Identification and characterization of human DAPPER1 and DAPPER2 genes in silico.
WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled (DVL) proteins are WNT signaling molecules implicated in beta-catenin pathway and PCP pathway. Xenopus Dapper and Frodo are Dvl-binding proteins, showing 89.8% total-amino-acid identity. Here, we identified and characterized human homologs of Xenopus Dapper and Frodo using bioinformatics. Human DAPPER1 gene was located within human genome draft sequence NT_025892.9 (nucleotide position 39378960-39387891 in the forward orientation), and human DAPPER2 gene within NT_007302.10 (nucleotide position 660279-672480 in the reverse orientation). DAPPER1 (799-amino-acids) and DAPPER2 (774-amino-acids) showed 28.8% total-amino-acid identity. Seven DAPPER homologous (DAPH) domains, including DAPH2 (leucine zipper), DAPH3 (serine rich) and DAPH7 (PDZ binding), were conserved between DAPPER1 and DAPPER2. Phylogenetic analysis of vertebrate Dapper proteins revealed that Xenopus Dapper and Frodo are orthologs of human DAPPER1. DAPPER1 mRNA was expressed in amnion, fetal brain, eye, heart, adult brain medulla, gastric cancer (signet ring cell features), RER+ colon tumor, acute lymphoblastic leukemia, germ cell tumor, chondrosarcoma, and parathyroid tumor. DAPPER2 mRNA was expressed in placenta, genitourinary tract tumor, and endometrial adenocarcinoma. DAPPER1 and DAPPER2 genes were mapped to human chromosome 14q22.3 and 6q27, respectively. Human chromosome 14q22.3 is deleted in astrocytoma, while human chromosome 6q27 is deleted in breast, ovarian, and gastric cancer. Based on evolutionary and functional conservation of WNT signaling molecules as well as human chromosomal localization, DAPPER1 and DAPPER2 genes are predicted to be potent cancer-associated genes.
Katoh
Masuko
M
M&M Medical BioInformatics, Narashino 275-0022, Japan. mkatoh@ncc.go.jp
Katoh
Masaru
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002874:Chromosome Mapping; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D009687:Nuclear Proteins; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D029867:Xenopus Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C454443:DACT1 protein, Xenopus; C491683:DACT1 protein, human; C478653:DACT2 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins