FGL1
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Fibrinogen-like protein 1 (FGL-1) is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that is structurally related to
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
. In humans, FGL-1 is encoded by the ''FGL1''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. It is classified as a
hepatokine Hepatokines (Greek ''heapto-'', liver; and ''-kinos'', movement) are proteins produced by liver cells (hepatocytes) that are Secretion, secreted into the Circulatory system, circulation and function as hormones across the organism. Research is most ...
. Four splice variants exist for this gene.


Function

Fibrinogen-like protein 1 is a member of the fibrinogen family of proteins, which also includes fibrinogen, fibrinogen-like protein 2, and clotting factors V, VIII, and
XIII XIII may refer to: * 13 (number) or XIII in Roman numerals * 13th century in Roman numerals * ''XIII'' (comics), a Belgian comic book series by Jean Van Hamme and William Vance ** ''XIII'' (2003 video game), a 2003 video game based on the comic b ...
. FGL-1 is homologous to the
carboxy terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
of the fibrinogen
beta Beta (, ; uppercase , lowercase , or cursive ; or ) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Ancient Greek, beta represented the voiced bilabial plosive . In Modern Greek, it represe ...
- and
gamma Gamma (; uppercase , lowercase ; ) is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter normally repr ...
- subunits which contains the four conserved
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
s of that are common to all members of the fibrinogen family. However, FGL-1 lacks the platelet-binding site, cross-linking region, and
thrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
-sensitive site which allow the other members of the fibrinogen family to aid in
fibrin Fibrin (also called Factor Ia) is a fibrous protein, fibrous, non-globular protein involved in the Coagulation, clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerization, polymerize. ...
clot formation. FGL-1 has also been observed to strongly bind to and activate
LAG-3 Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the ''LAG3'' gene. LAG3, which was discovered in 1990 and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Diffe ...
, a regulatory protein expressed on
T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...
. As LAG-3 has an important role in controlling activated T cells, manipulating FGL-1 binding to T cells has been proposed for both
cancer immunotherapy Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the basic research, fundamental research of cancer im ...
and
anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
treatments.


Clinical significance

FGL-1 may play a role in the development of
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...
s.


References


Further reading

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