A member of the

tenascin Tenascins are extracellular matrix glycoproteins. They are abundant in the extracellular matrix of developing vertebrate embryos and they reappear around healing wounds and in the stroma of some tumors. Types There are four members of the tenasc ...

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 In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Gene

This gene localizes to the major histocompatibility complex (

MHC class III MHC class III is a group of proteins belonging the class of major histocompatibility complex (MHC). Unlike other MHC types such as MHC class I and MHC class II, of which their structure and functions in immune response are well defined, MHC class I ...

) region on chromosome 6. The structure of this gene is unusual in that it overlaps the

CREBL1 CAMP responsive element binding protein-like 1, also known as CREBL1, is a protein which in humans is encoded by the ''CREBL1'' gene. Function The protein encoded by this gene bears sequence similarity with the Creb/ATF subfamily of the bZip s ...

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 aldosteron ...

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 Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

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 ...

tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...

lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

s, mammary and

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...

testis A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...

, and

ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...

. It is also found in different compartments of the

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

, including

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previous ...

ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine ma ...

, 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 Epimysium (plural ''epimysia'') (Greek ''epi-'' for on, upon, or above + Greek ''mys'' for muscle) is the fibrous tissue envelope that surrounds skeletal muscle. It is a layer of dense irregular connective tissue which ensheaths the entire muscle ...

and

perimysium Perimysium is a sheath of connective tissue that groups muscle fibers into bundles (anywhere between 10 and 100 or more) or fascicles. Studies of muscle physiology suggest that the perimysium plays a role in transmitting lateral contractile ...

(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, III and V, as well as

FACIT Facit (''Facit AB'') was an industrial corporation and manufacturer of office products including furniture. It was based in Åtvidaberg, Sweden, and founded in 1922 as ''AB Åtvidabergs Industrier''. Facit AB, a manufacturer of mechanical calcu ...

(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 Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

and

Decorin Decorin is a protein that in humans is encoded by the ''DCN'' gene. Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a p ...

, a small 100 kDa

dermatan sulfate Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. It is also referred to as chondroitin sulfate B, although it is no longer classifie ...

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 Fibrillogenesis is the development of fine fibrils normally present in collagen fibers of connective tissue. It is derived from the Greek ''fibrillo'' (meaning fibrils, or pertaining to fibrils) and ''genesis'' (to create, the process by which some ...

. ''In vivo'',

transmission electron microscopy Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a g ...

coupled with immuno-labelling confirms the very close location of TN-X with collagen fibbers in dermis, tendons and kidney glomeruli. In addition to this architectural function, TN-X also demonstrated counter-adhesive properties, at least for human

osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) (or simply bone cancer) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) a ...

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 The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

cells (ECV-304).

Clinical significance

Homozygous mutations, heterozygous compound (bi-allelic) mutations or

haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

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 Hypermobility, also known as double-jointedness, describes joints that stretch farther than normal. For example, some hypermobile people can bend their thumbs backwards to their wrists, bend their knee joints backwards, put their leg behind the h ...

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

External links

GeneReviews/NCBI/NIH/UW entry on Ehlers-Danlos Syndrome, Hypermobility Type
{{Fibrous proteins Tenascins

Gene

Function

Clinical significance

References

Further reading

External links