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1 Citations 17 Q&As
Facts about Growth arrest-specific protein 6.
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Human | |
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Gene Name: | GAS6 |
Uniprot: | Q14393 |
Entrez: | 2621 |
Belongs to: |
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No superfamily |
AXLLG; AXLLGAXL stimulatory factor; AXSFAXL receptor tyrosine kinase ligand; DKFZp666G247; FLJ34709; Gas6; GAS-6; growth arrest-specific 6; growth arrest-specific protein 6
Mass (kDA):
74.925 kDA
Human | |
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Location: | 13q34 |
Sequence: | 13; NC_000013.11 (113820549..113864076, complement) |
Plasma. Isoform 1 and isoform 2 are widely expressed, isoform 1 being expressed at higher levels than isoform 2 in most tissues. Isoform 2 is the predominant form in spleen.
Secreted.
Protein S has been found to be a target for treatments against fibrosis. Even though Gas6 shares a great deal of structural homology with this protein, it is most effective as a biomarker in research. We'll go over its benefits and possible uses. For more information, visit Boster Bio Best Uses Of The GAS6 Marker. Check it out! These are some examples and suggestions to help you get the most out of this gene.
The over-activation of fibroblasts can lead to the deposition of extracellular matrix elements, which cause organ cirrhosis and other complications. A variety of novel antifibrotic drugs based on proteins have shown promise for treating these conditions. These drugs are not suitable for human consumption since they require repeated parenteral administration over a lengthy period of time. Biodegradable polymeric microspheres can be used for long-term delivery.
We designed a 3-D model to determine whether Boster Bio GAS6 shares high homology in structure with protein S. We used the Molecular Assoc. Group's Look 3.5 homology modeling program. To minimize the structure and to explore possible interactions with SP we also employed TRIPOS Sybyl. This 3-D structure is highly refined.
The structure of Gas6 reveals a g-carboxyl-serine-binding domain (Glam). This Gla domain is extremely conserved among vitamin K-dependent proteins. The Gla domain of Gas6 is conserved across species and has shown significant conservation in pairwise analysis of Gla-containing proteins. PS was predicted to be associated with the protein through two identical interfaces.
In addition to the TAM receptor, Gas6 has another TAM receptor-independent function in blood coagulation. It interacts with three tyrosine kinase receptors (TAMs) and releases a soluble form. The soluble form acts as a decoy receptor by diminishing the transmembrane receptors. The g-carboxylation of Gas6 proteins is necessary for activation of TAM receptors.
Both LG1 (and LG2) contain an calcium binding site as well as numerous water molecules. Although the interface between these domains is not obvious There is a Phe471/Pro671 packing pocket at C terminus. The LG2-Gas6–LG structures also show a large-sized Cys283, which forms a disulfide link with Cys570.
Both molecules are closely connected. Gas6 is more similar to MERTK in both its structure and functional characteristics. Both axl and MerTK are PS sensors. The presence of PS ligands is a prerequisite for activation of Tyro3 and Mertk. Although the two proteins have structural similarities however their binding properties to ligands are very different.
Although the Gas6-LG structure doesn't provide the full picture of the Gas6 complex, it gives an important first glimpse of the mechanisms through which RTKs attach to their targets. It is still important to understand the mechanism through which RTKs interact with gas6 to achieve desired biological effects. This study provides a solid basis for minimal Gas6Axl complex structures.
Studies have shown that Gas6 has been linked to a range of illnesses. These include systemic Lupus Erythematosus, Rheumatoid arthritis, and Sjogren's syndrome. The interaction is also implicated in regulating the function of platelets, controlling phagocytosis and turning off inflammation. These results suggest that gas6 and mertk could be biomarkers of inflammatory diseases.
Although Gas6 and MERTK are not yet known to play a role in AD myelin deposition however, it has been proven that they facilitate the migration of microglia to damaged tissues and facilitate the elimination of debris. Mertk is also implicated in activation of microglia. Mertk-/ mice demonstrated diminished remyelination after withdrawal of cuprizone. In addition, higher Gas6 levels in AD patients were associated with higher cognitive scores.
The Gas6-LG fragment contains domains LG1 and LG2. The L-g–gl–G–gl–G–gl–G last disulfide-bonded loop in the EG tandem. It is composed of residues 261-277. The LG1 domain interacts with residues E54 and E64 on one surface, while the PS2 molecule interacts with E55 and E74 on the other side.
PMID: 8336730 by Manfioletti G., et al. The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.
PMID: 15108283 by Munoz X., et al. Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke.
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