fibrillin-1 (FBN1 FBN)

Function

• fibrillins are structural components of 10-12 nm extracellular Ca+2-binding microfibrils, which occur either in association with elastin or in elastin-free bundles
• fibrillin-1-containing microfibrils provide long-term force bearing structural support
• regulates osteoblast maturation by controlling TGF-beta bioavailability & calibrating TGF-beta & BMP levels, respectively (putative)
• forms intermolecular disulfide bonds either with other fibrillin-1 molecules or with other components of the microfibrils
• interacts with COL16A1
• interacts with integrin alpha-V/beta-3
• interacts with ADAMTSL4

Structure

• belongs to the fibrillin family
• contains 47 EGF-like domains
• contains 9 TB (TGF-beta binding) domains

Compartment

• secreted, extracellular space, extracellular matrix

Pathology

• the majority of the > 600 mutations in FBN1 known are point mutations
• frameshifts & splice site mutations are also known
• defects in FBN1 are a cause of
  • Marfan syndrome
  • isolated ectopia lentis
  • Shprintzen-Goldberg craniosynostosis syndrome
  • overlap connective tissue disease
  • stiff skin syndrome
• defects in FBN1 are the cause
  • Weill-Marchesani syndrome (autosomal dominant)
  • geleophysic dysplasia type 2
  • acromicric dysplasia

More general terms

• fibrillin
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2200
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2200
• OMIM: https://mirror.omim.org/entry/102370
• OMIM: https://mirror.omim.org/entry/129600
• OMIM: https://mirror.omim.org/entry/134797
• OMIM: https://mirror.omim.org/entry/154700
• OMIM: https://mirror.omim.org/entry/182212
• OMIM: https://mirror.omim.org/entry/184900
• OMIM: https://mirror.omim.org/entry/604308
• OMIM: https://mirror.omim.org/entry/608328
• OMIM: https://mirror.omim.org/entry/614185
• UniProt: http://www.uniprot.org/uniprot/P35555.html