RAB18 Human

RAB18, Member RAS Oncogene Family Human Recombinant
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Cat. No.
BT7202
Source
E.coli.
Synonyms
RAB18 member RAS oncogene family, RAB18LI1, WARBM3, RAB18 small GTPase, ras-related protein Rab-18.
Appearance
Sterile Filtered colorless solution.
Purity
Greater than 90% as determined by SDS-PAGE.
Usage
THE BioTek's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.
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Description

Vesicle Trafficking and Autophagy

  • Regulates vesicle transport between ER, Golgi, and lipid droplets (LDs) .

  • Facilitates autophagy by promoting lysosomal degradation of cellular debris .

Lipid Droplet Dynamics

  • LD growth: Tethers ER to LDs via the Rab18-NRZ-SNARE complex, enabling lipid transfer for LD expansion .

    • Rab18-deficient cells show 88% fewer mature LDs and increased supersized LDs due to impaired lipid transfer .

  • Lipid metabolism: Modulates triacylglycerol (TAG) synthesis and storage .

Table 2: Impact of Rab18 Depletion on Lipid Droplets

ParameterWild-Type CellsRab18-Deficient Cells
Mature LDs per cell938 ± 105117 ± 13
Supersized LDs (>2 µm)RareIncreased 8-fold
TAG synthesis rateNormalReduced by 40%

ER Organization

  • Maintains ER tubule integrity; loss of Rab18 disrupts ER morphology and increases ER stress .

Cell Migration and Focal Adhesion Dynamics

  • Promotes directional cell migration by regulating ER transport to focal adhesions (FAs) .

  • Silencing Rab18 reduces FA assembly rate by 2.4-fold and increases disassembly rate by 3-fold .

Warburg Micro Syndrome

  • Cause: Loss-of-function mutations in RAB18 (e.g., nonsense, frameshift) .

  • Symptoms:

    • Severe intellectual disability, vision loss, hypogonadotropic hypogonadism .

    • ER fragmentation and neuronal migration defects .

Table 3: Reported RAB18 Mutations in Warburg Micro Syndrome

Mutation TypeClinical PhenotypeReferences
c.565C>T (p.Arg189*)Early-onset cataracts, microcephaly
c.2T>C (p.Met1?)Severe motor delay, cortical blindness

Metabolic Disorders

  • Obesity: Rab18 mRNA levels correlate with adiposity in humans, particularly in omental adipose tissue .

  • Insulin resistance: Rab18 mediates insulin-stimulated lipogenesis in adipocytes .

Sex- and Depot-Specific Expression

  • Adipose tissue: Higher Rab18 expression in subcutaneous vs. omental fat in obese males .

  • Sex differences: Females exhibit higher baseline Rab18 levels in omental fat .

Table 4: Rab18 mRNA Levels in Human Adipose Tissue

GroupSubcutaneous (copies/ng RNA)Omental (copies/ng RNA)
Lean males2.1 × 10³1.5 × 10³
Obese males (BMI >48)4.8 × 10³3.2 × 10³
Lean females3.0 × 10³2.7 × 10³

Future Directions

  • Therapeutic targeting: Modulating Rab18 activity could address lipid storage disorders or ER stress-related pathologies.

  • Mechanistic studies: Elucidate Rab18’s role in neuronal migration and autophagy .

Product Specs

Introduction
RAB18, a member of the Ras superfamily of small GTPases, is localized to the cytoplasmic side of the cell membrane. This protein plays a crucial role in various cellular processes, including apical recycling, endocytosis, and protein trafficking between early endosomes and the plasma membrane.
Description
Recombinant human RAB18, expressed in E. coli, is a non-glycosylated polypeptide chain consisting of 221 amino acids (residues 1-206) with a molecular weight of 24.5 kDa. This protein is engineered with a 15-amino acid His-tag at the N-terminus to facilitate purification using proprietary chromatographic methods.
Physical Appearance
Clear, colorless solution, sterile filtered.
Formulation
The RAB18 protein is provided as a 1 mg/ml solution in 20 mM Tris-HCl buffer (pH 7.5) containing 1 mM DTT.
Stability
For short-term storage (up to 2-4 weeks), keep refrigerated at 4°C. For extended periods, store the protein frozen at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Repeated freezing and thawing should be avoided.
Purity
Purity is determined to be greater than 90% as assessed by SDS-PAGE analysis.
Synonyms
RAB18 member RAS oncogene family, RAB18LI1, WARBM3, RAB18 small GTPase, ras-related protein Rab-18.
Source
E.coli.
Amino Acid Sequence
MASMTGGQQM GRGSHMDEDV LTTLKILIIG ESGVGKSSLL LRFTDDTFDP ELAATIGVDF KVKTISVDGN KAKLAIWDTA GQERFRTLTP SYYRGAQGVI LVYDVTRRDT FVKLDNWLNE LETYCTRNDI VNMLVGNKID KENREVDRNE GLKFARKHSM LFIEASAKTC DGVQCAFEEL VEKIIQTPGL WESENQNKGV KLSHREEGQG GGACGGYCSV L

Product Science Overview

Introduction

RAB18 is a gene that encodes a protein belonging to the Rab family of small GTPases. These proteins are key regulators of intracellular membrane trafficking, which includes the formation, movement, and fusion of transport vesicles within cells . The RAB18 protein is involved in various cellular processes, including vesicle trafficking, lipid droplet formation, and maintaining endoplasmic reticulum structure .

Gene and Protein Structure

The RAB18 gene is located on chromosome 10 in humans . It produces a protein that is ubiquitously expressed, with particularly high expression levels in the brain . The protein encoded by RAB18 cycles between an inactive GDP-bound form and an active GTP-bound form, which allows it to recruit different sets of downstream effectors responsible for vesicle formation, movement, tethering, and fusion .

Functions and Pathways

RAB18 plays a crucial role in several cellular functions:

  • Vesicle Trafficking: RAB18 regulates the movement of proteins and other molecules within cells by controlling vesicle trafficking .
  • Lipid Droplet Formation: It is required for the localization of ZFYVE1 to lipid droplets and mediates the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts .
  • Endoplasmic Reticulum Structure: RAB18 is essential for maintaining the structure of the endoplasmic reticulum .
  • Eye and Brain Development: It plays a key role in the development of the eye and brain, and its dysfunction is associated with neurodegeneration .
Associated Diseases

Mutations in the RAB18 gene are linked to Warburg Micro Syndrome, a rare genetic disorder characterized by developmental abnormalities of the eye and brain . This syndrome is caused by disruptions in the function of RAB18, which affects vesicle trafficking and other cellular processes .

Research and Clinical Implications

Research on RAB18 has provided insights into its role in cellular processes and its association with diseases. Understanding the function of RAB18 and its pathways can help in developing therapeutic strategies for conditions like Warburg Micro Syndrome .

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