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{PDOC00965}
{PS01253; FN1_1}
{PS51091; FN1_2}
{BEGIN}
***************************************************
* Fibronectin type-I domain signature and profile *
***************************************************

Fibronectin is a plasma protein that binds cell surfaces and various compounds
including collagen, fibrin, heparin, DNA, and  actin.   The major part  of the
sequence of fibronectin consists  of the repetition of three types of domains,
which are called type I, II, and III [1]. Type I domain (FN1) is approximately
40 residues  in  length.    Four conserved cysteines are involved in disulfide
bonds. Fibronectin contains 12 repeats of this domain.

The 3D structure of the FN1 domain has been determined (see <PDB:1FBR>) [2-5].
It consists of two antiparallel beta-sheets, first a double-stranded one, that
is  linked  by  a  disulfide  bond to a triple-stranded beta-sheet. The second
conserved disulfide bridge links the C-terminal adjacent strands of the domain
(see the schematic representation below).

                                          +--------+
              +---------------------------|-+      |
              |                           | |      |
            xxCxxxxxxxxaxxxxxax+xxxxxxxxxxCxCxxxxxxCxxx
              **************************************
              bbb    bbb    bbbbb      bbbbb      bbbbb

'C': conserved cysteine involved in a disulfide bond.
'a': often conserved aromatic amino acid.
'b': position of sheet-forming amino acids.
'+': positively charged amino acid.
'*': position of the pattern.

In  human  tissue  plasminogen activator chain A, the FN1 domain together with
the  following epidermal growth factor (EGF)-like domain (see <PDOC00021>) are
involved  in  fibrin-binding [6]. It has been suggested that these two modules
form  a  single structural and functional unit [4]. The two domains keep their
specific  tertiary  structure,  but  interact intimately to bury a hydrophobic
core;  the  inter-module  linker makes up the third strand of the EGF-module's
major  beta-sheet.

The  FN1  domain  is  also  found  as a single copy in the following mammalian
proteins:

 - Blood  coagulation factor  XII  (Hageman  factor),  which  is composed of a
   fibronectin type-II domain, two EGF-repeats, one fibronectin type-I domain,
   followed by a kringle.
 - Hepatocyte   growth   factor   (HGF)  activator  (EC  3.4.21.-),  activates
   hepatocyte growth  factor    by  converting  it  from  a  single chain to a
   heterodimeric form.  It  has  the  same modular architecture than the blood
   coagulation factor XII.
 - Tissue-type  plasminogen  activator  (t-PA),  which  contains a fibronectin
   type-I domain, one EGF-repeat, and two kringles.

We  developed  a pattern, that spans the domain between the first and the last
conserved  cysteine.  We  also  developed  a profile that covers the whole FN1
domain.

-Consensus pattern: C-x(6,8)-[LFY]-x(5)-[FYW]-x-[RK]-x(8,10)-C-x-C-x(6,9)-C
                    [The 4 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: The  pattern  will,  in  a  few  cases,  miss one of the FN1 domains in
 fibronectin due to rare further variation in gap length or lack of one of the
 conserved aromatic amino acids.

-Expert(s) to contact by email:
           Potts J.; 
jenp@bioch.ox.ac.uk -Last update: March 2005 / Text revised; profile added. [ 1] Skorstengaard K., Jensen M.S., Sahl P., Petersen T.E., Magnusson S. "Complete primary structure of bovine plasma fibronectin." Eur. J. Biochem. 161:441-453(1986). PubMed=3780752 [ 2] Baron M., Norman D., Willis A., Campbell I.D. "Structure of the fibronectin type 1 module." Nature 345:642-646(1990). PubMed=2112232; DOI=10.1038/345642a0 [ 3] Downing A.K., Driscoll P.C., Harvey T.S., Dudgeon T.J., Smith B.O., Baron M., Campbell I.D. "Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance." J. Mol. Biol. 225:821-833(1992). PubMed=1602484 [ 4] Smith B.O., Downing A.K., Driscoll P.C., Dudgeon T.J., Campbell I.D. "The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator." Structure 3:823-833(1995). PubMed=7582899 [ 5] Potts J.R., Phan I., Williams M.J., Campbell I.D. Nat. Genet. 2:946-950(1995). [ 6] Bennett W.F., Paoni N.F., Keyt B.A., Botstein D., Jones A.J.S., Presta L., Wurm F.M., Zoller M.J. "High resolution analysis of functional determinants on human tissue-type plasminogen activator." J. Biol. Chem. 266:5191-5201(1991). PubMed=1900516 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}