HBB
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 6HBW,1A00,1A01,1A0U,1A0Z,1A3N,1A3O,1ABW,1ABY,1AJ9,1B86,1BAB,1BBB,1BIJ,1BUW,1BZ0,1BZ1,1BZZ,1C7B,1C7C,1C7D,1CBL,1CBM,1CH4,1CLS,1CMY,1COH,1DKE,1DXT,1DXU,1DXV,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,1THB,1UIW,1VWT,1XXT,1XY0,1XYE,1XZ2,1XZ4,1XZ5,1XZ7,1XZU,1XZV,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,2D5Z,2D60,2DN1,2DN2,2DN3,2DXM,2H35,2HBC,2HBD,2HBE,2HBF,2HBS,2HCO,2HHD,2HHE,2M6Z,2W6V,2W72,2YRS,3B75,3D17,3D7O,3DUT,3HXN,3IC0,3IC2,3KMF,3NL7,3NMM,3ODQ,3ONZ,3OO4,3OO5,3P5Q,3QJB,3QJC,3QJD,3QJE,3R5I,3S65,3S66,3SZK,3W4U,3WCP,3WHM,4FC3,4HHB,4IJ2,4L7Y,4M4A,4M4B,4MQC,4MQG,4MQH,4MQI,4N7N,4N7O,4N7P,4N8T,4NI0,4NI1,4ROL,4ROM,4WJG,4X0L,4XS0,5E29,5E6E,5EE4,5HU6,5JDO,5KDQ,5E83
Identifiers
Aliases	HBB, CD113t-C, beta-globin, hemoglobin subunit beta, ECYT6
External IDs	OMIM:141900;MGI:5474850;HomoloGene:68066;GeneCards:HBB;OMA:HBB - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.4 Start 5,225,464bp[1] End 5,229,395bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 E3|7 Start 103,461,731bp[2] End 103,463,203bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone vena cava periodontal fiber monocyte bone marrow triceps brachii muscle Skeletal muscle tissue of biceps brachii bone marrow cells glutes blood Top expressed in bone marrow spleen neural tube heart lung ganglionic eminence ventricular zone Mesencephalon esophagus zone of skin More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding oxygen binding oxygen carrier activity peroxidase activity metal ion binding hemoglobin binding protein binding heme binding haptoglobin binding Cellular component cytosol endocytic vesicle lumen blood microparticle extracellular region hemoglobin complex extracellular exosome haptoglobin-hemoglobin complex tertiary granule lumen ficolin-1-rich granule lumen extracellular space Biological process positive regulation of cell death protein heterooligomerization nitric oxide transport positive regulation of nitric oxide biosynthetic process oxygen transport blood coagulation receptor-mediated endocytosis regulation of blood pressure bicarbonate transport hydrogen peroxide catabolic process platelet aggregation response to hydrogen peroxide renal absorption cellular oxidant detoxification neutrophil degranulation transport Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 3043 101488143 Ensembl ENSG00000244734 ENSMUSG00000073940 UniProt P68871 P02088 RefSeq (mRNA) NM_000518 NM_008220 RefSeq (protein) NP_000509 NP_032246 NP_001188320 NP_001265090 Location (UCSC) Chr 11: 5.23 – 5.23 Mb Chr 7: 103.46 – 103.46 Mb PubMed search [3] [4]
Wikidata
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Hemoglobin subunit beta (beta globin,β-globin,haemoglobin beta,hemoglobin beta) is aglobinprotein, coded for by theHBB gene, which along with alpha globin (HBA), makes up the most common form ofhaemoglobin in adult humans,hemoglobin A (HbA).^[5] It is 147 amino acids long and has a molecular weight of 15,867Da. Normal adult human HbA is aheterotetramer consisting of two alpha chains and two beta chains.

