This report describes multiple endocrine neoplasia, type I (MEN1), which is a subtype of multiple endocrine neoplasia; MEN1 exhibits autosomal dominant inheritance. The human gene implicated in this disease, which also has the symbol MEN1 (Menin), is a nuclear scaffold protein that participates in the regulation gene transcription and has been identified as a component of a histone methyltransferase complex. Menin appears to interact with different sets of proteins in different tissues and to affect a wide range of cellular processes. MEN1 has been described as a tumor suppressor gene and has been implicated in several other cancers (MIM:613733). There is a single fly ortholog, Dmel\Mnn1, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A UAS construct of the human Hsap\MEN1 gene has been introduced into flies; overexpression of the human gene produces a heat-shock-sensitive phenotype similar to that observed for overexpression of Dmel\Mnn1.
Using drivers that result in lethal overexpression of UAS-Dmel\Mnn1, potential interacting partners have been identified in genetic screens. Roles in stress response and maintenance of genome integrity are supported.
[updated Nov. 2015 by FlyBase; FBrf0222196]
Multiple endocrine neoplasias are characterized by varying combinations of tumors derived from endocrine glands, including parathyroid, thyroid, pituitary, and adrenal glands. Frequently the tumors are nonmetastasizing, but can cause serious clinical effects due to the inappropriate secretion of endocrine substances. [from MIM:131100, MIM:171400, MIM:162300; 2014.07.03]
For additional information on classification and genetics see http://www.thyroidcancer.com/thyroid-cancer/medullary/genetics.
[MULTIPLE ENDOCRINE NEOPLASIA, TYPE I; MEN1](https://omim.org/entry/131100)
[MENIN 1 ; MEN1](https://omim.org/entry/613733)
A common sign of MEN1 is overactivity of the parathyroid glands (hyperparathyroidism). [from Genetics Home Reference, GHR_condition:multiple-endocrine-neoplasia, 2015.02.16]
MEN1 is characterized by varying combinations of tumors of parathyroids, pancreatic islets, duodenal endocrine cells, and the anterior pituitary. Most of the tumors are nonmetastasizing, but many can create clinical effects because of the secretion of endocrine substances such as gastrin, insulin, parathyroid hormone, prolactin, growth hormone, glucagon, or adrenocorticotropic hormone. (summary by Chandrasekharappa et al., 1997, pubmed:9103196) [from MIM:131100; 2015.02.16]
MEN1 is inherited as an autosomal dominant with 94% penetrance by age 50; it is caused by mutations in the MEN1 gene (summary by Chandrasekharappa et al., 1997, pubmed:9103196). Most identified mutations are predicted to result in loss of function. Development of the disease appears to require loss of heterozygosity, i.e., loss of the normal allele, in the affected tissue (multiple references cited in MIM:613733). MEN1 is described as a tumor suppressor gene. In most cases it appears that affected individuals inherit one affected copy of the MEN1 gene; tumors lose the other normal copy as a somatic event. Thus, although inherited as an autosomal dominant, the mechanism of tumorigenesis appears to be recessive. [from MIM:131100 and MIM:613733; 2015.02.16]
The MEN1 protein (menin) is a nuclear scaffold protein that regulates gene transcription by coordinating chromatin remodeling. Menin interacts with several transcription factors, including JUND, NFKB, and SMAD3. (summary by Canaff et al., 2012, pubmed:22275377) [from MIM:613733; 2015.02.16]
MEN1 protein is a component of a MLL/SET1 histone methyltransferase complex (H3K4 methylation). [from UniProt, entry O00255; 2015.02.16]
The menin protein is involved in a large and diverse range of biological functions; its interactions and regulation are complex. Recent work, in particular determination of its crystal structure with different interacting proteins, has allowed description of menin as a scaffold protein that interacts simultaneously with multiple proteins, perhaps facilitating formation of molecular complexes. Menin appears to interact with different sets of proteins in different tissues and affects a wide range of cellular processes, including regulation of transcription, both directly and by interactions with chromatin-modifying complexes, and regulation of multiple different signaling pathways. In addition, menin itself is regulated by multiple proteins, multiple signaling pathways, and several types of posttranslational modifications.
One to one: 1 human to 1 Drosophila.
Ortholog of human MEN1 (1 Drosophila to 1 human). Dmel\Mnn1 shares 38% identity and 51% similarity with human MEN1.
