Complete cDNA sequence and genomic organization of a human pancreas-specific gene homologous to Caenorhabditis elegans sel-1.
We have isolated the complete cDNA of a human SEL-1L gene, termed TSA305, that is abundantly expressed only in the pancreas. The cDNA contained an open reading frame of 2382 nucleotides, encoding a deduced protein of 794 amino acids whose predicted sequence showed 46% identity and 64% similarity with SEL-1 of Caenorhabditis elegans. SEL-1 is thought to be a negative regulator of the NOTCH, LIN-12, and GLP-1 receptors, which are required for differentiation and maturation of cells as well as cell-cell interactions during development in C. elegans. The degree of homology among these proteins suggests that the TSA305 gene product may be a member of the SEL-1 family and therefore involved in downregulation of mammalian Notch signaling. Direct sequencing revealed at least 20 coding exons in TSA305. We localized the gene to chromosome bands 14q24.3-q31 by radiation hybrid (RH) mapping and fluorescence in situ hybridization (FISH). The IDDM11 locus has been mapped in this region, and TSA305 may represent a candidate gene for predisposition in some families whose insulin-dependent diabetes is not linked to the HLA locus.
Harada
Y
Y
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Ozaki
K
K
Suzuki
M
M
Fujiwara
T
T
Takahashi
E
E
Nakamura
Y
Y
Tanigami
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary / Q000235:genetics*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008666:Metalloendopeptidases / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011817:Rabbits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D015801:Helminth Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; C101221:SEL-1 protein, C elegans; C117384:SEL1L protein, human; C492169:Sel1h protein, mouse; D008666:Metalloendopeptidases