ORC6 Human

Origin Recognition Complex, Subunit 6 Human Recombinant
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Cat. No.
BT2902
Source
Escherichia Coli.
Synonyms
Origin Recognition Complex Subunit 6, Origin Recognition Complex Subunit 6 Homolog-Like (Yeast), ORC6L.
Appearance
Sterile Filtered clear solution.
Purity
Greater than 90.0% as determined by SDS-PAGE.
Usage
Prospec's products are furnished for LABORATORY RESEARCH USE ONLY. They may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.
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Description

Molecular Structure of ORC6

Human ORC6 comprises three distinct domains (Figure 1):

  • N-terminal domain (HsOrc6-N): Involved in protein-protein interactions.

  • Middle domain (HsOrc6-M): Shares structural homology with transcription factor TFIIB, enabling DNA binding .

  • C-terminal domain (HsOrc6-C): Critical for interactions with ORC3 and chromatin association .

A distinct DNA-binding domain (HsOrc6-DBD) has been identified, with key residues (Q129, R137, K168) essential for DNA interaction . Mutations in these residues abolish DNA binding and reduce replication efficiency .

Table 2: ORC6 Overexpression and Cancer Outcomes

Cancer TypePrognostic Impact (High ORC6)Key Findings
LIHC (Liver)Reduced OS, DSS, PFILinked to tumor size, metastasis
GBMLGG (Brain)Shorter OS, PFIIndependent risk factor
BRCA (Breast)Poor DFI, PFICorrelates with proliferation

In vitro studies show ORC6 knockout in liver (HepG2, HCCLM3) and glioma cells reduces proliferation by 40–60% and inhibits migration .

Meier-Gorlin Syndrome

Mutations in ORC6 (e.g., Tyr232Ser) disrupt ORC3 binding, impairing pre-RC assembly and causing primordial dwarfism .

Therapeutic Potential

Targeting ORC6 may offer novel strategies for cancer treatment:

  • siRNA knockdown: Reduces tumor growth in xenograft models .

  • Small-molecule inhibitors: Potential to disrupt ORC6-DNA/MMR interactions .

Divergent Roles Across Species

SpeciesORC6 Function
DrosophilaIntegral ORC component; sequence-specific DNA binding
HumanORC-independent replication fork roles; MMR modulation
YeastPre-RC assembly; dispensable for cytokinesis

Product Specs

Introduction
ORC6, part of the origin recognition complex (ORC), is crucial for DNA replication initiation. This highly conserved six-protein complex interacts with DNA at replication start sites. Each subunit is essential for this process. Beyond replication, ORC6 participates in stress-responsive gene expression control. Its expression remains consistent throughout the cell cycle. ORC's assembly begins with a core of ORC2, ORC3, ORC4, and ORC5, followed by ORC6 and ORC1 joining.
Description
Recombinant human ORC6, produced in E. coli, is a single, non-glycosylated polypeptide chain. It comprises 275 amino acids (residues 1-252) with a molecular weight of 30.5 kDa. A 23 amino acid His-tag is fused at the N-terminus. Purification is achieved through proprietary chromatographic methods.
Physical Appearance
A clear solution, sterilized by filtration.
Formulation
The ORC6 solution (0.25 mg/ml) is buffered with 20 mM Tris-HCl (pH 8.0) and contains 0.2 M NaCl, 2 mM DTT, and 40% glycerol.
Stability
For short-term storage (up to 2-4 weeks), keep at 4°C. For extended periods, store frozen at -20°C. Adding a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Repeated freezing and thawing should be avoided.
Purity
Purity exceeds 90.0% based on SDS-PAGE analysis.
Synonyms
Origin Recognition Complex Subunit 6, Origin Recognition Complex Subunit 6 Homolog-Like (Yeast), ORC6L.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMGSELIG RLAPRLGLAE PDMLRKAEEY LRLSRVKCVG LSARTTETSS AVMCLDLAAS WMKCPLDRAY LIKLSGLNKE TYQSCLKSFE CLLGLNSNIG IRDLAVQFSC IEAVNMASKI LKSYESSLPQ TQQVDLDLSR PLFTSAALLS ACKILKLKVD KNKMVATSGV KKAIFDRLCK QLEKIGQQVD REPGDVATPP RKRKKIVVEA PAKEMEKVEE MPHKPQKDED LTQDYEEWKR KILENAASAQ KATAE

Product Science Overview

Structure and Function

ORC6 is encoded by the ORC6 gene located on chromosome 16 in humans . The protein is a part of the ORC complex that binds to origins of replication in an ATP-dependent manner . This binding is crucial for the assembly of the pre-replication complex, which is necessary to initiate DNA replication .

Role in DNA Replication

The ORC complex, including ORC6, binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins . This assembly is vital for the formation of the pre-replicative complex, which ensures that DNA replication occurs accurately and efficiently .

Cellular Localization and Interactions

During mitosis, ORC6 localizes to kinetochores and a reticular-like structure around the cell periphery . It has been shown to interact with several other proteins involved in DNA replication and cell division, including MCM5, ORC2, Replication protein A1, ORC4, DBF4, ORC3, CDC45-related protein, and MCM4 .

Biological Significance

Gene silencing studies using small interfering RNA have demonstrated that ORC6 plays an essential role in coordinating chromosome replication and segregation with cytokinesis . This coordination is crucial for maintaining genomic stability and ensuring proper cell division.

Recombinant ORC6

Human recombinant ORC6 is produced using recombinant DNA technology, which involves inserting the ORC6 gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein is used in various research applications to study its function and interactions in DNA replication and cell division.

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