EFEMP1 explained

EGF-containing fibulin-like extracellular matrix protein 1 is a protein that in humans is encoded by the EFEMP1 gene.^{[1] [2] [3]}

Gene

This gene encodes a member of the fibulin family of extracellular matrix glycoproteins. Like all members of this family, the encoded protein contains tandemly repeated epidermal growth factor-like repeats followed by a C-terminus fibulin-type domain. This gene is upregulated in malignant gliomas and may play a role in the aggressive nature of these tumors. Mutations in this gene are associated with Doyne honeycomb retinal dystrophy and with predisposition to hernias. Alternatively spliced transcript variants that encode the same protein have been described.[provided by RefSeq, Nov 2009]. This gene spans approximately 18 kb of genomic DNA and consists of 12 exons. Alternative splice patterns in the 5' UTR result in three transcript variants encoding the same extracellular matrix protein.

Clinical significance

Mutations in this gene are associated with Doyne honeycomb retinal dystrophy and with predisposition to hernias.^[4]

EFEMP1/Fibulin-3 has recently been reported as a potential biomarker to facilitate the identification of patients with pleural mesothelioma.^[5]

Interactions

EFEMP1 has been shown to interact with ARAF.^[6]

Further reading

• Héon E, Piguet B, Munier F . Linkage of autosomal dominant radial drusen (malattia leventinese) to chromosome 2p16-21 . Arch. Ophthalmol. . 114 . 2 . 193–8 . 1996 . 8573024 . 10.1001/archopht.1996.01100130187014. etal.
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Stone EM, Lotery AJ, Munier FL . A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy . Nat. Genet. . 22 . 2 . 199–202 . 1999 . 10369267 . 10.1038/9722 . 5613181 . etal.
• Giltay R, Timpl R, Kostka G . Sequence, recombinant expression and tissue localization of two novel extracellular matrix proteins, fibulin-3 and fibulin-4 . Matrix Biol. . 18 . 5 . 469–80 . 2000 . 10601734 . 10.1016/S0945-053X(99)00038-4 .
• Katsanis N, Venable S, Smith JR, Lupski JR . Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13 . Hum. Genet. . 106 . 1 . 66–72 . 2000 . 10982184 . 10.1007/s004390051011 . 2024-03-29 .
• Sauer CG, White K, Kellner U . EFEMP1 is not associated with sporadic early onset drusen . Ophthalmic Genet. . 22 . 1 . 27–34 . 2001 . 11262647 . 10.1076/opge.22.1.27.2239 . 31867997 . etal.
• Matsumoto M, Traboulsi EI . Dominant radial drusen and Arg345Trp EFEMP1 mutation . Am. J. Ophthalmol. . 131 . 6 . 810–2 . 2001 . 11384588 . 10.1016/S0002-9394(00)00926-0 .
• Tarttelin EE, Gregory-Evans CY, Bird AC . Molecular genetic heterogeneity in autosomal dominant drusen . J. Med. Genet. . 38 . 6 . 381–4 . 2001 . 11389162 . 10.1136/jmg.38.6.381 . 1734899 . etal.
• Marmorstein LY, Munier FL, Arsenijevic Y . Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration . Proc. Natl. Acad. Sci. U.S.A. . 99 . 20 . 13067–72 . 2002 . 12242346 . 10.1073/pnas.202491599 . 130587 . 2002PNAS...9913067M . etal. free .
• Guymer RH, McNeil R, Cain M . Analysis of the Arg345Trp disease-associated allele of the EFEMP1 gene in individuals with early onset drusen or familial age-related macular degeneration . Clin. Experiment. Ophthalmol. . 30 . 6 . 419–23 . 2003 . 12427233 . 10.1046/j.1442-9071.2002.00572.x . 11949463 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Yuryev A, Wennogle LP . Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis . Genomics . 81 . 2 . 112–25 . 2003 . 12620389 . 10.1016/S0888-7543(02)00008-3 .
• Blackburn J, Tarttelin EE, Gregory-Evans CY . Transcriptional regulation and expression of the dominant drusen gene FBLN3 (EFEMP1) in mammalian retina . Invest. Ophthalmol. Vis. Sci. . 44 . 11 . 4613–21 . 2003 . 14578376 . 10.1167/iovs.03-0112 . etal.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Klenotic PA, Munier FL, Marmorstein LY, Anand-Apte B . Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations . J. Biol. Chem. . 279 . 29 . 30469–73 . 2004 . 15123717 . 10.1074/jbc.M403026200 . free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Yáñez AJ, Bertinat R, Spichiger C . Novel expression of liver FBPase in Langerhans islets of human and rat pancreas . J. Cell. Physiol. . 205 . 1 . 19–24 . 2005 . 15965961 . 10.1002/jcp.20407 . etal. 10533/176131 . 40822845 . free .
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Hu B, Thirtamara-Rajamani KK, Sim H, Viapiano MS . Fibulin-3 is uniquely upregulated in malignant gliomas and promotes tumor cell motility and invasion . Mol. Cancer Res. . 7 . 11 . 1756–70 . November 2009 . 19887559 . 10.1158/1541-7786.MCR-09-0207 . 3896096.

Notes and References

1. Ikegawa S, Toda T, Okui K, Nakamura Y . Structure and chromosomal assignment of the human S1-5 gene (FBNL) that is highly homologous to fibrillin . Genomics . 35 . 3 . 590–2 . Dec 1996 . 8812496 . 10.1006/geno.1996.0402 .
2. Lecka-Czernik B, ((Lumpkin CK Jr)), Goldstein S . An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis . Mol Cell Biol . 15 . 1 . 120–8 . Jan 1995 . 7799918 . 231918 . 10.1128/mcb.15.1.120.
3. Web site: Entrez Gene: EFEMP1 EGF-containing fibulin-like extracellular matrix protein 1.
4. A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia - PubMed . 2015 . 26686553 . Jorgenson . E. . Makki . N. . Shen . L. . Chen . D. C. . Tian . C. . Eckalbar . W. L. . Hinds . D. . Ahituv . N. . Avins . A. . Nature Communications . 6 . 10130 . 10.1038/ncomms10130 . 4703831 .
5. Pass HI, Levin SM, Harbut MR, Melamed J, Chiriboga L, Donington J, Huflejt M, Carbone M, Chia D, Goodglick L, Goodman GE, Thornquist MD, Liu G, de Perrot M, Tsao MS, Goparaju C . Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma . N. Engl. J. Med. . 367 . 15 . 1417–27 . October 2012 . 23050525 . 3761217 . 10.1056/NEJMoa1115050 .
6. Yuryev A, Wennogle LP . Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis . Genomics . 81 . 2 . 112–25 . February 2003 . 12620389 . 10.1016/S0888-7543(02)00008-3 .