MEN1
Encyclopedia
Menin is a protein
that in humans is encoded by the MEN1 gene
. Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1
.
In vitro studies have shown that menin is localized to the nucleus, possesses two functional nuclear localization signal
s, and inhibits transcriptional activation by JunD
. However, the function of this protein is not known. Two messages have been detected on northern blot
s 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.
and the Karolinska Institute in Stockholm
mapped the MEN1 gene to the long arm of chromosome 11. The gene was finally cloned in 1997.
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.
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.
with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the MEN1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 or Wermer's syndrome is part of a group of disorders that affect the endocrine system.-Explanation:...
.
In vitro studies have shown that menin is localized to the nucleus, possesses two functional nuclear localization signal
Nuclear localization signal
A nuclear localization signal or sequence is an amino acid sequence which 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different...
s, and inhibits transcriptional activation by JunD
JunD
Transcription factor jun-D is a protein that in humans is encoded by the JUND gene.-Interactions:JunD has been shown to interact with ATF3, MEN1, DNA damage-inducible transcript 3 and BRCA1....
. However, the function of this protein is not known. Two messages have been detected on northern blot
Northern blot
The northern blot is a technique used in molecular biology research to study gene expression by detection of RNA in a sample. With northern blotting it is possible to observe cellular control over structure and function by determining the particular gene expression levels during differentiation,...
s but the larger message has not been characterized. Two variants of the shorter transcript have been identified where alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
affects the coding sequence. Five variants where alternative splicing takes place in the 5' UTR have also been identified.
History
In 1988, researchers at Uppsala University HospitalUppsala University Hospital
Uppsala University Hospital in Uppsala, Sweden is a teaching hospital for the Uppsala University Faculty of Medicine and the Nursing School. Uppsala University Hospital is owned and operated by the Uppsala County Council in cooperation with the university and serves, together with Enköping...
and the Karolinska Institute in Stockholm
Stockholm
Stockholm is the capital and the largest city of Sweden and constitutes the most populated urban area in Scandinavia. Stockholm is the most populous city in Sweden, with a population of 851,155 in the municipality , 1.37 million in the urban area , and around 2.1 million in the metropolitan area...
mapped the MEN1 gene to the long arm of chromosome 11. The gene was finally cloned in 1997.
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.
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. While these neoplasias are often benign (in contrast to tumours occurring in MEN2), 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.
Disease Database
MEN1 gene variant databaseInteractions
MEN1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- FANCD2FANCD2Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group currently includes FANCA, FANCB, FANCC, FANCD1 , FANCD2 , FANCE, FANCF, FANCG, and FANCL.- Function :Fanconi anemia is a genetically heterogeneous recessive disorder...
, - Glial fibrillary acidic proteinGlial fibrillary acidic proteinGlial fibrillary acidic protein is an intermediate filament protein that was thought to be specific for astrocytes in the central nervous system . Later, it was shown that GFAP is also expressed by other cell types in CNS, including ependymal cells...
, - JunDJunDTranscription factor jun-D is a protein that in humans is encoded by the JUND gene.-Interactions:JunD has been shown to interact with ATF3, MEN1, DNA damage-inducible transcript 3 and BRCA1....
, - NFKB1NFKB1Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and...
, - MLLMLL (gene)Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL gene.MLL is a histone methyltransferase deemed a positive global regulator of gene transcription...
, - RPA2RPA2Replication protein A 32 kDa subunit is a protein that in humans is encoded by the RPA2 gene.-Interactions:RPA2 has been shown to interact with Ku70, Replication protein A1, RPA3, DNA-PKcs, STAT3, Cyclin O, MEN1, TP53BP1 and Uracil-DNA glycosylase....
, and - VimentinVimentinVimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...
.