Summary: Fibrinogen alpha/beta chain family
This is the Wikipedia entry entitled "Fibrinogen". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Fibrinogen Edit Wikipedia article
||This article may be in need of reorganization to comply with Wikipedia's layout guidelines. (February 2012)|
|fibrinogen alpha chain|
|Locus||Chr. 4 q28|
|fibrinogen beta chain|
|Locus||Chr. 4 q28|
|fibrinogen gamma chain|
|Locus||Chr. 4 q28|
|Fibrinogen alpha/beta chain family|
crystal structure of native chicken fibrinogen with two different bound ligands
|Fibrinogen alpha C domain|
|Fibrinogen beta and gamma chains, C-terminal globular domain|
crystal structure of native chicken fibrinogen with two different bound ligands
Fibrinogen (factor I) is a glycoprotein in vertebrates that helps in the formation of blood clots. It consists of a linear array of 3 nodules held together by a very thin thread which is estimated to have a diameter between 8 and 15 A. The two end nodules are alike but the center one is slightly smaller. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 A. The length of the dried molecule is 475 +- 25 A.
The Fibrinogen molecule is a soluble, large, and complex glycoprotein, 340 kDa plasma glycoprotein, that is converted by thrombin into fibrin during blood clot formation. It has a rod-like shape with dimensions of 9 x 47.5 x 6nm and it shows a negative net charge at physiological pH (IP at pH 5.2). Fibrinogen is synthesized in the liver by the hepatocytes. The concentration of fibrinogen in the blood plasma is 200–400 mg/dL (normally measured using the Clauss method).
During normal blood coagulation, a coagulation cascade activates the zymogen prothrombin by converting it into the serine protease thrombin. Thrombin then converts the soluble fibrinogen into insoluble fibrin strands. These strands are then cross-linked by factor XIII to form a blood clot. FXIIa stabilizes fibrin further by incorporation of the fibrinolysis inhibitors alpha-2-antiplasmin and TAFI (thrombin activatable fibrinolysis inhibitor, procarboxypeptidase B), and binding to several adhesive proteins of various cells. Both the activation of Factor XIII by thrombin and plasminogen activator (t-PA) are catalyzed by fibrin. Fibrin specifically binds the activated coagulation factors factor Xa and thrombin and entraps them in the network of fibers, thus functioning as a temporary inhibitor of these enzymes, which stay active and can be released during fibrinolysis. Recent research has shown that fibrin plays a key role in the inflammatory response and development of rheumatoid arthritis.
Fibrinogen, the principal protein of vertebrate blood clotting, is a 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 contain the cysteines that participate in the cross-linking of the chains. The C-terminal parts of the α, β and γ chains contain a domain of about 225 amino-acid residues, which can function as a molecular recognition unit. In fibrinogen as well as in angiopoietin, this domain is implicated in protein-protein interactions. In lectins, such as mammalian ficolins and invertebrate tachylectin 5A, the fibrinogen C-terminal domain binds carbohydrates. On the fibrinogen α and β chains, there is a small peptide sequence (called a fibrinopeptide). These small peptides are what prevent fibrinogen from spontaneously forming polymers with itself.
The conversion of fibrinogen to fibrin occurs in several steps. First, thrombin cleaves the N-terminus of the fibrinogen alpha and beta chains to fibrinopeptide A and B respectively. The resulting fibrin monomers polymerize end to end to from protofibrils, which in turn associate laterally to form fibrin fibers. In a final step, the fibrin fibers associate to form the fibrin gel.
Congenital fibrinogen deficiency (afibrinogenemia) or disturbed function of fibrinogen has been described in a few cases.
It can lead to either bleeding or thromboembolic complications, or is clinically without pathological findings. More common are acquired deficiency stages that can be detected by laboratory tests in blood plasma or in whole blood by means of thrombelastometry. Acquired deficiency is found after hemodilution, blood losses and/or consumption such as in trauma patients, during some phases of disseminated intravascular coagulation (DIC), and also in sepsis. In patients with fibrinogen deficiency, the correction of bleeding is possible by infusion of fresh frozen plasma (FFP), cryoprecipitate (a fibrinogen-rich plasma fraction) or by fibrinogen concentrates. There is increasing evidence that correction of fibrinogen deficiency or fibrinogen polymerization disorders is very important in patients with bleeding.
