Human Gene HBB (ENST00000335295.4) from GENCODE V39
Description: Homo sapiens hemoglobin subunit beta (HBB), mRNA. (from RefSeq NM_000518) RefSeq Summary (NM_000518): The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. Mutant beta globin causes sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. The order of the genes in the beta-globin cluster is 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000335295.4 Gencode Gene: ENSG00000244734.4 Transcript (Including UTRs) Position: hg38 chr11:5,225,464-5,227,071 Size: 1,608 Total Exon Count: 3 Strand: - Coding Region Position: hg38 chr11:5,225,598-5,227,021 Size: 1,424 Coding Exon Count: 3
ID:HBB_HUMAN DESCRIPTION: RecName: Full=Hemoglobin subunit beta; AltName: Full=Beta-globin; AltName: Full=Hemoglobin beta chain; Contains: RecName: Full=LVV-hemorphin-7; FUNCTION: Involved in oxygen transport from the lung to the various peripheral tissues. FUNCTION: LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure. SUBUNIT: Heterotetramer of two alpha chains and two beta chains in adult hemoglobin A (HbA). INTERACTION: P69905:HBA2; NbExp=19; IntAct=EBI-715554, EBI-714680; TISSUE SPECIFICITY: Red blood cells. PTM: Glucose reacts non-enzymatically with the N-terminus of the beta chain to form a stable ketoamine linkage. This takes place slowly and continuously throughout the 120-day life span of the red blood cell. The rate of glycation is increased in patients with diabetes mellitus. PTM: S-nitrosylated; a nitric oxide group is first bound to Fe(2+) and then transferred to Cys-94 to allow capture of O(2). PTM: Acetylated on Lys-60, Lys-83 and Lys-145 upon aspirin exposure. PubMed:16916647 reports the identification of HBB acetylated on Lys-145 in the cytosolic fraction of HeLa cells. This may have resulted from contamination of the sample. MASS SPECTROMETRY: Mass=1310; Method=FAB; Range=33-42; Source=PubMed:1575724; DISEASE: Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:140700]. This is a form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency. DISEASE: Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:613985]. A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic. DISEASE: Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:603903]; also known as sickle cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues. DISEASE: Defects in HBB are the cause of beta-thalassemia dominant inclusion body type (B-THALIB) [MIM:603902]. An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood after splenectomy. MISCELLANEOUS: One molecule of 2,3-bisphosphoglycerate can bind to two beta chains per hemoglobin tetramer. SIMILARITY: Belongs to the globin family. WEB RESOURCE: Name=HbVar; Note=Human hemoglobin variants and thalassemias; URL="http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=directlink&gene=HBB"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HBB"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=HBB"; WEB RESOURCE: Name=Wikipedia; Note=Hemoglobin entry; URL="http://en.wikipedia.org/wiki/Hemoglobin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P68871
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC007075 - Homo sapiens hemoglobin, beta, mRNA (cDNA clone MGC:14540 IMAGE:4292125), complete cds. M11428 - Human beta-globin mRNA, 3' end. M25113 - Human sickle beta-hemoglobin mRNA. HW348671 - WO 2013147320-A/20: Microarray for detection of mutations of beta-globin gene and the method for detectioning of that. LX064374 - JP 2017045451-A/20: Microarray for detection of mutations of beta-globin gene and the method for detectioning of that. V00497 - Human messenger RNA for beta-globin. AY509193 - Homo sapiens hemoglobin beta mRNA, complete cds. V00500 - Human messenger RNA for beta-globin. A18171 - Beta globin gene seq ID No:3. AF181989 - Homo sapiens hemoglobin beta subunit variant (HBB) mRNA, complete cds. AF349114 - Homo sapiens beta globin chain variant (HBB) mRNA, complete cds. AF181832 - Homo sapiens hemoglobin beta subunit variant (HBB) mRNA, partial