Molecular cloning and initial characterization of the MG61/PORC gene, the human homologue of the Drosophila segment polarity gene Porcupine.
Insect and vertebrate Porcupine genes encode multi-pass endoplasmic reticulum proteins involved in the processing of Wnt (wingless and int homologue) proteins, a class of secreted glycoprotein factors homologous to the Drosophila melanogaster segment polarity gene Wingless (Wg). Here we report the cloning of cDNAs encoding the human homologue of the Drosophila gene Porcupine (Porc), the characterization of its genomic structure and the quantitative analysis of its expression in a comprehensive panel of human tissues. The human Porcupine locus (MG61/PORC) spans 15 exons over approximately 12 kb of genomic sequence on Xp11.23. Real-time quantitative expression analysis reveals that MG61/PORC transcripts are expressed in multiple tissues, but are particularly abundant in the brain. Like its mouse and Xenopus homologues, MG61/PORC encodes four protein isoforms (A-D) generated through alternative splicing and expressed in a tissue-specific fashion. Finally, we present evidence indicating that MG61/PORC can influence the activity of a human Wnt7A expression construct in a T-cell factor-responsive reporter assay.
Caricasole
Andrea
A
GlaxoSmithKline, Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy.
Ferraro
Teresa
T
Rimland
Joseph M
JM
Terstappen
Georg C
GC
D000217:Acyltransferases; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D029721:Drosophila Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C103067:por protein, Drosophila; D000217:Acyltransferases; C491188:PORCN protein, human; C491187:Porcn protein, mouse