Human Fibronectin

This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants. However, the full-length nature of some variants has not been determined. [provided by RefSeq]

Function: Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Ref.36 Ref.38 Ref.42 Ref.50Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling. Ref.36 Ref.38 Ref.42 Ref.50

Subunit structure: Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR, LGALS3BP and COL13A1. Interacts with FBLN7

By similarity. Interacts with COMP. Interacts with S.aureus fnbA. Interacts with TNR; the interaction inhibits cell adhesion and neurite outgrowth

By similarity. Interacts with FST3. Ref.34 Ref.36 Ref.37 Ref.39 Ref.40 Ref.45

Subcellular location: Secreted › extracellular space › extracellular matrix.

Tissue specificity: Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix. Ugl-Y1, Ugl-Y2 and Ugl-Y3 are found in urine. Ref.14 Ref.33 Ref.49

Developmental stage: Ugl-Y1, Ugl-Y2 and Ugl-Y3 are present in the urine from 0 to 17 years of age. Ref.14 Ref.33

Post-translational modification: Sulfated.It is not known whether both or only one of Thr-2064 and Thr-2065 are/is glycosylated. Ref.14 Ref.24 Ref.33 Ref.41 Ref.43 Ref.48 Ref.58Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers).Phosphorylation sites are present in the extracelllular medium.Proteolytic processing produces the C-terminal NC1 peptide, anastellin.

Involvement in disease: Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [

MIM:601894]; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Ref.72

Sequence similarities: Contains 12 fibronectin type-I domains.Contains 2 fibronectin type-II domains.Contains 16 fibronectin type-III domains.

Sequence caution: The sequence AAX76513.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAD93077.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence CAD91166.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence CAD97964.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence CAD97965.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence CAH18136.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.