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J Cell Biol. 1990 December 1; 111(6): 3155–3164.
PMCID: PMC2116371

Fibulin is an extracellular matrix and plasma glycoprotein with repeated domain structure


We have studied the expression of fibulin in cultured fibroblasts and determined its primary structure by cDNA cloning. Our results show that fibulin is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers. In addition, we find that fibulin is present in plasma at a level of 33 +/- 3 micrograms/ml. Sequencing of multiple fibulin cDNAs indicates that a process of alternative splicing results in the expression of three fibulin transcripts. The transcripts encode overlapping polypeptides differing only in carboxy- terminal segments. Common to the three predicted forms of fibulin is a unique 537-amino acid-long cysteine-rich polypeptide and a 29-residue signal peptide. The amino-terminal portion of fibulin contains a repeated element with potential disulfide loop structure resembling that of the complement component anaphylatoxins C3a, C4a, and C5a as well as proteins of the albumin gene family. The bulk of the remaining portion of the molecule is a series of nine EGF-like repeats.

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Selected References

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  • Argraves WS, Dickerson K, Burgess WH, Ruoslahti E. Fibulin, a novel protein that interacts with the fibronectin receptor beta subunit cytoplasmic domain. Cell. 1989 Aug 25;58(4):623–629. [PubMed]
  • Belt KT, Carroll MC, Porter RR. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Brown JR. Structural origins of mammalian albumin. Fed Proc. 1976 Aug;35(10):2141–2144. [PubMed]
  • Cooke NE, David EV. Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. J Clin Invest. 1985 Dec;76(6):2420–2424. [PMC free article] [PubMed]
  • de Bruijn MH, Fey GH. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci U S A. 1985 Feb;82(3):708–712. [PubMed]
  • Graceffa P, Wang CL, Stafford WF. Caldesmon. Molecular weight and subunit composition by analytical ultracentrifugation. J Biol Chem. 1988 Oct 5;263(28):14196–14202. [PubMed]
  • Hayman EG, Ruoslahti E. Distribution of fetal bovine serum fibronectin and endogenous rat cell fibronectin in extracellular matrix. J Cell Biol. 1979 Oct;83(1):255–259. [PMC free article] [PubMed]
  • Hunkapiller MW, Lujan E, Ostrander F, Hood LE. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. [PubMed]
  • Lehrach H, Diamond D, Wozney JM, Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. [PubMed]
  • Mautner V, Hynes RO. Surface distribution of LETS protein in relation to the cytoskeleton of normal and transformed cells. J Cell Biol. 1977 Dec;75(3):743–768. [PMC free article] [PubMed]
  • McKeown-Longo PJ, Mosher DF. Binding of plasma fibronectin to cell layers of human skin fibroblasts. J Cell Biol. 1983 Aug;97(2):466–472. [PMC free article] [PubMed]
  • Millán JL. Molecular cloning and sequence analysis of human placental alkaline phosphatase. J Biol Chem. 1986 Mar 5;261(7):3112–3115. [PubMed]
  • Morinaga T, Sakai M, Wegmann TG, Tamaoki T. Primary structures of human alpha-fetoprotein and its mRNA. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4604–4608. [PubMed]
  • Nishimura H, Kawabata S, Kisiel W, Hase S, Ikenaka T, Takao T, Shimonishi Y, Iwanaga S. Identification of a disaccharide (Xyl-Glc) and a trisaccharide (Xyl2-Glc) O-glycosidically linked to a serine residue in the first epidermal growth factor-like domain of human factors VII and IX and protein Z and bovine protein Z. J Biol Chem. 1989 Dec 5;264(34):20320–20325. [PubMed]
  • Ohlin AK, Linse S, Stenflo J. Calcium binding to the epidermal growth factor homology region of bovine protein C. J Biol Chem. 1988 May 25;263(15):7411–7417. [PubMed]
  • Rappolee DA, Mark D, Banda MJ, Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988 Aug 5;241(4866):708–712. [PubMed]
  • Ruoslahti E, Uotila M, Engvall E. Radioimmunoassay of alpha-fetoprotein with polyclonal and monoclonal antibodies. Methods Enzymol. 1982;84:3–19. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Saunders S, Jalkanen M, O'Farrell S, Bernfield M. Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol. 1989 Apr;108(4):1547–1556. [PMC free article] [PubMed]
  • Scott J, Urdea M, Quiroga M, Sanchez-Pescador R, Fong N, Selby M, Rutter WJ, Bell GI. Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science. 1983 Jul 15;221(4607):236–240. [PubMed]
  • Stenflo J, Ohlin AK, Owen WG, Schneider WJ. beta-Hydroxyaspartic acid or beta-hydroxyasparagine in bovine low density lipoprotein receptor and in bovine thrombomodulin. J Biol Chem. 1988 Jan 5;263(1):21–24. [PubMed]
  • Sugo T, Björk I, Holmgren A, Stenflo J. Calcium-binding properties of bovine factor X lacking the gamma-carboxyglutamic acid-containing region. J Biol Chem. 1984 May 10;259(9):5705–5710. [PubMed]
  • Szebenyi DM, Obendorf SK, Moffat K. Structure of vitamin D-dependent calcium-binding protein from bovine intestine. Nature. 1981 Nov 26;294(5839):327–332. [PubMed]
  • Takano E, Maki M, Mori H, Hatanaka M, Marti T, Titani K, Kannagi R, Ooi T, Murachi T. Pig heart calpastatin: identification of repetitive domain structures and anomalous behavior in polyacrylamide gel electrophoresis. Biochemistry. 1988 Mar 22;27(6):1964–1972. [PubMed]
  • Thomas PS. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. [PubMed]
  • Watson ME. Compilation of published signal sequences. Nucleic Acids Res. 1984 Jul 11;12(13):5145–5164. [PMC free article] [PubMed]
  • Wetsel RA, Ogata RT, Tack BF. Primary structure of the fifth component of murine complement. Biochemistry. 1987 Feb 10;26(3):737–743. [PubMed]
  • Yang F, Brune JL, Naylor SL, Cupples RL, Naberhaus KH, Bowman BH. Human group-specific component (Gc) is a member of the albumin family. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7994–7998. [PubMed]
  • Young RA, Davis RW. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. [PubMed]

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