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P68871

- HBB_HUMAN

UniProt

P68871 - HBB_HUMAN

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Protein
Hemoglobin subunit beta
Gene
HBB
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Involved in oxygen transport from the lung to the various peripheral tissues.2 Publications
LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.2 Publications
Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei2 – 212,3-bisphosphoglycerate; via amino nitrogen
Binding sitei3 – 312,3-bisphosphoglycerate
Sitei60 – 601Not glycated
Metal bindingi64 – 641Iron (heme distal ligand)
Binding sitei83 – 8312,3-bisphosphoglycerate
Sitei83 – 831Not glycated
Metal bindingi93 – 931Iron (heme proximal ligand)
Sitei96 – 961Not glycated
Sitei142 – 1421Susceptible to oxidation; associated with variant Atlanta, variant non-spherocytic haemolytic anemia and variant Christchurch
Binding sitei144 – 14412,3-bisphosphoglycerate

GO - Molecular functioni

  1. heme binding Source: InterPro
  2. hemoglobin binding Source: UniProtKB
  3. iron ion binding Source: InterPro
  4. oxygen binding Source: UniProtKB
  5. oxygen transporter activity Source: UniProtKB
  6. protein binding Source: IntAct

GO - Biological processi

  1. bicarbonate transport Source: Reactome
  2. blood coagulation Source: Reactome
  3. hydrogen peroxide catabolic process Source: BHF-UCL
  4. nitric oxide transport Source: UniProtKB
  5. oxidation-reduction process Source: GOC
  6. oxygen transport Source: UniProtKB
  7. positive regulation of cell death Source: BHF-UCL
  8. positive regulation of nitric oxide biosynthetic process Source: UniProtKB
  9. protein heterooligomerization Source: BHF-UCL
  10. regulation of blood pressure Source: UniProtKB-KW
  11. regulation of blood vessel size Source: UniProtKB-KW
  12. renal absorption Source: UniProtKB
  13. response to hydrogen peroxide Source: BHF-UCL
  14. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hypotensive agent, Vasoactive

Keywords - Biological processi

Oxygen transport, Transport

Keywords - Ligandi

Heme, Iron, Metal-binding, Pyruvate

Enzyme and pathway databases

ReactomeiREACT_121329. Erythrocytes take up carbon dioxide and release oxygen.
REACT_121380. Erythrocytes take up oxygen and release carbon dioxide.
REACT_160163. Scavenging of heme from plasma.
REACT_24970. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
Hemoglobin subunit beta
Alternative name(s):
Beta-globin
Hemoglobin beta chain
Cleaved into the following 2 chains:
Gene namesi
Name:HBB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:4827. HBB.

Subcellular locationi

GO - Cellular componenti

  1. blood microparticle Source: UniProt
  2. cytosol Source: Reactome
  3. endocytic vesicle lumen Source: Reactome
  4. extracellular region Source: Reactome
  5. extracellular vesicular exosome Source: UniProt
  6. haptoglobin-hemoglobin complex Source: BHF-UCL
  7. hemoglobin complex Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Heinz body anemias (HEIBAN) [MIM:140700]: 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.
Note: The disease may be caused by mutations affecting the gene represented in this entry.4 Publications
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Sickle cell anemia (SKCA) [MIM:603903]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Keywords - Diseasei

Congenital dyserythropoietic anemia, Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

MIMi140700. phenotype.
141900. gene+phenotype.
603902. phenotype.
603903. phenotype.
613985. phenotype.
Orphaneti330041. Autosomal dominant methemoglobinemia.
231222. Beta-thalassemia intermedia.
231214. Beta-thalassemia major.
231237. Delta-beta-thalassemia.
231226. Dominant beta-thalassemia.
178330. Heinz body anemia.
231242. Hemoglobin C - beta-thalassemia.
2132. Hemoglobin C disease.
90039. Hemoglobin D disease.
231249. Hemoglobin E - beta-thalassemia.
2133. Hemoglobin E disease.
330032. Hemoglobin Lepore - beta-thalassemia.
46532. Hereditary persistence of fetal hemoglobin - beta-thalassemia.
251380. Hereditary persistence of fetal hemoglobin - sickle cell disease.
251359. Sickle cell - beta-thalassemia disease.
251365. Sickle cell - hemoglobin C disease.
251370. Sickle cell - hemoglobin D disease.
251375. Sickle cell - hemoglobin E disease.
232. Sickle cell anemia.
PharmGKBiPA29202.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 147146Hemoglobin subunit beta
PRO_0000052976Add
BLAST
Peptidei33 – 4210LVV-hemorphin-72 Publications
PRO_0000296641
Peptidei33 – 397Spinorphin
PRO_0000424226

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylvaline By similarity
Modified residuei2 – 21N-pyruvate 2-iminyl-valine; in Hb A1b
Glycosylationi2 – 21N-linked (Glc) (glycation); in Hb A1c1 Publication
Glycosylationi9 – 91N-linked (Glc) (glycation)1 Publication
Glycosylationi18 – 181N-linked (Glc) (glycation)1 Publication
Modified residuei60 – 601N6-acetyllysine1 Publication
Glycosylationi67 – 671N-linked (Glc) (glycation)1 Publication
Modified residuei83 – 831N6-acetyllysine1 Publication
Modified residuei94 – 941S-nitrosocysteine2 Publications
Glycosylationi121 – 1211N-linked (Glc) (glycation)1 Publication
Modified residuei145 – 1451N6-acetyllysine; alternate1 Publication
Glycosylationi145 – 1451N-linked (Glc) (glycation); alternate1 Publication

Post-translational modificationi

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.
S-nitrosylated; a nitric oxide group is first bound to Fe2+ and then transferred to Cys-94 to allow capture of O2.
Acetylated on Lys-60, Lys-83 and Lys-145 upon aspirin exposure.1 Publication

Keywords - PTMi

Acetylation, Glycation, Glycoprotein, S-nitrosylation

Proteomic databases

MaxQBiP68871.
PaxDbiP68871.
PeptideAtlasiP68871.
PRIDEiP68871.

2D gel databases

REPRODUCTION-2DPAGEIPI00654755.
P68871.
SWISS-2DPAGEP68871.
UCD-2DPAGEP02023.
P68871.

PTM databases

PhosphoSiteiP68871.

Miscellaneous databases

PMAP-CutDBP68871.

Expressioni

Tissue specificityi

Red blood cells.1 Publication

Gene expression databases

ArrayExpressiP68871.
BgeeiP68871.
GenevestigatoriP68871.

Organism-specific databases

HPAiCAB009526.
HPA043234.

Interactioni

Subunit structurei

Heterotetramer of two alpha chains and two beta chains in adult hemoglobin A (HbA). Heterotetramer of two zeta chains and two beta chains in hemoglobin Portland-2, detected in fetuses and neonates with homozygous alpha-thalassemia.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HBA2P6990520EBI-715554,EBI-714680
HBZP020082EBI-715554,EBI-719843

Protein-protein interaction databases

BioGridi109293. 19 interactions.
IntActi