NF2

Merlin ;
Moesin-ezrin-radixin-like protein ;
Neurofibromin-2 ;
Schwannomerlin ;
Schwannomin ;

disease:Defects in NF2 are a cause of schwannomatosis [MIM:162091]; also called congenital cutaneous neurilemmomatosis. Schwannomas are benign tumors of the peripheral nerve sheath that usually occur singly in otherwise normal individuals. Multiple schwannomas in the same individual suggest an underlying tumor-predisposition syndrome. The most common such syndrome is NF2. The hallmark of NF2 is the development of bilateral vestibular-nerve schwannomas; but two-thirds or more of all NF2-affected individuals develop schwannomas in other locations, and dermal schwannomas may precede vestibular tumors in NF2-affected children. There have been several reports of individuals with multiple schwannomas who do not show evidence of vestibular schwannoma. Clinical report suggests that schwannomatosis is a clinical entity distinct from other forms of neurofibromatosis.,disease:Defects in NF2 are the cause of neurofibromatosis 2 (NF2) [MIM:101000]; also known as central neurofibromatosis. NF2 is a genetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality.,function:Probably acts as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity.,similarity:Contains 1 FERM domain.,subcellular location:In a fibroblastic cell line, isoform 1 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia.,subcellular location:In a fibroblastic cell line, isoform 10 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia.,subcellular location:Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia.,subcellular location:Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia.,subunit:Interacts with SLC9A3R1, HGS and AGAP2. Interacts with LAYN (By similarity). Interacts with SGSM3.,tissue specificity:Widely expressed. Isoforms 1 and 3 are predominant, isoforms 4, 5 and 6 are expressed moderately, isoform 8 is found at low frequency. Isoforms 7, 9 and 10 are not expressed in adult tissues, with the exception of adult retina expressing isoform 10. Isoform 9 is faintly expressed in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10 at similar levels.,

formation of primary germ layer, mesoderm formation, regulation of protein amino acid phosphorylation, negative regulation of protein amino acid phosphorylation, regulation of cell-matrix adhesion, negative regulation of cell-matrix adhesion, regulation of DNA replication, negative regulation of protein kinase activity, cytoskeleton organization,negative regulation of cell adhesion, gastrulation, ectoderm development, mesoderm development, negative regulation of DNA replication, cell proliferation, negative regulation of cell proliferation, negative regulation of biosynthetic process, negative regulation of signal transduction, negative regulation of macromolecule biosynthetic process, negative regulation of phosphorus metabolic process, negative regulation of macromolecule metabolic process, regulation of protein kinase cascade, positive regulation of organelle organization, negative regulation of cell communication, negative regulation of protein kinase cascade, regulation of cell-substrate adhesion, negative regulation of cell-substrate adhesion, glial cell proliferation, Schwann cell proliferation, regulation of phosphate metabolic process, regulation of cell-cell adhesion, negative regulation of cell-cell adhesion, actin filament-based process, actin cytoskeleton organization, regulation of cell adhesion, regulation of cell migration, negative regulation of cell migration, negative regulation of cellular biosynthetic process, regulation of protein modification process,negative regulation of protein modification process, regulation of actin filament bundle formation, positive regulation of actin filament bundle formation, regulation of cellular protein metabolic process, negative regulation of cellular protein metabolic process, regulation of actin cytoskeleton organization, regulation of actin filament-based process, regulation of organelle organization, negative regulation of kinase activity, cell junction organization, regulation of locomotion,negative regulation of locomotion, gliogenesis, regulation of cell proliferation, regulation of phosphorylation, negative regulation of phosphorylation, odontogenesis of dentine-containing tooth, odontogenesis, regulation of tyrosine phosphorylation of STAT protein, regulation of tyrosine phosphorylation of Stat3 protein, negative regulation of tyrosine phosphorylation of Stat3 protein, regulation of tyrosine phosphorylation of Stat5 protein, negative regulation of tyrosine phosphorylation of Stat5 protein, negative regulation of tyrosine phosphorylation of STAT protein, negative regulation of catalytic activity, regulation of MAPKKK cascade, negative regulation of MAPKKK cascade, regulation of kinase activity, regulation of cellular component biogenesis, negative regulation of molecular function, cell-cell junction organization, regulation of protein kinase activity, negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, negative regulation of phosphate metabolic process, regulation of JAK-STAT cascade,negative regulation of JAK-STAT cascade, mesoderm morphogenesis, embryonic morphogenesis, tissue morphogenesis, regulation of peptidyl-tyrosine phosphorylation, negative regulation of peptidyl-tyrosine phosphorylation, regulation of DNA metabolic process, negative regulation of DNA metabolic process, positive regulation of cellular component organization, negative regulation of nitrogen compound metabolic process, regulation of phosphorus metabolic process, negative regulation of protein metabolic process, regulation of cell motion, negative regulation of cell motion, regulation of transferase activity, negative regulation of transferase activity, regulation of stress fiber formation, regulation of cytoskeleton organization, positive regulation of cytoskeleton organization,positive regulation of stress fiber formation,

[Isoform 1]: Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. In a fibroblastic cell line, isoform 1 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia. Colocalizes with MPP1 in non-myelin-forming Schwann cells. Binds with DCAF1 in the nucleus. The intramolecular association of the FERM domain with the C-terminal tail promotes nuclear accumulation. The unphosphorylated form accumulates predominantly in the nucleus while the phosphorylated form is largely confined to the non-nuclear fractions.; [Isoform 7]: Cytoplasm, perinuclear region. Cytoplasmic granule. Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia.; [Isoform 9]: Cytoplasm, perinuclear region. Cytoplasmic granule. Observed in cytoplasmic granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia.; [Isoform 10]: Nucleus. Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm, perinuclear region. Cytoplasmic granule. Cytoplasm, cytoskeleton. In a fibroblastic cell line, isoform 10 is found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes and filopodia.

Widely expressed. Isoform 1 and isoform 3 are predominant. Isoform 4, isoform 5 and isoform 6 are expressed moderately. Isoform 8 is found at low frequency. Isoform 7, isoform 9 and isoform 10 are not expressed in adult tissues, with the exception of adult retina expressing isoform 10. Isoform 9 is faintly expressed in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10 at similar levels.