PMID- 9465067 OWN - NLM STAT- MEDLINE DCOM- 19980319 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 95 IP - 4 DP - 1998 Feb 17 TI - Menin, the product of the MEN1 gene, is a nuclear protein. PG - 1630-4 AB - The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood. FAU - Guru, S C AU - Guru SC AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Goldsmith, P K AU - Goldsmith PK FAU - Burns, A L AU - Burns AL FAU - Marx, S J AU - Marx SJ FAU - Spiegel, A M AU - Spiegel AM FAU - Collins, F S AU - Collins FS FAU - Chandrasekharappa, S C AU - Chandrasekharappa SC LA - eng PT - Journal Article PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Luminescent Proteins) RN - 0 (MEN1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Peptides) RN - 0 (Proto-Oncogene Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Amino Acid Sequence MH - Cell Compartmentation MH - Cell Nucleus/*metabolism MH - Fluorescent Antibody Technique, Indirect MH - Green Fluorescent Proteins MH - Humans MH - Luminescent Proteins MH - Microscopy, Fluorescence MH - Molecular Sequence Data MH - Neoplasm Proteins/immunology/*metabolism MH - Nuclear Proteins/*metabolism MH - Peptides/chemistry/immunology MH - *Proto-Oncogene Proteins PMC - PMC19125 EDAT- 1998/03/21 00:00 MHDA- 1998/03/21 00:01 PMCR- 1998/08/17 CRDT- 1998/03/21 00:00 PHST- 1998/03/21 00:00 [pubmed] PHST- 1998/03/21 00:01 [medline] PHST- 1998/03/21 00:00 [entrez] PHST- 1998/08/17 00:00 [pmc-release] AID - 4314 [pii] AID - 10.1073/pnas.95.4.1630 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1630-4. doi: 10.1073/pnas.95.4.1630.