• GPV

MAJOR LINKS FOR CD42d  

• NCBI LocusLink Record: 2814
• Mendelian Inheritance in Man (OMIM): 173511
• SwissProt annotated protein record: P40197

• 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 (GPIbalpha)

CELLULAR FUNCTION OF CD42d  

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

DISEASE RELEVANCE OF CD42d AND FUNCTION OF CD42d IN INTACT ANIMAL  

• The Bernard-Soulier syndrome (BSS, a bleeding disorder and presence of giant platelets) is characterized by the absence or very reduced expression of members of the GPIb/IX/V (CD42a-d) complex, so far mutations have been found in the genes encoding CD42a, CD42b and CD42c in patients with BSS**
• CD42d mouse monoclonal antibodies (MoAb) are used for detection of auto-and allo-anti-platelet antibodies with the MAIPA assay

• Families in which CD42d is a member
  • CD42d-->platelet-derived growth factor-->PTK-->protein kinase-->kinases

MOLECULAR STRUCTURE OF CD42d  

• Single chain integral membrane glycoprotein; forms a non-covalent complex with CD42a, b and c
• NH2-terminal extracytoplasmic region of 504 amino acids, a transmembrane domain of 24 amino acids and a short cytoplasmic region of 16 amino acids
• GPV contains 15 leucine-rich glycoprotein repeat sequences of 24 amino acids, flanked by consensus flanking sequences of 22 amino acids**
• GPV contains a thrombin cleavage site and cleavage sites for other physiological relevant proteases such as calpain

MOLECULAR MASS OF CD42d  

POST-TRANSCRIPTIONAL MODIFICATION OF CD42d   - No information

POST-TRANSLATIONAL MODIFICATION OF CD42d  

• There are eight potential N-glycosylation sites and, possibly, in the region near to the membrane, two or three O-glycosylation sites**

SUBSTRATES FOR CD42d   - No information

ENZYMES WHICH MODIFY CD42d  

LIGANDS FOR CD42d AND MOLECULES ASSOCIATED WITH CD42d  

• Note 1: CD42d forms a complex with CD42a, b and c. Transfection experiments showed that cotransfection of CD42d is not required for expression of the CD42a-c complex, whereas the CD42a, b and c subunits were all indispensable for efficient expression of CD42d*

• Expression restricted to platelets and megakaryocytes

• Co-expression studies suggest that CD42d may be essential for the formation of the high affinity thrombin receptor**

SELECTION OF OTHER CD42d-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. Dong JF, Sae-Tung G and Lopez JA. Role of glycoprotein V in the formation of the platelet high-affinity thrombin-binding site. Blood 1997 89:4355 ** PubMed

3. Hickey MJ, Hagen FS, Yagi M and Roth GJ. Human platelet glycoprotein V: characterization of the polypeptide and the related Ib-V-IX receptor system of adhesive, leucine-rich glycoproteins. Proc. Natl. Acad. Sci. U.S.A. 1993 90:8327 PubMed

4. Lanza F, Morales M, de La Salle C, Cazenave JP, Clemetson KJ, Shimomura T and Phillips DR. Cloning and characterization of the gene encoding the human platelet glycoprotein V. A member of the leucine-rich glycoprotein family cleaved during thrombin-induced platelet activation. J. Biol. Chem. 1993 268:20801 PubMed

5. Lopez JA, Leung B, Reynolds CC, Li CQ and Fox JE. Efficient plasma membrane expression of a functional platelet glycoprotein Ib-IX complex requires the presence of its three subunits. J. Biol. Chem. 1992 267:12851 PubMed

6. Modderman PW, Admiraal LG, Sonnenberg A and von dem Borne AE. Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane. J. Biol. Chem. 1992 267:364 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