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 >  Protein>GFR alpha-like >GFA-H52H3

Human GFR alpha-like Protein, His Tag (MALS verified)

分子别名(Synonym)

GFR alpha like,GFR alpha-like,GFRAL,GRAL

表达区间及表达系统(Source)

Human GFR alpha-like, His Tag (GFA-H52H3) is expressed from human 293 cells (HEK293). It contains AA Ser 19 - Glu 351 (Accession # Q6UXV0-1).

Predicted N-terminus: Ser 19

Request for sequence

蛋白结构(Molecular Characterization)

GFR alpha-like Structure

This protein carries a polyhistidine tag at the C-terminus.

The protein has a calculated MW of 39.7 kDa. The protein migrates as 43-60 kDa when calibrated against Star Ribbon Pre-stained Protein Marker under reducing (R) condition (SDS-PAGE) due to glycosylation.

内毒素(Endotoxin)

Less than 1.0 EU per μg by the LAL method.

纯度(Purity)

>95% as determined by SDS-PAGE.

>90% as determined by SEC-MALS.

制剂(Formulation)

Lyophilized from 0.22 μm filtered solution in PBS, pH7.4 with trehalose as protectant.

Contact us for customized product form or formulation.

重构方法(Reconstitution)

Please see Certificate of Analysis for specific instructions.

For best performance, we strongly recommend you to follow the reconstitution protocol provided in the CoA.

存储(Storage)

For long term storage, the product should be stored at lyophilized state at -20°C or lower.

Please avoid repeated freeze-thaw cycles.

This product is stable after storage at:

  1. -20°C to -70°C for 12 months in lyophilized state;
  2. -70°C for 3 months under sterile conditions after reconstitution.

质量管理控制体系(QMS)

  1. 质量管理体系(ISO, GMP)
  2. 质量优势
  3. 质控流程
 

电泳(SDS-PAGE)

GFR alpha-like SDS-PAGE

Human GFR alpha-like, His Tag on SDS-PAGE under reducing (R) condition. The gel was stained with Coomassie Blue. The purity of the protein is greater than 95% (With Star Ribbon Pre-stained Protein Marker).

SEC-MALS

GFR alpha-like SEC-MALS

The purity of Human GFR alpha-like, His Tag (Cat. No. GFA-H52H3) is more than 90% and the molecular weight of this protein is around 44-66 kDa verified by SEC-MALS.

Report

 

活性(Bioactivity)-ELISA

GFR alpha-like ELISA

Immobilized Human GDF-15, Fc Tag (Cat. No. GD5-H5269) at 5 μg/mL (100 μL/well) can bind Human GFR alpha-like, His Tag (Cat. No. GFA-H52H3) with a linear range of 0.02-0.313 μg/mL (QC tested).

Protocol

 
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背景(Background)

GFR alpha-like is also known as GDNF family receptor alpha-like, GFRAL, C6orf144, UNQ9356, PRO34128. Growth differentiation factor-15 (GDF15) is a circulating protein that has been implicated in multiple biological processes, including energy homeostasis, body weight regulation, and cachexia driven by cancer and chronic disease. GDNF family receptor α-like (GFRAL) was recently identified as the neuronal brainstem receptor responsible for mediating the anorectic actions of GDF15. Brainstem-restricted receptor for GDF15 which regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses . Upon interaction with its ligand, GDF15, interacts with RET and induces cellular signaling through activation of MAPK- and AKT- signaling pathways.

 

