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Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPkappa, mu, rho and PCP-2).

Besco J, Popesco MC, Davuluri RV, Frostholm A, Rotter A - BMC Genomics (2004)

Bottom Line: The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction.Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length.Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The Ohio State University, Columbus, Ohio 43210, USA. besco.1@osu.edu

ABSTRACT

Background: Four genes designated as PTPRK (PTPkappa), PTPRL/U (PCP-2), PTPRM (PTPmu) and PTPRT (PTPrho) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively.

Results: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from approximately 64 kb to approximately 1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPrho and PTPmu were most closely related, followed by PTPkappa. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction.

Conclusions: Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing.

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Organization of the murine PTPρ gene based on Celera genomic sequences. Left to right: Exon number, 3' splice site, exon sequence, 5' splice site, nucleotide number, exon size, intron size, intron phases and protein domain are shown. Amino acids (standard one letter code) are listed below the encoding nucleotides. D1 and D2 represent the first and second phosphatase domains, respectively; a to i designations indicate the individual exons within a single domain.
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Figure 2: Organization of the murine PTPρ gene based on Celera genomic sequences. Left to right: Exon number, 3' splice site, exon sequence, 5' splice site, nucleotide number, exon size, intron size, intron phases and protein domain are shown. Amino acids (standard one letter code) are listed below the encoding nucleotides. D1 and D2 represent the first and second phosphatase domains, respectively; a to i designations indicate the individual exons within a single domain.

Mentions: Murine and human R2B cDNA sequences were used to identify the corresponding genomic DNA contigs in the Celera and NCBI genomic databases, using BLAST and MEGABLAST programs. Alignments were used to establish exon and intron size, and junction phase. The genomic structure of human PTPρ has been reported previously [8]; the human PTPμ, κ and PCP-2 annotated structures are available from the authors (rotter.1@osu.edu) upon request. The sizes and genomic organization of the mouse R2B genes are derived from Figures 2, 3, 4, 5, and are summarized in Figure 6. The overall size of the mouse genes and their corresponding human orthologs was very similar. In general, gene size exceeded the average, especially in the case of PTPρ, which was the largest gene (~1,117,873 bp), followed by PTPμ (~686,308 bp), PTPκ (~521,813 bp) and PCP-2 (~63,884 bp) (Figure 6). The recent completion of the human chromosome 20 sequence [11] revealed that PTPρ is the largest confirmed gene on that chromosome, due primarily to expanded introns in the genomic region containing coding regions for the extracellular and juxtamembrane segments of the protein. Although the functional consequence of this large gene size is not clear, one predicted outcome is an extended time period for transcription of the corresponding mRNA.


Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPkappa, mu, rho and PCP-2).

Besco J, Popesco MC, Davuluri RV, Frostholm A, Rotter A - BMC Genomics (2004)

Organization of the murine PTPρ gene based on Celera genomic sequences. Left to right: Exon number, 3' splice site, exon sequence, 5' splice site, nucleotide number, exon size, intron size, intron phases and protein domain are shown. Amino acids (standard one letter code) are listed below the encoding nucleotides. D1 and D2 represent the first and second phosphatase domains, respectively; a to i designations indicate the individual exons within a single domain.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC373446&req=5

Figure 2: Organization of the murine PTPρ gene based on Celera genomic sequences. Left to right: Exon number, 3' splice site, exon sequence, 5' splice site, nucleotide number, exon size, intron size, intron phases and protein domain are shown. Amino acids (standard one letter code) are listed below the encoding nucleotides. D1 and D2 represent the first and second phosphatase domains, respectively; a to i designations indicate the individual exons within a single domain.
Mentions: Murine and human R2B cDNA sequences were used to identify the corresponding genomic DNA contigs in the Celera and NCBI genomic databases, using BLAST and MEGABLAST programs. Alignments were used to establish exon and intron size, and junction phase. The genomic structure of human PTPρ has been reported previously [8]; the human PTPμ, κ and PCP-2 annotated structures are available from the authors (rotter.1@osu.edu) upon request. The sizes and genomic organization of the mouse R2B genes are derived from Figures 2, 3, 4, 5, and are summarized in Figure 6. The overall size of the mouse genes and their corresponding human orthologs was very similar. In general, gene size exceeded the average, especially in the case of PTPρ, which was the largest gene (~1,117,873 bp), followed by PTPμ (~686,308 bp), PTPκ (~521,813 bp) and PCP-2 (~63,884 bp) (Figure 6). The recent completion of the human chromosome 20 sequence [11] revealed that PTPρ is the largest confirmed gene on that chromosome, due primarily to expanded introns in the genomic region containing coding regions for the extracellular and juxtamembrane segments of the protein. Although the functional consequence of this large gene size is not clear, one predicted outcome is an extended time period for transcription of the corresponding mRNA.

Bottom Line: The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction.Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length.Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, The Ohio State University, Columbus, Ohio 43210, USA. besco.1@osu.edu

ABSTRACT

Background: Four genes designated as PTPRK (PTPkappa), PTPRL/U (PCP-2), PTPRM (PTPmu) and PTPRT (PTPrho) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively.

Results: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from approximately 64 kb to approximately 1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPrho and PTPmu were most closely related, followed by PTPkappa. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction.

Conclusions: Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing.

Show MeSH
Related in: MedlinePlus