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3 March 2002

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Proteins 11, 281–296

The MUC family: an interactions to be mediated through their highly

elaborate structures. Their strategic position places
the mucins at centre stage in many disease processes

obituary in which the interactions of epithelial cells and their

surroundings have gone astray, as in inflammatory
and infectious diseases, cancer and metastasis.
Despite rapidly accumulating circumstantial
Jan Dekker, John W.A. Rossen, Hans A. Büller and evidence, most of the MUC-type mucins have no
unequivocally defined function that can be used as a
Alexandra W.C. Einerhand basis for terminology.
Biochemically, these molecules have always been
difficult to study because they are very large and
Mucins are glycoproteins that are common on the surfaces of many epithelial much of their structure is concealed by complex
cells; they are deemed to mediate many interactions between these cells and O-glycosylation. The study of the structures and
their milieu. Several of these mucins form the mucus layer that is found in functions of mucins is a growing field that has
many hollow organs. The biophysical properties of mucins are related to their received a recent boost from developments in
extensive O-linked glycosylation rather than directly to their polypeptide molecular biology. Each epithelial mucin gene
sequences. Despite the frequent absence of sequence homology, many human discovered was enthusiastically welcomed as a new
genes encoding mucins have been named MUC followed by a number, member of a gene family named MUC, established in
unjustly suggesting the existence of one large gene family. In this article, it is 1990. After the initial excitement over these
suggested that the mucin genes be renamed according to their sequence developments among the workers in the mucin field,
homologies. the realization grew that particular members of the
MUC-type mucin family were, in fact, very
Mucins are large, abundant, filamentous dissimilar. Currently, 14 mucin-type glycoproteins
glycoproteins that are present at the interface have been assigned to the MUC gene family, as
between many epithelia and their extracellular approved by the Human Genome Organization Gene
environments. This interface is often the lumen of a Nomenclature Committee (HUGO/GNC;
hollow organ within the body such as the http://www.hugo-international.org/hugo/). We aim
Jan Dekker*
John W.A. Rossen
gastrointestinal tract, lungs and urogenital tract. here to demonstrate that the existence of one MUC
Hans A. Büller Several of these mucins are known to form mucus gene family, encompassing all known human mucins,
Alexandra W.C. Einerhand layers, whereas others form the glycocalyx on the is not justified by the existing sequence data, and we
Laboratory of Paediatrics, intestinal enterocytes. As for their functions, these would like to provoke a discussion on the definition
Erasmus University and
Sophia Children’s
bulky and abundant glycoproteins are strategically and nomenclature of mucins.
Hospital, positioned to mediate the interactions between Box 1 gives a comprehensive overview of the
Dr Molewaterplein 50, epithelial cells and their milieu. They are considered terminology that is in use in the study of mucins.
3015GE Rotterdam,
to act as powerful two-edged swords, keeping Originally, the term ‘mucins’ was used for
The Netherlands.
*e-mail: dekker@ unwanted substances and organisms at an arm’s glycoproteins found in mucus that had been secreted
kgk.fgg.eur.nl length while, at the same time, allowing specific by epithelia. Later, these epithelia were found to

