UniProt functional annotation for P08514



	UniProt functional annotation for P08514

UniProt code: P08514.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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: Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-IIb associates with beta-3. Directly interacts with RNF181. Interacts (via C-terminus cytoplasmic tail region) with CIB1; the interaction is direct and calcium-dependent. Interacts (via C-terminus cytoplasmic tail region) with CIB2, CIB3 and CIB4; the interactions are stabilized/increased in a calcium and magnesium-dependent manner. ITGA2B:ITGB3 interacts with PPIA/CYPA; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin (By similarity). {ECO:0000250|UniProtKB:Q9QUM0, ECO:0000269|PubMed:10477286, ECO:0000269|PubMed:18331836, ECO:0000269|PubMed:21388953, ECO:0000269|PubMed:22283712, ECO:0000269|PubMed:22779914, ECO:0000269|PubMed:9030514}.

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Isoform 1 and isoform 2 are expressed in platelets and megakaryocytes, but not in reticulocytes. Not detected in Jurkat, nor in U937 cell lines (PubMed:2351656). Isoform 3 is expressed in prostate adenocarcinoma, as well as in several erythroleukemia, prostate adenocarcinoma and melanoma cell lines, including PC-3, DU- 145, HEL, WM983A, WM983B and WM35. Not detected in platelets, nor in normal prostate (at protein level) (PubMed:9809974). {ECO:0000269|PubMed:2351656, ECO:0000269|PubMed:9809974}.

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). {ECO:0000269|PubMed:10391209}.

Disease: Glanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. {ECO:0000269|PubMed:10607701, ECO:0000269|PubMed:11798398, ECO:0000269|PubMed:12083483, ECO:0000269|PubMed:12181054, ECO:0000269|PubMed:12424194, ECO:0000269|PubMed:12506038, ECO:0000269|PubMed:15099289, ECO:0000269|PubMed:15219201, ECO:0000269|PubMed:17018384, ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:7508443, ECO:0000269|PubMed:7706461, ECO:0000269|PubMed:8282784, ECO:0000269|PubMed:8704171, ECO:0000269|PubMed:9215749, ECO:0000269|PubMed:9473221, ECO:0000269|PubMed:9722314, ECO:0000269|PubMed:9734640, ECO:0000269|PubMed:9763559, ECO:0000269|PubMed:9920835}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Bleeding disorder, platelet-type 16 (BDPLT16) [MIM:187800]: An autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities. {ECO:0000269|PubMed:21454453, ECO:0000269|PubMed:9834222}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the integrin alpha chain family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:		Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-IIb associates with beta-3. Directly interacts with RNF181. Interacts (via C-terminus cytoplasmic tail region) with CIB1; the interaction is direct and calcium-dependent. Interacts (via C-terminus cytoplasmic tail region) with CIB2, CIB3 and CIB4; the interactions are stabilized/increased in a calcium and magnesium-dependent manner. ITGA2B:ITGB3 interacts with PPIA/CYPA; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin (By similarity). {ECO:0000250\|UniProtKB:Q9QUM0, ECO:0000269\|PubMed:10477286, ECO:0000269\|PubMed:18331836, ECO:0000269\|PubMed:21388953, ECO:0000269\|PubMed:22283712, ECO:0000269\|PubMed:22779914, ECO:0000269\|PubMed:9030514}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Tissue specificity:		Isoform 1 and isoform 2 are expressed in platelets and megakaryocytes, but not in reticulocytes. Not detected in Jurkat, nor in U937 cell lines (PubMed:2351656). Isoform 3 is expressed in prostate adenocarcinoma, as well as in several erythroleukemia, prostate adenocarcinoma and melanoma cell lines, including PC-3, DU- 145, HEL, WM983A, WM983B and WM35. Not detected in platelets, nor in normal prostate (at protein level) (PubMed:9809974). {ECO:0000269\|PubMed:2351656, ECO:0000269\|PubMed:9809974}.
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). {ECO:0000269\|PubMed:10391209}.
Disease:		Glanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. {ECO:0000269\|PubMed:10607701, ECO:0000269\|PubMed:11798398, ECO:0000269\|PubMed:12083483, ECO:0000269\|PubMed:12181054, ECO:0000269\|PubMed:12424194, ECO:0000269\|PubMed:12506038, ECO:0000269\|PubMed:15099289, ECO:0000269\|PubMed:15219201, ECO:0000269\|PubMed:17018384, ECO:0000269\|PubMed:20020534, ECO:0000269\|PubMed:7508443, ECO:0000269\|PubMed:7706461, ECO:0000269\|PubMed:8282784, ECO:0000269\|PubMed:8704171, ECO:0000269\|PubMed:9215749, ECO:0000269\|PubMed:9473221, ECO:0000269\|PubMed:9722314, ECO:0000269\|PubMed:9734640, ECO:0000269\|PubMed:9763559, ECO:0000269\|PubMed:9920835}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Bleeding disorder, platelet-type 16 (BDPLT16) [MIM:187800]: An autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities. {ECO:0000269\|PubMed:21454453, ECO:0000269\|PubMed:9834222}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the integrin alpha chain family. {ECO:0000305}.