Hemoglobin, alpha 2

This article is about a gene. For the similarly named Hemoglobin tetramer, HbA2, see Hemoglobin A2.

Hemoglobin, alpha 2^[5] also known as HBA2 is a gene that in humans codes for the alpha globin chain of hemoglobin.^[6][7]

HBA2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A00, 1A01, 1A0U, 1A0Z, 1A3N, 1A3O, 1A9W, 1ABW, 1ABY, 1AJ9, 1B86, 1BAB, 1BBB, 1BIJ, 1BUW, 1BZ0, 1BZ1, 1BZZ, 1C7B, 1C7C, 1C7D, 1CLS, 1CMY, 1COH, 1DKE, 1DXT, 1DXU, 1DXV, 1FDH, 1FN3, 1G9V, 1GBU, 1GBV, 1GLI, 1GZX, 1HAB, 1HAC, 1HBA, 1HBB, 1HBS, 1HCO, 1HDB, 1HGA, 1HGB, 1HGC, 1HHO, 1IRD, 1J3Y, 1J3Z, 1J40, 1J41, 1J7S, 1J7W, 1J7Y, 1JY7, 1K0Y, 1K1K, 1KD2, 1LFL, 1LFQ, 1LFT, 1LFV, 1LFY, 1LFZ, 1LJW, 1M9P, 1MKO, 1NEJ, 1NIH, 1NQP, 1O1I, 1O1J, 1O1K, 1O1L, 1O1M, 1O1N, 1O1O, 1O1P, 1QI8, 1QSH, 1QSI, 1QXD, 1QXE, 1R1X, 1R1Y, 1RPS, 1RQ3, 1RQ4, 1RQA, 1RVW, 1SDK, 1SDL, 1SHR, 1SI4, 1THB, 1UIW, 1VWT, 1XXT, 1XY0, 1XYE, 1XZ2, 1XZ4, 1XZ5, 1XZ7, 1XZU, 1XZV, 1Y01, 1Y09, 1Y0A, 1Y0C, 1Y0D, 1Y0T, 1Y0W, 1Y22, 1Y2Z, 1Y31, 1Y35, 1Y45, 1Y46, 1Y4B, 1Y4F, 1Y4G, 1Y4P, 1Y4Q, 1Y4R, 1Y4V, 1Y5F, 1Y5J, 1Y5K, 1Y7C, 1Y7D, 1Y7G, 1Y7Z, 1Y83, 1Y85, 1Y8W, 1YDZ, 1YE0, 1YE1, 1YE2, 1YEN, 1YEO, 1YEQ, 1YEU, 1YEV, 1YFF, 1YG5, 1YGD, 1YGF, 1YH9, 1YHE, 1YHR, 1YIE, 1YIH, 1YVQ, 1YVT, 1YZI, 1Z8U, 2D5Z, 2D60, 2DN1, 2DN2, 2DN3, 2DXM, 2H35, 2HBC, 2HBD, 2HBE, 2HBF, 2HBS, 2HCO, 2HHD, 2HHE, 2M6Z, 2W6V, 2W72, 2YRS, 3B75, 3D17, 3D7O, 3DUT, 3HXN, 3IA3, 3IC0, 3IC2, 3KMF, 3NL7, 3NMM, 3ODQ, 3ONZ, 3OO4, 3OO5, 3OVU, 3P5Q, 3QJB, 3QJC, 3QJD, 3QJE, 3R5I, 3S48, 3S65, 3S66, 3SZK, 3WCP, 3WHM, 4FC3, 4HHB, 4IJ2, 4L7Y, 4M4A, 4M4B, 4MQC, 4MQG, 4MQH, 4MQI, 4MQJ, 4MQK, 4N7N, 4N7O, 4N7P, 4N8T, 4NI0, 4NI1, 4ROL, 4ROM, 4WJG, 4X0L, 4XS0, 6HBW, 5E29, 5E6E, 5EE4, 5HU6, 5JDO, 5KDQ, 5E83,%%s1Y01, 1Z8U, 1BZ1
Identifiers
Aliases	HBA2, HBA-T2, HBH, Hemoglobin, alpha 2, hemoglobin subunit alpha 2, ECYT7
External IDs	OMIM: 141850; MGI: 96015; HomoloGene: 469; GeneCards: HBA2; OMA:HBA2 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.3 Start 172,876 bp[1] End 173,710 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 A4|11 18.86 cM Start 32,233,511 bp[2] End 32,234,465 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood bone marrow bone marrow cells placenta spleen apex of heart ganglionic eminence muscle of thigh olfactory zone of nasal mucosa Top expressed in bone marrow spleen lung yolk sac neural tube mesencephalon heart cerebellar cortex genital tubercle zone of skin More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding oxygen binding peroxidase activity oxygen carrier activity metal ion binding protein binding heme binding haptoglobin binding organic acid binding Cellular component cytosol endocytic vesicle lumen blood microparticle membrane extracellular region cytosolic small ribosomal subunit hemoglobin complex extracellular exosome haptoglobin-hemoglobin complex extracellular space Biological process positive regulation of cell death protein heterooligomerization oxygen transport receptor-mediated endocytosis bicarbonate transport hydrogen peroxide catabolic process response to hydrogen peroxide cellular oxidant detoxification transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3040 15122 Ensembl ENSG00000188536 ENSMUSG00000069919 UniProt P69905 Q91VB8 RefSeq (mRNA) NM_000517 NM_008218 RefSeq (protein) NP_000508 NP_000508.1 NP_000549.1 NP_001077424 Location (UCSC) Chr 16: 0.17 – 0.17 Mb Chr 11: 32.23 – 32.23 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000188536 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000069919 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "HBA2 gene: MedlinePlus Genetics".
6. Liebhaber SA, Goossens MJ, Kan YW (Dec 1980). "Cloning and complete nucleotide sequence of human 5'-alpha-globin gene". Proceedings of the National Academy of Sciences of the United States of America. 77 (12): 7054–8. Bibcode:1980PNAS...77.7054L. doi:10.1073/pnas.77.12.7054. PMC 350439. PMID 6452630.
7. Higgs DR, Vickers MA, Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (Apr 1989). "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081–104. doi:10.1182/blood.V73.5.1081.1081. PMID 2649166.
8. "Entrez Gene: HBA2 hemoglobin, alpha 2".