前沿进展

The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Emmerson, Wang, Du et al
Nat Med (2017) 23 (10), 1215-1219
Abstract: Growth/differentiation factor 15 (GDF15), also known as MIC-1, is a distant member of the transforming growth factor-β (TGF-β) superfamily and has been implicated in various biological functions, including cancer cachexia, renal and heart failure, atherosclerosis and metabolism. A connection between GDF15 and body-weight regulation was initially suggested on the basis of an observation that increasing GDF15 levels in serum correlated with weight loss in individuals with advanced prostate cancer. In animal models, overexpression of GDF15 leads to a lean phenotype, hypophagia and other improvements in metabolic parameters, suggesting that recombinant GDF15 protein could potentially be used in the treatment of obesity and type 2 diabetes. However, the signaling and mechanism of action of GDF15 are poorly understood owing to the absence of a clearly identified cognate receptor. Here we report that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15. GFRAL binds to GDF15 in vitro and is required for the metabolic actions of GDF15 with respect to body weight and food intake in vivo in mice. Gfral-/- mice were refractory to the effects of recombinant human GDF15 on body-weight, food-intake and glucose parameters. Blocking the interaction between GDF15 and GFRAL with a monoclonal antibody prevented the metabolic effects of GDF15 in rats. Gfral mRNA is highly expressed in the area postrema of mouse, rat and monkey, in accordance with previous reports implicating this region of the brain in the metabolic actions of GDF15 (refs. 4,5,6). Together, our data demonstrate that GFRAL is a receptor for GDF15 that mediates the metabolic effects of GDF15.
Loss of neurturin in frog--comparative genomics study of GDNF family ligand-receptor pairs
Hätinen, Holm, Airaksinen
Mol Cell Neurosci (2007) 34 (2), 155-67
Abstract: Four different GDNF family ligand (GFL)-receptor (GFRalpha) binding pairs exist in mammals, and they all signal via the RET receptor tyrosine kinase. However, the evolution of these molecules is poorly understood. We identified orthologs of all four GFRalpha receptors and GRAL (GDNF Receptor Alpha-Like) in all vertebrate classes, and a predicted GFR-like protein in several invertebrates. In addition, Gas1 (growth arrest-specific 1), a distant member of the GFR-superfamily, is present in both vertebrates and invertebrates. Analysis of exon structures suggests a common origin of GFR-superfamily proteins and early divergence of Gas1 from the common ancestor. Bony fishes have orthologs of all four mammalian GFLs, consistent with genome duplications in early vertebrates. Surprisingly, the clawed frog and chicken have only three GFLs: synteny analysis indicates loss of neurturin in frog and of persephin in chicken. Evolutionary trace analysis and protein structure homology modeling points at GDNF as the endogenous ligand of frog GFRalpha2.
Evolution of the GDNF family ligands and receptors
Airaksinen, Holm, Hätinen
Brain Behav Evol (2006) 68 (3), 181-90
Abstract: Four different ligand-receptor binding pairs of the GDNF (glial cell line-derived neurotrophic factor) family exist in mammals, and they all signal via the transmembrane RET receptor tyrosine kinase. In addition, GRAL (GDNF Receptor Alpha-Like) protein of unknown function and Gas1 (growth arrest specific 1) have GDNF family receptor (GFR)-like domains. Orthologs of the four GFRalpha receptors, GRAL and Gas1 are present in all vertebrate classes. In contrast, although bony fishes have orthologs of all four GDNF family ligands (GFLs), one of the ligands, neurturin, is absent in clawed frog and another, persephin, is absent in the chicken genome. Frog GFRalpha2 has selectively evolved possibly to accommodate GDNF as a ligand. The key role of GDNF and its receptor GFRalpha1 in enteric nervous system development is conserved from zebrafish to humans. The role of neurturin, signaling via GFRalpha2, for parasympathetic neuron development is conserved between chicken and mice. The role of artemin and persephin that signal via GFRalpha3 and GFRalpha4, respectively, is unknown in non-mammals. The presence of RET- and GFR-like genes in insects suggests that a ProtoGFR and a ProtoRET arose early in the evolution of bilaterian animals, but when the ProtoGFL diverged from existing transforming growth factor (TGFbeta)-like proteins remains unclear. The four GFLs and GFRalphas were presumably generated by genome duplications at the origin of vertebrates. Loss of neurturin in frog and persephin in chicken suggests functional redundancy in early tetrapods. Functions of non-mammalian GFLs and prechordate RET and GFR-like proteins remain to be explored.
Showing 1-3 of 3 papers.
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GFR alpha-like靶点信息
英文全称:GDNF family receptor alpha-like
中文全称:
种类:Homo sapiens
上市药物数量:0详情
临床药物数量:1详情
最高研发阶段:临床一期
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