivary mucin MUC7 | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 31791 | date = August 2016 | pmid = 27558399 | doi = 10.1038/srep31791 | pmc = 4997351 | bibcode = 2016NatSR...631791X }}

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 and biofilm formation of Streptococcus mutans, a bacterium with the potential to form cavities.{{cite journal | vauthors = Frenkel ES, Ribbeck K | title = Salivary mucins protect surfaces from colonization by cariogenic bacteria | journal = Applied and Environmental Microbiology | volume = 81 | issue = 1 | pages = 332–338 | date = January 2015 | pmid = 25344244 | pmc = 4272720 | doi = 10.1128/aem.02573-14 | bibcode = 2015ApEnM..81..332F }} 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. Similar effects of MUC5B and other mucins have been demonstrated with other pathogens, such as Candida albicans, Helicobacter pylori, and even HIV.{{cite journal | vauthors = Kavanaugh NL, Zhang AQ, Nobile CJ, Johnson AD, Ribbeck K | title = Mucins suppress virulence traits of Candida albicans | journal = mBio | volume = 5 | issue = 6 | pages = e01911 | date = November 2014 | pmid = 25389175 | pmc = 4235211 | doi = 10.1128/mBio.01911-14 | editor-first = Judith | editor-last = Berman }}{{cite journal | vauthors = Frenkel ES, Ribbeck K | title = Salivary mucins in host defense and disease prevention | journal = Journal of Oral Microbiology | volume = 7 | issue = 1 | pages = 29759 | date = January 2015 | pmid = 26701274 | pmc = 4689954 | doi = 10.3402/jom.v7.29759 }} In the mouth, mucins can also recruit anti-microbial proteins such as statherins and histatine 1, which further reduces risk of infection.

Eleven mucins are expressed by the eye 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 the tear film, and create a physical barrier to the outside world.

Mucin genes encode mucin monomers that are synthesized as rod-shaped 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, monomers are linked to one another mostly by non-covalent interactions, although intermolecular disulfide 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-filled vesicles within the specialized epithelial cells.{{cite journal | vauthors = Li Y, Martin LD, Spizz G, Adler KB | title = MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro | journal = The Journal of Biological Chemistry | volume = 276 | issue = 44 | pages = 40982–40990 | date = November 2001 | pmid = 11533058 | doi = 10.1074/jbc.M105614200 | doi-access = free }} 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.{{cite journal | vauthors = Rogers DF | title = Physiology of airway mucus secretion and pathophysiology of hypersecretion | journal = Respiratory Care | volume = 52 | issue = 9 | pages = 1134–46; discussion 1146–9 | date = September 2007 | pmid = 17716382 }}{{cite journal | vauthors = Perez-Vilar J | title = Mucin granule intraluminal organization | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 36 | issue = 2 | pages = 183–190 | date = February 2007 | pmid = 16960124 | pmc = 2176109 | doi = 10.1165/rcmb.2006-0291TR }}

Increased mucin production occurs in many adenocarcinomas, including cancers of the pancreas, lung, breast, ovary, colon and other tissues. Mucins are also overexpressed in lung diseases such as asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or cystic fibrosis.{{cite journal | vauthors = Morrison CB, Markovetz MR, Ehre C | title = Mucus, mucins, and cystic fibrosis | journal = Pediatric Pulmonology | volume = 54 | issue = Suppl 3 | pages = S84–S96 | date = November 2019 | pmid = 31715083 | doi = 10.1002/ppul.24530 | pmc = 6853602 | doi-access = free }} Two membrane mucins, MUC1 and MUC4 have been extensively studied in relation to their pathological implication in the disease process.{{cite journal | vauthors = Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK | title = Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis | journal = Cancer Research | volume = 64 | issue = 2 | pages = 622–630 | date = January 2004 | pmid = 14744777 | doi = 10.1158/0008-5472.CAN-03-2636 | doi-access = free }}{{cite journal | vauthors = Singh AP, Chauhan SC, Bafna S, Johansson SL, Smith LM, Moniaux N, Lin MF, Batra SK | display-authors = 6 | title = Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas | journal = The Prostate | volume = 66 | issue = 4 | pages = 421–429 | date = March 2006 | pmid = 16302265 | doi = 10.1002/pros.20372 | s2cid = 21904013 }}{{cite journal | vauthors = Singh AP, Chaturvedi P, Batra SK | title = Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy | journal = Cancer Research | volume = 67 | issue = 2 | pages = 433–436 | date = January 2007 | pmid = 17234748 | doi = 10.1158/0008-5472.CAN-06-3114 | doi-access = free }} 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 hypothyroidism. This edema is seen in the pretibial area as well.Hanberg, Allen "Medical Surgical Nursing: clinical management for positive outcomes" Black and Hawk (Eds.). ElSevier 2009.

