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Updated: Jul 18, 2026

Molecular Evolution of the Tre Recombinase
Published on: May 29, 2008
Molecular evolution of the transferrin receptor/glutamate carboxypeptidase II family
Lisa Ann Lambert1, Stacey L Mitchell
1Department of Biology, Chatham College, Woodland Road, Pittsburgh, PA 15232, USA. lambert@chatham.edu
Insights
This study identifies conserved residues in the transferrin receptor (TfR) family across species. Evolutionary analysis reveals gene duplications, suggesting a mechanism for the expansion of these essential iron uptake proteins.
Area of Science:
- * Molecular Biology and Evolutionary Genetics
- * Cellular Biology and Biochemistry
Background:
- * The transferrin receptor (TfR) family comprises at least seven homologous proteins in primates, crucial for iron uptake.
- * Transferrin receptor 1 (TfR1) is a type II membrane glycoprotein involved in iron transport.
- * Other family members include TfR2, glutamate carboxypeptidase II (GCP2), and related proteins.
Purpose of the Study:
- * To compare sequences within the TfR/GCP2 family across diverse species.
- * To identify conserved residues and understand the evolutionary history of this gene family.
Main Methods:
- * Comparative sequence analysis of 86 homologous sequences from 24 species (mammals to fungi).
- * Phylogenetic analysis to reconstruct the evolutionary history of the TfR/GCP2 family.
Main Results:
- * Identification of several highly conserved residues specific to each family member, not previously linked to clinical mutations.
- * Evolutionary history indicates repeated gene duplication events within the TfR/GCP2 family.
- * Findings support theories on gene family expansion from slowly evolving, non-essential genes.
Conclusions:
- * The TfR/GCP2 family has undergone significant evolutionary diversification through gene duplication.
- * Conserved residues identified may offer new insights into protein function and potential clinical relevance.
- * Evolutionary patterns provide a framework for understanding the development of multigene families.
Abstract:
The transferrin receptor family is represented by at least seven different homologous proteins in primates. Transferrin receptor (TfR1) is a type II membrane glycoprotein that, as a cell surface homodimer, binds iron-loaded transferrin as part of the process of iron transfer and uptake. Other family members include transferrin receptor 2 (TfR2), glutamate carboxypeptidase II (GCP2 or PSMA), N-acetylated alpha-linked acidic dipeptidase-like protein (NLDL), N-acetylated alpha-linked acidic dipeptidase 2 (NAALAD2), and prostate-specific membrane antigen-like protein (PMSAL/GCPIII). We compared 86 different sequences from 24 different species, from mammals to fungi. Through this comparison, we have identified several highly conserved residues specific to each family not previously associated with clinical mutations. The evolutionary history of the TfR/GCP2 family shows repeated episodes of duplications consistent with recent theories that nondispensable, slowly evolving genes are more likely to form multiple gene families.
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