Hemoglobin subunit alpha - Homo sapiens (Human)

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 binding Inferred from electronic annotation. Source: InterPro oxygen binding Inferred from electronic annotation. Source: InterPro oxygen transporter activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred 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

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

1

D → A in Sawara; O(2) affinity up.

VAR_002723

Natural variant

1

D → G in Swan River.

VAR_002724

Natural variant

1

D → N in Dunn; O(2) affinity up.

VAR_002725

Natural variant

1

D → V in Ferndown; O(2) affinity up.

VAR_002726

Natural variant

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

1

D → A in Cordele; unstable.

VAR_002763

Natural variant

1

D → G in Umi/Michigan; unstable.

VAR_002764

Natural variant

1

D → H in Hasharon/Sinai; unstable.

VAR_002765

Natural variant