Merlin (protein)
Encyclopedia
Merlin is a cytoskeletal protein
. In humans, it is a tumor suppressor protein
involved in Neurofibromatosis type II
. Sequence data reveal its similarity to the ERM protein family
.
The name "merlin" is an acronym for "Moesin-Ezrin-Radixin-Like Protein".
merlin gene (symbol Mer) is located on chromosome 1 and shares 58% similarity to its human homologue.
Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in early metazoa. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the protein 4.1 superfamily of proteins. Merlin is also known as schwannomin, a name derived from the most common type of tumor in the NF2 patient phenotype, the schwannoma.
protein. There are 10 known isoforms of human merlin molecule (the full molecule being 595 amino acid
s in length). The two most common these are also found in the mouse and are called type 1 and type 2, differing by the absence or presence of exon
16 or 17, respectively). All the known varieties have a conserved N-terminal part, which contains a FERM domain
(a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by an alpha-helical
domain and a hydrophilic tail. Merlin can dimer
ize with itself and heterodimerize with other ERM family proteins.
-cytoskeleton scaffolding protein, i.e. linking actin
filaments to cell membrane or membrane glycoprotein
s. Human merlin is predominantly found in nervous tissue
, but also in several other fetal tissues, and is mainly located in adherens junction
s. Its tumor suppressor properties are probably associated with contact-mediated growth inhibition
. Drosophila merlin is expressed in embryonic hindgut
, salivary gland
and imaginal disc
s and has apparently a slightly different role than in vertebrates.
The phosphorylation
of serine
518 is known to alter the functional state of merlin. The signaling pathway of merlin is proposed to include several salient cell growth controlling molecules, including eIF3c, CD44
, protein kinase A and p21 activated kinases.
Mutation
s of the NF2 gene cause a human autosomal dominant disease called neurofibromatosis type 2. It is characterized by the development of tumors of the nervous system, most commonly of bilateral vestibular schwannomas (also called acoustic neuromas). NF2 belongs to the tumor suppressor group of genes.
with HGS
, CUL4A
, EZR, SDCBP
, VPRBP
, RIT1
, SPTBN1
, MED28
and DDB1
.
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...
. In humans, it is a tumor suppressor protein
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
involved in Neurofibromatosis type II
Neurofibromatosis type II
Neurofibromatosis Type II is an inherited disease. The main manifestation of the disease is the development of symmetric, non-malignant brain tumours in the region of the cranial nerve VIII, which is the auditory-vestibular nerve that transmits sensory information from the inner ear to the...
. Sequence data reveal its similarity to the ERM protein family
ERM protein family
The ERM protein family consists of three closely related proteins, ezrin, radixin and moesin. The three paralogs, ezrin, radixin and moesin, are present in vertebrates whereas other species have only one ERM gene. Therefore, in vertebrates these paralogs likely arose by gene duplication.ERM...
.
The name "merlin" is an acronym for "Moesin-Ezrin-Radixin-Like Protein".
Genes
Human merlin is coded by the gene NF2 in Chromosome 22. Mouse merlin gene is located on the chromosome 11 and rat merlin gene on the chromosome 17. Fruit flyDrosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
merlin gene (symbol Mer) is located on chromosome 1 and shares 58% similarity to its human homologue.
Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in early metazoa. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the protein 4.1 superfamily of proteins. Merlin is also known as schwannomin, a name derived from the most common type of tumor in the NF2 patient phenotype, the schwannoma.
Structure
Vertebrate merlin is a 70 kDaDA
DA, da, or dA may refer to:* Da , a Tony-winning play by Hugh Leonard* Da , a movie adaptation of the play by Hugh Leonard* Adi Da, a spiritual leader once known as Da Free John, and Da Love-Ananda...
protein. There are 10 known isoforms of human merlin molecule (the full molecule being 595 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s in length). The two most common these are also found in the mouse and are called type 1 and type 2, differing by the absence or presence of exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
16 or 17, respectively). All the known varieties have a conserved N-terminal part, which contains a FERM domain
FERM domain
In molecular biology, the FERM domain is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton...
