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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 a) Marfan syndrome b) isolated ectopia lentis c) Shprintzen-Goldberg craniosynostosis syndrome d) overlap connective tissue disease e) stiff skin syndrome - defects in FBN1 are the cause a) Weill-Marchesani syndrome (autosomal dominant) b) geleophysic dysplasia type 2 c) acromicric dysplasia

General

fibrillin phosphoprotein

Properties

SIZE: entity length = 2871 aa MW = 312 kD COMPARTMENT: lysosome MOTIF: signal sequence {1-27} EGF domain {81-2687} (47) MOTIF: cysteine residue {C85} MODIFICATION: cysteine residue {C94} cysteine residue {C89} MODIFICATION: cysteine residue {C100} cysteine residue {C94} MODIFICATION: cysteine residue {C85} cysteine residue {C100} MODIFICATION: cysteine residue {C89} cysteine residue {C102} MODIFICATION: cysteine residue {C111} cysteine residue {C111} MODIFICATION: cysteine residue {C102} TGF-beta binding domain {184-236} (9) proline-rich region SITE: 402-446 MOTIF: proline residue (SEVERAL) N-glycosylation site {N448} N-glycosylation site {N2734} N-glycosylation site {N2750} N-glycosylation site {N2767}

Database Correlations

OMIM correlations MORBIDMAP 134797 UniProt P35555 PFAM correlations Entrez Gene 2200 Kegg hsa:2200

References

  1. UniProt :accession P35555
  2. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/FBN1