Reviewed,
UniProtKB/Swiss-Prot P69905 (HBA_HUMAN)
Last modified
November 25, 2008.
Version 65.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Hemoglobin subunit alpha Alternative name(s): Hemoglobin alpha chain Alpha-globin | |||||
| Gene names |
| |||||
| Organism | Homo sapiens (Human) | |||||
| Taxonomic identifier | 9606 [NCBI] | |||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 142 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in oxygen transport from the lung to the various peripheral tissues. |
| Subunit structure | Heterotetramer of two alpha chains and two beta chains in adult hemoglobin A (HbA); two alpha chains and two delta chains in adult hemoglobin A2 (HbA2); two alpha chains and two epsilon chains in early embryonic hemoglobin Gower-2; two alpha chains and two gamma chains in fetal hemoglobin F (HbF). |
| Tissue specificity | Red blood cells. |
| Post-translational modification | The initiator Met is not cleaved in variant Thionville and is acetylated. |
| Involvement in disease | Defects in HBA1/HBA2 may be a cause of Heinz body anemias [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. Defects in HBA1/HBA2 are the cause of alpha-thalassemia [MIM:141800, 604131]. The thalassemias are the most common monogenic diseases and occur mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of three alpha genes results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia known as hemoglobin H disease. Untreated, most patients die in childhood or early adolescence. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). The thalassemic phenotype is due to unstable globin alpha chains that are rapidly catabolized prior to formation of the alpha-beta heterotetramers. Alpha(0)-thalassemia is associated with nonimmune hydrops fetalis [MIM:236750]. Hydrops fetalis is a generalized edema of the fetus with fluid accumulation in the body cavities. |
| Miscellaneous | Gives blood its red color. |
| Sequence similarities | Belongs to the globin family. |
Ontologies
Keywords | |
|---|---|
| Biological process | Oxygen transport Transport |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Ligand | Heme Iron Metal-binding |
| PTM | Acetylation Glycation Glycoprotein Phosphoprotein |
| Technical term | 3D-structure Direct protein sequencing |
Gene Ontology (GO) | |
| Biological process | oxygen transport Traceable author statement. Source: UniProtKB |
| Cellular component | hemoglobin complex Traceable author statement. Source: UniProtKB |
| Molecular function | heme binding Inferred from electronic annotation. Source: InterPro iron ion bindingInferred from electronic annotation. Source: InterPro oxygen bindingInferred from electronic annotation. Source: InterPro oxygen transporter activityInferred from electronic annotation. Source: UniProtKB-KW protein bindingInferred from physical interaction. Source: UniProtKB |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| AHSP | Q9NZD4 | 1 | EBI-714680,EBI-720250 | |
| HBB | P68871 | 1 | EBI-714680,EBI-715554 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 142 | 141 | Hemoglobin subunit alpha | PRO_0000052653 | |||||
Sites | |||||||||
| Metal binding | 59 | 1 | Iron (heme distal ligand) | ||||||
| Metal binding | 88 | 1 | Iron (heme proximal ligand) | ||||||
