title: CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta.
abstract: Prolyl hydroxylation is a critical posttranslational modification that affects structure, function, and turnover of target proteins. Prolyl 3-hydroxylation occurs at only one position in the triple-helical domain of fibrillar collagen chains, and its biological significance is unknown. CRTAP shares homology with a family of putative prolyl 3-hydroxylases (P3Hs), but it does not contain their common dioxygenase domain. Loss of Crtap in mice causes an osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production. CRTAP can form a complex with P3H1 and cyclophilin B (CYPB), and Crtap-/- bone and cartilage collagens show decreased prolyl 3-hydroxylation. Moreover, mutant collagen shows evidence of overmodification, and collagen fibrils in mutant skin have increased diameter consistent with altered fibrillogenesis. In humans, CRTAP mutations are associated with the clinical spectrum of recessive osteogenesis imperfecta, including the type II and VII forms. Hence, dysregulation of prolyl 3-hydroxylation is a mechanism for connective tissue disease.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Morello
authors.forename: Terry K
authors.initials: TK
authors.lastname: Bertin
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Hicks
authors.forename: Laura
authors.initials: L
authors.lastname: Tonachini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Monticone
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
authors.forename: Janice
authors.initials: J
authors.lastname: Vranka
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Bächinger
authors.forename: James M
authors.initials: JM
authors.lastname: Pace
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schwarze
authors.forename: Peter H
authors.initials: PH
authors.lastname: Byers
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Weis
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Fernandes
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Yao
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Boyce
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D024022:Fibrillar Collagens / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: C108053:CRTAP protein, human; C486354:Crtap protein, mouse; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D018832:Molecular Chaperones; D011506:Proteins; D012333:RNA, Messenger; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase