Biology:Hemoglobin, alpha 2

Short description: Mammalian protein found in Homo sapiens

Generic protein structure example

Hemoglobin, alpha 2 also known as HBA2 is a gene that in humans codes for the alpha globin chain of hemoglobin.

Function

The human alpha globin gene cluster is located on chromosome 16 and spans about 30 kb, including seven alpha like globin genes and pseudogenes: 5'- HBZ - HBZP1 - HBM - HBAP1 - HBA2 - HBA1 - HBQ1 -3'. The HBA2 (α₂) and HBA1 (α₁) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions.

Protein

Two alpha chains plus two beta chains constitute HbA, which in normal adult life accounts for about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin), composed of alpha and gamma chains, make up the remaining 3% of adult hemoglobin.

Clinical significance

Alpha-thalassemias most commonly result from deletions of any of the four alpha alleles, although some alpha thalassemias have been reported that are due to mutations other than deletion. Deletion of 1 or 2 alleles is clinically silent. Deletion of 3 alleles causes HbH disease, resulting in anemia and hepatosplenomegaly. Deletion of all 4 alleles is lethal because it renders the body unable to make fetal hemoglobin (HbF), adult hemoglobin (HbA) or adult variant hemoglobin (HbA2), and results in hydrops fetalis.

Further reading

• "Neurons express hemoglobin alpha- and beta-chains in rat and human brains". The Journal of Comparative Neurology 515 (5): 538–47. Aug 2009. doi:10.1002/cne.22062. PMID 19479992. 
• "A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW))". Blood Cells, Molecules & Diseases 45 (2): 133–5. Aug 2010. doi:10.1016/j.bcmd.2010.05.004. PMID 20682466. 
• "Identification and molecular characterization of the --CAMPANIA deletion, a novel alpha (0) -thalassemic defect, in two unrelated Italian families [corrected]". American Journal of Hematology 85 (2): 143–4. Feb 2010. doi:10.1002/ajh.21591. PMID 20054848. 
• "Hemoglobin H disease in Guangxi province, Southern China: clinical review of 357 patients". Acta Haematologica 124 (2): 86–91. 2010. doi:10.1159/000314058. PMID 20639625. 
• "Description of two new alpha variants: Hb Canuts [alpha85(F6)Asp-->His (alpha1)] and Hb Ambroise Pare [alpha117(GH5)Phe-->Ile (alpha2)]; two new beta variants: Hb Beaujolais [beta84(EF8)Thr-->Asn] and Hb Monplaisir [beta147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)] and one new delta variant: Hb (A2)North Africa [delta59(E3)Lys-->Met]". Hemoglobin 33 (3): 196–205. 2009. doi:10.1080/03630260903058685. PMID 19657833. 
• "alpha-thalassaemia masked by beta gene defects and a new polyadenylation site mutation on the alpha2-globin gene". European Journal of Haematology 84 (4): 354–8. Apr 2010. doi:10.1111/j.1600-0609.2009.01380.x. PMID 19912309. 
• "Peroxidase activity of hemoglobin-haptoglobin complexes: covalent aggregation and oxidative stress in plasma and macrophages". The Journal of Biological Chemistry 284 (44): 30395–407. Oct 2009. doi:10.1074/jbc.M109.045567. PMID 19740759. 
• "Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC] occurs frequently on the Indian subcontinent". Hemoglobin 33 (6): 486–91. 2009. doi:10.3109/03630260903336164. PMID 19958194. 
• "The multiple functions of hemoglobin". Critical Reviews in Biochemistry and Molecular Biology 30 (3): 165–96. 1995. doi:10.3109/10409239509085142. PMID 7555018. 
• "A review of the molecular genetics of the human alpha-globin gene cluster". Blood 73 (5): 1081–104. Apr 1989. doi:10.1182/blood.V73.5.1081.1081. PMID 2649166. 
• "Regulation of human alpha-globin gene expression and alpha-thalassemia". Genetics and Molecular Research 7 (4): 1045–53. 2008. doi:10.4238/vol7-4gmr472. PMID 19048483. 
• "alpha-Thalassemia caused by two novel splice mutations of the alpha2-globin gene: IVS-I-1 (G>A and G>T)". Hemoglobin 33 (6): 519–22. 2009. doi:10.3109/03630260903333377. PMID 19958200. 
• "Novel large deletions in the human alpha-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment". Blood Cells, Molecules & Diseases 45 (2): 147–53. Aug 2010. doi:10.1016/j.bcmd.2010.05.010. PMID 20580289. http://repositorio.insa.pt/bitstream/10400.18/117/1/Novel%20large%20deletions%20in%20the%20human.pdf. 
• "Alpha globin gene numbers: an important modifier of HbE/beta thalassemia". Hematology 14 (5): 297–300. Oct 2009. doi:10.1179/102453309X446126. PMID 19843387. 
• "Alpha-hemoglobin stabilizing protein: molecular function and clinical correlation". Frontiers in Bioscience 15 (1): 1–11. 2010. doi:10.2741/3601. PMID 20036801. 
• "Controlling alpha-globin: a review of alpha-globin expression and its impact on beta-thalassemia". Haematologica 93 (12): 1868–76. Dec 2008. doi:10.3324/haematol.13490. PMID 18768527. 
• "Codon 24 (TAT>TAG) and codon 32 (ATG>AGG) (Hb Rotterdam): two novel alpha2 gene mutations associated with mild alpha-thalassemia found in the same family after newborn screening". Hemoglobin 34 (4): 354–65. 2010. doi:10.3109/03630269.2010.486341. PMID 20642333. 
• "Prevalence of hemoglobin alpha-chain gene deletion in neonates in North of Iran". European Review for Medical and Pharmacological Sciences 14 (10): 871–5. Oct 2010. PMID 21222374. 
• "Subunit-selective interrogation of CO recombination in carbonmonoxy hemoglobin by isotope-edited time-resolved resonance Raman spectroscopy". Biochemistry 48 (14): 3120–6. Apr 2009. doi:10.1021/bi802190f. PMID 19245215. 
• "Hemoglobin H disease due to a de novo mutation at the α2-globin gene and an inherited common α-thalassemia deletion found in a Chinese boy". Blood Cells, Molecules & Diseases 45 (3): 223–6. Oct 2010. doi:10.1016/j.bcmd.2010.07.005. PMID 20691621. 

External links

• GeneReviews/NCBI/NIH/UW entry on Alpha-Thalassemia
• OMIM entries on Alpha-Thalassemia

This article incorporates text from the United States National Library of Medicine, which is in the public domain.