HBB

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Hemoglobin, beta

HBB structure based on PyMOL rendering of PDB 1a00
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsHBB ; CD113t-C; beta-globin
External IDsOMIM141900 MGI96022 HomoloGene68066 ChEMBL: 4331 GeneCards: HBB Gene
Orthologs
SpeciesHumanMouse
Entrez304315129
EnsemblENSG00000244734ENSMUSG00000052305
UniProtP68871P02088
RefSeq (mRNA)NM_000518NM_008220
RefSeq (protein)NP_000509NP_032246
Location (UCSC)Chr 11:
5.25 – 5.25 Mb
Chr 7:
103.81 – 103.81 Mb
PubMed search[1][2]
 
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Hemoglobin, beta

HBB structure based on PyMOL rendering of PDB 1a00
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsHBB ; CD113t-C; beta-globin
External IDsOMIM141900 MGI96022 HomoloGene68066 ChEMBL: 4331 GeneCards: HBB Gene
Orthologs
SpeciesHumanMouse
Entrez304315129
EnsemblENSG00000244734ENSMUSG00000052305
UniProtP68871P02088
RefSeq (mRNA)NM_000518NM_008220
RefSeq (protein)NP_000509NP_032246
Location (UCSC)Chr 11:
5.25 – 5.25 Mb
Chr 7:
103.81 – 103.81 Mb
PubMed search[1][2]

Beta globin (HBB, β-globin or haemoglobin, beta or preferably haemoglobin subunit beta) is a globin protein, which along with alpha globin (HBA), makes up the most common form of hemoglobin in adult humans, the HbA.[1] It is 146 amino acids long and has a molecular weight of 15,867 Da. Normal adult human HbA is a heterotetramer consisting of two alpha chains and two beta chains.

Gene locus[edit]

HBB protein is produced by the gene HBB which is located in the multigene locus of β-globin locus on chromosome 11, specifically on the short arm position 15.5. Expression of beta globin and the neighboring globins in the β-globin locus is controlled by single locus control region (LCR), the most important regulatory element in the locus located upstream of the globin genes.[2] The normal allelic variant is 1600 base pairs (bp) long and contains three exons. The order of the genes in the beta-globin cluster is 5' - epsilongamma-Ggamma-Adeltabeta - 3'.[1]

Genetic Disorder and Disease linkage[edit]

More than a thousand of naturally occurring HBB variants have been discovered, of which HbS is the most common that causes sickle-cell anemia. HbS is produced by a point mutation in HBB in which the codon GAG is replaced by GTG. This results in the replacement of hydrophilic amino acid glutamic acid with the hydrophobic amino acid valine at the sixth position. This substitution creates a hydrophobic spot on the outside of the protein that sticks to the hydrophobic region of an adjacent hemoglobin molecule's beta chain. This further causes clumping HbS molecules into rigid fibers causes the "sickling" of the entire red blood cells in homozygous (HbS/HbS) condition, hence the disease called sickle cell anemia.[3] Remarkably, under heterozygous condition of the mutant gene (HbS/HbA), people acquire resistance to malaria while still developing minimal effects of the anemia.[4]

Total absence of HBB causes beta-zero-thalassemia. Reduced amounts of detectable HBB causes beta-plus-thalassemia.[1]

Interactions[edit]

HBB has been shown to interact with Hemoglobin, alpha 1.[5][6]

See also[edit]

References[edit]

  1. ^ a b c "Entrez Gene: HBB hemoglobin, beta". 
  2. ^ Levings PP, Bungert J (March 2002). "The human beta-globin locus control region". Eur. J. Biochem. 269 (6): 1589–99. doi:10.1046/j.1432-1327.2002.02797.x. PMID 11895428. 
  3. ^ Thom CS, Dickson CF, Gell DA, Weiss MJ (2013). "Hemoglobin variants: biochemical properties and clinical correlates". Cold Spring Harb Perspect Med 3 (3): a011858. doi:10.1101/cshperspect.a011858. PMID 23388674. 
  4. ^ Luzzatto L (2012). "Sickle cell anaemia and malaria". Mediterr J Hematol Infect Dis 4 (1): e2012065. doi:10.4084/MJHID.2012.065. PMC 3499995. PMID 23170194. 
  5. ^ Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–968. doi:10.1016/j.cell.2005.08.029. PMID 16169070. 
  6. ^ Shaanan, B (Nov 1983). "Structure of human oxyhaemoglobin at 2.1 A resolution". J. Mol. Biol. (ENGLAND) 171 (1): 31–59. doi:10.1016/S0022-2836(83)80313-1. ISSN 0022-2836. PMID 6644819. 

Further reading[edit]

  • Higgs DR, Vickers MA, Wilkie AO, et al. (1989). "A review of the molecular genetics of the human alpha-globin gene cluster.". Blood 73 (5): 1081–104. PMID 2649166. 
  • Giardina B, Messana I, Scatena R, Castagnola M (1995). "The multiple functions of hemoglobin.". Crit. Rev. Biochem. Mol. Biol. 30 (3): 165–96. doi:10.3109/10409239509085142. PMID 7555018. 
  • Salzano AM, Carbone V, Pagano L, et al. (2002). "Hb Vila Real [beta36(C2)Pro-->His] in Italy: characterization of the amino acid substitution and the DNA mutation.". Hemoglobin 26 (1): 21–31. doi:10.1081/HEM-120002937. PMID 11939509. 
  • Frischknecht H, Dutly F (2007). "A 65 bp duplication/insertion in exon II of the beta globin gene causing beta0-thalassemia.". Haematologica 92 (3): 423–4. doi:10.3324/haematol.10785. PMID 17339197.