cds. EU694432 - Homo sapiens hemoglobin beta chain variant (HBB) mRNA, HBB-Dothan allele, complete cds. AY136510 - Homo sapiens hemoglobin beta chain variant Hb S-Wake (HBB) mRNA, complete cds. AF117710 - Homo sapiens hemoglobin beta chain (HBB) mRNA, complete cds. M25079 - Human sickle cell beta-globin mRNA, complete cds. JD046448 - Sequence 27472 from Patent EP1572962. DQ893159 - Synthetic construct clone IMAGE:100005789; FLH194450.01X; RZPDo839B0680D hemoglobin, beta (HBB) gene, encodes complete protein. CR536530 - Homo sapiens full open reading frame cDNA clone RZPDo834D0222D for gene HBB, hemoglobin, beta; complete cds, incl. stopcodon. KJ896959 - Synthetic construct Homo sapiens clone ccsbBroadEn_06353 HBB gene, encodes complete protein. KR710226 - Synthetic construct Homo sapiens clone CCSBHm_00010498 HBB (HBB) mRNA, encodes complete protein. KR710227 - Synthetic construct Homo sapiens clone CCSBHm_00010525 HBB (HBB) mRNA, encodes complete protein. KR710228 - Synthetic construct Homo sapiens clone CCSBHm_00010601 HBB (HBB) mRNA, encodes complete protein. KR710229 - Synthetic construct Homo sapiens clone CCSBHm_00010626 HBB (HBB) mRNA, encodes complete protein. AK311825 - Homo sapiens cDNA, FLJ92086, Homo sapiens hemoglobin, beta (HBB), mRNA. DQ896453 - Synthetic construct Homo sapiens clone IMAGE:100010913; FLH194446.01L; RZPDo839B0670D hemoglobin, beta (HBB) gene, encodes complete protein. EU176774 - Synthetic construct Homo sapiens clone IMAGE:100011599; FLH263683.01L; RZPDo839F03256D hemoglobin, beta (HBB) gene, encodes complete protein. CR541913 - Homo sapiens full open reading frame cDNA clone RZPDo834E0633D for gene HBB, hemoglobin, beta; complete cds, without stopcodon. AM392537 - Synthetic construct Homo sapiens clone IMAGE:100002184 for hypothetical protein (HBB gene). AM393351 - Synthetic construct Homo sapiens clone IMAGE:100002185 for hypothetical protein (HBB gene). JC506088 - Sequence 107 from Patent EP2733219. JC506717 - Sequence 85 from Patent EP2733220. JC737512 - Sequence 107 from Patent WO2014075911. JC737829 - Sequence 85 from Patent WO2014075939. JC506939 - Sequence 307 from Patent EP2733220. JC738051 - Sequence 307 from Patent WO2014075939. LP986374 - Sequence 12 from Patent EP3201339. MA014034 - JP 2017536338-A/12: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT. CU675537 - Synthetic construct Homo sapiens gateway clone IMAGE:100016702 5' read HBB mRNA. DQ655983 - Homo sapiens clone Affy08248A01, mRNA sequence. JD027508 - Sequence 8532 from Patent EP1572962. M14574 - Human beta-globin gene mRNA precursor, 5' end. LP986372 - Sequence 10 from Patent EP3201339. MA014032 - JP 2017536338-A/10: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ahspPathway - Hemoglobin's Chaperone
Reactome (by CSHL, EBI, and GO)
Protein P68871 (Reactome details) participates in the following event(s):
R-HSA-2168884 Ferriheme is transferred from Methemoglobin to Hemopexin R-HSA-6798745 Exocytosis of tertiary granule lumen proteins R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-6806831 CYB5Rs reduce MetHb to HbA R-HSA-1237325 Hemoglobin A is protonated and carbamated causing release of oxygen R-HSA-1247668 Hemoglobin A binds oxygen and releases protons and carbon dioxide R-HSA-2168885 Haptoglobin binds Hemoglobin R-HSA-2168889 Haptoglobin-related Protein binds Hemoglobin R-HSA-2168883 Haptoglobin:Hemoglobin binds CD163 R-HSA-983231 Factors involved in megakaryocyte development and platelet production R-HSA-109582 Hemostasis R-HSA-2168880 Scavenging of heme from plasma R-HSA-6798695 Neutrophil degranulation R-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen R-HSA-1247673 Erythrocytes take up oxygen and release carbon dioxide R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors R-HSA-168249 Innate Immune System R-HSA-1480926 O2/CO2 exchange in erythrocytes R-HSA-5653656 Vesicle-mediated transport R-HSA-168256 Immune System R-HSA-382551 Transport of small molecules
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