Fibrillin 1

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FBN1
Protein FBN1 PDB 1apj.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FBN1, ACMICD, ECTOL1, FBN, GPHYSD2, MASS, MFS1, OCTD, SGS, SSKS, WMS, WMS2, MFLS, fibrillin 1
External IDs MGI: 95489 HomoloGene: 30958 GeneCards: FBN1
Gene location (Human)
Chromosome 15 (human)
Chr. Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for FBN1
Genomic location for FBN1
Band 15q21.1 Start 48,408,306 bp[1]
End 48,645,849 bp[1]
RNA expression pattern
PBB GE FBN1 202765 s at fs.png

PBB GE FBN1 202766 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000138

NM_007993

RefSeq (protein)

NP_000129

NP_032019

Location (UCSC) Chr 15: 48.41 – 48.65 Mb Chr 15: 125.3 – 125.51 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fibrillin-1 is a protein that in humans is encoded by the FBN1 gene, located on chromosome 15.[5][6]

FBN1 is a 230-kb gene with 65 coding exons that encode a 2,871-amino-acid long proprotein called profibrillin which is proteolytically cleaved near its C-terminus by the enzyme furin convertase to give fibrillin-1, a member of the fibrillin family, and the 140-amino-acid long protein hormone asprosin.[7][8]

Fibrillin-1 is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfibrils provide force bearing structural support in elastic and nonelastic connective tissue throughout the body.

Description[edit]

The sequence of fibrillin-1 includes 47 six-cysteine EGF-like domains, 7 eight-cysteine domains homologous with latent TGF-beta binding protein, and a proline-rich region.[9]

Fetal Cardiovascular Development[edit]

The FBN-1 gene is involved in a variety of embryonic developmental programs. The microfibrils that are made from fibrillin-1 contribute to both elastic and non-elastic structures. The formation of the elastic fibers in the heart valves and the aorta require the involvement of both FBN-1 and FBN-2.[10] It has been shown that both FBN-1 and FBN-2, along with the other components of elastic fibers, are expressed in the embryonic semilunar valves as early as 4 weeks of gestation.[11] These molecules interact to form the elastic fibers in the ventricularis layer of the semilunar valves. Fibrillin-1 and fibrillin-2 are also crucial for the development of elastic fibers in the aorta. While expression of fibrillin-2 decreases significantly after fetal development, the expression of fibrillin-1 continues into adulthood. This supports the idea that fibrilin-2 dictates the development of early elastic fibers, while fibrillin-1 provides the structural support of mature elastic fibers.[11]

When mutations in the FBN-1 or FBN-2 genes occur, significant deformations can result from the damage to the extracellular matrix. Marfan Syndrome is a congenital disease that arises from a mutation in the FBN-1 gene. This leads to the malformation and subsequent weakening of the microfibrils in the patient’s body, including the structures of the cardiovascular system. The weakened elastic fibers will result in an impaired durability and distensibility in the heart valves and aorta. This provides the explanation for the aortic aneurysms and prolapsed valves that are commonly associated with Marfan Syndrome.[12]

Clinical significance[edit]

Mutations in the FBN1 gene are associated with Marfan syndrome and its variant Marfanoid–progeroid–lipodystrophy syndrome, autosomal dominant Weill-Marchesani syndrome, isolated ectopia lentis, MASS phenotype, and Shprintzen-Goldberg syndrome.[13][14][15]

Mutations in FBN1 and FBN2 are associated with adolescent idiopathic scoliosis .[16]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000166147 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027204 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Biery NJ, Eldadah ZA, Moore CS, Stetten G, Spencer F, Dietz HC (Feb 1999). "Revised genomic organization of FBN1 and significance for regulated gene expression". Genomics. 56 (1): 70–7. PMID 10036187. doi:10.1006/geno.1998.5697. 
  6. ^ Faivre L, Gorlin RJ, Wirtz MK, Godfrey M, Dagoneau N, Samples JR, Le Merrer M, Collod-Beroud G, Boileau C, Munnich A, Cormier-Daire V (Jan 2003). "In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome". Journal of Medical Genetics. 40 (1): 34–6. PMC 1735272Freely accessible. PMID 12525539. doi:10.1136/jmg.40.1.34. 
  7. ^ Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR (April 2016). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–79. PMID 27087445. doi:10.1016/j.cell.2016.02.063. 
  8. ^ Jacquinet A, Verloes A, Callewaert B, Coremans C, Coucke P, Paepe A, Kornak U, Lebrun F, Lombret J, Pierard GE, Robinson PN, Symoens S, Van Maldergem L, Debray FG (2014). "Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene". Eur. J. Med. Genet. 57 (5): 230–234. doi:10.1016/j.ejmg.2014.02.012. 
  9. ^ Ramachandra CJ, Mehta A, Guo KW, Wong P, Tan JL, Shim W (2015). "Molecular pathogenesis of Marfan syndrome". Int. J. Cardiol. 187: 585–91. PMID 25863307. doi:10.1016/j.ijcard.2015.03.423. 
  10. ^ Quondamatteo F; Reinhardt DP; Charbonneau NL; Pophal G; Sakai LY; Herken R (Dec 2002). "Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development.". Matrix Biology. 21 (8): 637-646. 
  11. ^ a b Votteler M; Berrio DA; Horke A; Sabatier L; Reinhardt DP; Nsair A; Aikawa E; Schenke-Layland K (June 2013). "Elastogenesis at the onset of human cardiac valve development.". Development. 140: 2345-2353. PMID 23637335. doi:10.1242/dev.093500. 
  12. ^ Ammash, MD, Naser M.; Sundt, MD, Thoralf M.; Connolly, MD, Heidi M. (January 2008). "Marfan Syndrome—Diagnosis and Management". Current Problems in Cardiology. 33 (1): 7-39. 
  13. ^ "Entrez Gene: FBN1 fibrillin 1". 
  14. ^ "OMIM Entry - * 134797 - FIBRILLIN 1; FBN1". www.omim.org.  line feed character in |title= at position 11 (help)
  15. ^ OMIM entry #616914 - MARFAN LIPODYSTROPHY SYNDROME; MFLS; accessed 9 December 2016.
  16. ^ Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, Willing MC, Grange DK, Braverman AC, Miller NH, Morcuende JA, Tang NL, Lam TP, Ng BK, Cheng JC, Dobbs MB, Gurnett CA (Oct 2014). "Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis". Human Molecular Genetics. 23 (19): 5271–82. PMID 24833718. doi:10.1093/hmg/ddu224. 

External links[edit]

Further reading[edit]