|CD41||Glycoprotein IIb (GPIIb), ITGA2B(integrin αIIb platelet )gycoprotein|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Lineage Restricted Molecule|
Type 1 glycoprotein
|23 / 23|
120 / 120
135 / 135
|CD41 is expressed on platelets and megakaryocytes.|
|MOLECULAR FAMILY NAME: Belongs to the integrin a chain family.|
CD41 is a single-pass type-1 glycoprotein. The glycoprotein is cleaved into a disulfide-linked 120 kDa α chain and a 22 kDa β chain which forms a calcium-dependent complex with platelet glycoprotein CD61. The α chain contains an extracellular domain which contains 4 repeated sequences with similarity to the calcium-binding repeats of other proteins which may be involved in binding of divalent cations. The β chain is the membrane bound portion which contains a 91 aa extracellular domain which has 5 potential N-linked glycoslyation sites and is O-glycosylated on serine residues, a 26 aa transmembrane and a 20 aa C-terminal cytoplasmic region. CD41 is the a subunit of the CD41/CD61 complex and is expressed as a heterodimer non-covalently associated with the integrin b3 subunit CD61. CD41 is comprised of a heavy chain and CD61 is linked by a single disulfide bond. CD41 is post-translationally cleaved into a large 125 kDa N-terminal and a small 2 kDa fragment which are disulfide-linked. The transmembrane sequence is in the smaller fragment. The N-terminal sequences of both fragments have been determined. Whereas the N-terminus of the small fragment is usually at residue Gln891, a fragment with the N-terminus at Leu 902 has also been detected. Alternatively spliced mRNA which lacks sequence from an exon encoding the 34 residues Arg917-Gln950 has been reported in megakaryotes. The significance of the alternatively spliced mRNA is unclear since this detection interferes with the surface expression of the protein. Intramolecular disulfide bonds are formed between neighboring cysteines along the primary sequence, beginning at Cys56. Electron microscopy of purified CD41/CD61 has provided a structural model for all integrins.
Alternatively splicing yields 3 different isoforms and lacks exon 28.
The α chain 2b undergoespost-translational cleavage to yield disulfide-linked light and heavy chains that join with β3 to form a fibronectin receptor expressed in platlets that plays a crucial role in coagulation. CD41 has 5 potential sites for N-linked glycosylation and is O-glycosylated on serine residues. Following removal of 31 aa signal peptide and pairing with CD61 in the endoplasmic reticulum, 1,039 pro CD41 undergoes endo-proteoilytic cleavage into CD41 and CD61 in the Golgi apparatus.
|LIGANDS AND MOLECULES ASSOCIATED WITH CD41|
The ligands for CD41/CD61 include fibronogen, von Willebrand factor (vWf), fibronectin, vitronectin, and thrombospondin. After activation CD41/CD61 becomes a receptor for soluble fibrinogen and several other RGD-containing adhesive proteins including vWf. Binding to these ligands depends on the activation state of the platelets. Unstimulated platelets only bind immobilized fibrinogen. Binding to soluble fibrinogen and other ligands requires stimulation of platelets by agonists such as thrombin, ADP and collagen. Binding usually involves an RGD motif on ligands but CD41/CD61 also binds to the HHLGGAKQAGDV sequence in the g chain of fibrinogen. CD41/CD61 binding to multiple sites on fibrinogen is important for platelet adhesion.
|CD41/CD61 complex plays a central role in platelet activation, cohesion, coagulation, aggregation and platelet attachment to protein components of the extracellular matrix. This complex functions as an activation-dependent receptor for fibrinogen, fibronectin and von Willebrand and binds RGD-containing sequences in adhesion molecules. CD41 is also known to participate in cell surface mediated signaling. There are 3 missense mutations, G242D, R327H and G418D - numbered as in the mature protein, have been identified which result in the disease Glanzmann thrombasthenia (GT). Glanzmann thrombasthenia can also be caused by defects in the integrin b3 subunit (see CD61). Mutations of CD41 at Ile 843 give rise to the HPA-3 alloantigenic polymorphism. The HPA-3B allele Ser843 forms an additional O-glycosylation site, and is associated with neonatal alloimmune thrombocytopenia.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD41 IN INTACT ANIMAL
CD41 acts as a receptor for fibrinogen, von Willebrand factor and fibrionectin. Absence of CD41/CD61 on the platelet surface results in the inherited bleeding disorder GT. Numerous mutations giving rise to GT have been identified within CD4. CD41 bears several alloantigenic polymorphism, at least 2 of which are known to be involved in clinically relevant alloimmune thrombocytopenia. Some mAbs may be applicable for the diagnosis of GT and megakaryoblastic leukemia, deletion of alloantibodies and anti-thrombotic therapy. Mutations in CD41 give rise to a dysfunctional CD41/CD61 complex results in the development of Glanzmann's thrombasthenia.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD41
SUBSTRATES FOR CD41: No information.
ENZYMES WHICH MODIFY CD41: No information.
Database accession numbers
Revised June 25, 2008