MEN1

Multiple endocrine neoplasia I
Crystal Structure of Human Menin. PDB 3u84
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3U84, 3U85, 3U86, 3U88, 4GPQ, 4GQ3, 4GQ4, 4GQ6, 4I80, 4OG3, 4OG4, 4OG5, 4OG6, 4OG7, 4OG8
Identifiers
Symbols	MEN1 ; MEAI; SCG2
External IDs	OMIM: 613733 MGI: 1316736 HomoloGene: 7418 ChEMBL: 1615381 GeneCards: MEN1 Gene
Gene ontology Molecular function • four-way junction DNA binding • Y-form DNA binding • chromatin binding • double-stranded DNA binding • protein binding • histone-lysine N-methyltransferase activity • protein binding, bridging • sequence-specific DNA binding • transcription regulatory region DNA binding • protein N-terminus binding • R-SMAD binding Cellular component • chromatin • nucleus • nucleoplasm • nucleolus • cytoplasm • cytosol • nuclear matrix • cleavage furrow • histone methyltransferase complex • protein complex Biological process • negative regulation of transcription from RNA polymerase II promoter • MAPK cascade • leukocyte homeostasis • negative regulation of protein phosphorylation • osteoblast fate commitment • osteoblast development • DNA repair • chromatin remodeling • transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • cellular response to DNA damage stimulus • cell cycle arrest • transforming growth factor beta receptor signaling pathway • brain development • negative regulation of cell proliferation • response to UV • response to gamma radiation • gene expression • hemopoiesis • positive regulation of transforming growth factor beta receptor signaling pathway • positive regulation of histone methylation • positive regulation of protein binding • regulation of activin receptor signaling pathway • histone lysine methylation • positive regulation of apoptotic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • negative regulation of sequence-specific DNA binding transcription factor activity • negative regulation of osteoblast differentiation • positive regulation of osteoblast differentiation • negative regulation of cyclin-dependent protein serine/threonine kinase activity • negative regulation of cell cycle • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation of JNK cascade • negative regulation of organ growth • embryonic skeletal system morphogenesis • positive regulation of cell division • negative regulation of telomerase activity • palate development • maternal process involved in female pregnancy Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4221	17283
Ensembl	ENSG00000133895	ENSMUSG00000024947
UniProt	O00255	O88559
RefSeq (mRNA)	NM_000244	NM_001168488
RefSeq (protein)	NP_000235	NP_001161960
Location (UCSC)	Chr 11: 64.57 – 64.58 Mb	Chr 19: 6.33 – 6.34 Mb
PubMed search

Menin is a protein that in humans is encoded by the MEN1 gene.^[1] Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1 (MEN-1 syndrome).^[2]

In vitro studies have shown that 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. Two variants of the shorter transcript have been identified where alternative splicing affects the coding sequence. Five variants where alternative splicing takes place in the 5' UTR have also been identified.^[1]

History

In 1988, researchers at Uppsala University Hospital and the Karolinska Institute in Stockholm mapped the MEN1 gene to the long arm of chromosome 11.^[3] The gene was finally cloned in 1997.^[4]

Genomics

The gene is located on long arm of chromosome 11 (11q13) between base pairs 64,570,985 and 64,578,765. It has 10 exons and encodes a 610-amino acid protein.

Over 1300 mutations have been reported to date (2010). The majority (>70%) of these are predicted to lead to truncated forms are scattered throughout the gene. Four - c.249_252delGTCT (deletion at codons 83-84), c.1546_1547insC (insertion at codon 516), c.1378C>T (Arg460Ter) and c.628_631delACAG (deletion at codons 210-211) have been reported to occur in 4.5%, 2.7%, 2.6% and 2.5% of families.^[2]

Clinical implications

The MEN1 phenotype is inherited via an autosomal-dominant pattern and is associated with neoplasms of the pituitary gland, the parathyroid gland, and the pancreas (the 3 "P"s). While these neoplasias are often benign (in contrast to tumours occurring in MEN2A), they are adenomas and, therefore, produce endocrine phenotypes.

MEN1 pituitary tumours are adenomas of anterior cells, typically prolactinomas or growth hormone-secreting. Pancreatic tumours involve the islet cells, giving rise to gastrinomas or insulinomas. In rare cases, adrenal cortex tumours are also seen.

Interactions

MEN1 has been shown to interact with:

• FANCD2,^[5]
• GFAP,^[6]
• JunD,^[7]
• NFKB1,^[6]
• MLL,^[8]
• RPA2,^[9] and
• VIM.^[10]

References

Further reading

External links

• GeneReviews/NIH/NCBI/UW entry on Multiple Endocrine Neoplasia Type 1
• MEN1 gene variant database
• MEN1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)