http://tibs.trends.com 0968-0004/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0968-0004(01)02052-7
 Opinion TRENDS in Biochemical Sciences Vol.27 No.3 March 2002
Box 1. What are mucins? A matter of words
Mucin
The late W. Pigman was probably the first to define mucins as
having exclusively O-linked glycans, and to recognize that the
O-glycosylated peptide sequences were often tandemly repeated
[a]. However, we now know that additional N-glycosylation is a
feature common to most mucins [b]. Consensus tells us that
mucin molecules consist of at least 50% O-glycans by weight,
which are concentrated in particular regions of the polypeptide
referred to as ‘mucin domains’ or ‘PTS regions’.
Mucin domains/PTS regions
Mucin domains are the (putatively) O-glycosylated sequences
that are often found within (deduced) sequences encoding
mucins. These sequences are also referred to as PTS regions,
indicating regions within the polypeptide that are enriched in
proline, threonine and/or serine residues. Threonine and serine
are usually both present in PTS regions and, of all known human
PTS regions, only that of MUC2 does not contain any serines.
These large regions, up to 6000 amino acids in length, are
usually devoid of cysteine residues and composed of short
(8–169 amino acids) tandemly repeated peptides. PTS regions
are found in all MUC-type mucins but also in many other
glycoproteins, although the PTS regions in mucins are
exceptionally long and usually comprise more than half the
polypeptide.
Variable number of tandem repeats
Variable number of tandem repeats refers to the repetitive
nature of most of the PTS regions. However, it has often not been
proved that these sequences are actually ‘variable’ within each
MUC. As for ‘tandem repeats’, many cysteine-rich domains in
mucins are also repeated. For both reasons, this term should not
be used generically. ‘PTS region’ circumvents these definition
problems.
Non-PTS regions
Non-PTS regions are the N- and C-terminal parts of the mucin
polypeptides beyond the PTS regions. They usually contain all
the cysteine residues of the mucins. Non-PTS regions can be
called ‘unique’ because they are not excessively repeated, unlike
PTS regions. However, the term ‘unique’ can lead to confusion
because particular cysteine-rich domains, such as the von-
Willebrand-factor-like D domains in the 11p15 mucins, are
repeated within the non-PTS regions.
produce transmembrane glycoproteins that were also
described as mucins. The term mucin was thus used
for both secretory and membrane-bound epithelial
glycoproteins, which were included in the MUC
family on the basis of sequencing data [1]. As
discussed previously [2], there are many other
glycoproteins, such as the human endothelial and
leukocyte glycoproteins, that were also described as
mucins. However, these are historically viewed as a
separate group of glycoproteins with separate
functions, and were consequently not included in the
MUC nomenclature. For clarity, we see no reason for
http://tibs.trends.com
127
Cysteine-rich domains
Cysteine-rich domains are identifiable cysteine-rich peptide
motifs that occur in the non-PTS regions of mucins, such as the
epidermal-growth-factor-like domains in membrane-bound
mucins, the VWF-C and -D domains, and the C-terminal domains
found in 11p15 mucins.
MUC-type mucin
A MUC-type mucin is one of the 14 mucins that have been
incorporated in the MUC-plus-number nomenclature, officially
assigned by HUGO/GNC, that has been in use since 1990.
11p15 mucins
The 11p15 mucins are the most clearly described and related
family known among the assigned MUCs. This family comprises
MUC2, MUC5AC, MUC5B and MUC6, all of which are found at
chromosomal locus 11p15.5 [c]. These secretory mucus-gel-
forming mucins show significant homology in their non-PTS
regions. Because locus 7q22 also seems to harbour a cluster of
related mucin genes, the term ‘7q22 mucins’ has also been
used.
Mucoprotein
Mucoprotein is an obsolete term for mucin that also encompasses,
for example, ‘peptidoglycan’, ‘intrinsic factor’, ‘orosomucoid’ and
‘cell wall skeleton’. However, this term is still in use by the National
Library of Medicine (Bethesda, MD, USA), which lists mucins
under Mucoproteins as a Medical Subject Heading (MeSH).
Mucus glycoprotein
The term mucus glycoprotein only reflects the occurrence of
mucins in mucus. In fact, several molecules described as mucins
do not seem to be part of mucus, so ‘mucus glycoprotein’ should
be avoided as a generic term. ‘Mucin glycoprotein’ is also used
but is a definite misnomer. If we comply with the biochemical
