fibulin-1; FIBL-1 (FBLN1)

Function: - incorporated into fibronectin-containing matrix fibers - may play a role in cell adhesion & migration along protein fibers within the extracellular matrix - may have role in developmental processes & in supramolecular organization of extracellular matrix architecture, especially basement membranes - role in cellular transformation & tumor invasion - appears to be a tumor suppressor - may play a role in haemostasis & thrombosis owing to its ability to bind fibrinogen & incorporate into clots. - possible role in modulating neurotrophic activities of APP, particularly soluble APP - homomultimerizes & interacts with various extracellular matrix components such as FN1, LAMA1, LAMA2, NID, ACAN, CSPG2 & type 4 collagen - interacts also APP, NOV, FGB & HPV type 16, HPV type 18, HPV type 31 & BPV type 1 E6 proteins - interacts with FBLN7 (putative) Structure: - belongs to the fibulin family - contains 3 anaphylatoxin-like domains - contains 9 EGF-like domains Compartment: - secreted, extracellular space, extracellular matrix Alternative splicing: named isoforms=4; A,B,C,D Expression: - isoform A & isoform B are only expressed in placenta - isoform C & isoform D are expressed in a variety of tissues & cultured cells - widely expressed during embryonic development - prominent in the matrix of the leptomeninges, in basement membranes of the neuroepithelium & the perineurium of peripheral nerves - in embryos of gestational week 4, staining was observed in the early mesenchymal bone anlagen - in gestational week 4 6.5 & 8, all perichondrial structures showed expression - chondrocytes themselves showed no staining - in gestational week 10, expression is prominent in the interterritorial matrix surrounding the hypertrophic chondrocytes - induced expression increased by estrogen in ovarian cancer cells Pathology: - chromosomal translocation t(12;22)(p11.2;q13.3) involving FBLN1 with RASSF8 is found in a complex type of synpolydactyly associated with metacarpal & metatarsal synostoses - the t(12;22)(p11.2;q13.3) translocation may result in haploinsufficiency of the isoform D splice variant, which could lead to the observed limb malformation - elevated expression & altered processing of FBLN1 protein is associated with breast cancer

Properties

SIZE: entity length = 703 aa MW = 77 kD COMPARTMENT: extracellular matrix MOTIF: signal sequence {1-29} Anaphylatoxin-like 1 {36-76} MOTIF: cysteine residue {C36} MODIFICATION: cysteine residue {C61} cysteine residue {C37} MODIFICATION: cysteine residue {C68} cysteine residue {C50} MODIFICATION: cysteine residue {C69} cysteine residue {C61} MODIFICATION: cysteine residue {C36} cysteine residue {C68} MODIFICATION: cysteine residue {C37} cysteine residue {C69} MODIFICATION: cysteine residue {C50} Anaphylatoxin-like 2 {77-111} MOTIF: cysteine residue {C78} MODIFICATION: cysteine residue {C109} cysteine residue {C91} MODIFICATION: cysteine residue {C110} N-glycosylation site {N98} cysteine residue {C109} MODIFICATION: cysteine residue {C78} cysteine residue {C110} MODIFICATION: cysteine residue {C91} Anaphylatoxin-like 3 {112-144} MOTIF: cysteine residue {C112} MODIFICATION: cysteine residue {C136} cysteine residue {C113} MODIFICATION: cysteine residue {C143} cysteine residue {C126} MODIFICATION: cysteine residue {C144} cysteine residue {C136} MODIFICATION: cysteine residue {C112} cysteine residue {C143} MODIFICATION: cysteine residue {C113} cysteine residue {C144} MODIFICATION: cysteine residue {C126} EGF domain {176-355} (4) MOTIF: cysteine residue {C180} MODIFICATION: cysteine residue {C190} cysteine residue {C186} MODIFICATION: cysteine residue {C199} cysteine residue {C190} MODIFICATION: cysteine residue {C180} cysteine residue {C199} MODIFICATION: cysteine residue {C186} cysteine residue {C201} MODIFICATION: cysteine residue {C214} cysteine residue {C214} MODIFICATION: cysteine residue {C201} binding site SITE: 356-440 FOR-BINDING-OF: fibronectin MOTIF: EGF domain {356-398} cysteine residue {C360} MODIFICATION: cysteine residue {C373} cysteine residue {C367} MODIFICATION: cysteine residue {C382} cysteine residue {C373} MODIFICATION: cysteine residue {C360} cysteine residue {C382} MODIFICATION: cysteine residue {C367} cysteine residue {C384} MODIFICATION: cysteine residue {C397} cysteine residue {C397} MODIFICATION: cysteine residue {C384} EGF domain {399-440} cysteine residue {C403} MODIFICATION: cysteine residue {C415} cysteine residue {C411} MODIFICATION: cysteine residue {C424} cysteine residue {C415} MODIFICATION: cysteine residue {C403} cysteine residue {C424} MODIFICATION: cysteine residue {C411} cysteine residue {C426} MODIFICATION: cysteine residue {C439} cysteine residue {C439} MODIFICATION: cysteine residue {C426} EGF domain {441-578} (3) MOTIF: cysteine residue {C445} MODIFICATION: cysteine residue {C454} cysteine residue {C450} MODIFICATION: cysteine residue {C463} cysteine residue {C454} MODIFICATION: cysteine residue {C445} cysteine residue {C463} MODIFICATION: cysteine residue {C450} cysteine residue {C465} MODIFICATION: cysteine residue {C479} cysteine residue {C479} MODIFICATION: cysteine residue {C465}

Database Correlations

OMIM correlations UniProt P23142 PFAM correlations Entrez Gene 2192 Kegg hsa:2192

References

UniProt :accession P23142