Alternative titles; symbols
HGNC Approved Gene Symbol: PWP2
Cytogenetic location: 21q22.3 Genomic coordinates (GRCh38) : 21:44,107,399-44,131,181 (from NCBI)
PWP2 is a nucleolar protein that localizes predominantly to the dense fibrillar component, which is associated with early ribosomal RNA (rRNA)-processing events, and to the granular component, which is associated with late rRNA-processing events and assembly of ribosomal particles (Wada et al., 2014).
As part of a study to identify genes that might be implicated in Down syndrome, Lalioti et al. (1996) used exon trapping from cosmids that had been mapped to 21q22.3. An exon was isolated that encoded a predicted protein that was similar to the yeast PWP2 gene, a member of the tryptophan-aspartate (WD) repeat-containing superfamily. PWP2 is essential for viability and may play a role in the early G1 phase of the cell cycle. The complete coding region of human PWP2, obtained from fetal brain and fetal kidney cDNA libraries, encodes a 919-amino acid predicted protein with over 40% identity to the yeast protein. It also shares similarity to the beta subunits of the trimeric G protein family (e.g., 139380). The protein contains 5 complete WD repeats and an acidic domain between the second and third WD motifs. Northern blot analysis showed a 3.4-kb PWP2 mRNA in all fetal and adult tissues examined.
To identify candidate genes for diseases mapping to 21q22.3, Lafreniere et al. (1996) assembled a 770-kb cosmid and a BAC contig containing 8 tightly linked markers. They then restriction mapped these cosmids and BACs using 8 rare cutting enzymes, with the goal of identifying CpG-rich islands. A homology search using the sequence from one such island identified an expressed sequence tag (EST) with homology to PWP2 of yeast. Northern blot analysis revealed a 3.3-kb transcript that was highly expressed in all tissues tested. A 3,157-bp cDNA contained an open reading frame potentially encoding 919 amino acid residues. The predicted protein shows 42% identity and 57% similarity at the amino acid level to the yeast PWP2 protein.
By PCR of human prostate and testis cDNA libraries, Wada et al. (2014) cloned PWP2. Fluorescence-tagged PWP2 localized throughout nucleoli in transfected HeLa cells, predominantly to the dense fibrillar component and granular component. Fluorescence recovery after photobleaching showed that PWP2 associated stably with nucleoli, and association of PWP2 with nucleoli was not affected by inhibition of transcription.
Lafreniere et al. (1996) determined that the PWP gene is split into 21 exons, ranging in size from 53 to 516 bp, and spans an estimated 25 kb. The gene is transcribed in a 21cen-to-21qter direction, with its 5-prime end mapping approximately 195 kb proximal to the 5-prime end of the PFKL gene.
Based on cosmid contig analysis, Lalioti et al. (1996) mapped the PWP2 gene to chromosome 21q22.3, approximately 200 kb proximal to PFKL (171860).
Independently, Yamakawa et al. (1996) isolated the PWP2H gene from the 21q22.3 region.
Lafreniere, R. G., Rochefort, D. L., Chretien, N., Neville, C. E., Korneluk, R. G., Zuo, L., Wei, Y., Lichter, J., Rouleau, G. A. Isolation and genomic structure of a human homolog of the yeast periodic tryptophan protein 2 (PWP2) gene mapping to 21q22.3. Genome Res. 6: 1216-1226, 1996. [PubMed: 8973917] [Full Text: https://doi.org/10.1101/gr.6.12.1216]
Lalioti, M. D., Chen, H., Rossier, C., Shafaatian, R., Reid, J. D., Antonarakis, S. E. Cloning the cDNA of human PWP2, which encodes a protein with WD repeats and maps to 21q22.3. Genomics 35: 321-327, 1996. [PubMed: 8661145] [Full Text: https://doi.org/10.1006/geno.1996.0363]
Wada, K., Sato, M., Araki, N., Kumeta, M., Hirai, Y., Takeyasu, K., Furukawa, K., Horigome, T. Dynamics of WD-repeat containing proteins in SSU processome components. Biochem. Cell Biol. 92: 191-199, 2014. [PubMed: 24754225] [Full Text: https://doi.org/10.1139/bcb-2014-0007]
Yamakawa, K., Gao, D.-Q., Korenberg, J. R. A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3. Cytogenet. Cell Genet. 74: 140-145, 1996. [PubMed: 8893822] [Full Text: https://doi.org/10.1159/000134402]