definition, adding ‘glycoprotein’ is unnecessary; mucin-type
glycoprotein is the better phrase.
References
a Pigman, W. et al. (1973) The occurrence of repetitive glycopeptide sequences
in bovine submaxillary glycoprotein. Eur. J. Biochem. 32, 148–154
b Strous, G.J. and Dekker, J. (1992) Mucin-type glycoproteins. Crit. Rev.
Biochem. Mol. Biol. 27, 57–92
c Desseyn, J.L. et al. (1998) Evolutionary history of the 11p15 human mucin
gene family. J. Mol. Evol. 46, 102–106
any additions to the MUC-type mucin family. Instead,
we seek to end the forced cohabitation of particular
MUC family members.
Our primary concern is that the tendency to
incorporate more and more mucins into this one MUC
gene ‘family’ will not aid scientific understanding.
Furthermore, expansion of this family is against the
formal policy of HUGO/GNC, which strives towards a
logical and systematic nomenclature of related genes.
With hindsight, the confusion began with the naming
of MUC1 and MUC2, both coined in 1990 [3,4].
Although both of these mucins are widely recognized
128 Opinion TRENDS in Biochemical Sciences Vol.27 No.3 March 2002
MUC2
Y Y Y Y
Y
Y Y Y Y Y
Key:
MUC1
Y
Y
YY
X
Y Y
X Proteolytic processing site
Fig. 1. How do we recognize a mucin? Two well-characterized mucins,
MUC1 and MUC2, showing the superficial structural similarities of
these glycoproteins, and also showing that these molecules are, in fact,
very different (indicated by the different colouring schemes).
MUC1 has become the epitome of the membrane-bound mucins;
MUC2 represents the secretory mucins that form mucus layers.
as mucins (by the biochemical definition), they are
very dissimilar molecules (Fig. 1). Later additions to
the MUC gene family can be roughly divided into two
opposite camps, resembling either MUC1 or MUC2,
although still other MUC genes seem to have totally
unrelated sequences. In trying to illuminate these
matters, we cannot escape scrutinizing the definition
of a mucin.
Defining mucins: family values
One international authority (IUPAC–IUBMB)
defines glycoproteins and proteoglycans, but does not
mention mucins [5]. There are two approaches to the
definition of mucins but both are unsatisfactory when
it comes to defining the relationships of the mucin-
encoding genes. The first approach relates to the one
characteristic of mucins that has stuck through the
years: mucins contain many relatively short O-linked
glycans (2–20 monosaccharides per chain), which
usually form >50% of the molecular weight of the
mucin molecule [6]. The problem here is that a
(glyco-)protein is being defined not by polypeptide
sequence or function but by its post-translational
modifications. Using this criterion to define mucins
would be similar to conflating all lipoproteins based
http://tibs.trends.com
Y Y
Y
Y Y
Unique sequence MUC1
Unique sequence MUC2
PTS-domain: PTTTPITTTTTVTPTPTPTGTQT
PTS-domain: GSTAPPAHGVTSAPDTRPAP
Cysteine-rich domain
VWF-D-like domain
VWF-C-like domain
C-terminal domain
SEA-domain
Transmembrane domain
N-glycan
O-glycan
Plasma membrane
Ti BS
on their modification with lipid moieties and calling
the encoding genes ‘LIP-number’. Thus, post-
translational modifications seem to be a brittle basis
for gene nomenclature.
The second approach tries to define amino acid
sequences that are common to all mucins.
Unfortunately, there are no such sequences.
However, mucins are very densely O-glycosylated
and, consequently, contain sequences that are rich in
proline, threonine and/or serine (PTS regions; Fig. 1),
which are acceptors for the O-glycans during
biosynthesis. PTS regions usually comprise
relatively short, tandemly repeated sequences. The
peptide sequences of PTS regions have a limited
amino acid composition and, consequently, a limited
codon usage at DNA and mRNA levels; therefore,
these sequences are often superficially alike. It
seems probable that the PTS regions of the various
mucins have emerged through convergent rather
than divergent evolution (Box 2). Each human MUC-
type mucin has a distinctive repetitive PTS-rich
sequence, with respect to both amino acid sequence
and length of the repeated unit. Also, the number of
PTS regions can vary with the mucin; for example, in
MUC1, the PTS-region is uninterrupted, whereas
MUC2 contains two distinct PTS-regions (Fig. 1).
Strikingly, the known MUC orthologues in other
mammals do not usually show conservation of either
sequence or length of the repeated amino acid
sequence (Box 2). If there are any significant
sequence homologies among the MUC-type mucins,
 Opinion TRENDS in Biochemical Sciences Vol.27 No.3 March 2002 129

