DCTN6 Human

Dynactin 6 Human Recombinant
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Description

Intracellular Transport

  • Dynactin Complex: DCTN6 forms a heterodimer with DCTN5 (p25), stabilizing the pointed-end complex critical for dynein-mediated retrograde transport .

  • Cargo Specificity: Interacts with reticulon 3 (RTN3) to regulate tubular endoplasmic reticulum (ER) trafficking in axons. Deficiencies impair ER dynamics, leading to dystrophic neurites in aging brains .

Mitotic Regulation

  • Kinetochore Targeting: Phosphorylation at Thr-186 recruits polo-like kinase 1 (Plk1) to kinetochores, facilitating chromosome alignment and anaphase onset .

  • Spindle Integrity: Unlike dynein/dynactin depletion, DCTN6 loss does not disrupt spindle formation but delays metaphase progression .

Neurodegenerative Disorders

  • Alzheimer’s Disease (AD):

    • DCTN6 interacts with RTN3’s N-terminal domain to prevent abnormal ER clustering. Hippocampal DCTN6 levels decline with age, exacerbating RTN3 aggregation and dystrophic neurite formation in transgenic mice .

    • Key data:

      ParameterWT MiceDCTN6-Deficient Mice
      RTN3 Protein LevelsBaseline1.8-fold increase
      RIDN FormationRareHippocampus-specific

Cancer Biology

  • Hepatocellular Carcinoma (HCC):

    • DCTN6 mRNA is downregulated in HCC tissues (-1.626-fold, P = 6.35E-04), contrasting with upregulated DCTN1/DCTN2/DCTN4 .

    • Prognostic relevance: Reduced DCTN6 correlates with advanced tumor stages (Table 1).

DCTN SubunitFold Change (HCC vs. Normal)P-value
DCTN1+1.5230.001
DCTN2+1.6812.15E-11
DCTN6-1.6266.35E-04

Interaction Network and Partners

DCTN6 collaborates with multiple proteins to regulate dynein activity (STRING database) :

Interaction PartnerFunctionScore
DCTN1 (p150)Dynein tethering to microtubules; enhances processivity0.999
ACTR1A (α-centractin)Microtubule-based vesicle motility0.999
DYNC1H1Cytoplasmic dynein motor for organelle transport0.991
RTN3Tubular ER trafficking; linked to Alzheimer’s pathologyN/A

Pathological Implications and Therapeutic Insights

  • Aging Brain: Hippocampal DCTN6 deficiency accelerates ER-derived dystrophic neurites, suggesting a protective role against age-related cognitive decline .

  • Cancer: While most dynactin subunits are oncogenic, DCTN6’s tumor-suppressive potential in HCC warrants further exploration .

Product Specs

Introduction
Dynactin 6, also known as DCTN6, is a protein belonging to the dynactin subunits 5/6 family. This protein is characterized by an RGD (Arg-Gly-Asp) motif located in its N-terminal region, which is known to contribute to the adhesive properties of large proteins like fibronectin. DCTN6 shares significant sequence similarity with its mouse counterpart, which has been implicated in the process of mitochondrial biogenesis. However, the precise biological function of DCTN6 remains to be fully elucidated.
Description
Recombinant human DCTN6, produced in E. coli, is a single, non-glycosylated polypeptide chain consisting of 213 amino acids (specifically, amino acids 1 to 190). It has a molecular mass of 23.1 kDa. The protein is engineered with a 23 amino acid His-tag fused to its N-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A clear, colorless solution that has been sterilized by filtration.
Formulation
The DCTN6 protein is supplied in a solution with a concentration of 1 mg/ml. The solution also contains Phosphate Buffered Saline (pH 7.4) and 10% glycerol.
Stability
For short-term storage (up to 2-4 weeks), the product can be stored at 4°C. For extended storage, it is recommended to freeze the product at -20°C. To further enhance stability during long-term storage, the addition of a carrier protein (0.1% HSA or BSA) is advisable. It is important to avoid repeated cycles of freezing and thawing.
Purity
The purity of the DCTN6 protein is greater than 85.0%, as determined by SDS-PAGE analysis.
Synonyms
Dynactin 6, WS3, Dynactin Subunit P27, Protein WS-3, P27, Novel RGD-Containing Protein, Dynactin Subunit 6, WS-3, Dynactin subunit 6.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMAEKTQK SVKIAPGAVV CVESEIRGDV TIGPRTVIHP KARIIAEAGP IVIGEGNLIE EQALIINAYP DNITPDTEDP EPKPMIIGTN NVFEVGCYSQ AMKMGDNNVI ESKAYVGRNV ILTSGCIIGA CCNLNTFEVI PENTVIYGAD CLRRVQTERP QPQTLQLDFL MKILPNYHHL KKTMKGSSTP VKN.

Product Science Overview

Introduction

Dynactin 6, also known as DCTN6, is a protein-coding gene that plays a crucial role in cellular processes. It is a subunit of the dynactin complex, which is essential for the function of the molecular motor protein dynein. Dynein is responsible for minus-end directed transport along microtubules, a critical aspect of intracellular motility.

Structure and Function

The protein encoded by the DCTN6 gene contains an RGD (Arg-Gly-Asp) motif in the N-terminal region. This motif confers adhesive properties to macromolecular proteins like fibronectin . Dynactin 6 shares a high degree of sequence similarity with its mouse homolog, which has been suggested to play a role in mitochondrial biogenesis .

Dynactin 6 is part of the dynactin complex that activates dynein for ultra-processive transport along microtubules . This complex is essential for various cellular processes, including the transport of organelles, vesicles, and other cargoes within the cell.

Biological Significance

The dynactin complex, including Dynactin 6, is vital for the proper functioning of dynein. Dynein-dynactin complexes are fast and processive motors that move along microtubules in cells . These complexes are involved in the organization, positioning, and motility of organelles, mRNA, and proteins within the cell .

Clinical Relevance

Mutations or dysregulation of the DCTN6 gene can lead to various diseases. For example, diseases associated with DCTN6 include Arthrogryposis, Distal, Type 1B, and Intellectual Developmental Disorder, Autosomal Recessive 24 . Understanding the function and regulation of Dynactin 6 is crucial for developing potential therapeutic strategies for these conditions.

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