[C.elegansII] rh169 : progressive detachment of muscles during larval development, possibly defective in reformation of muscle-cuticle links at each molt. Cloned: encodes predicted 3617 aa protein with TM domain, large extracellular domain containing 52 EGF repeats, 5 LDL repeats, etc. [NJ]
Predicted to enable collagen binding activity and intermediate filament binding activity. Involved in cell-matrix adhesion. Located in hemidesmosome and intermediate filament. Expressed in several structures, including amphid neurons; enteric muscle; excretory system; phasmid sensillum; and rectum. Used to study Marfan syndrome. Human ortholog(s) of this gene implicated in multiple epiphyseal dysplasia 5 and osteoarthritis. Is an ortholog of human MATN3 (matrilin 3).
Inferred by orthology to human genes with DO annotation (HGNC:6909)
Disease_relevance
Mutations in the human gene FBN1 (Fibrillin 1) are implicated in Marfan syndrome, a heritable autosomal dominant disorder of fibrous connective tissue; signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression; the primary features of Marfan syndrome are vision problems caused by a dislocated lens, connective tissue and skeletal defects such as elongated extremities, joint hypermobility and scoliosis; C. elegans mua-3 shares high homology with FBN1, mua-3 is required for tissue integrity and attachment, mua-3 mutants show internal organ detachment; further studies in C. elegans indicate that dpy-17, a collagen acts as a genetic suppressor of mua-3, and interacts with dpy-31, a BMP-1/Tolloid-like metalloprotease required for TGF activation in mammals; knock-down of dbl-1, a TGF homolog, in mua-3 modestly rescued the lethality of mua-3 mutants, suggesting a potentially conserved interaction between MUA-3 and a TGF pathway; these genes provide a genetic model to study TGF function in development of Marfan pathology.