alphaglobin

Alpha-globin, also called the alpha chain, is a primary component of hemoglobin, the oxygen-carrying protein in red blood cells. Each hemoglobin molecule in adults contains two alpha-globin and two beta-globin subunits. The alpha-globin chains play a crucial structural and functional role in binding and delivering oxygen.

In the human genome, the alpha-globin genes HBA1 and HBA2 encode the mature alpha-globin protein. They are located on chromosome 16 within the alpha-globin gene cluster, together with the zeta-globin gene. HBA1 and HBA2 are highly similar, differing by only a few nucleotides, and each gene contains three exons and two introns.

The mature alpha-globin chain is approximately 141 amino acids long and folds into a helix-rich structure that surrounds a heme group. A proximal histidine residue anchors the iron atom of heme, enabling reversible oxygen binding alongside the beta-globin chain in HbA.

Expression of alpha-globin occurs in erythroid cells throughout development. The alpha-globin genes are regulated by erythroid-specific transcription factors, and their expression complements the gamma-globin and beta-globin genes to produce adult hemoglobin HbA, as well as fetal hemoglobin HbF and other developmental forms.

Mutations or deletions involving HBA1 or HBA2 lead to alpha-thalassemia, a hemoglobinopathy characterized by reduced alpha-globin production and imbalanced globin chains. Severity ranges from trait to hydrops fetalis, depending on the number and nature of affected alleles. Alpha-globin genes also serve as models in studies of gene regulation and globin switching.