A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens

Schuh, Andre C.; Watkins, Nick; Nguyen, Quang Tri; Harmer, Nicholas J.; Lin, Martin; Prosper, Joseph; Campbell, Kate; Sutherland, D. Robert; Metcalfe, Paul; Horsfall, Wendy; Ouwehand, Willem H.

doi:10.1182/blood.v99.5.1692

Cited by 81 publications

(98 citation statements)

References 14 publications

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“…The conservation of other large amino acids blocks in the amino terminus is also much higher than in the block around the GCGEQ motif indicating that these amino acid 'blocks' may have an important functional or structural role. Evolutionarily speaking, the change which resulted in the Gov a/b alleles is probably due to the ''Gov b'' serine being replaced by a tyrosine in ''Gov a'' Schuh et al, 2002), because the murine sequence contains a serine, not a tyrosine, at a similar position.…”

Section: Discussionmentioning

confidence: 98%

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

Solomon

Sharma

Chan

et al. 2004

Gene

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Section: Discussionmentioning

confidence: 98%

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

Solomon

Sharma

Chan

et al. 2004

Gene

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“…K02404.) nucleotide polymorphism of the cDNA reported here (see accompanying article by Schuh et al, 53 page 1692). Nevertheless, the presence of multiple CD109 transcripts by Northern blot analysis and the presence of an additional CD109-related peptide that could not be accounted for by our cDNA raise the possibility that additional CD109 cDNA variants may exist.…”

Section: Discussionmentioning

confidence: 99%

Cell surface antigen CD109 is a novel member of the α2 macroglobulin/C3, C4, C5 family of thioester-containing proteins

Lin

Sutherland

Horsfall

et al. 2002

Blood

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169

163

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Cell surface antigen CD109 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein of approximately 170 kd found on a subset of hematopoietic stem and progenitor cells and on activated platelets and T cells. Although it has been suggested that T-cell CD109 may play a role in antibodyinducing T-helper function and it is known that platelet CD109 carries the Gov alloantigen system, the role of CD109 in hematopoietic cells remains largely unknown. As a first step toward elucidating the function of CD109, we have isolated and characterized a human CD109 cDNA from KG1a and endothelial cells. The isolated cDNA comprises a 4335 bp open-reading frame encoding a 1445 amino acid (aa) protein of approximately 162 kd that contains a 21 aa Nterminal leader peptide, 17 potential Nlinked glycosylation sites, and a C-terminal GPI anchor cleavage-addition site. We report that CD109 is a novel member of the ␣2 macroglobulin (␣2M)/C3, C4, C5 family of thioester-containing proteins, and we demonstrate that native CD109 does indeed contain an intact thioester. Analysis of the CD109 aa sequence suggests that CD109 is likely activated by proteolytic cleavage and thereby becomes capable of thioester-mediated covalent binding to adjacent molecules or cells. In addition, the predicted chemical reactivity of the activated CD109 thioester is complementlike rather than resembling that of ␣2M proteins. Thus, not only is CD109 potentially capable of covalent binding to carbohydrate and protein targets, but the t ½ of its activated thioester is likely extremely short, indicating that CD109 action is highly restricted spatially to the site of its activation. IntroductionTo identify new surface antigens expressed by primitive hematopoietic stem and progenitor cells, we raised a series of monoclonal antibodies (mAbs) against the primitive CD34 ϩ acute myeloid leukemia cell line, KG1a. 1-3 Four of these mAbs-8A3, 7D1, 8A1, and 7C5-recognized a novel glycoprotein of approximately 170 kd that was expressed in a restricted pattern in the hematopoietic compartment and by endothelial cells. 4 Subsequently found to be identified by a number of additional mAbs, this antigen was designated CDw109 in 1993 5 and CD109 in 1996. 6 Antibodies to CD109 recognize monomeric polypeptides of about 170 kd and 150 kd in lysates of KG1a cells, T-cell lines, and activated T lymphoblasts, endothelial cells, and activated platelets. 3,[7][8][9][10][11] Peptide mapping and amino acid (aa) analysis indicate that the 150-kd form is likely derived proteolytically from the 170-kd form. 3,10 An additional band of about 120 kd that is occasionally observed arises through calcium-dependent proteolysis of the larger forms. 3,10 CD109 contains several N-linked endoglycosidase H-sensitive hybrid-type glycans but no O-linked glycans. 3,10 Consistent with this finding, ABH blood group antigens have recently been shown to be carried by platelet CD109. 12 KG1a CD109 is susceptible to cleavage with phosphatidylinositolspecific phospholipase C (PI-PLC), indicating that CD109 is bo...

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“…Most HPAs are based on single-nucleotide polymorphisms resulting in amino acid substitutions localized on the main platelet receptors: integrin αIIbβ3 (GPIIb/IIIa, CD41/CD61: the fibrinogen receptor), the GPIb-IX-V complex (CD42, von Willebrand factor receptor), and the GPIa/IIa complex (α2β1, CD29, the collagen receptor) 9,10. HPA-15 is the only exception; this biallelic system is carried by the platelet membrane protein CD109,11 which is a part of the transforming growth factor-β receptor system 12. For a more comprehensive presentation of platelet membrane glycoproteins, the recent review by Zdravic et al13 is suggested.…”

Section: Pathogenesismentioning

confidence: 99%

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Tiller

Husebekk

Ahlén

et al. 2017

IJWH

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Differences in platelet type between the fetus and the mother can lead to maternal immunization and destruction of the fetal platelets, a condition named fetal and neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is reported to occur in ~1 per 1,000 live born neonates. The major risk is intracranial hemorrhage in the fetus or newborn, which is associated with severe neurological complications or death. Since no countries have yet implemented a screening program to detect pregnancies at risk, the diagnosis is typically established after the birth of a child with symptoms. Reports on broader clinical impact have increased clinical concern and awareness. Along with new treatment options for FNAIT, the debate around antenatal screening to detect pregnancies at risk of FNAIT has been revitalized.

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A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens

Cited by 81 publications

References 14 publications

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

Cell surface antigen CD109 is a novel member of the α2 macroglobulin/C3, C4, C5 family of thioester-containing proteins

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

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A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens

Cited by 81 publications

References 14 publications

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

CD109 represents a novel branch of the α2-macroglobulin/complement gene family

Cell surface antigen CD109 is a novel member of the α2 macroglobulin/C3, C4, C5 family of thioester-containing proteins

Current perspectives on fetal and neonatal alloimmune thrombocytopenia &ndash; increasing clinical concerns and new treatment opportunities

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Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities