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	PROSITE documentation PDOC00022

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 II domain (FN2) is approximately 40 residues long, contains four conserved cysteines involved in disulfide bonds and is part of the collagen-binding region of fibronectin [2]. In fibronectin the minimal collagen binding region is formed by one FN1 and two FN2 domains. This suggests that the collagen-binding sites spans multiple modules.

A schematic representation of the position of the invariant residues and the topology of the disulfide bonds in FN2 domain is shown below.

                        +----------------------+
                        |                      |
        xxCxxPFx#xxxxxxxCxxxxxxxxWCxxxxx#xxx#x#Cxx
          |                       |
          +-----------------------+

'C': conserved cysteine involved in a disulfide bond.
'#': large hydrophobic residue.

The 3D-structure of the FN2 domain has been determined (see <PDB:2FN2>) [3]. The structure consists of two double-stranded anti-parallel β-sheets, oriented approximately perpendicular to each other, and two irregular loops, one separating the two β-sheets and the other between the two strands of the second β-sheet. The minimal collagen-binding region (FN1-FN2-FN2) adopts a hairpin structure where the conserved aromatic residues of FN2 form a hydrophobic pocket which is thought to provide a binding site for non polar residues in collagen [4].

Some proteins that contain an FN2 domain are listed below:

• Blood coagulation factor XII (Hageman factor) (1 copy).
• Bovine seminal plasma proteins PDC-109 (BSP-A1/A2) and BSP-A3 [5] (twice).
• Cation-independent mannose-6-phosphate receptor (which is also the insulin- like growth factor II receptor) [6] (1 copy).
• Mannose receptor of macrophages [7] (1 copy).
• 180 Kd secretory phospholipase A2 receptor (1 copy) [8].
• DEC-205 receptor (1 copy) [9]. 72 Kd and 92 Kd type IV collagenases (EC 3.4.24.24) (MMP-2 and MMP-9) [10] (3 copies). Both metalloproteinases are strongly expressed in malignant tumors and have been attributed to metastasize. They both degradate collagen-IV thus facilitating penetration of the basement membranes by tumor cells.
• Hepatocyte growth factor activator [11] (1 copy).

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

Last update:

March 2005 / Text revised; profile added.

PROSITE methods (with tools and information) covered by this documentation:

FN2_2, PS51092; Fibronectin type-II collagen-binding domain profile  (MATRIX)

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 59
  • detected by PS51092: 58 (true positives)
  • undetected by PS51092: 1 (0 false negative and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS51092:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS51092
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51092
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS51092
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS51092
• View ligand binding statistics of PS51092
• Matching PDB structures: 1CK7 1CXW 1E88 1E8B ... [ALL]

FN2_1, PS00023; Fibronectin type-II collagen-binding domain signature  (PATTERN)

• Consensus pattern:
  C-x(2)-P-F-x-[FYWIV]-x(7)-C-x(8,10)-W-C-x(4)-[DNSR]-[FYW]-x(3,5)-[FYW]-x-[FYWI]-C
  The 4 C's are involved in disulfide bonds
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 57
  • detected by PS00023: 55 (true positives)
  • undetected by PS00023: 2 (1 false negative and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00023:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00023
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00023
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00023
• View ligand binding statistics of PS00023
• Matching PDB structures: 1CK7 1CXW 1E88 1E8B ... [ALL]

1	Authors	Skorstengaard K., Jensen M.S., Sahl P., Petersen T.E., Magnusson S.
	Title	Complete primary structure of bovine plasma fibronectin.
	Source	Eur. J. Biochem. 161:441-453(1986).
	PubMed ID	3780752

2	Authors	Forastieri H., Ingham K.C.
	Title	Interaction of gelatin with a fluorescein-labeled 42-kDa chymotryptic fragment of fibronectin.
	Source	J. Biol. Chem. 260:10546-10550(1985).
	PubMed ID	3928622

3	Authors	Pickford A.R., Potts J.R., Bright J.R., Phan I., Campbell I.D.
	Title	Solution structure of a type 2 module from fibronectin: implications for the structure and function of the gelatin-binding domain.
	Source	Structure 5:359-370(1997).
	PubMed ID	9083105

4	Authors	Pickford A.R., Smith S.P., Staunton D., Boyd J., Campbell I.D.
	Title	The hairpin structure of the (6)F1(1)F2(2)F2 fragment from human fibronectin enhances gelatin binding.
	Source	EMBO J. 20:1519-1529(2001).
	PubMed ID	11285216
	DOI	10.1093/emboj/20.7.1519

5	Authors	Seidah N.G., Manjunath P., Rochemont J., Sairam M.R., Chretien M.
	Title	Complete amino acid sequence of BSP-A3 from bovine seminal plasma. Homology to PDC-109 and to the collagen-binding domain of fibronectin.
	Source	Biochem. J. 243:195-203(1987).
	PubMed ID	3606570

6	Authors	Kornfeld S.
	Title	Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors.
	Source	Annu. Rev. Biochem. 61:307-330(1992).
	PubMed ID	1323236
	DOI	10.1146/annurev.bi.61.070192.001515

7	Authors	Taylor M.E., Conary J.T., Lennartz M.R., Stahl P.D., Drickamer K.
	Title	Primary structure of the mannose receptor contains multiple motifs resembling carbohydrate-recognition domains.
	Source	J. Biol. Chem. 265:12156-12162(1990).
	PubMed ID	2373685

8	Authors	Lambeau G., Ancian P., Barhanin J., Lazdunski M.
	Title	Cloning and expression of a membrane receptor for secretory phospholipases A2.
	Source	J. Biol. Chem. 269:1575-1578(1994).
	PubMed ID	8294398

9	Authors	Jiang W., Swiggard W.J., Heufler C., Peng M., Mirza A., Steinman R.M., Nussenzweig M.C.
	Title	The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing.
	Source	Nature 375:151-155(1995).
	PubMed ID	7753172
	DOI	10.1038/375151a0

10	Authors	Collier I.E., Wilhelm S.M., Eisen A.Z., Marmer B.L., Grant G.A., Seltzer J.L., Kronberger A., He C., Bauer E.A., Goldberg G.I.
	Source	J. Biol. Chem. 263:6579-6587(1988).

11	Authors	Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y., Kitamura N.
	Source	J. Biol. Chem. 268:10024-10028(1993).

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