Further reading

• Richter F, Meurers BH, Zhu C, Medvedeva VP, Chesselet MF (Aug 2009). "Neurons express hemoglobin alpha- and beta-chains in rat and human brains". The Journal of Comparative Neurology. 515 (5): 538–47. doi:10.1002/cne.22062. PMC 3123135. PMID 19479992.
• Phylipsen M, Vogelaar IP, Schaap RA, Arkesteijn SG, Boxma GL, van Helden WC, Wildschut IC, de Bruin-Roest AC, Giordano PC, Harteveld CL (Aug 2010). "A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW))". Blood Cells, Molecules & Diseases. 45 (2): 133–5. doi:10.1016/j.bcmd.2010.05.004. PMID 20682466.
• Sessa R, Puzone S, Ammirabile M, Piscopo C, Pagano L, Colucci S, Izzo P, Grosso M (Feb 2010). "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. doi:10.1002/ajh.21591. PMID 20054848. S2CID 26190193.
• Yin XL, Zhang XH, Zhou TH, Zhang TL, Luo RG, Wang L, Zhou YL, Chen YS, Kong XJ, Liang B, He YY, Peng L, Lu LB, Fang SP, Wu ZK (2010). "Hemoglobin H disease in Guangxi province, Southern China: clinical review of 357 patients". Acta Haematologica. 124 (2): 86–91. doi:10.1159/000314058. PMID 20639625. S2CID 38841342.
• Joly P, Lacan P, Bererd M, Garcia C, Zanella-Cleon I, Becchi M, Aubry M, Couprie N, Francina A (2009). "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. doi:10.1080/03630260903058685. PMID 19657833. S2CID 26959240.
• Harteveld CL, Oosterhuis WP, Schoenmakers CH, Ananta H, Kos S, Bakker Verweij M, van Delft P, Arkesteijn SG, Phylipsen M, Giordano PC (Apr 2010). "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. doi:10.1111/j.1600-0609.2009.01380.x. PMID 19912309. S2CID 20511683.
• Kapralov A, Vlasova II, Feng W, Maeda A, Walson K, Tyurin VA, Huang Z, Aneja RK, Carcillo J, Bayir H, Kagan VE (Oct 2009). "Peroxidase activity of hemoglobin-haptoglobin complexes: covalent aggregation and oxidative stress in plasma and macrophages". The Journal of Biological Chemistry. 284 (44): 30395–407. doi:10.1074/jbc.M109.045567. PMC 2781594. PMID 19740759.
• Roy P, Bhattacharya G, Banerjee D, Chandra S, Ghosh M, Choudhuri U, Das M, Dasgupta UB (2009). "Hb Sallanches [alpha104(G11)Cys-->Tyr, TGC>TAC] occurs frequently on the Indian subcontinent". Hemoglobin. 33 (6): 486–91. doi:10.3109/03630260903336164. PMID 19958194. S2CID 22370275.
• Giardina B, Messana I, Scatena R, Castagnola M (1995). "The multiple functions of hemoglobin". Critical Reviews in Biochemistry and Molecular Biology. 30 (3): 165–96. doi:10.3109/10409239509085142. PMID 7555018.
• Higgs DR, Vickers MA, Wilkie AO, Pretorius IM, Jarman AP, Weatherall DJ (Apr 1989). "A review of the molecular genetics of the human alpha-globin gene cluster". Blood. 73 (5): 1081–104. doi:10.1182/blood.V73.5.1081.1081. PMID 2649166.
• Ribeiro DM, Sonati MF (2008). "Regulation of human alpha-globin gene expression and alpha-thalassemia". Genetics and Molecular Research. 7 (4): 1045–53. doi:10.4238/vol7-4gmr472. PMID 19048483.
• Waye JS, Eng B, Dutly F, Frischknecht H (2009). "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. doi:10.3109/03630260903333377. PMID 19958200. S2CID 41033036.
• Coelho A, Picanço I, Seuanes F, Seixas MT, Faustino P (Aug 2010). "Novel large deletions in the human alpha-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment" (PDF). Blood Cells, Molecules & Diseases. 45 (2): 147–53. doi:10.1016/j.bcmd.2010.05.010. hdl:10400.18/117. PMID 20580289.
• Sharma V, Kumar B, Kumar G, Saxena R (Oct 2009). "Alpha globin gene numbers: an important modifier of HbE/beta thalassemia". Hematology. 14 (5): 297–300. doi:10.1179/102453309X446126. PMID 19843387. S2CID 11461489.
• Turbpaiboon C, Wilairat P (2010). "Alpha-hemoglobin stabilizing protein: molecular function and clinical correlation". Frontiers in Bioscience. 15 (1): 1–11. doi:10.2741/3601. PMID 20036801.
• Voon HP, Vadolas J (Dec 2008). "Controlling alpha-globin: a review of alpha-globin expression and its impact on beta-thalassemia". Haematologica. 93 (12): 1868–76. doi:10.3324/haematol.13490. PMID 18768527.
• Giordano PC, Cnossen MH, Joosten AM, Jansen CA, Hakvoort TE, Bakker-Verweij M, Arkesteijn SG, van Delft P, Waye JS, Bouva MJ, Harteveld CL (2010). "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. doi:10.3109/03630269.2010.486341. PMID 20642333. S2CID 35413104.
• Mahdavi MR, Kowsarian M, Karami H, Mohseni A, Vahidshahi K, Roshan P, Hojjati MT, Ebrahimzadeh MA (Oct 2010). "Prevalence of hemoglobin alpha-chain gene deletion in neonates in North of Iran". European Review for Medical and Pharmacological Sciences. 14 (10): 871–5. PMID 21222374.
• Balakrishnan G, Zhao X, Podstawska E, Proniewicz LM, Kincaid JR, Spiro TG (Apr 2009). "Subunit-selective interrogation of CO recombination in carbonmonoxy hemoglobin by isotope-edited time-resolved resonance Raman spectroscopy". Biochemistry. 48 (14): 3120–6. doi:10.1021/bi802190f. PMC 2722936. PMID 19245215.
• Zhu C, Yu W, Xie J, Chen L, Ding H, Shang X, Xu X (Oct 2010). "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. 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.