Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP. (updated: Nov. 25, 2008)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 0%
No model available.
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The reference OMIM entry for this protein is 135820
Fibulin 1; fbln1
DESCRIPTION
Fibulin-1 is an extracellular matrix protein similar to fibulin-2 (FBLN2;
135821).
CLONING
By sequencing multiple fibulin cDNAs, Argraves et al. (1990) found that alternative splicing results in the expression of 3 fibulin transcripts. The transcripts encode overlapping polypeptides differing only in carboxy-terminal segments. Common to the 3 predicted forms of fibulin-1 is a unique 537-amino acid cysteine-rich polypeptide and a 29-residue signal peptide. The N terminus of fibulin contains a repeated element with a potential disulfide loop structure. The multiple forms of fibulin-1 that differ in their C-terminal regions are produced by alternative splicing. Tran et al. (1997) reported the isolation and sequencing of cDNA corresponding to a 2.7-kb fibulin-1 transcript which encodes the 'D' isoform of human FBLN1. The deduced amino acid sequence of the D isoform is identical in its first 566 residues to the 3 known FBLN1 variants (fibulin-1 A-C); however, it has a unique 137-amino acid C-terminal segment encoded by the alternatively spliced portion of its transcript. RNA hybridization analysis showed that the FBLN1-D transcript is coordinately expressed with the FBLN1-C transcript in tissues and in cultured cells. Comparative sequence analysis showed that the unique C-terminal region of FBNL1-D is similar to the C-terminal region of FBLN1-C and fibulin-2. Pan et al. (1999) stated that fibulin-1 has a molecular mass of 90 kD and that FBLN1-C and -D are the major expressed variants. In the mouse, Pan et al. (1999) showed that the C and D variants are encoded by alternative exons in the 3-prime end of the gene.
GENE STRUCTURE
Pan et al. (1999) determined that the mouse fibulin-1 gene contains 18 exons. Database analysis showed that the human fibulin-1 gene has 2 additional exons encoding the A and B variants. They noted that the structure of the fibulin-1 gene is similar to that of the fibulin-2 gene.
MAPPING
By in situ hybridization of tritium-labeled cDNA probes, Mattei et al. (1994) assigned the human FBLN1 gene to 22q13.2-q13.3 and assigned its counterpart in mouse to the E-F band of chromosome 15. Korenberg et al. (1995) assigned the FBLN1 gene to 22q13.3 by fluorescence in situ hybridization.
GENE FUNCTION
Fibulin-1 was first described as an integrin-binding fibulin from human placenta by Argraves et al. (1989), who found that it is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix when expressed in cultured cells or added exogenously to cell monolayers. Preliminary electron microscopic data suggested a rod-like structure for fibulin-1, consistent with the sequence predictions. Calcium-binding to fibulin-1 is apparently required to mediate its binding to laminin and nidogen (
131390). Using in situ hybridization and immunofluorescent staining, Zhang et al. (1996) detected fibulin-1 expression in several tissues during organogenesis in the developing mouse embryo. Fibulin-1 mRNA was detected at sites of epithelial-mesenchymal interactions and in the mesenchymal tissues of the central nervous system, corresponding to its role in the formation of the extracellular matrix. Miosge et al. (1996) localized fibulin-1 in several areas in early human embryos. In the heart, it was detected in endocardial cushion tissue and endocardium, but not the myocardium, and in the basement membrane zones and adventitia of the blood vessels. Staining was ...
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Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 135820 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).