Box 2. Mucins: a successful convergence

Biochemically, mucins share many common features, such as
their huge size, filamentous structure, many O-linked glycans and
an amino acid composition rich in threonine and serine. However,
some mucins currently included in the MUC family show no
sequence homology. Apparently, mucins were developed
independently several times through convergent evolution.
The addition of the O-linked glycans to the polypeptides of
mucins is used to maintain an extended conformation to create a
long, filamentous structure. O-Glycosylation begins by the
addition of single N-acetyl-galactosamine (GalNAc) residues,
which are relatively small and can be fitted on adjacent threonine
and/or serine residues. N-Glycosylation cannot serve such a
function because this involves the addition of very bulky
oligosaccharides. In practice, N-glycosylation is always spaced
along polypeptides, whereas O-glycans can be packed very tightly.
If there was selection pressure during evolution to develop
hydrophilic, elongated structures, then some proteins will have
developed dense O-glycosylation. Any peptide that must act as a
ligand for O-GalNAc transferases (the enzymes that add the first
GalNAc to a serine or threonine residue) will meet similar
constraints and will consequently contain: (1) many threonines
and/or serines as targets for O-GalNAc addition; (2) many proline
and small neutral amino acids to enable an elongated, flexible,
random coil peptide; (3) no cysteines, because these would coil up
the polypeptides by forming disulfide bonds; and (4) very few
bulky hydrophobic amino acids, because these would clot up the
polypeptide. As a result of these special constrictions, the SMART
software invariably marks the PTS regions of mucins as regions of
‘low complexity’ [a]. Once a polypeptide had developed a
successful ligand for O-glycosylation (i.e. a small PTS region), and
while there was still selection pressure to develop even longer
molecules, natural selection apparently favoured duplication of
this successful peptide sequence within the polypeptide, resulting
in the repeated peptide sequence of the PTS region.
The PTS region apparently evolved independently many times
during evolution. Also, there appears to have been little selective
pressure to maintain the exact PTS region. Comparison of known
MUC-type mucins between humans and rodents reveals that the
non-PTS regions are particularly conserved whereas the PTS
regions are not [b–k]. Apparently, the constraints as sketched
above rule the overall amino acid composition of the PTS region
but lay no burden on the exact sequence as long as it functions as
an O-glycan acceptor. Naturally, evolution found more ways to
form extended structures from polypeptide chains, such as the
coiled coil structures found in myosin and the triple-stranded
helical structure found in collagen. Furthermore, these types of
extended polypeptide structures have a typical repeated peptide
structure.
References
a Schultz, J. et al. (2000) SMART: a web-based tool for the study of genetically
mobile domains. Nucleic Acids Res. 28, 231–234
b van Klinken, B.J. et al. (1999) Gastrointestinal expression and partial cDNA
cloning of murine Muc2. Am. J. Physiol. 276, G115–G124
c Shekels, L.L. et al. (1995) Mouse gastric mucin: cloning and chromosomal
localisation. Biochem. J. 311, 775–785
d Vos, H.L. et al. (1991) The mouse episialin (Muc1) gene and its promoter:
rapid evolution of the repetitive domain in the protein. Biochem. Biophys.
Res. Commun. 181, 121–130
e Spicer, A.P. et al. (1991) Molecular cloning and analysis of the mouse
homologue of the tumor-associated mucin, MUC1, reveals conservation of
potential O-glycosylation sites, transmembrane, and cytoplasmic domains
and a loss of minisatellite-like polymorphism. J. Biol. Chem. 66, 5099–5159
f Shekels, L.L. et al. (1998) Cloning and characterisation of mouse intestinal
MUC3 mucin: 3′ sequence contains epidermal-growth-factor-like domains.
Biochem. J. 330, 1301–1308
g Inatomi, T. et al. (1997) Cloning of rat Muc5AC mucin gene: comparison of its
structure and tissue distribution to that of human and mouse homologues.
Biochem. Biophys. Res. Commun. 236, 789–797
h Wu, K. et al. (1994) Molecular cloning and sequencing of the mucin subunit of
a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat
mammary adenocarcinoma cells. J. Biol. Chem. 269, 11950–11955
i Gum, J.R. et al. (1991) Molecular cloning of rat intestinal mucin. Lack of
conservation between mammalian species. J. Biol. Chem. 266, 22733–22738
j Ohmori, H. et al. (1994) Molecular cloning of the amino-terminal region of a
rat MUC 2 mucin gene homologue. Evidence for expression in both intestine
and airway. J. Biol. Chem. 269, 17833–17840
k Khatri, I.A. et al. (1997) The carboxyl-terminal sequence of rat intestinal
mucin RMuc3 contains a putative transmembrane region and two EGF-like
motifs. Biochim. Biophys. Acta 1326, 7–11

