Fibronectin type II domain | |||||||||
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Identifiers | |||||||||
Symbol | fn2 | ||||||||
Pfam | PF00040 | ||||||||
InterPro | IPR000562 | ||||||||
SMART | SM00059 | ||||||||
PROSITE | PDOC00022 | ||||||||
SCOP2 | 1pdc / SCOPe / SUPFAM | ||||||||
OPM superfamily | 115 | ||||||||
OPM protein | 1h8p | ||||||||
CDD | cd00062 | ||||||||
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Fibronectin type II domain is a collagen-binding protein domain. Fibronectin is a multi-domain glycoprotein, found in a soluble form in plasma, and in an insoluble form in loose connective tissue and basement membranes, that binds cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in a number of important functions e.g., wound healing; cell adhesion; blood coagulation; cell differentiation and migration; maintenance of the cellular cytoskeleton; and tumour metastasis. [2] 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. [3]
Type II domain is approximately sixty amino acids long, [4] 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; [5] cation-independent mannose-6-phosphate receptor; [6] mannose receptor of macrophages; [7] 180 Kd secretory phospholipase A2 receptor; [8] DEC-205 receptor; [9] 72 Kd and 92 Kd type IV collagenase (EC 3.4.24.24); [10] and hepatocyte growth factor activator. [11]
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. [12] K441 and R443 together make up a membrane-binding motif that allows EphA2 receptors to attach to the cell membrane. [12]
BSPH1; ELSPBP1; F12; FN1; HGFAC; IGF2R; LY75; MMP2; MMP9; MRC1; MRC1L1; MRC2; PLA2R1; SEL1L;
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collagen, fibrin, and heparan sulfate proteoglycans.
Annexin is a common name for a group of cellular proteins. They are mostly found in eukaryotic organisms.
Kringle Domains are autonomous protein domains that fold into large loops stabilized by 3 disulfide linkages. These are important in protein–protein interactions with blood coagulation factors. Their name refers to the Kringle, a Scandinavian pastry which they somewhat resemble.
The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320. Although it has been shown that Factor Xa can activate prothrombin when unassociated with the prothrombinase complex, the rate of thrombin formation is severely decreased under such circumstances. The prothrombinase complex can catalyze the activation of prothrombin at a rate 3 x 105-fold faster than can Factor Xa alone. Thus, the prothrombinase complex is required for the efficient production of activated thrombin and also for adequate hemostasis.
Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.
The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).
CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.
The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates.
Collagen alpha-1(V) chain is a protein that in humans is encoded by the COL5A1 gene.
Collagen alpha-5(IV) chain is a protein that in humans is encoded by the COL4A5 gene.
The EGF-like domain is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. An exception to this is the prostaglandin-endoperoxide synthase. The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds. The structures of 4-disulfide EGF-domains have been solved from the laminin and integrin proteins. The main structure of EGF-like domains is a two-stranded β-sheet followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets. EGF-like domains frequently occur in numerous tandem copies in proteins: these repeats typically fold together to form a single, linear solenoid domain block as a functional unit.
EPH receptor A2 is a protein that in humans is encoded by the EPHA2 gene.
Collagen alpha-3(IV) chain is a protein that in humans is encoded by the COL4A3 gene.
Collagen alpha-4(IV) chain is a protein that in humans is encoded by the COL4A4 gene.
Collagen alpha-2(IV) chain is a protein that in humans is encoded by the COL4A2 gene.
Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene.
Collagen alpha-6(IV) chain is a protein that in humans is encoded by the COL4A6 gene.
Collagen alpha-1(XIV) chain is a protein that in humans is encoded by the COL14A1 gene. It likely plays a role in collagen binding and cell-cell adhesion.
Collagen alpha-1(XIII) chain is a protein that in humans is encoded by the COL13A1 gene.
Collagen receptors are membrane proteins that bind the extracellular matrix protein collagen, the most abundant protein in mammals. They control mainly cell proliferation, migration and adhesion, coagulation cascade activation and they affect ECM structure by regulation of MMP.