Integrin alpha-IIb precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Integrin alpha-IIb
Alternative name(s):
    Platelet membrane glycoprotein IIb
    GPalpha IIb
      Short name(s)=GPIIb
    CD_antigen=CD41
Cleaved into 3 chains:
  Recommended name:
      Integrin alpha-IIb heavy chain
  Recommended name:
      Integrin alpha-IIb light chain, form 1
  Recommended name:
      Integrin alpha-IIb light chain, form 2

Gene names

Name:	ITGA2B
Synonyms:	GP2B, ITGAB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	1039 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.
Subunit structure	Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of an heavy and a light chain linked by a disulfide bond. Alpha-IIb associates with beta-3.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Isoform 1 and isoform 2 were identified in platelets and megakaryocytes, but not in reticulocytes or in Jurkat and U937 white blood cell line. Isoform 3 is expressed by leukemia, prostate adenocarcinoma and melanoma cells but not by platelets or normal prostate or breast epithelial cells.
Polymorphism	Position 874 is associated with platelet-specific alloantigen HPA-3/BAK/LEK. HPA-3A/BAK(A)/LEK(A) has Ile-874 and HPA-3B/BAK(B)/LEK(B) has Ser-874. HPA-3B is involved in neonatal alloimmune thrombocytopenia (NAIT or NATP).
Involvement in disease	Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:273800]; also known as thrombasthenia of Glanzmann and Naegeli. This autosomal recessive disorder is the most common inherited disease of platelets. GT is characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.
Sequence similarities	Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats.

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Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Ligand	Calcium
Molecular function	Integrin Receptor
PTM	Cleavage on pair of basic residues Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc platelet alpha granule membrane Inferred from Experiment. Source: Reactome
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-702693,EBI-702693

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P08514-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P08514-2) The sequence of this isoform differs from the canonical sequence as follows: 948-981: Missing.

Isoform 3 (identifier: P08514-3) The sequence of this isoform differs from the canonical sequence as follows: 910-1039: SCDSAPCTVV...PLEEDDEEGE → VSRLSGLWPG...ATLGPWEHFK

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 31

31

Chain

32 – 1039

1008

Integrin alpha-IIb

Chain

32 – 887

856

Integrin alpha-IIb heavy chain

Chain

891 – 1039

149

Integrin alpha-IIb light chain, form 1

Chain

903 – 1039

137

Integrin alpha-IIb light chain, form 2

Regions

Topological domain

32 – 993

962

Extracellular Potential

Transmembrane

994 – 1019

26

Potential

Topological domain

1020 – 1039

20

Cytoplasmic Potential

Repeat

47 – 107

61

FG-GAP 1

Repeat

108 – ?

FG-GAP 2

Repeat

? – 262

FG-GAP 3

Repeat

263 – 316

54

FG-GAP 4

Repeat

317 – 384

68

FG-GAP 5

Repeat

385 – 444

60

FG-GAP 6

Repeat

445 – 497

53

FG-GAP 7

Calcium binding

274 – 282

9

Potential

Calcium binding

328 – 336

9

Potential

Calcium binding

396 – 404

9

Potential

Calcium binding

457 – 465

9

Potential

Motif

1022 – 1026

5

GFFKR motif

Amino acid modifications

Modified residue

891

1

Pyrrolidone carboxylic acid; in light chain form 1

Glycosylation

46

1

N-linked (GlcNAc...)

Glycosylation

280

1

N-linked (GlcNAc...)

Glycosylation

601

1

N-linked (GlcNAc...)

Glycosylation

711

1

N-linked (GlcNAc...)

Glycosylation

874

1

O-linked (GalNAc...); in alloantigen HPA-3B

Glycosylation

878

1

O-linked (GalNAc...)

Glycosylation

962

1

N-linked (GlcNAc...)

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Interchain (between heavy and light chains)

Disulfide bond

916 ↔ 921

Natural variations

Alternative sequence

910 – 1039

130

SCDSA…DEEGE → VSRLSGLWPGLPGTHGAEGM GGGRGVRVCCGPLWATLGPW EHFK in isoform 3.

Alternative sequence

948 – 981

34

Missing in isoform 2.

Natural variant

40

1

T → I: dbSNP rs5915.

Natural variant

86

1

L → P in GT; cells co-transfected with mutated alpha-IIb and wild-type beta-3 scarcely expressed the alpha-IIb/beta-3 complex.

Natural variant

139

1

A → V in GT.

Natural variant

161

1

C → W in GT.

Natural variant

174

1

Y → H in GT; abolishes the binding function of alpha-IIb/beta-3 for soluble ligands without disturbing alpha-IIb/beta-3 expression; functional defect is likely caused by its allosteric effect rather than by a defect in the ligand-binding site itself.

Natural variant

176

1

P → A in GT; impairs surface expression of alpha-IIb/beta-3 and abrogates ligand binding to the activated integrin.

Natural variant

176

1

P → L in GT; impairs surface expression of alpha-IIb/beta-3.

Natural variant

202

1

F → C in GT; associated with abrogation of alpha-IIb/beta-3 complex formation.

Natural variant

207

1

T → I in GT.

Natural variant

214

1

L → P in GT; disrupts the structural conformation and the ligand binding properties of the heterodimeric complex; in addition the mutation appears to confer susceptibility to proteolysis.

Natural variant

222

1

F → L in GT.

Natural variant

267

1

G → E in GT.

Natural variant

273

1

G → D in GT; alters the heterodimer conformation thus impairing their intracellular transport.

Natural variant

320

1

F → S in GT; type I; impairs surface expression of alpha-IIb/beta-3.

Natural variant

329

1

V → F in GT; expression of mutant subunit alpha-IIb/bet-3 is 28% of control; mutant pro-alpha-IIb subunit is retained in the endoplasmic reticulum.

Natural variant

355

1

E → K in GT; type I; impairs surface expression of alpha-IIb/beta-3.

Natural variant

358

1

R → H in GT; type II.

Natural variant

380

1

G → D in GT.

Natural variant

405

1

I → T in GT; expression of mutant subunit alpha-IIb/bet-3 is 11% of control; mutant pro-alpha-IIb subunit is retained in the endoplasmic reticulum.

Natural variant

412

1

G → R in GT.

Natural variant

449

1

G → D in GT; type I.

Natural variant

456 – 457

2

Missing in GT; alteres the conformation of heterodimers such that they were neither recognized by the heterodimer-specific antibody A2A9 nor able to undergo further intracellular processing or transport to the cell surface.

Natural variant

581

1

A → D in GT.

Natural variant

596

1

I → T in GT; type I.

Natural variant

705

1

C → R in GT; type II; the rate of subunit maturation and the surface exposure of ghlycoprotein IIb/beta-3 are strongly reduced.