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Encyclopedia > Fibrin
fibrinogen alpha chain
Identifiers
Symbol FGA
Entrez 2243
HUGO 3661
OMIM 134820
RefSeq NM_000508
UniProt P02671
Other data
Locus Chr. 4 q28

Fibrin is a protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets) over a wound site. The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Hugo is a masculine name. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 4 is one of the 23 pairs of chromosomes in humans. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... An example of alkene polymerisation, in which each Styrene monomer units double bond reforms as a single bond with another styrene monomer and forms polystyrene. ... Hemostasis refers to a process whereby bleeding is halted in most animals with a closed circulatory system. ... A 250 ml bag of newly collected platelets. ...


Fibrin is made from its zymogen fibrinogen, a soluble plasma glycoprotein that is synthesised by the liver. Processes in the coagulation cascade activate the zymogen prothrombin to the serine protease thrombin, which is responsible for converting fibrinogen into fibrin. Fibrin is then cross linked by factor XIII to form a clot. A zymogen or a proenzyme, is an inactive enzyme precursor. ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (an oligosaccharide). ... The liver is an organ present in vertebrates and some other animals. ... Coagulation is a complex process by which blood forms solid clots. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... Crystal structure of Trypsin, a typical serine protease. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... Factor XIII or fibrin stabilizing factor is an enzyme (EC 2. ...

Contents

Physiology

Fibrinogen (also called factor I) is a 340 kDa glycoprotein synthesised in the liver hepatocytes and megakaryocytes, which normally has a concentration between 1.5 - 4.0 g/L (normally measured using the Clauss method) in blood plasma. Therefore the concentration in plasma is about 7 microM. In its natural form, fibrinogen is useful in forming bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; though fibrinogen's major use is as a precursor to fibrin. Look up da in Wiktionary, the free dictionary. ... Hepatocytes make up 60-80% of the cytoplasmic mass of the liver. ... The megakaryocyte is a bone marrow cell responsible for the production of blood platelets when cytoplasm processes become fragmented. ... In health-related fields, a reference range is a set of values of some measurement that a physician or other health professional can use to interpret a set of results for a particular patient. ...


Fibrinogen, the principal protein of vertebrate blood clotting is an hexamer containing two sets of three different chains (α, β, and γ), linked to each other by disulfide bonds. The N-terminal sections of these three chains are evolutionary related and contain the cysteines that participate in the cross-linking of the chains. However, there is no similarity between the C-terminal part of the α chain and that of the β and γ chains. The C-terminal part of the β and γ chains forms a domain of about 270 amino-acid residues. As shown in the schematic representation this domain contains four conserved cysteines involved in two disulfide bonds. On the alpha and beta chains, there is a small peptide sequence (called a fibrinopeptide). It is these small peptides that prevent fibrinogen spontaneously forming polymers with itself. Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ...

 ***** xxxxxxCxxxxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxCxxxxxCxxxxxxxxxxxxx | | | | +------------+ +-----+ 

'C': conserved cysteine involved in a disulfide bond. '*': position of the pattern.


Such a domain has been recently found in other proteins which are listed below.

  • Two sea cucumber fibrinogen-like proteins (FReP-A and FReP-B). These are proteins, of about 260 amino acids, which have a fibrinogen β/γ C- terminal domain.
  • In the C-terminus of Drosophila protein scabrous (gene sca). Scabrous is involved in the regulation of neurogenesis in Drosophila and may encode a lateral inhibitor of R8 cells differentiation.
  • In the C-terminus of mammalian Tenascin-X, an extracellular matrix protein that seems to be involved in cell adhesion.
  • In the C-terminus of mammalian prothrombinase.

The function of this domain is not yet known, but it has been suggested that it could be involved in protein-protein interactions. As a signature pattern for this domain, we selected the region around the fourth cysteine. (According to http://www.expasy.org/prosite/PDOC00445)

  1. FUNCTION: Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
  1. SUBUNIT: Heterohexamer; disulfide linked. Contains 2 sets of 3 nonidentical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.

DOMAIN: A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.


Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers. According to: http://www.expasy.org/uniprot/FIBA_HUMAN http://www.expasy.org/uniprot/FIBB_HUMAN http://www.expasy.org/uniprot/FIBG_HUMAN


Following the activation of prothrombin to thrombin (Factor IIa). Thrombin cleaves fibrinopeptide A off the alpha chain and reveals a site in the E domain that can bind to the carboxy terminal end of the gamma chain. Beta chain cleavage occurs more slowly and contributes to the fibril and fiber associations of fibrinogen. These processes convert fibrinogen to fibrin.


The active molecules of fibrin stack up on each other, usually incorporating (by trapping) aggregrates of platelets and molecules of thrombin. The soluble fibrin molecules are later cross-linked (by factor XIII) with covalent bonds, to form a stable hemostatic plug, thus effectively stopping bleeding. Covalent bonding is a form of chemical bonding characterized by the sharing of one or more pairs of electrons between atoms, in order to produce a mutual attraction, which holds the resultant molecule together. ... Hemostasis refers to a process whereby bleeding is halted in most animals with a closed circulatory system. ...


Role in disease

Excessive generation of fibrin due to activation of the coagulation cascade leads to thrombosis, while ineffective generation predisposes to hemorrhage. Thrombosis is the formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system. ... To meet Wikipedias quality standards, this article or section may require cleanup. ...


Dysfunction or disease of the liver can lead to a decrease in fibrinogen production or the production of abnormal fibrinogen molecules with reduced activity (dysfibrinogenaemia). Hereditary abnormalities of fibrinogen (the gene is carried on chromosome 4) are of both quantitative and qualitative in nature and include; afibrinogenaemia, hypofibrinogenaemia, dysfibrinogenaemia, and hypodysfibrinogenaemia.


Diagnostic use

Fibrinogen levels can be measured in venous blood. Normal levels are about 150-300mg/dL. Higher levels are, amongst others, associated with cardiovascular disease (>460mg/dL). It may be elevated in any form of inflammation, as it is an acute phase protein. In the circulatory system, a vein is a blood vessel that carries blood toward the heart. ... Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. ...


It is used in veterinary medicine as an inflammatory marker: in horses a level above the normal range of 1.0-4.0 g/L suggests some degree of systemic inflammatory response. Veterinary medicine is the application of medical, diagnostic, and therapeutic principles to companion, domestic, exotic, wildlife, and production animals. ...


Low levels of fibrinogen can indicate a systemic activation of the clotting system, with consumption of clotting factors faster than synthesis. This excessive clotting factor consumption condition is known as Disseminated Intravascular Coagulation or "DIC." DIC can be difficult to diagnose, but a strong clue is low fibrinogen levels in the setting of prolonged clotting times (PT or PTT), in the context of acute critical illness such as sepsis or trauma.


See also


  Results from FactBites:
 
Fibrin - LoveToKnow 1911 (132 words)
FIBRIN, or Fibrine, a protein formed by the action of the so-called fibrin-ferment on fibrinogen, a constituent of the bloodplasma of all vertebrates.
To obtain pure coagulated fibrin it is best to heat blood-plasma (preferably that of the horse) to 56° C. The usual method of beating a blood-clot with twigs and removing the filamentous fibrin which attaches itself to them yields a very impure product containing haemoglobin and much globulin; moreover, it is very difficult to purify.
Fibrin is a very voluminous, tough, strongly elastic, jelly-like substance; when denaturalized by heat, alcohol or salts, it behaves as any other coagulated albumin.
eMedicine - Dysfibrinogenemia : Article Excerpt by: Wendy Brick, MD (582 words)
In normal fibrin clot formation, a fibrin monomer forms after thrombin cleaves fibrinopeptide A and B from the alpha and beta chains of the fibrinogen molecule.
The impairment of the fibrinogen, which is manufactured in the liver, is due to a structural defect caused by an increased carbohydrate content impairing the polymerization of the fibrin, depending on the degree of abnormality of the fibrinogen molecule.
One of the rarer disorders of coagulation is congenital dysfibrinogenemia, a qualitative abnormality of the fibrin molecule.
  More results at FactBites »

 
 

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