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HGNC Approved Gene Symbol: PPBP
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:73,986,439-73,988,190 (from NCBI)
Pro-platelet basic protein (PPBP) is the precursor of the 2 platelet alpha-granule proteins, platelet basic protein (PBP) and connective tissue-activating peptide III (CTAP3). Upon platelet activation they are released and further processed in plasma to beta-thromboglobulin (TGB) and neutrophil-activating peptide-2 (NAP2).
By purifying proteins with antibacterial activity from platelet granules, followed by cation exchange chromatography, continuous acid urea polyacrylamide gel electrophoresis, mass spectrometry, and N-terminal sequencing, Krijgsveld et al. (2000) identified the thrombocidins, TC1 and TC2, as variants of the NAP2 and CTAP3 forms of PPBP, respectively. TC1 and TC2 differ from NAP2 and CTAP3 by a C-terminal truncation of 2 amino acids (ala and asp) and by their bactericidal and fungicidal properties, which apparently do not involve pore formation.
CTAP3 is a platelet-derived growth factor that stimulates a variety of specific metabolic and cellular activities including mitogenesis, extracellular matrix synthesis, glucose metabolism, and plasminogen activator synthesis in human fibroblast cultures (Castor et al., 1983; Castor et al., 1985).
Using mass spectrometry, Aivado et al. (2007) generated serum proteome profiles from 122 patients with myelodysplastic syndrome (MDS), 72 non-MDS patients with cytopenia, and 24 controls, and identified a profile that distinguished MDS from non-MDS cytopenias. Peptide mass fingerprinting and quadrupole SELDI-TOF mass spectrometry identified 2 differential proteins, CXCL4 (PF4) and CXCL7, both of which had significantly decreased serum levels in MDS. The decrease was confirmed with independent antibody assays, and subtype analyses revealed decreased serum levels of these 2 proteins in advanced MDS. Aivado et al. (2007) suggested that there may be a concerted disturbance of transcription or translation of these chemokines in advanced MDS.
Majumdar et al. (1991) compared beta-thromboglobulin with platelet factor-4 (PF4; 173460). The TGB gene is 1,139 bp long and, like other members of the small inducible gene (SIG) family, it is divided into 3 exons.
By PCR analysis of human/hamster somatic cell hybrids, Majumdar et al. (1991) demonstrated that the TGB gene, like the PF4 gene, is located on chromosome 4. Southern blot analysis of genomic DNA suggested that, as with the PF4 gene, there are multiple copies of the TGB gene in the human genome. Wenger et al. (1991) mapped the CTAP3 gene to chromosome 4q12-q13 by in situ hybridization.
Tunnacliffe et al. (1992) stated that all of the CXC SIGs map to chromosome 4. By pulsed field gel electrophoresis (PFGE), Tunnacliffe et al. (1992) demonstrated that the TGB genes (which are duplicate) are closely linked to the duplicated PF4 genes and to other previously mapped CXC SIGs, namely, IL8 (146930), GRO1 (155730), GRO2 (139110), and GRO3 (139111), on a single 700-kb restriction fragment located in bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-kD protein (SCYB10; 147310), which is located in band 4q21. By analysis of lambda genomic clones, Tunnacliffe et al. (1992) demonstrated that the TGB1 and PF4 genes are separated by less than 7 kb, and the TGB2 and PF4-alternate (PF4V1; 173461) genes by approximately 5 kb. Within each TGB/PF4 duplication, the TGB-like gene is upstream of its linked PF4-like gene. The genes in this closely linked complex are expressed in a megakaryocyte-specific fashion.
By PCR analysis and mapping of YAC clones, O'Donovan et al. (1999) localized a number of CXC chemokine genes to 4q12-q21. They proposed that the order in this region is centromere--IL8--GRO1/PPBP/PF4--SCYB5 (600324)/SCYB6 (138965)--GRO2/GRO3--SCYB11 (604852)--SCYB10--MIG (601704)--telomere.
Aivado, M., Spentzos, D., Germing, U., Alterovitz, G., Meng, X.-Y., Grall, F., Giagounidis, A. A. N., Klement, G., Steidl, U., Otu, H. H., Czibere, A., Prall, W. C., Iking-Konert, C., Shayne, M., Ramoni, M. F., Gattermann, N., Haas, R., Mitsiades, C. S., Fung, E. T., Libermann, T. A. Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease. Proc. Nat. Acad. Sci. 104: 1307-1312, 2007. [PubMed: 17220270] [Full Text: https://doi.org/10.1073/pnas.0610330104]
Castor, C. W., Furlong, A. M., Carter-Su, C. Connective tissue activation. XXIX. Stimulation of glucose transport by connective tissue activating peptide-III. Biochemistry 24: 1762-1767, 1985. [PubMed: 4005226] [Full Text: https://doi.org/10.1021/bi00328a029]
Castor, C. W., Miller, J. W., Walz, D. A. Structural and biological characteristics of connective tissue activating peptide (CTAP-III), a major human platelet derived growth factor. Proc. Nat. Acad. Sci. 80: 765-769, 1983. [PubMed: 6572368] [Full Text: https://doi.org/10.1073/pnas.80.3.765]
Krijgsveld, J., Zaat, S. A. J., Meeldijk, J., van Veelen, P. A., Fang, G., Poolman, B., Brandt, E., Ehlert, J. E., Kuijpers, A. J., Engbers, G. H. M., Feijen, J., Dankert, J. Thrombocidins, microbicidal proteins from human blood platelets, are C-terminal deletion products of CXC chemokines. J. Biol. Chem. 275: 20374-20381, 2000. [PubMed: 10877842] [Full Text: https://doi.org/10.1074/jbc.275.27.20374]
Majumdar, S., Gonder, D., Koutsis, B., Poncz, M. Characterization of the human beta-thromboglobulin gene: comparison with the gene for platelet factor 4. J. Biol. Chem. 266: 5785-5789, 1991. [PubMed: 1826003]
O'Donovan, N., Galvin, M., Morgan, J. G. Physical mapping of the CXC chemokine locus on human chromosome 4. Cytogenet. Cell Genet. 84: 39-42, 1999. [PubMed: 10343098] [Full Text: https://doi.org/10.1159/000015209]
Tunnacliffe, A., Majumdar, S., Yan, B., Poncz, M. Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4. Blood 79: 2896-2900, 1992. [PubMed: 1316786]
Wenger, R. H., Hameister, H., Clemetson, K. J. Human platelet basic protein/connective tissue activating peptide-III maps in a gene cluster on chromosome 4q12-q13 along with other genes of the beta-thromboglobulin superfamily. Hum. Genet. 87: 367-368, 1991. [PubMed: 1830861] [Full Text: https://doi.org/10.1007/BF00200921]