PROSITE documentation PDOC50853

Fibronectin type-III domain profile

Fibronectin is a dimeric glycoprotein composed of disulfide-linked subunits with a molecular weight of 220-250 kDa each. It is involved in cell adhesion, cell morphology, thrombosis, cell migration, and embryonic differentiation [1]. Fibronectin is a modular protein composed of homologous repeats of three prototypical types of domains known as types I, II, and III [2].

Fibronectin type-III (FN3) repeats are both the largest and the most common of the fibronectin subdomains. Domains homologous to FN3 repeats have been found in various animal protein families including other extracellular-matrix molecules, cell-surface receptors, enzymes, and muscle proteins [3]. Structures of individual FN3 domains have revealed a conserved β sandwich fold with one β sheet containing four strands and the other sheet containing three strands (see for example <PDB:1TEN>) [4,5]. This fold is topologically very similar to that of Ig-like domains (see <PDOC50835>), with a notable difference being the lack of a conserved disulfide bond in FN3 domains. Distinctive hydrophobic core packing and the lack of detectable sequence homology between immunoglobulin and FN3 domains suggest, however, that these domains are not evolutionarily related [4].

FN3 exhibits functional as well as structural modularity. Sites of interaction with other molecules have been mapped to short stretch of amino acids such as the Arg-Gly-Asp (RGD) sequence found in various FN3 domains. The RGD sequences is involved in interactions with integrin. Small peptides containing the RGD sequence can modulate a variety of cell adhesion invents associated with thrombosis, inflammation, and tumor metastasis. These properties have led to the investigation of RGD peptides and RGD peptide analogs as potential therapeutic agents [6].

Some proteins known to contain an FN3 domain are listed below:

• Contactin 2 or axonin-1 protein.
• Collagen α 1 chain.
• Neural cell adhesion protein L1.
• Leukocyte common antigen.
• Contactin protein.
• Cytokine receptor common β chain.
• Down syndrome cell adhesion protein.
• Ephrin type-A receptor 1 to 8.
• Ephrin type-B receptor 1 to 6.
• Erythropoietin receptor.
• Fibronectin.
• Leucine-rich repeat transmembrane protein FLRT1.
• Growth hormone receptor.
• Interleukin-12 β chain.
• Insulin-like growth factor I receptor.
• Interleukin-2 receptor β chain.
• Interferon-γ receptor β chain.
• Insulin receptor.
• Anosmin 1 protein.
• Myosin light chain kinase.
• Proto-oncogene tyrosine-protein kinase ROS.
• Leptin receptor (LEP-R) (OB receptor).
• Leukemia inhibitory factor receptor (LIF-R).
• Proto-oncogene tyrosine-protein kinase MER (C-mer).
• Neural cell adhesion molecule 1.
• Neogenin protein.
• Neurofascin protein.
• Nephrin protein.
• Photoreceptor-associated LRR superfamily protein.
• Prolactin receptor.
• Sortilin-related receptor.
• Tenascin protein.
• Tyrosine-protein kinase receptor Tie-1.
• Angiopoietin 1 receptor.
• Thrombopoietin receptor.
• Tyrosine-protein kinase receptor TYRO3.
• Tyrosine-protein kinase receptor UFO.
• Drosophila Sevenless protein.
• Drosophila Domeless protein, a cytokine receptor.
• Drosophila Fasciclin II protein, a neuronal protein.
• Several animal proteinn-tyrosine phosphatases.
• Yeast Chitin biosynthesis protein CHS5.
• Thermoanaerobacterial amylopullulanase.
• Several bacterial chitinase.
• Several bacterial endoglucanase.
• Bacillus subtilis penicillin-binding protein 1A.

The profile we developed covers the whole FN3 domain.