Beyond the better-studied vertebrate mucins, other animals also express (not necessarily related) proteins with similar properties. These include:

• Drosophila is known to express mucin proteins containing PTS-rich repeats.{{cite journal | vauthors = Syed ZA, Härd T, Uv A, van Dijk-Härd IF | title = A potential role for Drosophila mucins in development and physiology | journal = PLOS ONE | volume = 3 | issue = 8 | pages = e3041 | date = August 2008 | pmid = 18725942 | doi = 10.1371/journal.pone.0003041 | pmc = 2515642 | bibcode = 2008PLoSO...3.3041S | doi-access = free }}
• Trypanosoma cruzi express cell-surface mucins ({{Pfam|PF01456}}).{{cite journal | vauthors = Cámara ML, Balouz V, Centeno Cameán C, Cori CR, Kashiwagi GA, Gil SA, Macchiaverna NP, Cardinal MV, Guaimas F, Lobo MM, de Lederkremer RM, Gallo-Rodriguez C, Buscaglia CA | display-authors = 6 | title = Trypanosoma cruzi surface mucins are involved in the attachment to the Triatoma infestans rectal ampoule | journal = PLOS Neglected Tropical Diseases | volume = 13 | issue = 5 | pages = e0007418 | date = May 2019 | pmid = 31107901 | doi = 10.1371/journal.pntd.0007418 | pmc = 6544316 | doi-access = free }}

Some other organisms produce mucilage that does not have a protein component, only polysacchides.

Misuse of skincare products containing snail secretions of mucin have resulted in pain, swelling, and oozing.{{cite journal |title=Kids These Days: Social Media's Influence on Adolescent Behaviors |journal= The Journal of Clinical and Aesthetic Dermatology|date=2024 |pmid=38779370 |last1=McCoy |first1=K. |last2=Class |first2=M. M. |last3=Ricles |first3=V. |last4=Wagoner |first4=G. |last5=Cross |first5=D. |last6=Trautz |first6=A. |last7=Krakowski |first7=A. C. |volume=17 |issue=5 |pages=40–42 |pmc=11107899 }}{{cite journal |title=Snail extract for skin: A review of uses, projections, and limitations |journal=Journal of Cosmetic Dermatology |date=2024 |doi=10.1111/jocd.16269 |last1=Singh |first1=Nupur |last2=Brown |first2=Angela N. |last3=Gold |first3=Michael H. |volume=23 |issue=4 |pages=1113–1121 |pmid=38429932|doi-access=free }} Counterfeit versions of a Korean snail mucin product called COSRX have been selling online, putting users at risk.{{cite journal |title=Online Shopping Has Become a Giant Fake Product Machine |author=Amanda Mull |date=June 17, 2024 |journal=Businessweek |url=https://www.bloomberg.com/news/articles/2024-06-17/online-shopping-has-become-a-giant-fake-product-machine |access-date=June 28, 2024}} It’s important to follow manufacturer guidelines on their use and buy skin products from authorized vendors.

• Bovine submaxillary mucin coatings
• Verotoxin-producing Escherichia coli

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• {{cite journal | vauthors = Ali MS, Hutton DA, Wilson JA, Pearson JP | title = Major secretory mucin expression in chronic sinusitis | journal = Otolaryngology–Head and Neck Surgery | volume = 133 | issue = 3 | pages = 423–428 | date = September 2005 | pmid = 16143194 | doi = 10.1016/j.otohns.2005.06.005 | s2cid = 42482788 }}
• {{cite journal | vauthors = Ramsey KA, Rushton ZL, Ehre C | title = Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins | journal = Journal of Visualized Experiments | volume = 112 | issue = 112 | page = 54153 | date = June 2016 | pmid = 27341489 | pmc = 4927784 | doi = 10.3791/54153 }}

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• {{MeshName|Mucins}}
• {{DorlandsDict|five/000067870|Mucin}}

{{Mucoproteins}}

{{Authority control}}

Category:Glycoproteins