| Site | 12 | 1 | Not glycated | ||||||
| Site | 57 | 1 | Not glycated | ||||||
| Site | 61 | 1 | Not glycated | ||||||
| Site | 91 | 1 | Not glycated | ||||||
| Site | 100 | 1 | Not glycated | ||||||
Amino acid modifications | |||||||||
| Modified residue | 25 | 1 | Phosphotyrosine | ||||||
| Modified residue | 43 | 1 | Phosphotyrosine | ||||||
| Glycosylation | 8 | 1 | N-linked (Glc) (glycation) | ||||||
| Glycosylation | 17 | 1 | N-linked (Glc) (glycation) | ||||||
| Glycosylation | 41 | 1 | N-linked (Glc) (glycation) | ||||||
| Glycosylation | 62 | 1 | N-linked (Glc) (glycation) | ||||||
Natural variations | |||||||||
| Natural variant | 2 | 1 | V → E in Thionville; O(2) affinity down. | VAR_002719 | |||||
| Natural variant | 3 | 1 | L → R in ChongQing; O(2) affinity up. | VAR_002720 | |||||
| Natural variant | 6 | 1 | A → D in J-Toronto. | VAR_002721 | |||||
| Natural variant | 6 | 1 | A → P in Karachi. | VAR_002722 | |||||
| Natural variant | 7 | 1 | D → A in Sawara; O(2) affinity up. | VAR_002723 | |||||
| Natural variant | 7 | 1 | D → G in Swan River. | VAR_002724 | |||||
| Natural variant | 7 | 1 | D → N in Dunn; O(2) affinity up. | VAR_002725 | |||||
| Natural variant | 7 | 1 | D → V in Ferndown; O(2) affinity up. | VAR_002726 | |||||
| Natural variant | 7 | 1 | D → Y in Woodville; O(2) affinity up. | VAR_002727 | |||||
| Natural variant | 8 | 1 | K → E in Kurosaki. | VAR_002728 | |||||
| Natural variant | 10 | 1 | N → T in Broomfield. | VAR_038149 | |||||
| Natural variant | 11 | 1 | V → F: dbSNP rs1799896. | VAR_014605 | |||||
| Natural variant | 12 | 1 | K → E in Anantharaj. | VAR_002729 | |||||
| Natural variant | 13 | 1 | A → D in J-Paris 1/J-Aljezur. | VAR_002730 | |||||
| Natural variant | 14 | 1 | A → P in Ravenscourt Park; causes alpha-thalassemia. | VAR_038150 | |||||
| Natural variant | 15 | 1 | W → R in Evanston; O(2) affinity up. | VAR_002731 | |||||
| Natural variant | 16 | 1 | G → R in Ottawa/Siam. | VAR_002732 | |||||
| Natural variant | 17 | 1 | K → M in Harbin; slightly unstable. | VAR_002733 | |||||
| Natural variant | 17 | 1 | K → N in Beijing. | VAR_002734 | |||||
| Natural variant | 19 | 1 | G → D in Al-Ain Abu Dhabi. | VAR_002735 | |||||
| Natural variant | 19 | 1 | G → R in Handsworth. | VAR_002736 | |||||
| Natural variant | 20 | 1 | A → D in J-Kurosh. | VAR_002737 | |||||
| Natural variant | 20 | 1 | A → E in J-Tashikuergan. | VAR_002738 | |||||
| Natural variant | 21 | 1 | H → Q in Le Lamentin. | VAR_002739 | |||||
| Natural variant | 21 | 1 | H → R in Hobart. | VAR_002740 | |||||
| Natural variant | 22 | 1 | A → D in J-Nyanza. | VAR_002741 | |||||
| Natural variant | 22 | 1 | A → P in Fontainebleau. | VAR_002742 | |||||
| Natural variant | 23 | 1 | G → D in J-Medellin. | VAR_002743 | |||||
| Natural variant | 24 | 1 | E → G in Reims; slightly unstable. | VAR_002744 | |||||
| Natural variant | 24 | 1 | E → K in Chad. | VAR_002745 | |||||
| Natural variant | 25 | 1 | Y → H in Luxembourg; unstable. | VAR_002746 | |||||
| Natural variant | 27 | 1 | A → E in Shenyang; unstable. | VAR_002747 | |||||
| Natural variant | 27 | 1 | A → V in Campinas. | VAR_025387 | |||||
| Natural variant | 28 | 1 | E → D in Hekinan. | VAR_002748 | |||||
| Natural variant | 28 | 1 | E → G in Fort Worth. | VAR_002749 | |||||