(a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by an alpha-helical
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
domain and a hydrophilic tail. Merlin can dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
ize with itself and heterodimerize with other ERM family proteins.
Function
Merlin is a membraneCell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
-cytoskeleton scaffolding protein, i.e. linking actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments to cell membrane or membrane glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s. Human merlin is predominantly found in nervous tissue
Nervous tissue
Nervous tissue is one of four major classes of vertebrate tissue.Nervous tissue is the main component of the nervous system - the brain, spinal cord, and nerves-which regulates and controls body functions...
, but also in several other fetal tissues, and is mainly located in adherens junction
Adherens junction
Adherens junctions are protein complexes that occur at cell–cell junctions in epithelial tissues, usually more basal than tight junctions...
s. Its tumor suppressor properties are probably associated with contact-mediated growth inhibition
Contact inhibition
Contact inhibition is the natural process of arresting cell growth when two or more cells come into contact with each other. Oncologists use this property to distinguish between normal and cancerous cells....
. Drosophila merlin is expressed in embryonic hindgut
Hindgut
The hindgut is the posterior part of the alimentary canal. In mammals, it includes the distal third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and rectum.-Blood flow:...
, salivary gland
Salivary gland
The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
and imaginal disc
Imaginal disc
An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation. Contained within the body of the larva, there are pairs of discs that will form, for instance, the wings or legs or antennae or other...
s and has apparently a slightly different role than in vertebrates.
The phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
518 is known to alter the functional state of merlin. The signaling pathway of merlin is proposed to include several salient cell growth controlling molecules, including eIF3c, CD44
CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene.- Tissue distribution and isoforms :...
, protein kinase A and p21 activated kinases.
Mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of the NF2 gene cause a human autosomal dominant disease called neurofibromatosis type 2. It is characterized by the development of tumors of the nervous system, most commonly of bilateral vestibular schwannomas (also called acoustic neuromas). NF2 belongs to the tumor suppressor group of genes.
Interactions
Merlin (protein) 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 HGS
HGS (gene)
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.-Interactions:HGS has been shown to interact with TSG101, STAM2, Merlin, DLG4, IL2RB, EPS15, CLTC and Signal transducing adaptor molecule.-Further reading:...
, CUL4A
CUL4A
Cullin-4A is a protein that in humans is encoded by the CUL4A gene.-Interactions:CUL4A has been shown to interact with Merlin, DDB2, CAND1, RBX1, DDB1 and P21.-Further reading:...
, EZR, SDCBP
SDCBP
Syntenin-1 is a protein that in humans is encoded by the SDCBP gene.-Interactions:SDCBP has been shown to interact with Merlin, ULK1, Interleukin 5 receptor alpha subunit, SOX4, RAB5A, EFNB1, TRAF6, GRIK1 and GRIK2.-Further reading:...
, VPRBP
VPRBP
Protein VPRBP is a protein that in humans is encoded by the VPRBP gene.-Interactions:VPRBP has been shown to interact with Merlin.-Further reading:...
, RIT1
RIT1
GTP-binding protein Rit1 is a protein that in humans is encoded by the RIT1 gene.-Interactions:RIT1 has been shown to interact with KLHL12 and Merlin.-Further reading:...
, SPTBN1
SPTBN1
Spectrin beta chain, brain 1 is a protein that in humans is encoded by the SPTBN1 gene.-Interactions:SPTBN1 has been shown to interact with Merlin.-Further reading:...
, MED28
MED28
Mediator of RNA polymerase II transcription subunit 28 is an enzyme that in humans is encoded by the MED28 gene.-Interactions:MED28 has been shown to interact with Merlin, Grb2 and MED26.-Further reading:...
and DDB1
DDB1
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.- Function :This gene encodes the large subunit of DNA damage-binding protein which is a heterodimer composed of a large and a small subunit. This protein functions in nucleotide excision repair...
.
External links
- GeneReviews/NCBI/NIH/UW entry on Neurofibromatosis 2
- FlyBase synopsis of gene Mer - Calculated spatial position of Radixin in membrane