ALKBH - alkB homolog | Elisa - Clia - Antibody - Protein

Background:

ALKBH, short for alkB homolog, refers to a family of proteins that are involved in DNA repair processes. The name "alkB homolog" comes from the fact that these proteins are homologous to the E. coli protein alkB, which is known for its ability to repair DNA damage caused by alkylating agents. In humans, there are nine known ALKBH proteins: ALKBH1 through ALKBH8 and ALKBH9. These proteins play various roles in DNA repair, RNA modification, and other cellular processes. For example, ALKBH2 and ALKBH3 are involved in repairing DNA damage caused by alkylating agents, while ALKBH5 and ALKBH8 are implicated in RNA demethylation.

Protein Structure:

• Domains: ALKBH proteins generally contain a conserved Fe(II)- and 2-oxoglutarate-dependent oxygenase domain, which is responsible for their catalytic activity.
• Active Site: The active site typically coordinates an iron ion and binds alpha-ketoglutarate, facilitating the oxidative demethylation of substrates.

Classification and Subtypes:

• Members: The ALKBH family includes several members, such as ALKBH1, ALKBH2, ALKBH3, and others, each with distinct substrate specificities and biological functions.
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• Paralogs: These proteins are paralogs, meaning they evolved from a common ancestral gene and have diverged to acquire specific functions.

Function and Biological Significance:

• DNA Repair: ALKBH2 and ALKBH3 are directly involved in DNA repair. They remove alkyl lesions from DNA, specifically demethylating 1-methyladenine and 3-methylcytosine residues, thus protecting the genome from damage induced by alkylating agents.
• RNA Modification: ALKBH5 and some other family members are involved in RNA demethylation. For example, ALKBH5 demethylates N6-methyladenosine (m6A) in mRNA, which influences mRNA stability, splicing, and translation.
• Cellular Processes: By maintaining the integrity of DNA and RNA, ALKBH proteins play essential roles in various cellular processes, including gene expression regulation, cell cycle control, and response to environmental stress.

Interactions:

• Protein Partners: ALKBH proteins interact with various other proteins involved in DNA repair, RNA metabolism, and chromatin remodeling. These interactions are crucial for their function and regulation.
• DNA/RNA Substrates: ALKBH proteins recognize and bind to specific nucleic acid substrates, allowing them to precisely target and modify damaged or modified bases.

Clinical Issues:

• Cancer: Dysregulation of ALKBH proteins has been linked to cancer. For instance, overexpression of ALKBH3 has been observed in certain cancers, including prostate cancer, where it may contribute to tumorigenesis by promoting genome stability and cell survival.
• Genetic Disorders: Mutations in genes encoding ALKBH proteins can lead to genetic disorders associated with defects in DNA repair and RNA metabolism, though specific conditions linked to ALKBH mutations are still under investigation.
• Therapeutic Potential: Targeting ALKBH proteins, particularly those involved in cancer-related pathways, holds potential for therapeutic intervention. Inhibitors of ALKBH enzymes are being explored as possible treatments for cancers with specific ALKBH dependencies.

Summary:

The ALKBH family comprises alpha-ketoglutarate-dependent dioxygenases involved in critical DNA and RNA metabolic processes. These proteins play a pivotal role in repairing alkylated DNA lesions and modifying RNA, ensuring genomic stability and proper gene expression. Given their involvement in cancer and other diseases, ALKBH proteins are of significant interest for understanding disease mechanisms and developing targeted therapies. Further research into their specific functions, interactions, and regulatory mechanisms will provide deeper insights into their roles in health and disease.