Mucin
Pap stain. | |
Identifiers | |
---|---|
Symbol | Mucin |
Membranome | 111 |
Mucins (
Although some mucins are
Genes and proteins
Human mucins include genes with the HUGO 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]
Mucin | gel | chromosome | repeat size (aa) | tissue expression |
---|---|---|---|---|
MUC2 | Y | 11p15.5 | 23 | Jejunum, ileum, colon, endometrium |
MUC5A | Y | 11p15.5 | 8 | Respiratory tract, stomach, conjunctiva, endocervix, endometrium |
MUC5B | Y | 11p15.5 | 29 | Respiratory tract, submandibular glands, endocervix |
MUC6 | Y | 11p15.5 | 169 | Stomach, ileum, gall bladder, endocervix, endometrium |
MUC19 | Y | 12q12 | 19 | corneal and conjunctival epithelia; lacrimal gland[12] |
MUC7 | N | 4q13–q21 | 23 | Sublingual and submandibular glands |
MUC8 | N | 12q24.3 | 13/41 | Respiratory tract, uterus, endocervix, endometrium |
MUC9
|
N | 1p13 | 15 | Fallopian tubes |
MUC20 | N | 3 | 19 | kidney (high), moderately in placenta, lung, prostate, liver, digestive system |
- Membrane-bound ()
The major secreted airway mucins are
Protein structure
Mature mammalian mucins are composed of two distinct regions:[7]
- The .
- A large central region ("PTS domain") formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of the oligosaccharidesare also found on mucins, but in less abundance than O-linked sugars.
Evolutionary classification
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 to
- The EGF-like domain containing mucins. These include MUC3(A,B), MUC4, MUC12, MUC13, and MUC17.[16]
- 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.[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.
- 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.[17]
Function in humans
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.[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 as Candida albicans, Helicobacter pylori, and even HIV.[19][20] In the mouth, mucins can also recruit anti-microbial proteins such as statherins and histatine 1, which further reduces risk of infection.[20]
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.[12]
Glycosylation and aggregation
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
Mucins are secreted as massive aggregates of proteins with molecular masses of roughly 1 to 10 million
Secretion
Upon stimulation,
Clinical significance
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.[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 facial edema seen in untreated hypothyroidism. This edema is seen in the pretibial area as well.[28]
Non-vertebrate mucins
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.[29]
- Trypanosoma cruzi express cell-surface mucins (PF01456).[30]
See also
- Bovine submaxillary mucin coatings
- Verotoxin-producing Escherichia coli
References
- ^ PMID 17950376.
- PMID 10770949.
- PMID 12952166.
- PMID 8953277.
- PMID 18407586.
- S2CID 232191632.
- ^ PMID 11578969.
- ISBN 9780124437104.
- PMID 21385362.
- ^ PMID 30875782.
- PMID 24821013.
- ^ PMID 33775913.
- PMID 28360230.
- ^ PMID 17911254.
- PMID 27189557.
- S2CID 211044898.
- PMID 27558399.
- ^ PMID 25344244.
- PMID 25389175.
- ^ PMID 26701274.
- PMID 11533058.
- PMID 17716382.
- PMID 16960124.
- PMID 31715083.
- PMID 14744777.
- S2CID 21904013.
- PMID 17234748.
- ^ Hanberg, Allen "Medical Surgical Nursing: clinical management for positive outcomes" Black and Hawk (Eds.). ElSevier 2009.
- PMID 18725942.
- PMID 31107901.
Further reading
- 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. S2CID 42482788.
- Ramsey KA, Rushton ZL, Ehre C (June 2016). "Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins". Journal of Visualized Experiments. 112 (112): 54153. PMID 27341489.
External links
- Mucins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- "Mucin" at Dorland's Medical Dictionary