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HGNC Approved Gene Symbol: PPAN
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38) : 19:10,106,223-10,112,012 (from NCBI)
Using P2Y4 (P2RY4; 300038) as probe, Suarez-Huerta et al. (2000) cloned PPAN, which they called SSF1, from a human placenta cDNA library. The deduced 473-amino acid protein shares 40% identity overall with the S. cerevisiae Ssf1 and Ssf2 proteins. Northern blot analysis detected a 1.7-kb transcript in all tissues examined. Strongest expression was detected in heart, skeletal muscle, kidney, and liver.
PPAN-P2RY11 Spliced Read-Through Transcript
During the screening of a placenta cDNA library to isolate new P2Y receptors, Communi et al. (2001) cloned a cDNA representing an SSF1-P2Y11 (P2RY11; 602697) chimeric transcript. The fusion is produced by transgenic splicing that removes the genomic sequence between part of the last exon of the SSF1 gene and exon 2 of the P2Y11 gene. Splicing occurs in the absence of a consensus splicing donor site. Northern blot analysis with probes specific for SSF1 and P2Y11 detected a common 5.6-kb transcript representing the SSF1-P2Y11 chimeric message in all 12 tissues examined. Transfection of the chimeric cDNA into CHO cells resulted in expression of a protein with an apparent molecular mass of about 90 kD.
Welch et al. (2000) identified PPAN as a putative tumor suppressor in HF cells, a nontransformed revertant of HeLa cells. Exposure of HF cells to a PPAN-specific ribozyme decreased PPAN expression and promoted growth in soft agar. The authors confirmed their results using ribozymes directed against other sites in the PPAN message. All ribozymes reduced the level of PPAN mRNA in cells and promoted anchorage-independent growth. Exogenous expression of PPAN in HeLa and lung tumor cells reduced their ability to grow in soft agar.
Suarez-Huerta et al. (2000) found upregulated expression of SSF1 in myeloid leukemia cells in response to granulocyte-colony stimulating factor (GCSF; 138970) and dibutyryl-cAMP.
PPAN-P2RY11 Spliced Read-Through Transcript
Communi et al. (2001) determined that expression of the SSF1-P2Y11 fusion protein in transfected CHO cells generated a cAMP response following ATP exposure. The response was similar to but weaker than that obtained with transfected P2Y11 alone. Expression of endogenous SSF1-P2Y11 chimeric transcript was upregulated during granulocyte differentiation of a myeloid leukemia cell line induced by retinoic acid.
Suarez-Huerta et al. (2000) determined that the SSF1 gene contains 12 exons and spans about 6 kb. There are 2 characteristic CpG islands upstream of exon 1 and exon 6, and both have TATA elements nearby, suggesting 2 potential promoter regions.
Suarez-Huerta et al. (2000) mapped the SSF1 gene to chromosome 19p31. SSF1 lies 5-prime to the P2Y11 gene. The EIF3S4 gene (603913) maps 3-prime to SSF1 on the opposite strand. Since chromosome 19p31 is not a valid location, the P2RY11 gene was presumed to be on chromosome 19p13, and this localization was confirmed by genomic sequence analysis.
Communi, D., Suarez-Huerta, N., Dussossoy, D., Savi, P, Boeynaems, J.-M. Cotranscription and intergenic splicing of human P2Y11 and SSF1 genes. J. Biol. Chem. 276: 16561-16566, 2001. [PubMed: 11278528] [Full Text: https://doi.org/10.1074/jbc.M009609200]
Suarez-Huerta, N., Boeynaems, J.-M., Communi, D. Cloning, genomic organization, and tissue distribution of human Ssf-1. Biochem. Biophys. Res. Commun. 275: 37-42, 2000. [PubMed: 10944437] [Full Text: https://doi.org/10.1006/bbrc.2000.3259]
Welch, P. J., Marcusson, E. G., Li, Q.-X., Beger, C., Kruger, M., Zhou, C., Leavitt, M., Wong-Staal, F., Barber, J. R. Identification and validation of a gene involved in anchorage-independent cell growth control using a library of randomized hairpin ribozymes. Genomics 66: 274-283, 2000. [PubMed: 10873382] [Full Text: https://doi.org/10.1006/geno.2000.6230]