• GPIX

MAJOR LINKS FOR CD42a  

• NCBI LocusLink Record: 2815
• Mendelian Inheritance in Man (OMIM): 173515
• SwissProt annotated protein record: P14770

• The CD42a-d-complex serves as receptor for von Willebrand factor (vWf) and thrombin
• The actual binding site for vWf and thrombin lies on CD42b (GPIb alpha)

CELLULAR FUNCTION OF CD42a  

• The complex mediates adhesion of platelets to subendothelial matrices (exposed upon damage to the endothelium) at high shear rates and amplifies the platelet response to thrombin during platelet activation where thrombin is involved

DISEASE RELEVANCE OF CD42a AND FUNCTION OF CD42a IN INTACT ANIMAL  

• Absence of the CD42 complex leads to the Bernard-Soulier syndrome (BSS), which is a bleeding disorder characterized by thrombocytopenia and giant platelets. So far, mutations have been found in the genes encoding CD42a, CD42b and CD42c in patients with BSS**
• CD42a mouse monoclonal antibodies (MoAbs) are used for detection of auto-anti-platelet antibodies with the monoclonal antibody-specific immobilization of platelet antibodies (MAIPA) assay

• Families in which CD42a is a member
  • CD42a-->platelet-derived growth factor-->PTK-->protein kinase-->kinases

MOLECULAR STRUCTURE OF CD42a  

• Single chain integral membrane glycoprotein; forms a non-covalent linked complex with CD42b, c and d
• NH2-terminal extracytoplasmic region of 134 amino acids, a transmembrane region of 20 amino acids and a short intracellular region of 6 amino acids
• GPIX contains a leucine-rich glycoprotein repeat sequence of 24 amino acids, flanked by consensus flanking sequences of 22 amino acids**
• Unlike GPIb alpha, which is rich in O-linked oligosaccharides, GPIb beta has only N-linked chains of the lactosamine type (Wicki and Clemetson 1987)**

MOLECULAR MASS OF CD42a  

POST-TRANSCRIPTIONAL MODIFICATION OF CD42a   - No information

POST-TRANSLATIONAL MODIFICATION OF CD42a  

• There is one N-glycosylation site and the protein may be myristoylated

SUBSTRATES FOR CD42a   - No information

ENZYMES WHICH MODIFY CD42a   - No information

LIGANDS FOR CD42a AND MOLECULES ASSOCIATED WITH CD42a  

• Expression restricted to platelets and megakaryocytes

SELECTION OF OTHER CD42a-SPECIFIC REFERENCE MAB  

REVIEWS

PRIMARY CITATIONS

1. Clemetson KJ, McGregor JL, James E, Dechavanne M and Luscher EF. Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis. J. Clin. Invest. 1982 70:304 PubMed

2. Fox JE, Aggerbeck LP and Berndt MC. Structure of the glycoprotein Ib.IX complex from platelet membranes. J. Biol. Chem. 1988 263:4882 PubMed

3. Hickey MJ, Williams SA and Roth GJ. Human platelet glycoprotein IX: an adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures. Proc. Natl. Acad. Sci. U.S.A. 1989 86:6773 PubMed

4. Muszbek L and Laposata M. Glycoprotein Ib and glycoprotein IX in human platelets are acylated with palmitic acid through thioester linkages. J. Biol. Chem. 1989 264:9716 PubMed

5. Nurden AT, Dupuis D, Kunicki TJ and Caen JP. Analysis of the glycoprotein and protein composition of Bernard-Soulier platelets by single and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. J. Clin. Invest. 1981 67:1431 PubMed

6. Schick PK and Walker J. The acylation of megakaryocyte proteins: glycoprotein IX is primarily myristoylated while glycoprotein Ib is palmitoylated. Blood 1996 87:1377 PubMed

7. Wicki AN and Clemetson KJ. The glycoprotein Ib complex of human blood platelets. Eur. J. Biochem. 1987 163:43 PubMed

8. Wright SD, Michaelides K, Johnson DJ, West NC and Tuddenham EG. Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome. Blood 1993 81:2339 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov