Paired domain

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Structure of a typical paired domain

Identifiers
Symbol	?
Pfam	PF00292
Pfam clan
InterPro	IPR001523
SMART
PROSITE
CATH
MEROPS
SCOP2

The paired domain is a conserved protein domain found in a family of transcription factors known as the paired box (PAX) proteins. These proteins play crucial roles in the regulation of developmental processes, including organogenesis, cell differentiation, and embryogenesis. The paired domain is named after the paired gene in Drosophila melanogaster, where it was first identified.

Structure

The paired domain is approximately 128 amino acids in length and is characterized by a bipartite structure consisting of two subdomains: the N-terminal subdomain (PAI) and the C-terminal subdomain (RED). These subdomains are connected by a linker region and together form a DNA-binding domain that recognizes specific DNA sequences to regulate gene expression.

The PAI subdomain typically contains a helix-turn-helix motif, which is a common structural motif in DNA-binding proteins. The RED subdomain also contributes to DNA binding and specificity, allowing the paired domain to interact with a wide range of target sequences.

Function

Paired domain-containing proteins are involved in a variety of developmental processes. They function primarily as transcription factors, binding to specific DNA sequences to regulate the expression of target genes. This regulation is essential for proper development and differentiation of tissues and organs.

In humans, mutations in genes encoding paired domain proteins can lead to developmental disorders. For example, mutations in the PAX6 gene, which contains a paired domain, are associated with aniridia, a condition characterized by the absence of the iris in the eye.

Evolution

The paired domain is highly conserved across metazoans, indicating its fundamental role in development. It is found in a variety of organisms, from fruit flies to humans, and is a key component of the PAX gene family.

Clinical Significance

Mutations in paired domain-containing genes can result in a range of developmental disorders. For instance, PAX3 mutations are linked to Waardenburg syndrome, a genetic condition that affects pigmentation and hearing. Understanding the function and regulation of paired domain proteins is crucial for elucidating the molecular basis of these conditions.

Research Techniques

Several techniques are used to study paired domain proteins, including:

• X-ray crystallography and NMR spectroscopy for structural analysis.
• Electrophoretic mobility shift assay (EMSA) to study DNA-binding properties.
• Chromatin immunoprecipitation (ChIP) to identify target genes in vivo.

Also see

• Homeobox
• Transcription factor
• PAX genes
• Developmental biology