CD61 ITGβ3 (integrin β3 platelet glycoprotein IIIa antigen), GPIIIa
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
Platelet
Fibroblast
Monocyte
Macrophage
Endothelial Cell
Osteoclast
Mast Cell
Megakaryocyte
Endothelium
Muscle, Smooth
B Cell
Tumor Cell
90 / 90
110 / 110

Expression
CD61 is expressed with CD41 on platelets and megakaryocytes. Expression with CD51 is on a wide variety of cell types including endothelium, endothelial cell, smooth muscle, some B cells, monocytes, macrophages, platelets, osteoclasts, mast cells, fibroblasts and tumor cells.

Structure
MOLECULAR FAMILY NAME: Belongs to the integrin b family.

CD61 is a cysteine-rich single-pass type-1 glycoprotein.  It contains a 26 aa N-terminal signal peptide, an 856 aa extracellular domain, a 26 aa transmembrane domain and a 41 aa cytoplasmic domain.  CD61 is a integrin b3 subunit that forms a calcium-dependent complex with platelet glycoprotein GP11b which is recognized by CD41 antibodies.  CD41/CD61 (GPIIb-IIIa, integrin aIIb b3) and CD51/CD61 (vitronectin receptor, integrin aVb3) are complexes that are non-covalently associated heterodimers that require divalent cations to a differing extent for complex integrity and receptor functions.  There are 2 large loops extending from Cys5-Cys435 and Cys405-Cys655 that have been proposed.  At least 6 CD61 polymorphisms have been identified with one (Arg636-Cys) shown to induce an alloimmune response.  An alternative cytoplasmic domain of CD61 has been detected at the mRNA level in human placental tissue and 2 human cell lines.

MOLECULAR MASS OF CD61
Cell Type Unreduced Reduced
Platelets 90 kDa 110 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD61 has 6 potential sites for N-linked glycosylation.


Ligands
The resting form of CD41/CD61 complex is involved in platelet activation and aggregation and binds to immobilized fibronogen.  After activation, CD41/CD61 becomes a receptor for soluble fibronogen and several other RGD-containing adhesive proteins such as vonWillebrand Factor (vWF) and fibronectin.  CD51/CD61 does not require activation to bind a soluble ligand.  This complex is a receptor for several RGD-containing adhesive proteins, including vitronectin, fibronectin, vWF and fibronogen.  CD61 cytoplasmic region interacts with cytoskeletal proteins, such as a-actinin, paxilin and talin.  The signal transducing proteins that interact with the CD61 cytoplasmic region are b3 endonexin, integrin-linked kinases (ILK) and focal adhesion kinase (FAK).  CD61 combines with CD41 to form the platelet glycoprotein Ilb/IIIa integrin aIIbb3 and with CD51 to form the vitronectin receptor integrin aVb3.  The cytoplasmic tail of CD61 has been shown to interact with the molecule b3-endonexin.

Function
CD61 participates in cell adhesion as well as cell-surface mediated signaling and mediate platelet aggregation.  CD41/CD61 mediates attachment to cells to diverse matrix proteins.  See CD41 and CD51 for the functions of the CD41/CD61 and CD51/CD61 complexes respectively.  Variations in the CD61 sequence are associated with platelet-specific alloantigens, L33P HPA-1A/B, R143Q HPA-4A/B, P407A MO+; R489Q CA+ and R636C SR a+.  There are 5 missense mutations of CD61 that have been associated with Glanzmann thrombasthenia.  The residue locations are given according to the sequence of the mature protein, D119Y, R214Q and R214W.  These lead to the loss of ligand binding activities of CD41/CD61 complexes. C374Y results in the diminished expression of CD41/CD61 on platelets although ligand binding specificities appear to remain intact, and S752P in the cytoplasmic domain renders the CD41/CD61 nonresponsive to platelet activation.  Other mutations, including deletions and erroneous splicing, have been described.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD61 IN INTACT ANIMAL

An absence or dysfunction of CD41/CD61 on the platelet surface results in an inherited bleeding disorder called Glanzmann thrombasthemia (GT).  Several mutations have been identified within CD61 that results in GT.  CD61 is polymorphic within the human gene pool.  At least 6 allelic forms have been identified, including those containing Leu33-Pro, Arg143-Gln, Pro407-Ala, Arg489-Gln and Arg636-Cys aa substitutions, which can induce an alloimmune response.  CD51/CD61 plays a role in tumor metastasis and adenoviral infection.  Some mAbs may be applicable for diagnosis of GT and megakaryoblastic leukemias, detection of alloantibodies and antithrombotic therapy.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD61: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD61: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3690P05106
Antibodies
JM2E5   View Reactivity
PM6/13   View Reactivity
VIPL2   View Reactivity
Y2/51   View Reactivity

Revised June 25, 2008


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