UniProt functional annotation for P07359



	UniProt functional annotation for P07359

UniProt code: P07359.

Organism: Homo sapiens (Human).

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

Function: GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.

Subunit: Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage (PubMed:17008541, PubMed:2070794). Interacts with FLNB (PubMed:9651345). Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23) (PubMed:19828450). {ECO:0000269|PubMed:17008541, ECO:0000269|PubMed:19828450, ECO:0000269|PubMed:2070794, ECO:0000269|PubMed:9651345}.

Subunit: (Microbial infection) Interacts with Staphylococcus aureus protein SSL5. {ECO:0000269|PubMed:21552524}.

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

Ptm: Glycocalicin is the product of a proteolytic cleavage/shedding, catalyzed by ADAM17, which releases most of the extracellular domain. Binding sites for vWF and thrombin are in this part of the protein. {ECO:0000269|PubMed:17445093}.

Polymorphism: Position 161 is associated with platelet-specific alloantigen Siba (PubMed:1586750). Siba(-) has Thr-161 and Siba(+) has Met-161 (PubMed:1586750). Siba is involved in neonatal alloimmune thrombocytopenia (NATP) (PubMed:1586750, PubMed:7632942). {ECO:0000269|PubMed:1586750, ECO:0000269|PubMed:7632942}.

Polymorphism: Polymorphisms arise from a variable number of tandem 13- amino acid repeats of S-E-P-A-P-S-P-T-T-P-E-P-T in the mucin-like macroglycopeptide (Pro/Thr-rich) domain (PubMed:1577776, PubMed:7632942). Allele D contains one repeat starting at position 415, allele C contains two repeats, allele B (shown here) contains three repeats and allele A contains four repeats (PubMed:1577776). Allele B is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy (PubMed:1577776). {ECO:0000269|PubMed:1577776, ECO:0000269|PubMed:7632942}.

Disease: Non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:258660]: An ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage. {ECO:0000269|PubMed:14711733}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption. {ECO:0000269|PubMed:10089893, ECO:0000269|PubMed:1730088, ECO:0000269|PubMed:7690774, ECO:0000269|PubMed:7819107, ECO:0000269|PubMed:7873390, ECO:0000269|PubMed:9639514}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Bernard-Soulier syndrome A2, autosomal dominant (BSSA2) [MIM:153670]: A coagulation disorder characterized by mild to moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. Some individuals have no symptoms. Mild bleeding tendencies manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery. {ECO:0000269|PubMed:11222377}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Pseudo-von Willebrand disease (VWDP) [MIM:177820]: A bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation. {ECO:0000269|PubMed:14521605, ECO:0000269|PubMed:2052556, ECO:0000269|PubMed:8384898, ECO:0000269|PubMed:8486780}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.

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:		GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.


Subunit:		Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage (PubMed:17008541, PubMed:2070794). Interacts with FLNB (PubMed:9651345). Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23) (PubMed:19828450). {ECO:0000269\|PubMed:17008541, ECO:0000269\|PubMed:19828450, ECO:0000269\|PubMed:2070794, ECO:0000269\|PubMed:9651345}.
Subunit:		(Microbial infection) Interacts with Staphylococcus aureus protein SSL5. {ECO:0000269\|PubMed:21552524}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Ptm:		Glycocalicin is the product of a proteolytic cleavage/shedding, catalyzed by ADAM17, which releases most of the extracellular domain. Binding sites for vWF and thrombin are in this part of the protein. {ECO:0000269\|PubMed:17445093}.
Polymorphism:		Position 161 is associated with platelet-specific alloantigen Siba (PubMed:1586750). Siba(-) has Thr-161 and Siba(+) has Met-161 (PubMed:1586750). Siba is involved in neonatal alloimmune thrombocytopenia (NATP) (PubMed:1586750, PubMed:7632942). {ECO:0000269\|PubMed:1586750, ECO:0000269\|PubMed:7632942}.
Polymorphism:		Polymorphisms arise from a variable number of tandem 13- amino acid repeats of S-E-P-A-P-S-P-T-T-P-E-P-T in the mucin-like macroglycopeptide (Pro/Thr-rich) domain (PubMed:1577776, PubMed:7632942). Allele D contains one repeat starting at position 415, allele C contains two repeats, allele B (shown here) contains three repeats and allele A contains four repeats (PubMed:1577776). Allele B is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy (PubMed:1577776). {ECO:0000269\|PubMed:1577776, ECO:0000269\|PubMed:7632942}.
Disease:		Non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:258660]: An ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage. {ECO:0000269\|PubMed:14711733}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption. {ECO:0000269\|PubMed:10089893, ECO:0000269\|PubMed:1730088, ECO:0000269\|PubMed:7690774, ECO:0000269\|PubMed:7819107, ECO:0000269\|PubMed:7873390, ECO:0000269\|PubMed:9639514}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Bernard-Soulier syndrome A2, autosomal dominant (BSSA2) [MIM:153670]: A coagulation disorder characterized by mild to moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. Some individuals have no symptoms. Mild bleeding tendencies manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery. {ECO:0000269\|PubMed:11222377}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Pseudo-von Willebrand disease (VWDP) [MIM:177820]: A bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation. {ECO:0000269\|PubMed:14521605, ECO:0000269\|PubMed:2052556, ECO:0000269\|PubMed:8384898, ECO:0000269\|PubMed:8486780}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.