A member of the
tenascin family, tenascin X (TN-X) also known as flexillin or hexabrachion-like protein is a 450kDa
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
that is expressed in connective tissues. TN-X possesses a modular structure composed, from the N- to the C-terminal part by a Tenascin assembly domain (TAD), a series of 18.5 repeats of
epidermal growth factor (EGF)-like motif, a high number of
Fibronectin type III (FNIII) module, and a fibrinogen (FBG)-like globular domain. In humans, tenascin X is encoded by the ''TNXB''
gene.
Gene
This gene localizes to the major histocompatibility complex (
MHC class III) region on chromosome 6. The structure of this gene is unusual in that it overlaps the
CREBL1 and
CYP21A2
Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone ...
genes at its 5' and 3' ends, respectively.
''TNXB'' also possesses a pseudogene, ''TNXA,'' which is a consequence of MHC classe III locus duplication during evolution. Strong 3' homology between ''TNXB'' and ''TNXA'' can provoke
genetic recombination
Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryo ...
between the two loci, thus leading to the apparition of ''TNXA/TNXB'' chimera
''.''
Function
TN-X is constitutively expressed in adult tissues such as
skin,
ligament
A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the:
* Peritoneal li ...
s,
tendons,
lungs,
kidneys,
optic nerves, mammary and
adrenal glands,
blood vessels,
testis, and
ovaries. It is also found in different compartments of the
digestive tract, including
pancreas,
stomach,
jejunum,
ileum, and colon. In this wide variety of organs, TN-X is mainly located within the
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
such as peritendineum (external structural component of tendons),
epimysium and
perimysium (muscle components), renal glomeruli, blood vessels and skin dermis. TN-X has been proposed to have an important structural and architectural function, especially within the skin. In fact, ''in vitro'' experiments demonstrate that TN-X physically interacts with fibrillar
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
s
type I Type 1 or Type I or ''variant'', may refer to:
Health
*Diabetes mellitus type 1 (also known as "Type 1 Diabetes"), insulin-dependent diabetes
* Type I female genital mutilation
* Type 1 personality
*Type I hypersensitivity (or immediate hypersensit ...
,
III
III or iii may refer to:
Companies
* Information International, Inc., a computer technology company
* Innovative Interfaces, Inc., a library-software company
* 3i, formerly Investors in Industry, a British investment company
Other uses
* Ins ...
and
V, as well as
FACIT (Fibrillar Associated Collagen with Interruption of the Triple helix) including type XII and XIV collagens. It also interacts with
Transforming Growth Factor (TGF)-β which is a pro-
fibrotic cytokine and
Decorin, a small 100 kDa
dermatan sulfate proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
that plays a crucial role in collagen
fibrillogenesis. ''In vivo'',
transmission electron microscopy coupled with immuno-labelling confirms the very close location of TN-X with collagen fibbers in dermis, tendons and
kidney glomeruli
The glomerulus (plural glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally s ...
.
In addition to this architectural function, TN-X also demonstrated counter-adhesive properties, at least for human
osteosarcoma cells (MG-63), murine embryonic
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s (MRC-5) as well as human
endothelial cells (ECV-304).
Clinical significance
Homozygous mutations, heterozygous compound (bi-allelic) mutations or
haploinsufficiency in TN-X cause classical-like
Ehlers-Danlos syndrome (EDS), a rare and hereditary connective tissue disorder in mice and human. This pathology is characterized by skin hyperlaxity,
joint hypermobility and global tissue weakness as a consequence of
elastin
Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bod ...
fragmentation and reduced collagen density, especially in skin.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Ehlers-Danlos Syndrome, Hypermobility Type
{{Fibrous proteins
Tenascins