β-globin is encoded by theHBB gene onhuman chromosome 11. Mutations in the gene produce several variants of the proteins which are implicated with genetic disorders such assickle-cell disease andbeta thalassemia, as well as beneficial traits such asgenetic resistance to malaria.^[6][7] At least 50 disease-causing mutations in this gene have been discovered.^[8]

Beta-globin is produced by the geneHBB which is located in the multigene locus ofβ-globin locus onchromosome 11, specifically on the short arm position 15.4.Expression of beta globin and the neighbouring globins in the β-globin locus is controlled by singlelocus control region (LCR), the most important regulatory element in the locus located upstream of the globin genes.^[9] The normal allelic variant is 1600base pairs (bp) long and contains threeexons. The order of the genes in the beta-globin cluster is 5' -epsilon –gamma-G –gamma-A –delta – beta - 3'.^[5]

Beta-globininteracts withalpha-globin to form haemoglobin A, the major haemoglobin in adult humans.^[10][11] The interaction is two-fold. First, one β-globin molecule and one α-globin molecule combine by electrostatic attraction to form adimer.^[12] Secondly, two dimers combine to form the four-chaintetramer, and this becomes the functional haemoglobin.^[13]

Beta thalassemia is an inherited genetic mutation in one (Beta thalassemia minor) or both (Beta thalassemia major) of the Beta globin alleles on chromosome 11. The mutant alleles are subdivided into two groups: β0, in which no functional β-globin is made, and β+, in which a small amount of normal β-globin protein is produced. Beta thalassemia minor occurs when an individual inherits one normal Beta allele and one abnormal Beta allele (either β0, or β+). Beta thalassemia minor results in a mild microcytic anemia that is often asymptomatic or may cause fatigue and or pale skin. Beta thalassemia major occurs when a person inherits two abnormal alleles. This can be either two β+ alleles, two β0 alleles, or one of each. Beta thalassemia major is a severe medical condition. A severe anemia is seen starting at 6 months of age. Without medical treatment death often occurs before age 12.^[14] Beta thalassemia major can be treated by lifelongblood transfusions orbone marrow transplantation.^[15][16]

More than a thousand naturally occurringHBB variants have been discovered. The most common is HbS, which causessickle cell disease. HbS is produced by apoint mutation inHBB in which thecodon GAG is replaced by GTG. This results in the replacement of hydrophilic amino acidglutamic acid with the hydrophobic amino acidvaline at the seventh position (β6Glu→Val). 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 of HbS molecules into rigid fibers, causing "sickling" of the entirered blood cells in thehomozygous (HbS/HbS) condition.^[17] The homozygous allele has become one of the deadliest genetic factors,^[18] whereas people heterozygous for the mutant allele (HbS/HbA) are resistant tomalaria and develop minimal effects of the anaemia.^[19]

Sickle cell disease is closely related to another mutant haemoglobin calledhaemoglobin C (HbC), because they can be inherited together.^[20] HbC mutation is at the same position in HbS, but glutamic acid is replaced bylysine (β6Glu→Lys). The mutation is particularly prevalent in West African populations. HbC provides near full protection againstPlasmodium falciparumin homozygous (CC) individuals and intermediate protection in heterozygous (AC) individuals.^[21] This indicates that HbC has stronger influence than HbS, and is predicted to replace HbS in malaria-endemic regions.^[22]

Another point mutation in HBB, in which glutamic acid is replaced with lysine at position 26 (β26Glu→Lys), leads to the formation ofhaemoglobin E (HbE).^[23] HbE has a very unstable α- and β-globin association. Even though the unstable protein itself has mild effect, inherited with HbS and thalassemia traits, it turns into a life-threatening form of β-thalassemia. The mutation is of relatively recent origin suggesting that it resulted from selective pressure against severe falciparum malaria, as heterozygous allele prevents the development of malaria.^[24]

Malaria due toPlasmodium falciparum is a major selective factor inhuman evolution.^[7][25] It has influenced mutations inHBB in various degrees resulting in the existence of numerous HBB variants. Some of these mutations are not directly lethal and instead confer resistance to malaria, particularly in parts of the world where malaria is epidemic.^[26][27] For example, there is evidence that the sickle cell mutation, common in people of African descent, provides a degree of resistance to severe malaria.^[28] Thus, HBB mutations are the sources of positive selection in these regions and are important for their long-term survival.^[6][29] Such selection markers are important for tracing human ancestry anddiversification from Africa.^[30]

• Hemoglobin subunit alpha
• Human β-globin locus

• Overview of all the structural information available in thePDB forUniProt:P68871 (Human Hemoglobin subunit beta) at thePDBe-KB.
• Overview of all the structural information available in thePDB forUniProt:P02088 (Mouse Hemoglobin subunit beta-1) at thePDBe-KB.

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• Genes on human chromosome 11
• Hemoglobins

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