these are found within the non-PTS regions at the N-
and C-termini of the polypeptides. Thus, unravelling
any kinship among the MUC-type mucins comes
down to analysing the homologies of their non-PTS
regions.
All in the family?
There is good reason to believe that selection pressure
to preserve the polypeptide sequences of mucins was
mainly on the non-PTS regions (Box 2). As sequence
data on the PTS regions are therefore not informative,
we are left with the N and C termini of the mucins to
establish their consanguinity. The most easily
identifiable relationships are found among the four
MUC-type mucins located within the 11p15 locus:
MUC2, MUC5AC, MUC5B and MUC6 [3,7–18].
These mucins have von-Willebrand-factor (VWF)
domains (C and D types) and a conserved C-terminal
domain (Fig. 2). None of these domains is specific for
mucins because VWF-C, VWF-D and C-terminal
domains are found in 78, 44 and 40 other human
proteins, respectively [19]. By contrast, the cysteine-
rich domains of MUC2, MUC5AC and MUC5B, with a
consensus sequence as previously identified [20], are
so far unique to these mucins [19]. The 11p15 mucins
share considerable overall homology in their non-PTS
regions (21–33%) and have probably evolved through
gene duplication of one ancestral gene [21]. Therefore,
these 11p15 mucins do, after all, form a closely knit
family. A great deal of evidence indicates that these
mucins are responsible for the formation of the mucus
layers in the body [1,2].
Several membrane-bound mucins are probably
related to each other, especially those localized to
chromosomal locus 7q22: MUC3A, MUC3B and
MUC12 [22–27]. These mucins characteristically
have a transmembrane domain, a sea-urchin-sperm-
protein–enterokinase–agrin (SEA) domain and one or

