{PDOC50853}
{PS50853; FN3}
{BEGIN}
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* Fibronectin type-III domain profile *
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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 beta sandwich
fold  with  one  beta  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 alpha 1 chain.
 - Neural  cell  adhesion  protein  L1.
 - Leukocyte common antigen.
 - Contactin protein.
 - Cytokine receptor common beta 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 beta chain.
 - Insulin-like growth factor I receptor.
 - Interleukin-2 receptor beta chain.
 - Interferon-gamma receptor beta 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2013 / Profile revised.

[ 1] Hynes, R.O.
     (In) Fibronectins, Springer-Verlag, New York, (1990).
[ 2] Petersen T.E., Thogersen H.C., Skorstengaard K., Vibe-Pedersen K.,
     Sahl P., Sottrup-Jensen L., Magnusson S.
     Proc. Natl. Acad. Sci. U.S.A. 80:137-141(1983).
[ 3] Bork P., Doolittle R.F.
     "Proposed acquisition of an animal protein domain by bacteria."
     Proc. Natl. Acad. Sci. U.S.A. 89:8990-8994(1992).
     PubMed=1409594
[ 4] Leahy D.J., Hendrickson W.A., Aukhil I., Erickson H.P.
     "Structure of a fibronectin type III domain from tenascin phased by
     MAD analysis of the selenomethionyl protein."
     Science 258:987-991(1992).
     PubMed=1279805
[ 5] de Vos A.M., Ultsch M., Kossiakoff A.A.
     Science 255:306-312(1992).
[ 6] Leahy D.J., Aukhil I., Erickson H.P.
     "2.0 A crystal structure of a four-domain segment of human fibronectin
     encompassing the RGD loop and synergy region."
     Cell 84:155-164(1996).
     PubMed=8548820

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