| Natural variant | 28 | 1 | E → V in Spanish town. | VAR_002750 | |||||
| Natural variant | 31 | 1 | E → K in O-Padova. | VAR_002751 | |||||
| Natural variant | 32 | 1 | R → K Causes alpha-thalassemia. | VAR_025002 | |||||
| Natural variant | 32 | 1 | R → S in Prato; unstable. | VAR_002752 | |||||
| Natural variant | 35 | 1 | L → R in Queens/Ogi. | VAR_002753 | |||||
| Natural variant | 38 | 1 | P → PE in Catonsville. | VAR_002755 | |||||
| Natural variant | 38 | 1 | P → R in Bourmedes. | VAR_002754 | |||||
| Natural variant | 41 | 1 | K → M in Kanagawa; O(2) affinity up. | VAR_002756 | |||||
| Natural variant | 42 | 1 | T → S in Miyano; O(2) affinity up. | VAR_002757 | |||||
| Natural variant | 44 | 1 | F → L in Hirosaki; unstable. | VAR_002758 | |||||
| Natural variant | 45 | 1 | P → L in Milledgeville; O(2) affinity up. dbSNP rs41514946. | VAR_002759 | |||||
| Natural variant | 45 | 1 | P → R in Kawachi; O(2) affinity up. | VAR_002760 | |||||
| Natural variant | 46 | 1 | H → Q in Bari. | VAR_002761 | |||||
| Natural variant | 46 | 1 | H → R in Fort de France; O(2) affinity up. | VAR_002762 | |||||
| Natural variant | 48 | 1 | D → A in Cordele; unstable. | VAR_002763 | |||||
| Natural variant | 48 | 1 | D → G in Umi/Michigan; unstable. | VAR_002764 | |||||
| Natural variant | 48 | 1 | D → H in Hasharon/Sinai; unstable. | VAR_002765 | |||||
| Natural variant | 48 | 1 | D → Y in Kurdistan. | VAR_002766 | |||||
| Natural variant | 49 | 1 | L → R in Montgomery. | VAR_002767 | |||||
| Natural variant | 50 | 1 | S → R in Savaria. | VAR_002768 | |||||
| Natural variant | 51 | 1 | H → R in Aichi; slightly unstable. | VAR_002769 | |||||
| Natural variant | 52 | 1 | G → D in J-Abidjan. | VAR_002770 | |||||
| Natural variant | 52 | 1 | G → R in Russ. | VAR_002771 | |||||
| Natural variant | 54 | 1 | A → D in J-Rovigo; unstable. | VAR_002772 | |||||
| Natural variant | 55 | 1 | Q → R in Hikoshima/Shimonoseki. | VAR_002773 | |||||
| Natural variant | 57 | 1 | K → R in Port Huron. | VAR_002774 | |||||
| Natural variant | 57 | 1 | K → T in Thailand. | VAR_002775 | |||||
| Natural variant | 58 | 1 | G → R in L-Persian Gulf. | VAR_002776 | |||||
| Natural variant | 59 | 1 | H → Q in Boghe. | VAR_025388 | |||||
| Natural variant | 59 | 1 | H → Y in M-Boston/M-Osaka; O(2) affinity down. | VAR_002777 | |||||
| Natural variant | 60 | 1 | G → D in Adana; unstable; causes alpha-thalassemia. dbSNP rs28928878. | VAR_002778 | |||||
| Natural variant | 60 | 1 | G → V in Tottori; unstable. | VAR_002779 | |||||
| Natural variant | 61 | 1 | K → N in Zambia. dbSNP rs28928887. | VAR_002780 | |||||
| Natural variant | 61 | 1 | Missing in Clinic; unstable; causes alpha-thalassemia. | VAR_002781 | |||||
| Natural variant | 62 | 1 | K → N in J-Buda. | VAR_002782 | |||||
| Natural variant | 62 | 1 | K → T in J-Anatolia. | VAR_002783 | |||||
| Natural variant | 63 | 1 | V → M in Evans; unstable. | VAR_002784 | |||||
| Natural variant | 64 | 1 | A → D in Pontoise; unstable. | VAR_002785 | |||||
| Natural variant | 65 | 1 | D → Y in Persepolis. | VAR_002786 | |||||
| Natural variant | 69 | 1 | N → K in G-Philadelphia. dbSNP rs1060339. | VAR_002787 | |||||
| Natural variant | 72 | 1 | A → E in J-Habana. | VAR_002788 | |||||

Clusters with