http://tibs.trends.com
130 Opinion TRENDS in Biochemical Sciences Vol.27 No.3 March 2002
(Varying from 2334 to 6334 aa)
Signal sequence Transmembrane domain
VWF-D-like domain EGF-like domain
PTS-region Nidogen domain
VWF-C-like domain Cysteine-rich domain
C-terminal domain SEA-domain
AMOP-domain
Fig. 2. A MUC family album. The relationships between the deduced
polypeptide sequences of the mucins presently assigned to the MUC
gene family by HUGO/GNC (http://www.hugo-international.org/hugo/).
The chromosomal location of each mucin gene is also indicated. All
mucin sequences were aligned with their C terminus to the right, and
any known peptide domains present were detected in the sequences
using the SMART software [19]. In addition, MUC4 was found to contain
the very recently discovered AMOP domain [33]. Each type of peptide
domain is depicted in a separate colour, indicated in the key. The PTS
regions in the sequences were invariably recognized by the SMART
software as structures with ‘low complexity’ and are depicted in blue.
MUC16, MUC7 and MUC8 show no homology to any other known
mucin. MUC11 cannot be aligned because it is so far only characterized
by its PTS region; its gene has the same chromosomal location as
MUC3A, MUC3B and MUC12, and the possibility cannot be excluded
that the MUC11 cDNA sequence is, in fact, continuous with the MUC12
cDNA, of which only the C terminus has been identified. The
representations are based on the full-length cDNA sequences. Any
splice variants (e.g. MUC1, MUC3A, MUC3B and MUC4) are not
accounted for, and allelic variation (known to exist in at least some
MUCs as variations in the number of tandemly repeated PTS
sequences) was also not taken into account. Dashed lines indicate
unknown sequences. The brackets around the N terminus of MUC6
indicate that this sequence is not publicly available but has been
reported [18]. The scale of the deduced polypeptides is indicated by the
bar representing 500 amino acids (aa).
Acknowledgements
Our work on mucins has
been made possible by
grants from the
two epidermal-growth-factor (EGF)-like domains.
Netherlands Digestive Although these features distinguish these mucins
Diseases Foundation from the 11p15 mucins, neither the SEA nor the EGF
(Nieuwegein), the Irene
domains are specific to mucins; both occur in many
Foundation (Arnhem),
ASTRA/Zeneca other non-mucin human proteins (28 and 182,
(Zoetermeer), the respectively). MUC3 was one of the first MUC
Netherlands Foundation proteins found, in 1990 [4], but it has recently been
for Scientific Research
(the Hague), the Sophia
discovered that there are, in fact, two closely related
Foundation for Scientific and adjacent genes (MUC3A and MUC3B) with 98%
Research (Rotterdam), the homology [26]. The membrane-bound MUC12 is the
Jan Dekker/Ludgardine most similar to MUC3A and MUC3B (29% homology
Bouman Foundation
(Amsterdam) and the
within the C-terminal non-PTS region). MUC12 and
Gastrostart Foundation the recently discovered MUC11 were localized to
(Haarlem). We apologize chromosome region 7q22 [27], so MUC12, MUC11,
to the colleagues whose
MUC3A and MUC3B might share a common
primary work could not be
cited because of space ancestral gene. However, only PTS sequences of
limitations. MUC11 are known, and it is still possible that this
http://tibs.trends.com
MUC6 11p15
MUC2 11p15
MUC5B 11p15
MUC5AC 11p15
MUC4 3q29
MUC12 7q22
MUC13 3q13
MUC3A 7q22
MUC3B 7q22
MUC1 1q21
MUC16 17q21
MUC7 4q13-q21
MUC8 12q24
MUC11 7q22
500 aa
Ti BS
cDNA fragment could prove to be continuous with
another mucin cDNA fragment (e.g. with the
C-terminal domain assigned to MUC12).
The membrane-bound MUC13, whose gene is at
locus 3q13.3 [28], also shares some homology with the
7q22 mucins, in particular in the SEA, EGF and
transmembrane domains (Fig. 2). MUC4 is an
extremely large membrane-bound mucin that lies on
the same chromosomal arm as MUC13 (3q29) [29–32].
MUC4 seems to be a crossbreed, sharing limited
homology with the 7q22 mucins (one transmembrane
and three EGF domains) and with the 11p15 mucins
(VWF-D domain; Fig. 2) [19]. MUC4 also has a
nidogen domain, which has not been identified in any
other MUC protein but is found in 15 human non-
mucin polypeptides [19]. In addition, MUC4 is the only
MUC family member to contain the newly discovered
‘adhesion-associated domain in MUC4 and other
proteins’ (AMOP domain; Fig. 2) [33]. The membrane-
bound MUC1 is also related to the 7q22 mucins as it
contains a transmembrane and a SEA domain (Fig. 2)
[34–36]. The homology between MUC1, MUC3A,
MUC3B, MUC4, MUC12 and MUC13 can be taken as
sufficient evidence for a second mucin family.
Putting this aside, some strange characters
remain. The sketchy data around MUC8 hamper
definite conclusions but, from the available sequence
data, there is no homology between this protein and
any other MUC-type mucin [37]. MUC7 is an
unusually small secretory mucin (Fig. 2), sharing no
homology with other MUC proteins [38,39]. MUC16
is the most recent addition to the MUC family (Fig. 2).
It was characterized from a partial cDNA sequence
encoding a membrane-bound mucin that has long
been known as the tumour marker CA125 [40].
MUC16 does not appear to be related to the other
MUC-type mucins (Fig. 2). Whereas MUC16 might be
a candidate for the transmembrane mucin family, the
unique sequences of MUC7 and MUC8 suggest that
 Opinion TRENDS in Biochemical Sciences Vol.27 No.3 March 2002 131

these mucins are true orphans. Meanwhile, HUGO mucins; and (2) the mucin genes at loci 7q22, 3q and
has reserved the names MUC15 and MUC17 for 1q21, presumably encoding membrane-bound
further (still anonymous) additions to the MUC mucins. Currently, several orphan MUCs remain:
family. Bearing the above considerations in mind, we MUC7 and MUC8, and probably also MUC16, which
are holding our breath about the nature of these have no identifiable homology to any other human
newly assigned MUC proteins. protein. Because of the dissimilarity of these
molecules, we would like to see an adaptation of the
Conclusions: families and orphans mucin nomenclature to distinguish at least two
Most of the MUC-type mucins have no unequivocally separate families.
defined function on which to base a terminology. If we Mucins might have evolved through convergent
wish to define mucin relationships, it must be by evolution, and this less usual form of evolution could
primary structure instead of function. Yet, there is no satisfactorily explain why particular mucins share
unifying sequence homology for the MUC-type biochemical and cell biological similarities but have
mucins. Based on sequence homology, two families of no apparent common evolutionary descent. This
mucins can be distinguished: (1) the mucin genes at insight will hopefully soften the pain of dividing up
locus 11p15, which probably encode mucus-forming the MUC family.
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