Tenascin X
Tenascin X, also known as flexillin or hexabrachion-like protein, is a 450kDa glycoprotein, a member of the tenascin family, that is expressed in connective tissues. In humans it is encoded by the TNXB gene.
The TN-X protein is expressed in many parts of the human body, including the skin, muscles, kidneys, blood vessels, and digestive tract.
Deficiencies in the TN-X protein due to mutations or not enough of it being produced can lead to a rare condition called classical-like Ehlers-Danlos syndrome. People with EDS may have loose joints and weak tissues because their bodies make defective collagen.
Structure
TN-X possesses a modular structure composed, from the N- to the C-terminal part by a Tenascin assembly domain, a series of 18.5 repeats of epidermal growth factor -like motif, a high number of Fibronectin type III module, and a fibrinogen -like globular domain.Gene
TNXB (functional gene)
The TNXB gene localizes to the major histocompatibility complex region on chromosome 6. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively.TNXA (pseudogene)
The TNXB gene has an associated pseudogene, TNXA.Both TNXA and TNXB genes are located within the RCCX cluster, which consists of a series of modules with genes close to each other: serine/threonine kinase 19, complement 4, steroid 21-hydroxylase, and tenascin-X. In a monomodular structure of the RCCX cluster, all of the genes are functional, i.e. protein-coding, but if there are two or more modules within the cluster, there is only one copy of each functional gene rest being non-coding pseudogenes with the exception of the C4 gene which always has active copies. For example, in a bimodular configuration most common among Europeans, the cluster consists of the following genes: STK19-C4A-CYP21A1P-TNXA-STK19B-C4B-CYP21A2-TNXB. As such, TNXA is a duplicated copy of TNXB, but is incomplete, therefore, TNXA a pseudogene that is transcribed but does not encode a protein.
The presence of the pseudogene is a consequence of MHC class III locus duplication during evolution. Strong 3' homology between TNXB and TNXA can provoke genetic recombination 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, ligaments, 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 such as peritendineum, epimysium and perimysium, 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 collagens type I, III and V, as well as FACIT including type XII and XIV collagens. It also interacts with Transforming Growth Factor -β which is a pro-fibrotic cytokine and Decorin, a small 100 kDa dermatan sulfate proteoglycan 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 fibers in dermis, tendons and kidney glomeruli.In addition to this architectural function, TN-X also demonstrated counter-adhesive properties, at least for human osteosarcoma cells, murine embryonic fibroblasts as well as human endothelial cells.