Fibronectin type II domain is a
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
-binding
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
.
Fibronectin
Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...
is a multi-domain
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
, found in a soluble form in plasma, and in an insoluble form in loose
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
and
basement membranes
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tissues including mesothelium and ...
, that binds cell surfaces and various compounds including
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
,
fibrin
Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
,
heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...
,
DNA, and
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
. Fibronectins are involved in a number of important functions e.g.,
wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
;
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
;
blood coagulation;
cell differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellula ...
and migration; maintenance of the cellular
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
; and tumour
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
.
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.
Type II domain is approximately sixty amino acids long,
contains four conserved cysteines involved in disulfide bonds and is part of the collagen-binding region of fibronectin. Type II domains occur two times in fibronectin. Type II domains have also been found in a range of proteins including
blood coagulation factor XII; bovine seminal plasma proteins
PDC-109 (BSP-A1/A2) and
BSP-A3;
cation-independent mannose-6-phosphate receptor;
mannose receptor of macrophages;
180 Kd secretory phospholipase A2 receptor;
DEC-205 receptor;
72 Kd and 92 Kd type IV collagenase ();
and hepatocyte growth factor activator.
Fibronectin type II domain and Lipid bilayer interaction
Fibronectin type II domain is part of the extracellular portions of EphA2 receptor proteins. FN2 domain on EphA2 receptors bears positively-charged components, namely K441 and R443, which attract and almost exclusively bind to anionic lipids such as anionic membrane lipid phosphatidylglycerol.
K441 and R443 together make up a membrane-binding motif that allows EphA2 receptors to attach to the cell membrane.
Human proteins containing this domain
BSPH1;
ELSPBP1;
F12;
FN1;
HGFAC
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.
The protein encoded by this gene belongs to peptidase family S1. It is first synthesized as an inactive single-chain precursor before being activated to ...
;
IGF2R;
LY75
CD205 also called Lymphocyte antigen 75 is a protein that in humans is encoded by the ''LY75'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''ge ...
;
MMP2
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the ''MMP2'' gene. The ''MMP2'' gene is located on chromosome 16 at position 12.2.
Function
Proteins of the ...
;
MMP9
Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extrace ...
;
MRC1;
MRC1L1;
MRC2;
PLA2R1;
SEL1L
Protein sel-1 homolog 1 is a protein that in humans is encoded by the ''SEL1L'' gene.
Clinical relevance
A mutation in this gene in Finnish Hound dogs have been implicated in cases of cerebellar ataxia
Cerebellar ataxia is a form of ataxia orig ...
;
*Fibronectin type I domain:
F12;
FN1;
HGFAC
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.
The protein encoded by this gene belongs to peptidase family S1. It is first synthesized as an inactive single-chain precursor before being activated to ...
;
PLAT
In the United States, a plat ( or ) (plan) is a cadastral map, drawn to scale, showing the divisions of a piece of land. United States General Land Office surveyors drafted township plats of Public Lands Surveys to show the distance and bear ...
;
References
External links
Fibronectin type-II collagen-binding domainin
PROSITE
PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformati ...
Protein domains
Peripheral membrane proteins
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