Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1).
To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 gene. By an exon-amplification method, we recovered three exon-like sequences from one of these clones, cCI11-367, and using these sequences as probes we were able to isolate new clones from cerebrum, cerebellum, and fetal-liver cDNA libraries. Sequence analysis of these cDNA clones revealed that the transcribed gene, designated ZFM1, encodes a novel 623-amino-acid protein containing domains with interesting structural properties including a nuclear transport domain, a metal binding motif, and glutamine- and proline-rich regions. Analysis by the reverse-transcriptase polymerase chain reaction (RT-PCR) indicated that this gene is expressed in various tissues including endocrine organs such as thyroid gland, pancreas, adrenal gland, and ovary. These data suggest that ZFM1 might be a candidate for mutations that cause MEN1.
Toda
T
T
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Iida
A
A
Miwa
T
T
Nakamura
Y
Y
Imai
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005091:Exons; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000072260:RNA Splicing Factors; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; C107467:SF1 protein, human; D014157:Transcription Factors