MEN1
This gene encodes menin, a putative tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. In vitro studies have shown menin is localized to the nucleus, possesses two functional nuclear localization signals, and inhibits transcriptional activation by JunD, however, the function of this protein is not known. Two messages have been detected on northern blots but the larger message has not been characterized. Alternative splicing results in multiple transcript variants.
Function
Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity).
May be involved in DNA repair.
Biological Process
Brain development Source: Ensembl
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to glucose stimulus Source: Ensembl
Cellular response to peptide hormone stimulus Source: Ensembl
Chromatin organization Source: UniProtKB-KW
Decidualization Source: Ensembl
DNA repair Source: UniProtKB
Histone H3-K4 methylation Source: UniProtKB
MAPK cascade Source: UniProtKB
Mitotic cell cycle Source: Ensembl
Negative regulation of cell cycle Source: UniProtKB
Negative regulation of cell cycle G1/S phase transition Source: Ensembl
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of cell-substrate adhesion Source: Ensembl
Negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
Negative regulation of DNA-binding transcription factor activity Source: UniProtKB
Negative regulation of epithelial cell proliferation Source: Ensembl
Negative regulation of JNK cascade Source: UniProtKB
Negative regulation of osteoblast differentiation Source: MGI
Negative regulation of protein phosphorylation Source: UniProtKB
Negative regulation of telomerase activity Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Osteoblast development Source: MGI
Positive regulation of protein binding Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
Regulation of activin receptor signaling pathway Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Regulation of type B pancreatic cell proliferation Source: Ensembl
Response to gamma radiation Source: UniProtKB
Response to transforming growth factor beta Source: Ensembl
Response to UV Source: UniProtKB
Type B pancreatic cell differentiation Source: Ensembl
Cellular Location
Nucleus
Note: Concentrated in nuclear body-like structures. Relocates to the nuclear matrix upon gamma irradiation.
Involvement in disease
Familial multiple endocrine neoplasia type I (MEN1):
Autosomal dominant disorder characterized by tumors of the parathyroid glands, gastro-intestinal endocrine tissue, the anterior pituitary and other tissues. Cutaneous lesions and nervous-tissue tumors can exist. Prognosis in MEN1 patients is related to hormonal hypersecretion by tumors, such as hypergastrinemia causing severe peptic ulcer disease (Zollinger-Ellison syndrome, ZES), primary hyperparathyroidism, and acute forms of hyperinsulinemia.
MEN1 inactivating mutations are responsible for hyperfunctioning of the parathyroid glands and subsequent primary hyperparathyroidism. Primary hyperparathyroidism can occur in isolation or in association with multiple endocrine neoplasia.