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Related Concept Videos

Ankle Joint01:10

Ankle Joint

The ankle is formed by the talocrural joint (crural = leg). It consists of the articulations between the talus bone of the foot and the distal ends of the tibia and fibula of the leg. The superior aspect of the talus bone is square-shaped and has three areas of articulation. The top of the talus articulates with the inferior tibia. This is the portion of the ankle joint that carries the body weight between the leg and foot. The sides of the talus are firmly held in position by the articulations...
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The tibia is the main weight-bearing bone of the lower leg. It is larger than the fibula with which it is paired. The tibia is also the second longest bone in the body and is located right below the skin. The proximal end of the tibia forms the medial and the lateral condyle, which articulates with the condyles of the femur to form the knee joint. Between the articulating surfaces is the irregular elevated area known as the intercondylar eminence that serves as the inferior attachment point for...
Convergent Evolution01:54

Convergent Evolution

Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
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Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
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Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...

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Updated: May 17, 2026

A Mouse Model of Ankle-Subtalar Complex Joint Instability
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Published on: October 28, 2022

Sequence and structural alignments reveal insights into ANKLE2 evolution and function.

Adam T Fishburn1, Cole J Florio1, Chase L S Skawinski2

  • 1Department of Microbiology and Molecular Genetics, University of California, Davis, California, USA.

Protein Science : a Publication of the Protein Society
|May 16, 2026
PubMed
Summary
This summary is machine-generated.

The ANKLE2 protein, involved in cell division and development, has evolved unique domains. Structural analysis reveals conserved core domains and suggests new functions, linking ANKLE2 loss to DNA damage response.

Keywords:
ANKLE2AlphaFoldLEM‐domainankyrin repeat domainevolutionsequence alignmentstructural prediction

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Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Cell Biology

Background:

  • ANKLE2 protein plays roles in cell division, development, and viral replication.
  • ANKLE2 possesses conserved ankyrin repeat and LEM domains, alongside less understood structured domains.
  • Evolutionary analysis of ANKLE2 orthologs is crucial for understanding its diverse functions.

Purpose of the Study:

  • To investigate the evolutionary trajectory and functional roles of ANKLE2 protein domains.
  • To elucidate the structural conservation and potential functions of ANKLE2's uncharacterized domains.
  • To correlate ANKLE2's function with cellular processes like DNA damage response.

Main Methods:

  • Sequence and structural alignments of ANKLE2 orthologs.
  • Identification of conserved structural domains and potential functional motifs.
  • Experimental validation of domain functions and correlation with DNA damage response.

Main Results:

  • The transmembrane domain of ANKLE2 likely evolved recently, coinciding with the loss of VAPA interaction.
  • ANKLE2's ankyrin repeat and LEM domains show high structural conservation across orthologs.
  • Uncharacterized domains share structural similarities with nucleases/nucleic acid-binding proteins but lack key functional motifs; ANKLE2 loss impacts DNA damage response and micronuclei formation.

Conclusions:

  • ANKLE2's structural evolution reveals conserved core domains and recently acquired features.
  • Despite structural similarities, ANKLE2's uncharacterized domains do not possess nuclease or nucleic acid-binding activity.
  • ANKLE2 plays a role in maintaining genomic stability, as evidenced by its impact on DNA damage response and micronuclei formation.