Fibrinogen levels can be measured in venous blood. Normal levels are about 1.5-3 g/L, depending on the method used. In typical circumstances, fibrinogen is measured in citrated plasma samples in the laboratory, however the analysis of whole-blood samples by use of thromboelastometry (platelet function is inhibited with cytochalasin D) is also possible. Higher levels are, amongst others, associated with cardiovascular disease (>3.43 g/L). It may be elevated in any form of inflammation, as it is an acute-phase protein; for example, it is especially apparent in human gingival tissue during the initial phase of periodontal disease. Fibrinogen levels increase in pregnancy to an average of 4.5 g/l, compared to an average of 3 g/l in non-pregnant people.
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 aPTT), in the context of acute critical illness such as sepsis or trauma. Besides low fibrinogen level, fibrin polymerization disorders that can be induced by several factors, including plasma expanders, can also lead to severe bleeding problems. Fibrin polymerization disorders can be detected by viscoelastic methods such as thrombelastometry.
- PDB 1FZC; Everse SJ, Spraggon G, Veerapandian L, Riley M, Doolittle RF (June 1998). "Crystal structure of fragment double-D from human fibrin with two different bound ligands". Biochemistry 37 (24): 8637–42. doi:10.1021/bi9804129. PMID 9628725.
- Hall, Ph.D., Cecil E.; HENRY S. SLAYTER (18 August 1958). "The Fibrinogen Molecule: Its Size, Shape, and Mode of Polymerization". The Journal of Biophysical and Biochemical Cytology. Plate 1 (in English) (Cambridge, M: e Department of Biology, Massachusetts Institute of Technology). Volume 5 (1): 11–6. PMC 2224630. PMID 13630928. Retrieved 24 May 2014.
- Marucco, Arianna; et al (2013). "Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases". Journal of Physics. Conference Series 429 (Issue 1). Retrieved 24 May 2014.
- Muszbek L, Bagoly Z, Bereczky Z, Katona E (July 2008). "The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis". Cardiovascular & Hematological Agents in Medicinal Chemistry 6 (3): 190–205. doi:10.2174/187152508784871990. PMID 18673233.
- Kaiser B (2003). "DX-9065a, a direct inhibitor of factor Xa". Cardiovascular Drug Reviews 21 (2): 91–104. doi:10.1111/j.1527-3466.2003.tb00108.x. PMID 12847561.
- Gilliam BE; Reed, Melinda R; Chauhan, Anil K; Dehlendorf, Amanda B; Moore, Terry L (2011). "Evidence of Fibrinogen as a Target of Citrullination in IgM Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis". Pediatric Rheumatology 9 (8): xx–xx. doi:10.1186/1546-0096-9-8. ISSN 1546-0096. PMC 3071779. PMID 21439056.
- PDOC00445 Fibrinogen C-terminal domain in PROSITE
- Blombäck B, Hessel B, Hogg D, Therkildsen L (October 1978). "A two-step fibrinogen--fibrin transition in blood coagulation". Nature 275 (5680): 501–5. doi:10.1038/275501a0. PMID 692730.
- Hermans J, McDonagh J (January 1982). "Fibrin: structure and interactions". Semin. Thromb. Hemost. 8 (1): 11–24. doi:10.1055/s-2007-1005039. PMID 7036348.
- Lorand L, Credo RB; John W. Fenton; Kenneth G. Mann (1977). "hrombin and fibrin stabilization". In Mann KG, Lundblad RL, Fenton J. Chemistry and Biology of Thrombin. Ann Arbor, Mich: Ann Arbor Science Publishers. pp. 311–323. ISBN 0-250-40160-6.
- Acharya SS, Dimichele DM (November 2008). "Rare inherited disorders of fibrinogen". Haemophilia : the Official Journal of the World Federation of Hemophilia 14 (6): 1151–8. doi:10.1111/j.1365-2516.2008.01831.x. PMID 19141154.
