HBA1 and α-thalassemia
This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
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Interactions of HBA1 with other proteins

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This interaction network was generated by String.

Interactions are shown with HBB, which encodes the β-chain of hemoglobin.  Additionally, an interaction is shown with HBE1, which is an epsilon(ε)-globin.  Two
ε-globin chains form a heterotetramer with two α-globin chains to produce an embryonic form of hemoglobin [1].

ERAF is also annotated as AHSP, or alpha hemoglobin stabilizing protein.  Its role is illustrated in the diagram below.  It functions as a chaperone to aid in the proper assembly of normal hemoglobin A (HbA) heterotetramers [2].

GATA1 is a transcription factor that binds to the HS-40 regulatory region upstream of the α-globin gene cluster [3].  GATA1 can be seen activating transcription in the diagram below.

The other proteins on the interaction map have less significant interactions with HBA1.


Interestingly, attempting to find interactions using Osprey software yielded no interacting proteins for HBA1.  The String data may therefore be more up-to-date or thorough.


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Hemoglobin assembly in red blood cells. Adapted from BioCarta [2,4,5].
This schematic shows the role of GATA1 in activating the transcription of the α- and β-globin genes, as well as AHSP (or ERAF).  It also illustrates the role of AHSP/ERAF in the assembly of hemoglobin tetramers, and how improper assembly may lead to either α- or β-thalassemia.

References
  1. Embryonic hemoglobin: sequence of the epsilon and zeta chains. Clegg J.B. Tex. Rep. Biol. Med. 40:23-28, 1981. (PubMed)
  2. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Kihm A.J., Kong Y., Hong W., Russell J.E., Rouda S., Adachi K., Simon M.C., Blobel G.A., Weiss M.J. Nature 417:758-763, 2002. (PubMed)
  3. Structure and evolution of a human erythroid transcription factor. Trainor C.D., Evans T., Felsenfeld G., Boguski M.S. Nature 343:92-96, 1990. (PubMed)
  4. Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein. Gell D, Kong Y, Eaton SA, Weiss MJ, Mackay JP. J Biol Chem. 2002 Oct 25;277(43):40602-9. (PubMed)
  5. Luzzatto L, Notaro R. Haemoglobins chaperone. Nature. 2002 Jun 13;417(6890):703-5. (PubMed)
  6. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, von Mering C. Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8. Epub 2010 Nov 2. (PubMed)