title: Collagen XII: Protecting bone and muscle integrity by organizing collagen fibrils.
abstract: Collagen XII, largest member of the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α-chains encoded by the COL12A1 gene. The molecule consists of three threadlike N-terminal noncollagenous NC3 domains, joined by disulfide bonds and a short interrupted collagen triple helix toward the C-terminus. Splice variants differ considerably in size and properties: "small" collagen XIIB (220 kDa subunit) is similar to collagen XIV, whereas collagen XIIA (350 kDa) has a much larger NC3 domain carrying glycosaminoglycan chains. Collagen XII binds to collagen I-containing fibrils via its collagenous domain, whereas its large noncollagenous arms interact with other matrix proteins such as tenascin-X. In dense connective tissues and bone, collagen XII is thought to regulate organization and mechanical properties of collagen fibril bundles. Accordingly, recent findings show that collagen XII mutations cause Ehlers-Danlos/myopathy overlap syndrome associated with skeletal abnormalities and muscle weakness in mice and humans.
authors.affiliation: Department of Orthodontics and Dentofacial Orthopedics, School of Dental Medicine, University of Bern, Bern, Switzerland. Electronic address: matthias.chiquet@zmk.unibe.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Chiquet
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Birk
authors.affiliation: Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
authors.affiliation: Institute for Dental Research and Oral Musculoskeletal Biology, Center for Molecular Medicine Cologne, and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Centro de Biologia Ambiental, Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D024082:Collagen Type XII / Q000235:genetics* / Q000378:metabolism; D003286:Contracture / Q000235:genetics / Q000473:pathology; D004535:Ehlers-Danlos Syndrome / Q000235:genetics / Q000473:pathology; D024021:Fibril-Associated Collagens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D009132:Muscles / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics / Q000473:pathology; D024041:Non-Fibrillar Collagens / Q000235:genetics* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024082:Collagen Type XII; D024021:Fibril-Associated Collagens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C547160:COL12A1 protein, human
keywords: Bethlem myopathy; Collagen XII; Collagen fiber; Ehlers–Danlos syndrome; Osteogenesis