- Lang T, Johanning K, Metzler H, Piepenbrock S, Solomon C, Rahe-Meyer N, Tanaka KA (March 2009). "The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia". Anesthesia and Analgesia 108 (3): 751–8. doi:10.1213/ane.0b013e3181966675. PMID 19224779.
- Fries D, Innerhofer P, Schobersberger W (April 2009). "Time for changing coagulation management in trauma-related massive bleeding". Current Opinion in Anaesthesiology 22 (2): 267–74. doi:10.1097/ACO.0b013e32832678d9. PMID 19390253.
- Page RC, Schroeder HE (March 1976). "Pathogenesis of inflammatory periodontal disease. A summary of current work". Lab. Invest. 34 (3): 235–49. PMID 765622.
- Salvi, Vinita (2003). Medical and Surgical Diagnostic Disorders in Pregnancy. Jaypee Brothers Publishers. p. 5. ISBN 978-81-8061-090-5.
- Jennifer McDowall/Interpro: Protein Of The Month: Fibrinogen.
- D'Eustachio/reactome: fibrinogen → fibrin monomer + 2 fibrinopeptide A + 2 fibrinopeptide B
Fibrinogen alpha/beta chain family Provide feedback
Fibrinogen is a protein involved in platelet aggregation and is essential for the coagulation of blood. This domain forms part of the central coiled coiled region of the protein which is formed from two sets of three non-identical chains (alpha, beta and gamma).
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR012290
Fibrinogen plays key roles in both blood clotting and platelet aggregation. During blood clot formation, the conversion of soluble fibrinogen to insoluble fibrin is triggered by thrombin, resulting in the polymerisation of fibrin, which forms a soft clot; this is then converted to a hard clot by factor XIIIA, which cross-links fibrin molecules. Platelet aggregation involves the binding of the platelet protein receptor integrin alpha(IIb)-beta(3) to the C-terminal D domain of fibrinogen [PUBMED:12799374]. In addition to platelet aggregation, platelet-fibrinogen interaction mediates both adhesion and fibrin clot retraction.
Fibrinogen occurs as a dimer, where each monomer is composed of three non-identical chains, alpha, beta and gamma, linked together by several disulphide bonds [PUBMED:11460466]. The N-terminals of all six chains come together to form the centre of the molecule (E domain), from which the monomers extend in opposite directions as coiled coils, followed by C-terminal globular domains (D domains). Therefore, the domain composition is: D-coil-E-coil-D. At each end, the C-terminal of the alpha chain extends beyond the D domain as a protuberance that is important for cross-linking the molecule.
During clot formation, the N-terminal fragments of the alpha and beta chains (within the E domain) in fibrinogen are cleaved by thrombin, releasing fibrinopeptides A and B, respectively, and producing fibrin. This cleavage results in the exposure of four binding sites on the E domain, each of which can bind to a D domain from different fibrin molecules. The binding of fibrin molecules produces a polymer consisting of a lattice network of fibrins that form a long, branching, flexible fibre [PUBMED:11593005, PUBMED:15837518]. Fibrin fibres interact with platelets to increase the size of the clot, as well as with several different proteins and cells, thereby promoting the inflammatory response and concentrating the cells required for wound repair at the site of damage.
This entry represents the coiled-coil domain and part of the N-terminal E domain found in all three fibrinogen polypeptides, namely the alpha, beta and gamma chains.
More information about these proteins can be found at Protein of the Month: Fibrinogen [PUBMED:].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||fibrinogen complex (GO:0005577)|
|Molecular function||protein binding, bridging (GO:0030674)|
|receptor binding (GO:0005102)|
|Biological process||protein polymerization (GO:0051258)|
|signal transduction (GO:0007165)|
|platelet activation (GO:0030168)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Seed source:||pdb_1m1j & pdb_2a45|
|Number in seed:||20|
|Number in full:||256|
|Average length of the domain:||130.80 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||29.67 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||5|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
There are 2 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fib_alpha domain has been found. There are 240 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...