Identification and characterization of rat Desert hedgehog and Indian hedgehog genes in silico.
Sonic hedgehog (SHH), Desert hedgehog (DHH) and Indian hedgehog (IHH) bind to Patched family receptors (PTCH1 and PTCH2) to transduce signals to GLI1, GLI2 and GLI3. GLI family transcription factors then activate transcription of Hedgehog target genes, such as FOXE1 and FOXM1 encoding Forkhead-box transcription factors. Hedgehog signaling pathway plays a pivotal role in a variety of human tumors, such as gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, prostate cancer, basal cell carcinoma and brain tumors. Rat orthologs for human DHH and IHH remain to be identified. Here, we identified and characterized rat Dhh and Ihh genes by using bioinformatics. Rat Dhh complete coding sequence (CDS) was determined by assembling nucleotide positions 426397-426963, 429715-429976 and 430244-430898 of the AC114446.3 genome sequence. Rat Ihh complete CDS was determined by assembling nucleotide positions 63433-64033, 66432-66693 and 68242-69169 of AC095777.6 genome sequence. Rat Dhh mRNA was expressed in prostate, duodenum and dorsal root ganglia, while rat Ihh mRNA was expressed in cartilage. Rat Dhh showed 99.7% total-amino-acid identity with mouse Dhh, and 96.5% total-amino-acid identity with human DHH. Rat Ihh and human IHH were shorter than mouse Ihh by 38 amino acids. Rat Ihh showed 97.6% total-amino-acid identity with mouse Ihh and 94.4% total-amino-acid identity with human IHH. Hedgehog family proteins consist of signal peptide, Hedgehog ligand peptide and C-terminal peptide. Hedgehog ligand peptides derived from mammalian Hedgehog family proteins were conserved well, while C-terminal peptides were relatively divergent. The HPLGMXXXXS motif in the C-terminus was conserved in Shh orthologs and Ihh orthologs, but not in Dhh orthologs.
Katoh
Yuriko
Y
M and M Medical BioInformatics, Hongo 113-0033, Japan.
Katoh
Masaru
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D053823:Hedgehog Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*
D053823:Hedgehog Proteins; D010455:Peptides; D012333:RNA, Messenger; C509239:SHH protein, human; D015534:Trans-Activators